Acute Polymyositis Following Renal Transplantation

Myositis is a rare complication following renal transplantation and is most commonly the result of drug-mediated myotoxicity. Other causative disorders include viral infection, electrolyte imbalance and myositis of autoimmune origin. We describe a 60-year-old patient who developed acute polymyositis 4 weeks after a 000 human leukocyte antigen (HLA) mismatch cadaveric renal transplant. Following an uncomplicated transplant course with maintenance triple immunosuppression (prednisolone, mycophenolate mofetil and cyclosporine), the patient presented with severe symmetrical proximal muscle weakness associated with a rise in serum creatine kinase to 46800 U/L. Electromyography confirmed myopathic changes and muscle biopsy demonstrated extensive muscle-fiber necrosis with an inflammatory infiltrate. There were no obviously culpable drugs and viral studies were negative. Prompt initiation of high-dose steroid therapy led to clinical and biochemical recovery. Acute polymyositis may occur following renal transplantation. Potential mechanisms include viral antigen transmission or a localized form of graft vs. host disease.     

Pituitary volume in pediatric obsessive-compulsive disorder.

BACKGROUND: Abnormalities in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). To our knowledge, however, no prior study has measured pituitary gland volume in OCD. METHODS: Volumetric magnetic resonance imaging studies were conducted in 31 psychotropic drug-na?ve children (10 boys, 21 girls) aged 8-17 years and 31 case-matched healthy comparison subjects. RESULTS: Pituitary volume was significantly smaller in patients with OCD as compared with healthy control subjects (11% smaller). Smaller pituitary volume in patients with OCD was associated with increased compulsive but not obsessive symptom severity. Boys with OCD had smaller pituitary gland volumes compared with control boys (20% smaller). No significant differences in pituitary volume were observed between girls with OCD and control girls. Boys with OCD had significantly smaller pituitary volumes than girls with OCD (31% smaller), whereas control boys also had smaller pituitary gland volumes compared with control girls (21% smaller). CONCLUSIONS: These findings provide new evidence of reduced pituitary volume in pediatric OCD that seems to be more prominent in male patients. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the LHPA axis in OCD.     

A series of novel, highly potent and selective agonists for the kappa-opioid receptor.

1. This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzene-acetamidopiperidine and benzeneacetamidopiperazine analogues. 2. These compounds all showed potent, naloxone-reversible, full agonist activity in the field-stimulated rabbit vas deferens, indicating that they are kappa-opioid agonists; but showed very little activity in the rat or hamster vas deferens, indicating good selectivity with regard to mu- and delta-opioid receptors. 3. They were all potent antinociceptive agents, the most potent compound, GR 103545, having an ED50 value in the mouse abdominal constriction test of 0.25 micrograms kg-1 s.c. The compounds also produced sedation and diuresis, but had little effect on respiration rate or gastrointestinal motility. 4. It is concluded that the seven novel compounds described are all potent and selective agonists for the kappa-opioid receptor.     

Natural history of morbid obesity without surgical intervention.

BACKGROUND: To study the mortality among morbidly obese patients qualifying for bariatric surgery. Mortality from bariatric surgery for morbid obesity has been widely reported; however, little is known about the mortality in morbidly obese patients who defer surgery. METHODS: Consecutive patients evaluated for bariatric surgery with an initial encounter between 1997 and 2004 were identified. The Social Security Death Index and office records were used to identify mortality through 2006. We conducted telephone interviews to determine whether the 305 patients who did not undergo bariatric surgery at our institution had undergone the surgery elsewhere. Using Cox proportional hazards models, we compared the mortality in patients undergoing surgery with that of those who did not. To evaluate bias resulting from missing data, we conducted analyses assuming that all patients with missing data had (1) undergone surgery and (2) not undergone surgery. RESULTS: A total of 908 patients underwent bariatric surgery (880 patients at our institution and 28 patients elsewhere). A total of 112 patients did not undergo surgery. Data regarding surgery on 165 patients could not be obtained. The mortality in those patients who did not undergo surgery was 14.3% compared with 2.9% for those who did undergo surgery. Adjusting for age, gender, and body mass index, patients who had undergone surgery had an 82% reduction in mortality (hazard ratio 0.18, 95% confidence interval 0.09-0.35, P <.0001). Sensitivity analysis, assuming that all patients with missing data received surgery resulted in an 85% mortality reduction (P <.001) and assuming that patients did not receive surgery resulted in a 50% mortality reduction (P = .04). CONCLUSIONS: Mortality among morbidly obese patients without surgery was 14.3% during the study period. Surgical intervention offered a 50%-85% mortality reduction benefit.     

Pituitary function before, during, and after chronic gonadotropin-releasing hormone agonist therapy.

OBJECTIVE: To examine possible adverse effects on pituitary function of long-term administration of gonadotropin-releasing hormone agonist (GnRH-a). DESIGN: Prospective analysis of blood sampling before, during, and after GnRH-a therapy. SETTING: Tertiary institutional outpatient care. PATIENTS: Twelve normally ovulatory women with a diagnosis of endometriosis. INTERVENTIONS: Six-month suppression with GnRH-a. MAIN OUTCOME MEASURES: Serum levels of follicle-stimulating hormone, luteinizing hormone, free thyroxin index, cortisol (F), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH). RESULTS: Basal and stimulated values of gonadotropins, PRL, F, TSH, and GH were normal and unchanged by 6 months of GnRH-a after resumption of menses. CONCLUSIONS: Utilizing dynamic pituitary function tests, we were unable to demonstrate an adverse effect of long-term GnRH-a therapy on pituitary function.     

Effects of Myocardial Water Exchange on T1 Enhancement during Bolus Administration of MR Contrast Agents

Interpretation of first-pass myocardial perfusion studies employing bolus administration of T₁ magnetic resonance (MR) contrast agents requires an understanding of the relationship between contrast concentration and image pixel intensity. The potential effects of myocardial water exchange rates among the intravascular, interstitial, and cellular compartments on this relationship are controversial. We directly studied these issues in isolated, nonbeating canine interventricular septa. Myocardial T₁ was measured three times/s during bolus transit of intravascular (albumin-Gd-DTPA and poly-lysine-Gd-DTPA) and extracellular (gadoteridol) contrast agents. For polylsine-Gd-DTPA, the peak changes in myocardial 1/T₁ (ΔR1) scaled nonlinearly with perfusate contrast concentration whereas a linear relationship would be expected for fast water exchange among the vascular, interstitial, and cellular compartments. For all agents, the peak ΔR1 were much smaller than the values expected on the basis of fast myocardial water exchange. The data demonstrate that in isolated myocardial tissue, myocardial T₁ enhancement during bolus administration of contrast can be strongly affected by myocardial water exchange for both intravascular and extracellular MR contrast agents.     

2-deoxy-D-glucose inhibits the antitumor effects of α-difluoromethylornithine on the growth of colon cancer in vivo

Summary The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to inhibit the growth of certain cancers. -Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the ratelimiting enzyme in polyamine biosynthesis. DFMO has been shown to inhibit cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on MC-26 mouse colon adenocarcinoma tumors growing in vivo. Twenty-eight male Balb/c mice were inoculated with 250,000 MC-26 cells, and then randomized into four groups of 7 each: group I served as control; group II received DFMO (3% in drinking water); group III received 2-DG (500 mg/kg/d IP); group IV received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation. MC-26 tumor area was reduced 73% by DFMO compared to a 24% reduction caused by 2-DG. The tumor weight was reduced 80% by DFMO and 52% by 2-DG. The tumor contents of DNA, RNA, and protein were significantly reduced by DFMO but not 2-DG. The tumor concentration of the polyamines putrescine and spermidine were reduced by DFMO alone or combined with 2-DG while spermine levels remained unchanged. 2-DG alone did not alter polyamine levels. These results indicate that both 2-DG and DFMO, when added as single agents, inhibit tumor growth. However, the addition of 2-DG to the DFMO regimen inhibited the antitumor effects of DFMO. Survival studies performed on MC-26 cells in vitro corroborated the antagonisms between DFMO and 2-DG that were shown in vivo.Dr. Upp was awarded a fellowship grant from the American Cancer Society Texas Division.     

Traf6 is essential for murine tooth cusp morphogenesis.

Ectodermal appendages such as skin, hair, teeth, and sweat glands are affected in patients with hypohidrotic (anhydrotic) ectodermal dysplasia (HED). It has been established that mutations in the tumor necrosis factor (TNF) superfamily of molecules, i.e., ectodysplasin (EDA), EDA receptor (EDAR), and EDAR-associated death domain (EDARADD; the intracellular adaptor for EDAR), are responsible for several forms of HED in humans and mice. We show here by in situ hybridisation that another TNF family (orphan) receptor, TROY (also known TAJ, TAJ-alpha, TRADE, and TNFRSF19), is strongly coexpressed with Edar in the epithelial enamel knot signalling centres that are believe to regulate cuspal morphogenesis during murine tooth development. Traf6 is known to function as an intracellular adaptor protein for Troy and examination of Traf6 mutant mice revealed abnormalities in molar teeth that are similar but more severe than those produced by mutations in Eda signalling molecules. This finding suggests that, in additional to ectodysplasin, another TNF pathway involving Troy/Traf6 is involved in molar tooth cusp formation and identifies an essential role for a Traf in tooth development. Developmental Dynamics 229:131-135, 2004.