The breasts are present in both sexes and have similar characteristics • The deep veins: consist of venae comitantes (veins which accom- until puberty when buy extra super avana 260 mg low price erectile dysfunction for women, in the female order extra super avana 260 mg with visa impotence guide, they enlarge and develop the capac- pany arteries). The breasts are essentially specialized skin The superﬁcial veins of the upper limb are of extreme clinical import- glands comprising fat, glandular and connective tissue. The base of the ance for phlebotomy and peripheral venous access. The most com- breast lies in a constant position on the anterior chest wall. It extends monly used sites are the median cubital vein in the antecubital fossa and from the 2nd to 6th ribs anteriorly and from the lateral edge of the ster- the cephalic vein in the forearm. A part of the breast, the axillary tail, extends laterally through the deep fascia beneath pectoralis to enter Lymphatic drainage of the chest wall and the axilla. Each breast comprises 15–30 functional ducto-lobular units upper limb (Fig. The lobes are separated by ﬁbrous Lymph from the chest wall and upper limb drains centrally via axillary, septa (suspensory ligaments) which pass from the deep fascia to the supratrochlear and infraclavicular lymph nodes. A lactiferous duct arises from each lobe and converges on the nipple. In its terminal por- Axillary lymph node groups tion the duct is dilated (lactiferous sinus) and thence continues to the There are approximately 30–50 lymph nodes in the axilla. The areola is the darkened arranged into ﬁve groups: skin that surrounds the nipple. Its surface is usually irregular due to • Anterior (pectoral) group: these lie along the anterior part of the multiple small tuberclesaMontgomery’s glands. They receive lymph from the upper anterior • Blood supply: is from the perforating branches of the internal part of the trunk wall and breast. The venous drainage corres- the medial wall of the axilla. They receive lymph from the upper pos- ponds to the arterial supply. Lymph from the medial breast drains into the They receive lymph from the upper limb and the breast. They receive lymph Lymph drainage in carcinoma of the breast from all of the groups mentioned above. From here lymph is passed to The axillary lymph nodes represent an early site of metastasis from prim- the thoracic duct (on the left) or right lymphatic trunks (see Fig. Damage to axillary lymphatics during surgical clearance of axillary nodes or resulting from radio- Lymph node groups in the arm therapy to the axilla increases the likelihood of subsequent upper limb • The supratrochlear group of nodes lie subcutaneously above the lymphoedema. The venous and lymphatic drainage of the upper limb and the breast 69 30 Nerves of the upper limb I Fig. These are the anterior primary rami of wrist and hand. The roots lie between scalenus anterior and scalenus • Effect of injury (Fig. They pass over the 1st rib to lie behind the clavicle. It pierces the deep fascia • Type: mixed sensory and motor nerve. Here it supplies the skin of the lateral forearm as far as the • Course: it passes through the quadrangular space with the posterior wrist. It provides: a motor supply to deltoid and teres minor; a sensory supply to the skin overlying deltoid; and an articu- The median nerve (C6,7,8,T1) (Fig. Loss of teres minor function is not detectable clinically. The median nerve passes deep to the bicipital aponeurosis lower half of deltoid. A short distance below this the anterior interosseous branch is given off. This branch descends The radial nerve (C5,6,7,8,T1) (Fig. In the forearm the median nerve lies between plexus. A short between the long and medial heads of triceps into the posterior com- distance above the wrist it emerges from the lateral side of ﬂexor partment and down between the medial and lateral heads of triceps. It ter- eminence (but not adductor pollicis); the branches to the 1st and 2nd minates by dividing into two major nerves: lumbricals; and the cutaneous supply to the palmar skin of the thumb, • The posterior interosseous nerveapasses between the two heads index, middle and lateral half of the ring ﬁngers. Nerves of the upper limb I 71 31 Nerves of the upper limb II Fig. These are very variable 72 Upper limb The ulnar nerve (C8,T1) (Fig. Supraclavicular branches • Origin: from the medial cord of the brachial plexus. It winds under the medial epicondyle and passes between the two heads of Infraclavicular branches ﬂexor carpi ulnaris to enter the forearm and supplies ﬂexor cari ulnaris • Medial and lateral pectoral nerves: supply pectoralis major and and half of ﬂexor digitorum profundus. Here • Medial cutaneous nerves of the arm and forearm. The ulnar nerve • Thoracodorsal nerve (C6,7,8): supplies latissimus dorsi. Erb–Duchenne paralysis • The deep terminal branchasupplies the hypothenar muscles as Excessive downward traction on the upper limb during birth can result well as two lumbricals, the interossei and adductor pollicis. This results in paralysis of the deltoid, • Effect of injury (Fig. The combined fracture of the medial epicondyle) or at the wrist due to a laceration. This has been termed the ‘waiter’s tip’ to the loss of interossei and lumbrical function the metacarpopha- position. The ‘clawing’ is attributed to the un- Klumpke’s paralysis opposed action of the extensors and ﬂexor digitorum profundus. Excessive upward traction on the upper limb can result in injury to the When injury occurs at the elbow or above, the ring and little ﬁngers T1 root. As the latter is the nerve supply to the intrinsic muscles of the are straighter because the ulnar supply to ﬂexor digitorum profun- hand this injury results in ‘clawing’ (extension of the metacarpopha- dus is lost. The small muscles of the hand waste with the exception langeal joints and ﬂexion of the interphalangeal joints) due to the of the thenar and lateral two lumbrical muscles (supplied by the unopposed action of the long ﬂexors and extensors of the ﬁngers. The loss is highly variable due to cervical sympathetic chain. Nerves of the upper limb II 73 32 The pectoral and scapular regions Costoclavicular Clavicle ligament Intra-articular disc Sternocleidomastoid Pectoralis major (clavicular head) Deltopectoral triangle Trapezius First costal Manubrium Deltoid cartilage sterni Thoracoacromial artery Cephalic vein Pectoralis major Fig. The main bond between the clavicle and the and clavicle.
The ﬁgure provides some rationale for choosing the optimal therapy before a planned transplantation buy cheapest extra super avana erectile dysfunction doctors boise idaho. The recommendation above is based on the fact that patients with a poor-risk karyotype have a lower chance to respond to IC than patients with normal cytogenetics ( 40% vs 70%) cheap extra super avana amex impotence erectile dysfunction. In patients with poor-risk karyotype and no identiﬁed donor, a soft “bridging” (although with a lower chance of response than with IC) that avoids the immediate toxicities of IC might be a reasonable alternative. Alternatively, patients with a good-risk karyotype have a good chance of responding to IC, which might therefore be considered as an option even in the immediate absence of a compatible donor. An stances, mainly in younger and medically ﬁt MDS patients (Figure important prerequisite before the initiation of IC may be the 2). A recent study by our group in AML patients 60 years of age availability of a suitable donor, mainly to be able rescuing nonre- in remission demonstrated less toxicity with RIC compared with sponding patients. In addition, several predictive factors for A large body of evidence exists from retrospective studies long-term outcome with HMAs have been determined (Figure 1) showing that systemic iron overload (SIO) in MDS patients and might therefore guide treatment decisions regarding when to (mainly as a result of RBC-TD before HCT) is associated with ﬁnally proceed to transplantation. Given the limitation of serum ferritin measurement, including its association with variables important for transplanta- better than MAC? In fact, we and others36,37 have recently presented data demonstrat- patients. Because the intensity of transplantation conditioning is linked to NRM, the development of RIC regimens and the use of ing that MRI-based liver iron concentration rather than ferritin is alternative donor sources have allowed the successful application of of prognostic signiﬁcance after allogeneic HCT. Labile plasma HCT in older and comorbid patients with MDS as well. Conversely, iron is released as a result of pretransplantation conditioning; RIC transplantations rely on the GVL effect and have been however, so far, the direct consequences of this observation in associated with a higher risk of disease relapse compared with vivo and on the posttransplantation period are largely unknown. It is recommended to use iron irradiation or busulfan and treosulfan, but no regimen has been chelation before HCT in selected patients with SIO, although no formally shown to be superior compared with others. The results of deﬁnitive cutoff for ferritin or liver iron has been systematically these studies have been summarized in several recent reviews. Alternatively, allogeneic HCT should be performed Nevertheless, MAC regimens are still considered in certain circum- earlier, before SIO becomes clinically evident. Hematology 2013 525 Relapse after allogeneic HCT: who is at risk and how MRD-guided therapy, which offers treatment to patients with to prevent it detectable MRD only after HCT. Until recently, the majority of Relapse still remains a major challenge in the care of patients after patients with MDS often lacked a disease-speciﬁc molecular marker allogeneic HCT, also due to the wide application of RIC transplanta- for MRD detection. Our group has recently reported the ﬁrst trial evaluating the factors inﬂuencing relapse risks after transplantation are disease efﬁcacy of a preemptive treatment with AZA for MRD deﬁned by a decreasing CD34 donor chimerism to prevent or delay hemato- burden before HCT (reﬂected by blast count and RBC-TD) and logic relapse in patients with CD34 MDS or AML after allogeneic cytogenetic risk group. In fact, in a recent publication by the Seattle 8 HSCT. Therefore, these patients need to be carefully evaluated for their curative potential with an allogeneic HCT to determine whether they should be exposed to the immediate hazards Summary of the procedure or if alternative treatment options exist. Should allogeneic HCT be a potential curative option in older patients with MDS? Yes, but the risks of the underlying disease Generally, the prognosis of MDS patients relapsing after allogeneic have to be balanced against comorbidities, hazards of the allogeneic HCT is poor, especially in the case of an early relapse within the ﬁrst procedure, patient’s preferences, and therapeutic alternatives. If 6 months after HCT because patients are still recovering from the possible, these patients should be treated within prospective trials sequelae of the overall approach. At this time, further intensive investigating the outcome of allogeneic HCT compared with therapeutic interventions often result in excessive NRM. The conventional treatment options with quality of life as a secondary optimal treatment strategy for MDS patients relapsing after HCT end point. In the absence of these studies, a careful individual also remains undeﬁned because prospective trials comparing differ- selection should be done. Most importantly, allogeneic HCT in its ent approaches are lacking. Several therapeutic approaches to current form needs to be further developed and improved, including controlling disease, including withdrawal of immunosuppression, ﬁnding a method for better prevention of GVHD. Additional attention should be drawn to the monitoring and treatment of MRD donor lymphocyte infusions, chemotherapy, and a second HCT, are using allogeneic HCT as a platform for MDS-speciﬁc interventions. In Hopefully, all of these efforts will help to better identify the particular, patients with poor-risk cytogenetics, overt disease, and a subgroup of MDS patients who will most beneﬁt from this short interval ( 1 year) from the time of allogeneic HCT have a approach. Recently, AZA has been investigated in the treatment of relapsed Acknowledgments MDS or AML patients after allogeneic HCT. Apart from the direct antiproliferative and cytotoxic effects Ades (Paris) for their helpful comments. Faber from system, thereby enhancing the GVL effect. Considering the Disclosures limited treatment opportunities in MDS patients relapsing after Conﬂict-of-interest disclosure: The author has received research HCT, prevention of disease recurrence after HCT should be one of funding and honoraria from Celgene and Novartis. Off-label drug the major goals for future clinical research. Due to its tolerabil- Correspondence ity, AZA can be administered on an outpatient basis, which is an Uwe Platzbecker, Universita¨tsklinikum Carl-Gustav-Carus, Me- ideal prerequisite for this kind of approach. In fact, a recent study dizinische Klinik I, Fetscherstraße 74, 01307 Dresden, Germany; conﬁrmed that early posttransplantation maintenance therapy with Phone: 49351/4582583/4373; Fax: 49351/4582583/4373; e-mail: AZA is feasible without serious side effects and without increased uwe. Another potentially appealing drug for mainte- allogeneic bone marrow transplantation for the myelodysplastic nance therapy is lenalidomide, mainly in case of del(5q) disease. Azacitidine (AZA) treatment prolongs overall survival (OS) in higher-risk MDS In general, during maintenance therapy, there will be a subset of patients compared with conventional care regimens (CCR): MDS patients who will never relapse after HCT and will thus Results of the AZA-001 phase III study. The optimal strategy to circumvent this situation is a 3. Allogeneic stem cell 526 American Society of Hematology transplantation for older advanced MDS patients: improved myelodysplastic syndromes or secondary acute myeloid leuke- survival with young unrelated donor in comparison with mia. Who is the better donor outcome of reduced-intensity hematopoietic cell transplanta- for older hematopoietic transplant recipients: an older-aged tion for older patients with acute myeloid leukemia in ﬁrst sibling or a young, matched unrelated volunteer? How I assess comorbidities versus bone marrow from unrelated donors. Parameters detected for graft-versus-host disease prevention. Prognostic factors for mide results in outcomes equivalent to those of contemporane- response and overall survival in 282 patients with higher-risk ous HLA-matched related and unrelated donor transplantation. TP53 mutations classiﬁcation, monosomal karyotype, and outcome after hema- in myelodysplastic syndrome are strongly correlated with topoietic cell transplantation for MDS or acute leukemia aberrations of chromosome 5, and correlate with adverse evolving from MDS. Outcome of high-risk azacitidine compared with that of conventional care regimens in myelodysplastic syndrome after azacitidine treatment failure. A decision analysis of for patients with myelodysplastic syndromes (MDSs) and acute reduced-intensity conditioning allogeneic hematopoietic stem myeloid leukemia following MDS. Pretransplantation novo high-risk myelodysplastic syndrome or secondary acute therapy with azacitidine vs induction chemotherapy and post- myelogenous leukemia: comparison with patients lacking do- transplantation outcome in patients with MDS.
The following bony landmarks and nal jugular and subclavian veins discount extra super avana uk erectile dysfunction drugs not working. This occurs posterior to the sterno- their corresponding vertebral levels are given: clavicular joints order extra super avana with american express erectile dysfunction juice drink. The breast • Subcostal plane (lowest part of the costal margin): L3. The position of the nipple is variable The trachea in the female but in the man it is usually in the 4th intercostal space in The trachea commences at the lower border of the cricoid cartilage (C6 the mid-clavicular line. It runs downwards in the midline and ends slightly to the right by bifurcating into the left and right main bronchi. The bifurca- The internal thoracic vessels tion occurs at the level of the sternal angle (T4/5). These arteries and veins descend 1 cm lateral to the edge of the sternum. The lines of pleural reﬂection pass behind the sternoclavicu- In mid-inspiration the highest part of the right dome reaches as far as lar joints to meet in the midline at the level of the sternal angle. The the upper border of the 5th rib in the mid-clavicular line. The left dome right pleura then passes downwards to the 6th costal cartilage. The left reaches only the lower border of the 5th rib. Surface anatomy of the thorax 27 11 The abdominal wall Serratus anterior Cut edge of external oblique Linea alba Linea semilunaris Cut edge of external oblique Internal oblique Fig. Internal oblique A: above the costal margin Inferior B: above the umbilicus epigastric Transversus abdominis C: above the pubic symphysis artery Peritoneum 28 Abdomen and pelvis (a) External oblique aponeurosis Superficial ring Ilioinguinal nerve Femoral artery and vein in Spermatic cord femoral sheath Femoral canal (b) Testicular artery and Transversus pampiniform plexus of veins Position of deep ring Vas deferens Lymphatics Internal oblique Transversalis fascia Internal spermatic Position of fascia superficial ring Cremasteric fascia and Femoral artery and vein in muscle (striated) femoral sheath Femoral canal External spermatic fascia Fig. A schematic cross section through the spermatic cord (a) The superficial inguinal ring. The external spermatic fascia has been removed (b) After removal of the external oblique Internal thoracic Anterior cutaneous branches of Musculophrenic intercostal nerves T7 Superior epigastric T10 T12 Lumbar Iliohypogastric (lateral branch) Para-umbilical veins Iliohypogastric anastomose with (anterior cutaneous) epigastric veins Ilioinguinal Fig. The two lower intercostal and four lumbar arteries supply the extraperitoneal fat, and parietal peritoneum. The lateral lower six thoracic intercostal and iliohypogastric (L1) nerves. The canal passes obliquely from the deep inguinal ring brane. The ﬁbrous fascial layer is in a medial direction to the superﬁcial inguinal ring. It lies half- way between the anterior superior iliac spine and the pubic tubercle. These comprise: external oblique, internal oblique, transversus abdo- • The superﬁcial ring: is not a ring but a triangular-shaped defect in minis, rectus abdominis and pyramidalis (see Muscle index, p. It contains also the super- • Superior: internal oblique arches posteriorly to form the roof of the ior and inferior epigastric vessels and anterior rami of the lower six canal. The conjoint tendon (the combined common insertion of the inter- anterior abdominal wall. The linea alba represents the fusion of the nal oblique and transversus into the pectineal line) forms the medial aponeuroses in the midline. Throughout the major part of the length of part of the posterior wall. The composition of the sheath Contents of the inguinal canal is, however, different above the costal margin and above the pubic • The spermatic cord (or round ligament in the female). These are the: rectus muscle, leaving only the transversalis fascia. The lateral border of the rectusathe linea semilunarisacan usually • Cremasteric fascia and muscle: from the internal oblique be identiﬁed in thin subjects. It crosses the costal margin in the trans- aponeurosis. Three tendinous intersections ﬁrmly attach the anterior sheath wall The contents of the spermatic cord include the: to the muscle itself. They are situated at the level of the xiphoid, the • Ductus (vas) deferens (or round ligament). These give the abdominal ‘six- • Testicular artery: a branch of the abdominal aorta. Short gastric Red labels: ventral branches Spleen Blue labels: lateral branches Green labels: branches to body wall Gastroduodenal Superior Pancreatic pancreatico- branches duodenal Left Right gastroepiploic gastro- epiploic Omental branch Inferior pancreatico- duodenal Jejunal and Superior ileal branches Superior mesenteric pancreaticoduodenal artery Inferior Fig. Superior The three primary branches are labelled in red mesenteric Middle colic Jejunal and ileal branches Right colic Ileocolic Anterior and posterior caecal branches Fig. Note the anastomosis with the inferior rectal artery (green) halfway down the anal canal The abdominal aorta (Fig. It descends in the of the oesophagus to the second part of the duodenum. The vertebral part of the duodenum to the distal transverse colon. The main relation to the right of the abdominal transverse colon to the upper half of the anal canal. These include the: • Ileocolic artery: passes in the root of the mesentery over the right • Left gastric artery: passes upwards to supply the lower oesophagus ureter and gonadal vessels to reach the caecum where it divides into ter- by branches which ascend through the oesophageal hiatus in the minal caecal and appendicular branches (Fig. The left gastric then descends in the lesser omentum along • Jejunal and ileal branches: a total of 12–15 branches arise from the the lesser curve of the stomach which it supplies. These branches divide and reunite within the • Splenic artery: passes along the superior border of the pancreas small bowel mesentery to form a series of arcades which then give rise in the posterior wall of the lesser sac to reach the upper pole of the left to small straight terminal branches which supply the gut wall. From here it passes to the hilum of the spleen in the lienorenal • Right colic artery: passes horizontally in the posterior abdominal ligament. The splenic artery also gives rise to short gastric branches, wall to supply the ascending colon. It then passes between These arise from the abdominal aorta at the level of L2. Before reaching the porta hepatis it divides into right and left on the posterior abdominal wall to reach the ovary in the female, or pass hepatic arteries and from the right branch the cystic artery is usually through the inguinal canal in the male to reach the testis. Prior to its ascent towards the porta hepatis the hepatic artery gives rise to gastroduodenal and right gastric branches. The former The inferior mesenteric artery arises from the abdominal aorta at the passes behind the ﬁrst part of the duodenum and then branches further level of L3. It passes downwards and to the left and crosses the left into superior pancreaticoduodenal and right gastroepiploic branches. Its branches include: curvature to supply the stomach.
There were allergic reactions in 5% of the Italian group 260mg extra super avana with mastercard impotence jokes, none serious purchase extra super avana online from canada erectile dysfunction 16, whereas 4% in the Danish study, 2 cases of which were serious anaphylactic reactions. Progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy is a serious, progressive neurologic disorder caused by infection of the central nervous system by JC virus, a member of the papovavirus family. JC virus is carried in a latent form by 70% to 75% of the general population but generally does not cause symptoms. Progressive multifocal leukoencephalopathy is rare, but when it occurs it frequently results in irreversible neurologic deterioration and death, and there is no known 186 effective treatment for the disease. From initial trial data, 2 patients with multiple sclerosis and 1 with Crohn’s disease ® treated with natalizumab (Tysabri ) were reported to have developed progressive multifocal 187-189 leukoencephalopathy. An evaluation of all patients who had received natalizumab in clinical trials or via compassionate use criteria or after US Food and Drug Administration 190 approval (n=3417) was undertaken. Data were then examined by an expert panel; 43 potential cases were ruled out, and 1 patient refused further follow-up. The authors then estimated the incidence of progressive multifocal leukoencephalopathy at 1. Because these 3 patients had also been receiving immunomodulators or immunosuppressants, it was recommended that natalizumab be used only as monotherapy. Since that time, additional cases have been reported in patients on monotherapy as well. The risk appeared to increase with greater time on therapy. According to the US Food and Drug Administration who have reviewed all the cases of progressive multifocal leukoencephalopathy, there have been no reports of progressive multifocal leukoencephalopathy in patients treated for ® less than 12 months since the remarketing of natalizumab (Tysabri ) in 2006. In patients treated with 24 to 36 infusions, the overall worldwide rate and the rate in the United States of developing progressive multifocal leukoencephalopathy is similar to the rate seen during clinical trials (1 case per 1000 patients treated). For unknown reasons, the rate outside of the United States is approximately 2 cases per 1000 patients. As of June 2010, 55 cases of progressive multifocal leukoencephalopathy associated with natalizumab use have been reported worldwide. At the first signs of progressive multifocal leukoencephalopathy, patients are to receive plasma ® exchange or immunoadsorption to decrease circulating natalizumab (Tysabri ) levels which can lead to the development of immune reconstitution inflammatory syndrome. Immune reconstitution inflammatory syndrome is characterized by a severe inflammatory response as the immune system recovers and can cause a profound decline in a patient’s condition. Mitoxantrone ® No studies offered direct evidence comparing mitoxantrone (Novantrone ) to another disease- modifying drug for multiple sclerosis. A well-conducted systematic review compared ® 92 mitoxantrone (Novantrone ) to placebo using data from 4 trials (Table 37). Pooled data found withdrawals due to adverse events to be significantly higher among mitoxantrone patients Disease-modifying drugs for multiple sclerosis Page 76 of 120 Final Report Update 1 Drug Effectiveness Review Project relative to placebo (9. No serious adverse events were reported in any of the 4 included trials, including serious cardiac events. A non-serious decrease in left ventricular ejection fraction below 50% was reported in 5 of 138 (3. Other commonly-reported adverse events in mitoxantrone patients were nausea and vomiting, alopecia, amenorrhea, and urinary tract infection (Table 37). Adverse events in placebo-controlled trials of mitoxantrone Adverse event Mitoxantrone (%) Placebo (%) P value a Amenorrhea 20/77 (26%) 0/75 (0%) P=0. One small trial compared mitoxantrone to placebo in 51 patients with relapsing-remitting 72 multiple sclerosis. No patients reported any serious adverse events, and there were no withdrawals from either group due to adverse events. Transient amenorrhea was reported in 5 of 17 (29%) women in the mitoxantrone group and these cases resolved with treatment cessation. Other adverse events reported in mitoxantrone patients were nausea and vomiting (18%), urinary tract infection (6%), headache (6%), and respiratory infection (4%). For unexplained reasons, no adverse event data for the placebo arm was provided by the study authors. One non-randomized open-label study compared mitoxantrone to cyclophosphamide whereby patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis were alternately prescribed 1 of the study drugs, although given the safety profile of each drug, patients with higher post-void residual were given mitoxantrone and patients with 191 reduced left ventricular systolic function were given cyclophosphamide. The mean age of patients in the mitoxantrone group was 43. Consistent with the placebo-controlled trials, the most common side effects were nausea (27%), amenorrhea (38%), and mild alopecia (17%). The drug was discontinued in 5% of patients due to side effects. Transthoracic echocardiograms were repeated at 6, 12, and 24 months and no cases of cardiac side effects were reported. Small (N=7 to 31) before-after studies of patients with various categories of multiple 192-194 2 sclerosis have been reported. These studies used differing dosing and schedules (5 mg/m 2 2 every 3 months x 12, compared with 8 mg/m every 3 weeks x 7, compared with 10mg/m every 2 month x 3, then every 3 months to a total dose of 150 mg/m ). The most common adverse events reported were nausea (39 to 71%), alopecia (13 to 29%), fatigue (7%), and in 1 study 57% of women reported transient secondary amenorrhea. Disease-modifying drugs for multiple sclerosis Page 77 of 120 Final Report Update 1 Drug Effectiveness Review Project Cardiotoxicity 2 Thirteen percent of 31 patients receiving 5 mg/m every 3 months required discontinuation of treatment due to reduction of left ventricular ejection fraction to = 50%, although cumulative 192 dose at the time of discontinuation was not reported. In a very small study, 7 patients who had 2 received cumulative doses of 66 to 198 mg/m had “normal quantitative cardiac function” after 194 12 months of treatment. The meta-analysis was based on patient data (N=1378) from 1 phase-III trial and 2 open-label, 96 noncomparative studies available in abstract form only. The full results of the trial were included in the Martinelli Boneschi systematic review discussed above. Two cases of fatal congestive heart failure were reported (0. Asymptomatic left ventricular ejection fraction<50% was reported in 17/779 patients for whom data was available (2. Further analysis by the study’s authors 2 found that patients receiving a cumulative dose <100mg/m had a lower incidence of 2 asymptomatic left ventricular ejection fraction <50% than those patients receiving ≥100mg/m , although this did not reach statistical significance (incidence of 1. Observational studies have reported a reduction in left ventricular ejection fraction in the 196, 197 3-5 % range. One small study of 18 patients monitored cardiac function with repeat transthoracic echocardiograms every 3 months before each infusion and found 4 cases in 18 198 patients (22%). Further monitoring found that these were transient in 2 of these cases, bringing their percentage to 11%, but they do suggest that more frequent cardiac monitoring might influence the infusion regimen and minimize risk of non-reversible cardiotoxicity. Long-term randomized trials would help to better appreciate whether these transient changes have any long- term associated harm. Cancer The risk of therapy-related acute leukemia (t-AL) in a mixed multiple sclerosis population (N=1378) was assessed in a meta-analysis that included patient data from 3 studies (1 placebo- 199 controlled trial and 2 open-label studies; mean length of follow-up 36 months).
Amphotericin B Manufacturer: Bristol-Myers Squibb (Amphotericin B) buy discount extra super avana 260 mg on-line impotence kit, Gilead (Ambisome) generic 260 mg extra super avana with mastercard how to get erectile dysfunction pills, Dermapharm (Ampho-Moronal). Indications and trade names: amphotericin B is indicated for organ mycoses and generalized mycoses, primarily candidiasis, aspergillosis, cryptococcosis and histo- plasmosis. The indication also Drug Profiles 679 applies to visceral leishmaniasis. Suspension and tablets are only licensed for oral candidiasis. Amphotericin is a component of the following: • Amphotericin B injection vial, 50 mg powder • AmBisome injection vial, 50 mg dry agent • Ampho-Moronal suspension, 100 mg/ml • Ampho-Moronal lozenges, 10 mg Dosage: when using Amphotericin B, always apply test dose first (see below). In case of overdosage, respiratory and cardiac arrest can occur. Dose of Ambisome: initial 1 mg/kg QD, if necessary may be gradually increased to 3 mg/kg. Side effects: nephrotoxicity, hypokalemia and gastrointestinal complaints. Frequent: fever, chills, and hypotension approximately 10–20 min after starting infusions. Thrombophlebitis (non-liposomal amphotericin B only via a central venous line). Side effects are generally less severe with Ambisome. Comments: daily monitoring of electrolytes, creatinine, BUN, ALT, blood count. A central venous line is always necessary due to hypokalemia and the usually required potassium substitution. Always test first dose with 5 mg in 250 ml 5% glucose over 30–60 min with strict monitoring of blood pressure and pulse for the first hour. If the test dose is tolerated, then half of the planned main- tenance dose may subsequently be given on the same day. In cases of fever or chills (can be very impressive), the following may be repeated after 30 min: 50 mg pethi- dine (e. If side effects are severe, then switch to Ambisome, which is probably not more effective than conventional amphotericin B but significantly better tolerated and less nephrotoxic (no test dose, no prehydration, no central line necessary). Never mix amphotericin infusions, and always protect from light. The longer the infusion time (>3 hours), the better the tolerability. Amprenavir (Agenerase), replaced by fosamprenavir in 2008. Indications and trade names: HIV infection, as part of a combination, adults and children >6 years of age, for both pretreated and ART-naïve patients. Atazanavir is a component of the following: • Reyataz capsules, 150 mg, 200 mg, 300 mg • Reyataz oral powder for oral suspension, 50 mg packet • Evotaz film-coated tablets, 300 mg plus 150 mg cobicistat Dosage: 300 mg atazanavir QD combined with 100 mg ritonavir (instead of riton- avir, cobicistat may also be used as a booster). If ritonavir is not tolerated, atazanavir can be given 400 mg QD, without booster (combination with tenofovir should then be avoided). If atazanavir is combined with efavirenz (even if boosted), increase 680 Drugs dosage to 400 mg. The capsules should be swallowed (not chewed) and taken with a meal. Recommended dosage of atazanavir/r in pediatric patients as follows: Children less than 15 kg: not recommended; 15–20 kg: 150/100 mg; 20–40 kg: 200/ 100 mg; at least 40 kg: 300/100 mg. Side effects: very often hyperbilirubinemia (up to 50%), also with jaundice; rarer elevated transaminases. Diarrhea, nausea, vomiting, headache, insomnia and abdom- inal pain are also relatively rare. In contrast to other PIs, there is less dyslipidemia. Interactions, warnings: do not combine with indinavir. Atazanavir is contraindicated in patients with Child-Pugh B and C. Combinations with the following pharmaceuticals are contraindicated: cisapride, midazolam, triazolam, simvastatin, lovastatin, ergotamines, calcium antagonists. Life-threatening interactions may occur with concomitant administration of amio- darone, lidocaine (systemic dosing), tricyclic anti-depressants and quinidine (measure plasma levels). Do not combine boosted atazanavir with clarithromycin. Reduce the rifabutin dose by 75% (instead of 300 mg daily, give only 150 mg every other day or three times per week). Be careful with proton pump inhibitors (PPI) and antacids! The most important side effect is hyper- bilirubinemia, which often presents as jaundice. There are some relevant interactions – primarily with proton pump inhibitors and antacids, but also with tenofovir, efavirenz, nevirapine and ddI. For detailed information see page: 92 Atovaquone Manufacturer: GlaxoSmithKline. Indications and trade names: mild or moderate PCP in cases of hypersensitivity to cotrimoxazole; in combination with proguanil for the treatment and prophylaxis of malaria. Off-label, can be used as PCP prophylaxis (as reserve) and as acute treat- ment of cerebral toxoplasmosis. Atovaquone is a component of the following: • Wellvone suspension, 750 mg atovaquone/5 ml • Malarone film-coated tablets, 250 mg atovaquone and 100 mg proguanil Dosage: as therapy for acute PCP (or toxoplasmosis): 750–1500 mg BID (i. Side effects: nausea, vomiting and diarrhea are frequent (but often mild), as are rashes, which occur in approximately 20% of patients. Interactions, warnings: atovaquone should be taken with meals, ideally with fatty dishes, as this improves absorption. Rifampin and possibly also rifabutin lower plasma levels of atovaquone by 50%. Atovaquone is considerably more expen- sive than other drugs for PCP prophylaxis. Drug Profiles 681 Atripla Manufacturer: co-manufactured by Gilead Sciences, Bristol-Myers Squibb and MSD. Indications and trade name: adult HIV-infected patients. It should be noted that in Europe, approval for Atripla is more strict than in the US. The EMA has only approved the use of Atripla in patients who have already achieved virologic sup- pression to below 50 copies/ml on their current ART for at least three months. Furthermore, patients must not have experienced virologic failure with an earlier treatment combination or be known to have resistance to any of the drugs in Atripla. Comments: the first complete ART in one single tablet per day.
Insomnia Page 82 of 86 Final Report Update 2 Drug Effectiveness Review Project Appendix D buy extra super avana 260 mg with mastercard impotence erecaid system esteem battery operated vacuum impotence device. Summary of results of trials comparing newer insomnia drugs compared with benzodiazepines (No new trials were identified for Update #2) (No extra super avana 260mg mastercard erectile dysfunction doctors in south jersey. Rebound insomnia: Rebound, withdrawal effects b See Evidence Tables 4 through 9 for details of the population, interventions, and outcomes of these studies. Insomnia Page 84 of 86 Final Report Update 2 Drug Effectiveness Review Project References 1. Walsh JK, Fry J, Erwin CW, Scharf M, Roth T, Vogel GW. Efficacy and tolerability of 14-day administration of zaleplon 5 mg and 10 mg for the treatment of primary insomnia. Dose-response effects of zaleplon as compared with triazolam (0. Fleming J, Moldofsky H, Walsh JK, Scharf M, Nino MG, Radonjic D. Comparison of the residual effects and efficacy of short term zolpidem, flurazepam and placebo in patients with chronic insomnia. Leppik IE, Roth-Schechter GB, Gray GW, Cohn MA, Owens D. Double-blind, placebo- controlled comparison of zolpidem, triazolam, and temazepam in elderly patients with insomnia. Zolpidem is not superior to temazepam with respect to rebound insomnia: a controlled study. Subjective hypnotic efficacy of trazodone and zolpidem in DSMIII-R primary insomnia. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Rebound insomnia after abrupt discontinuation of hypnotic treatment: Double-blind randomized comparison of zolpidem versus triazolam. Monti JM, Attali P, Monti D, Zipfel A, de la Giclais B, Morselli PL. Zolpidem and rebound insomnia--a double-blind, controlled polysomnographic study in chronic insomniac patients. Nair NP, Schwartz G, Dimitri R, Le Morvan P, Thavundayil JX. A dose-range finding study of zopiclone in insomniac patients. Comparison of zopiclone and flurazepam treatments in insomnia. Effects of flurazepam and zopiclone on the performance of chronic insomniac patients: a study of ethanol-drug interaction. The influence of age-dependent pharmacokinetics on the pharmacodynamics of hypnotic drugs: comparison of two hypnotics with different half- lives. Zopiclone versus flurazepam in insomnia: prolonged administration and withdrawal. Zopiclone and nitrazepam: a multicenter placebo controlled comparative study of efficacy and tolerance in insomniac patients in general practice. Insomnia Page 85 of 86 Final Report Update 2 Drug Effectiveness Review Project 16. Zopiclone versus nitrazepam: a double-blind comparative study of efficacy and tolerance in elderly patients with chronic insomnia. Effects of zopiclone and temazepam on sleep, behaviour and mood during the day. Double-blind, placebo-controlled study comparing effects of zopiclone and temazepam on cognitive functioning of insomniacs. A comparative study of zopiclone and triazolam in patients with insomnia. Rebound insomnia after hypnotic withdrawal in insomniac outpatients. European Archives of Psychiatry & Clinical Neuroscience. Comparative efficacy and safety of triazolam and zopiclone in insomniacs seen in general practice. Current Therapeutic Research - Clinical and Experimental. Fleming JA, McClure DJ, Mayes C, Phillips R, Bourgouin J. A comparison of the efficacy, safety and withdrawal effects of zopiclone and triazolam in the treatment of insomnia. Insomnia Page 86 of 86 Drug Class Review Newer Drugs for Insomnia Final Report Update 2 Evidence Tables October 2008 The Agency for Healthcare Research and Quality has not yet seen or approved this report. The purpose of this report is to make available information about comparative effectiveness and safety profiles of different drugs within a pharmaceutical class. This report does not provide usage guidelines nor should it be read as an endorsement of, or recommendation for, any particular drug, use, or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. McDonagh, PharmD Sujata Thakurta, MPA:HA Po-Yin Yen, MS Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2008 by Oregon Health & Science University Portland, Oregon 97239. Final Report Update 2 Drug Effectiveness Review Project TABLE OF CONTENTS Evidence Table 1. Characteristics of head-to-head trials of newer insomnia drugs……………. Results of head-to-head trials of newer insomnia drugs…………………….. Characteristics of placebo controlled trials of newer insomnia drugs…….. Results of placebo-controlled trials of newer insomnia drugs…………….. Characteristics of active control trials of newer insomnia drugs…………. Results of active control trials of newer insomnia drugs………………….. Adverse events reported in trials of newer insomnia drugs……………… 221 Evidence Table 8a. Quality assessment of randomized controlled trials of newer drugs for insomnia………………………………………………………………………………………………239 Evidence Table 8b. Quality assessment of randomized controlled trials (new for Update #2)……………………………………………………………………………………………261 Evidence Table 9.
The ﬁbres of this tough membrane run obliquely down- • Muscles (Fig discount 260 mg extra super avana free shipping erectile dysfunction treatment testosterone. The muscles of the superﬁcial layer arise from the common extensor origin on the lateral epicondyle of the humerus buy extra super avana 260mg line impotence exercises for men. The muscles of the The contents of the anterior (ﬂexor) compartment of deep layer arise from the backs of the radius, ulna and interosseous the forearm membrane (see Muscle index, p. With the exceptions of ﬂexor carpi ulnaris and the ulnar half The forearm 85 38 The carpal tunnel and joints of the wrist and hand Ulna nerve and artery Thenar Hypothenar muscles muscles Flexor retinaculum Flexor Median nerve carpi radialis Tendons of flexor Vein Flexor pollicis digitorum superficialis longus Tendons of flexor Trapezium digitorum profundus Trapezoid Hamate Capitate Fig. It is through this tunnel that most, but not all, of the fore- by movements at the midcarpal joint. Of a total of 80° of wrist ﬂexion arm tendons and the median nerve pass. The ﬂexor retinaculum is the majority occurs at the midcarpal joint whereas in extension a corres- attached to four bony pointsathe pisiform, the hook of the hamate, the ponding increased amount occurs at the wrist joint. The muscles acting on the wrist joint include: The carpal tunnel is narrow and no arteries or veins are transmitted • Flexion: all long muscles crossing the joint anteriorly. The median nerve is how- • Extension: all long muscles crossing the joint posteriorly. Note that the ulnar nerve and artery • Adduction: ﬂexor carpi ulnaris and extensor carpi ulnaris. It can be seen that ﬂexor pollicis longus participates in wrist movement (see above). This is a saddle-shaped joint between the trapezium and the 1st metacarpal. It is a condyloid synovial joint which The wrist (radiocarpal) joint (Fig. The distal radius and a similar to that of a ball and socket joint. The most important movement triangular disc of ﬁbrocartilage covering the distal ulna form the prox- of the thumb is opposition in which the thumb is opposed to the ﬁngers imal articulating surface. This disc is attached to the edge of the ulnar as in holding a pen. The distal • Interphalangeal joints: are synovial hinge joints. The anatomical snuffbox • Capsule: a deﬁned capsule surrounds the joint. The carpal tunnel and joints of the wrist and hand 87 39 The hand Adductor pollicis Flexor pollicis longus Superficial transverse metacarpal ligament Palmar aponeurosis Abductor digiti minimi Flexor pollicis brevis Flexor digiti minimi Abductor pollicis brevis Flexor retinaculum Opponens pollicis Pisiform Flexor carpi ulnaris Abductor pollicis longus Flexor carpi radialis Long flexor tendons Flexor pollicis longus Palmaris longus Fig. Note particularly the recurrent branch of the median nerve which supplies the thenar muscles 88 Upper limb The palm of the hand (Fig. These movements occur around the middle ﬁnger hence • Skin: the skin of the palm is bound to underlying fascia by ﬁbrous adduction is the bringing together of all ﬁngers towards the middle bands. The • Deep fascia: the palmar aponeurosis is a triangular layer which is dorsal interossei each arise from two metacarpals and insert into the attached to the distal border of the ﬂexor retinaculum. Distally the proximal phalanges so as to provide adduction (P. The dorsal aponeurosis splits into four slips at the bases of the ﬁngers which blend interossei arise from only one metacarpal and are inserted into the prox- with the ﬁbrous ﬂexor sheaths (see below). The aponeurosis provides imal phalanges so as to provide abduction (D. Note that the middle ﬁrm attachment of the overlying skin with protection of the underlying ﬁnger cannot be adducted (and hence has no palmar interosseous) but structures. They arise from the metacarpal heads and pass to the bases of the distal phalanges on the anterior aspect The dorsum of the hand of the digits. These sheaths • Skin: unlike the palm of the hand the skin is thin and freely mobile are lax over the joints and thick over the phalanges and hence do not over the underlying tendons. On the dorsum of the hand the ﬂexor tendons and the carpal tunnel and ﬁbrous ﬂexor sheaths. The ED tendon to the little ﬁnger is accompanied by the (FDS) divide into two halves at the level of the proximal phalanx and double tendon of extensor digiti minimi. The ED tendons of the little, pass around ﬂexor digitorum profundus (FDP) where they reunite. At ring and middle ﬁngers are connected to each other by ﬁbrous slips. On this point they then split again to insert into the sides of the middle pha- the posterior surface of each ﬁnger the extensor tendon spreads to form lanx. FDP continues along its path to insert into the distal phalanx. This expansion is triangular shaped and at its Flexor pollicis longus (FPL) passes through the carpal tunnel in its own apex splits into three parts: a middle slip which is attached to the base of synovial sheath and inserts into the distal phalanx. The tendons of the middle phalanx; and two lateral slips which converge to attach to ﬂexor carpi radialis, palmaris longus and ﬂexor carpi ulnaris pass the base of the distal phalanx. The base of the expansion receives the through the forearm and also insert in the proximal hand (see Muscle appropriate interossei and lumbricals. They include abductor digiti minimi, ﬂexor digiti minimi and The hand is required to perform a versatile range of movement extend- opponens digiti minimi. They insert into the radial side of each of the prox- the thumb is used to oppose the index ﬁnger in which the interpha- imal phalanges and into the dorsal extensor expansions. The lumbricals langeal joint is extended and the metacarpophalangeal joint is ﬂexed. Since the thumb is at right angles to the plane of the ﬁngers, ﬂexion at the metacarpophalangeal joints and extension of the interpha- abduction of the thumb is a movement away from the plane of the palm. They also perform abduction and adduction movements This is used in testing the integrity of the median nerve (abductor pollicis). The hand 89 40 Surface anatomy of the upper limb Pectoralis major Latissimus dorsi and teres major Serratus Cephalic vein anterior Biceps brachii Biceps tendon Aponeurosis Basilic vein Fig. Palmaris longus is a guide to the position of the median nerve Details are shown in Fig. The distal transverse crease lies at the level of line the ﬁrst bony structure palpated is the spinous process of the 7th the proximal border of the ﬂexor retinaculum. The spine, superior angle, inferior angle and medial border are palpable posteriorly. The coracoid process can Vessels be palpated below the clavicle anteriorly within the lateral part of the • The subclavian artery can be felt pulsating as it crosses the 1st rib. This is the • Humerus: the head is palpable in the axilla with the shoulder pulse used when taking blood pressure measurements. The lesser tuberosity can be felt lateral to the coracoid pro- • At the wrist the radial artery courses on the radial side of ﬂexor carpi cess. When the arm is externally and internally rotated the lesser radialis (Fig. The pulses of both are easily felt at these • Elbow: the medial and lateral epicondyles of the humerus and ole- points.