Citations

99mTc-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-Sestamibi), a new myocardial perfusion radiopharmaceutical, was injected intravenously in 11 patients within 4 hours of the onset of acute myocardial infarction before treatment with intravenous tissue-type plasminogen activator and 6-14 days later. Five patients with acute myocardial infarction who did not receive intravenous thrombolytic therapy underwent a similar injection of radiopharmaceutical. The absence of redistribution of Tc-Sestamibi permitted imaging with single-photon emission computed tomography up to 6 hours after intravenous injection to assess the distribution of myocardial perfusion at the time of administration. The region of hypoperfused myocardium on the initial images varied widely from 9% to 68% of the left ventricle and was significantly greater in anterior than in inferior infarcts (p less than 0.01). The region of hypoperfused myocardium on the final images varied widely from 0% to 63% of the left ventricle and was also greater in anterior infarcts (p less than 0.01). The final hypoperfused region correlated (r = -0.82) with the late resting ejection fraction and with the late regional wall motion score in the infarct segment for both anterior (r = -0.74) and inferior (r = -0.97) infarcts. There was a significant decrease (-13 +/- 11%, p less than 0.003) in the extent of hypoperfused myocardium between the initial and final studies in the patients who received thrombolytic therapy compared with an insignificant increase (4 +/- 6%, p greater than 0.5) in the patients who did not receive thrombolytic therapy. Tomographic imaging with Tc-Sestamibi permits determination of the amount of hypoperfused myocardium "at risk" in acute myocardial infarction. The change in myocardial perfusion determined by Tc-Sestamibi before and after therapy in acute myocardial infarction is a promising tool for assessing treatment.

Rehabilitation offers means by which persons disabled after a stroke can be returned to patterns of daily living as close to normal as possible. Often simple and readily available restorative techniques suffice, but sophisticated methods and facilities may be needed in many cases. Certain complex problems require specialized attention by persons with detailed knowledge and specific training. Among these are rehabilitation of language and the management of incontinence, sensory loss, pain, spasticity, and psychosocial problems. High-quality rehabilitation is best delivered by a closely cooperating team, including the family physician, medical specialists, nurses, allied health professionals (physical therapist, occupational therapist, social worker, dietitian, rehabilitation counselor, speech therapist, psychologist), the patient's family, and also the patient. To accomplish these ends, hospitals, rehabilitation centers, extended care facilities, and nursing homes should give specific attention to the special needs of stroke patients. Careful discharge planning and follow-up are necessary in all cases. The home environment and the family attitudes may require considerable revision to meet the patient's individual needs. The family physician can offer many rehabilitation services in his office, and additional education in medical school and on a postgraduate level will belp him to reach his full potential in aiding both the acutely ill and the chronically disabled stroke patient.

Background and Purpose— There is uncertainty whether warfarin-treated patients (despite international normalized ratio <1.7) have increased risks of symptomatic intracerebral hemorrhage after intravenous thrombolysis. Methods— Vascular risk factors, stroke subtype, and outcome measures were compared between warfarin- and nonwarfarin-treated patients undergoing acute thrombolysis within 3 hours of symptom onset. Results— From 212 patients (mean age, 74±14 years; 50% men) studied, 14 (6.5%) had prior warfarin use. After adjusting for age, baseline National Institutes of Health Stroke Scale, and stroke subtype, warfarin-treated patients had significantly increased risks of developing symptomatic intracerebral hemorrhage (adjusted OR, 14.7; 95% CI, 1.3 to 54.3). A trend for poorer stroke recovery and increased mortality was observed in warfarin-treated patients on univariate, but not on multivariable, analyses. Conclusions— Warfarin-treated patients with stroke have increased risks of symptomatic intracerebral hemorrhage after thrombolytic treatment. These data raise safety concerns of thrombolytic treatment in warfarin-treated patients with subtherapeutic international normalized ratio.

Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW).Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups.Results. 457 kidney transplant recipients treated with RSW were included; 46 (10%) experienced SR, and 36 (7.8%) had CR. Mean HLA mismatch was significantly higher in the CR group. The Banff grade of rejection was higher in the CR group. There was a larger proportion of patients in both rejection groups with the combination of IFTA and persistent inflammation on the follow-up protocol biopsy done at 1 year. The estimated 5-year death-censored graft survival was 81% in SR, 78% in CR, and 97% in the control group (P<.0001). Significant differences were observed in allograft survival between the CR and control group (HR 9.06, 95% CI 3.39–24.2) and between the SR and control group (HR 4.22, 95% CI 1.30–13.7).Conclusion. Both SR and CR are associated with an inferior graft survival in recipients on RSW.

ABSTRACT Introduction Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. Aim To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. Methods An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. Results Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to men’s and women’s individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie’s disease; and priapism. Conclusions Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

ABSTRACTIntroductionOver the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced. Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new and established therapies. Given the abundance of high level research it seemed like an opportune time for the International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical set of clinical guidelines for the diagnosis and treatment of PE.AimDevelop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts.MethodReview of the literature.ResultsThis article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory latency. Brief assessment procedures are delineated and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients.ConclusionDevelopment of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. Therefore, it is strongly recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.

BACKGROUNDNewborn screening (NBS) for inborn errors of propionate, methionine, and cobalamin metabolism relies on finding abnormal concentrations of methionine and propionylcarnitine. These analytes are not specific for these conditions and lead to frequent false-positive results. More specific markers are total homocysteine (tHCY), methylmalonic acid (MMA), and methylcitric acid (MCA), but these markers are not detected by current NBS methods. To improve this situation, we developed a method for the detection of tHCY, MMA, and MCA in dried blood spots (DBSs) by liquid chromatography–tandem mass spectrometry (LC-MS/MS).METHODSThe analytes were extracted from a single 4.8-mm DBS punch with acetonitrile:water:formic acid (59:41:0.42) containing dithiothreitol and isotopically labeled standards (d3-MMA, d3-MCA, d8-homocystine). The extract was dried and treated with 3 N HCl in n-butanol to form butylesters. After evaporation of the butanol, the residue was reconstituted and centrifuged and the supernatant was subjected to LC-MS/MS analysis. Algorithms were developed to apply this method as an efficient and effective second-tier assay on samples with abnormal results by primary screening.RESULTSThe 99th percentiles determined from the analysis of 200 control DBSs for MMA, MCA, and HCY were 1.5, 0.5, and 9.8 μmol/L, respectively. Since 2005, prospective application of this second-tier analysis to 2.3% of all NBS samples led to the identification of 13 affected infants.CONCLUSIONSApplication of this assay reduced the false-positive rate and improved the positive predictive value of NBS for conditions associated with abnormal propionylcarnitine and methionine concentrations.

We tested the hypothesis that diaphragm muscle shortening modulates volume displacement and kinematics of the lower rib cage in dogs and that posture and mode of ventilation affect such modulation. Radiopaque markers were surgically attached to the lower three ribs of the rib cage and to the midcostal region of the diaphragm in six dogs of ∼8 kg body masses, and the locations of these markers were determined by a biplane fluoroscopy system. Three-dimensional software modeling techniques were used to compute volume displacement and surface area of the midcostal diaphragm and the lower three ribs during quiet spontaneous breathing, mechanical ventilation, and bilateral phrenic nerve stimulation at different lung volumes spanning the vital capacity. Volume displaced by the diaphragm relative to that displaced by the lower ribs is disproportionately greater under mechanical ventilation than during spontaneous breathing in the supine position ( P < 0.05). At maximal stimulation, diaphragm volume displacement grows disproportionately larger than rib volume displacement as lung volume increases ( P < 0.05). Surface area of both the diaphragm and the lower ribs during maximal stimulation of the diaphragm is reduced compared with that at spontaneous breathing ( P < 0.05). In the prone posture, mechanical ventilation results in a smaller change in diaphragm surface area than spontaneous breathing ( P < 0.05). Our data demonstrate that during inspiration the lower rib cage moves not only through the pump- and bucket-handle motion, but also rotates around the spine. Taken together, these data support the observation that the kinematics of the lower rib cage and its mechanical interaction with the diaphragm are more complex than previously known.