Hereditary isolated renal magnesium loss maps to chromosome 11q23

Dendritic cells (DC) expanded in the presence of GM-CSF from the bone marrow of C57BL/6 mice process Gram-negative bacteria expressing the model antigen Crl-OVA for peptide presentation on MHC class I molecules. Here we show that presentation of OVA(257-264) processed by DC co-incubated with E. coli expressing Crl-OVA, which contains the Kb-binding OVA(257-264) epitope, occurs by a cytosolic MHC-I presentation pathway. First, we demonstrate the requirement for the transporter associated with antigen processing (TAP) by showing that DC from TAP1-/- mice co-incubated with E. coli expressing Crl-OVA did not result in Kb presentation of OVA(257-264). Second, the proteasome inhibitor MG132 abrogated presentation of OVA(257-264) on Kb when C57BL/6 DC phagocytosed and processed E. coli expressing Crl-OVA. Third, inhibiting protein synthesis using cycloheximide or blocking exocytosis of newly synthesized proteins from the endoplasmic reticulum using brefeldin A abrogated presentation of OVA(257-264) processed from bacteria expressing Crl-OVA by C57BL/6 DC. Finally, peptide regurgitation and loading of OVA(257-264) on neighboring bystander Kb-expressing antigen-presenting cells after BALB/c (H-2d) DC phagocytosed E. coli expressing Crl-OVA could not be detected. Together, these data support a cytosolic MHC-I presentation pathway for OVA(257-264) processed from E. coli expressing Crl-OVA by bone marrow-derived DC.     

Omission of temporary diversion in restorative proctocolectomy--is it safe?

PURPOSE: The aim of our study was to evaluate the safety and functional outcome of restorative proctocolectomy (RP) without diversion. METHODS: Fifty patients underwent RP without diversion for ulcerative colitis (82 percent), familial adenomatous polyposis (12 percent), and indeterminate colitis (6 percent). The perioperative course and functional outcome of these patients were compared with another group of 50 patients undergoing RP with diverting ileostomy during the same time period (1989-1991) and closely matched for age, gender, surgeon, diagnosis, extent and duration (median, 10 years) of colitis, prior colectomy (approximately 22 percent), steroid use (40 percent), type of pouch, distance of ileal pouch-anal anastomosis from the dentate line (median, 1.5 cm), and the duration of follow-up (median, 12 months). All patients had a stapled ileal pouch-anal anastomosis without mucosectomy and a smooth conduct of the operation. RESULTS: There was no operative mortality. Anastomotic leaks and pelvic abscess were more common in patients without ileostomy (7/50 or 14 percent vs. 2/50 or 4 percent); 8 of these 9 patients were taking > or = 20 mg of prednisone/day. Septic complications requiring relaparotomy (6 percent vs. 0 percent), prolonged ileus, and fever of unknown origin (10 percent vs. 4 percent) were also more common in patients without ileostomy. Despite similar functional results at 6 weeks and at 12 months after initial pouch function, patients without ileostomy had a poorer quality of life index (5 vs. 8; 10 being best) in the early period (0-6 weeks) of pouch function. CONCLUSION: In equally favorable cases, RP without diversion is not as safe as RP with diversion, especially in patients taking > or = 20 mg of prednisone/day.     

Treatment of axillary bromhidrosis with superficial liposuction

Axillary bromhidrosis or osmidrosis is a distressing problem that causes a serious personal and social handicap, especially in an Asian society. Surgical excision of the subcutaneous tissue, with or without skin excision in the axillary hair-bearing area, has been the treatment of choice for several decades. However, the complications of partial necrosis of wound edges or hematoma, and the possibility of the obvious unsightly scars, are always problems. We report our method of treatment of modified superficial liposuction with subdermal scraping under local anesthesia with tumescent infiltration. By using two tiny stab wounds, these two steps of liposuction can be done in the two-directional crisscross pattern. From August of 1995 to May of 1997, 20 patients (16 women and 4 men) received this surgery for bilateral axillas on an outpatient basis. The follow-up period ranged from 6 months to 27 months, and the mean follow-up period was 14 months. Eighteen patients (90 percent) had excellent to good results. Complication included only one minor wound infection that was cured easily. Two patients experienced transient subdermal fibrotic bands in one side of the axilla, and one patient experienced axillary skin with marked induration and retraction. All of these symptoms disappeared after 1 month or so. This minimal incision operation has the advantages of a high success rate, low complication rate, tiny to invisible scars, no change of hair distribution pattern, minimal postoperative care with a short term of compressive dressing (less than 2 days), and rapid recovery for daily activity and exercise.     

Final examination performance of medical students from ethnic minorities

Cause of death among 917 of the 959 subjects in a population-based incidence cohort with Alzheimer's disease (AD) during the years 1960 to 1984 was compared to that of an age- and gender-matched control group (n = 703). In general, a summary of the diagnostic codes entered anywhere on a death certificate suggests that control subjects had more cardiovascular disease and neoplasms than did patients, while patients more often had a diagnostic code of bronchitis/pneumonia (P < 0.01). By logistic regression, this difference remained statistically significant after adjusting for age and gender.     

Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data

A critical and comprehensive review of the safety information on erythritol was undertaken. Numerous toxicity and metabolic studies have been conducted on erythritol in rats, mice and dogs. The toxicity studies consist of long-term feeding studies conducted to determine carcinogenic potential, intravenous and oral teratogenicity studies to determine the potential for effects on the foetus, oral studies in which erythritol was administered over one or two generations to determine the potential for reproductive effects, and studies in bacterial and mammalian systems to determine mutagenic potential. The majority of the safety studies conducted were feeding studies in which erythritol was mixed into the diet at concentrations as high as 20%. The metabolic studies in animals have shown that erythritol is almost completely absorbed, not metabolized systemically and is excreted unchanged in the urine. The safety studies have demonstrated that erythritol is well tolerated and elicits no toxicological effects. The clinical program for erythritol involved a series of single-dose and repeat-dose, short-duration studies which have been used to investigate the human correlates to the physiological responses seen in the preclinical studies. The clinical studies showed erythritol to be well tolerated and not to cause any toxicologically relevant effects, even following high-dose exposure. Erythritol administered orally to humans was rapidly absorbed from the gastrointestinal tract and quantitatively excreted in the urine without undergoing metabolic change. At high oral doses, urinary excretion accounted for approximately 90% of the administered dose with minimal amounts appearing in the faeces. A comparison of the human and animal data indicated a high degree of similarity in the metabolism of erythritol and this finding supports the use of the animal species used to evaluate the safety of erythritol for human consumption. It can be concluded, based on the available studies that erythritol did not produce evidence of toxicity.     

Stable lipiodolized emulsions for hepatoma targeting and treatment by transcatheter arterial chemoembolization

We attempted to develop lipiodolized emulsions that remain in the tumour for a long period, release drug in a sustained release pattern, and thus improve the conventional treatment of hepatocellular carcinoma (HCC) [1]. Polyoxyethylene derivatives of hydrogenated castor oil (HCO) were the most suitable emulsifiers in stabilizing emulsions containing Lipiodol as an oil phase. The length of ethylene oxide coupled to HCO rather than the hydrophilic-lipophilic balance (HLB) values was an important factor in preparing stable emulsions and in achieving sustained-release characteristics. When distilled water was replaced with Iopamiro, a heavy water soluble contrast medium with a specific gravity of 1.335, more stable lipiodolized emulsions with longer sustained release behaviour could be prepared with smaller amount of HCO. To study the in vivo stability of the w/o Lipiodol emulsion and the sustained-release characteristics of doxorubicin from the emulsion, the pharmacokinetic study was performed with normal dogs using transcatheter arterial chemoembolization technique. The area under the plasma concentration-time curve for the first eight hours (AUC0-8) and AUCtotal values of the stabilized emulsion were three to four times higher than those of the coarse emulsion prepared lacking HCO 60. From the in vitro and in vivo studies, Lipiodol based water in oil emulsion with HCO 60 containing doxorubicin showed higher stability and released doxorubicin in a sustained fashion.     

Expression of measles virus V protein is associated with pathogenicity and control of viral RNA synthesis

Nonstructural proteins encoded by measles virus (MV) include the V protein which is translated from an edited P mRNA. V protein is not associated with intracellular or released viral particles and has recently been found to be dispensable for MV propagation in cell culture (H. Schneider, K. Kaelin, and M. A. Billeter, Virology 227:314-322, 1997). Using recombinant MVs (strain Edmonston [ED]) genetically engineered to overexpress V protein (ED-V+) or to be deficient for V protein (ED-V-), we found that in the absence of V both MV-specific proteins and RNAs accumulated to levels higher than those in the parental MV molecular clone (ED-tag), whereas MV-specific gene expression was strongly attenuated in human U-87 glioblastomas cells after infection with ED-V+. The titers of virus released from these cells 48 h after infection with either V mutant virus were lower than those from cells infected with ED-tag. Similarly, significantly reduced titers of infectious virus were reisolated from lung tissue of cotton rats (Sigmodon hispidus) after intranasal infection with both editing mutants compared to titers isolated from ED-tag-infected animals. In cell culture, expression of V protein led to a redistribution of MV N protein in doubly transfected Cos-7 cells, indicating that these proteins form heterologous complexes. This interaction was further confirmed by using a two-hybrid approach with both proteins expressed as Gal4 or VP16 fusion products. Moreover, V protein efficiently competed complexes formed between MV N and P proteins. These findings indicate that V protein acts to balance accumulation of viral gene products in cell culture, and this may be dependent on its interaction with MV N protein. Furthermore, expression of V protein may contribute to viral pathogenicity in vivo.     

Cytokine profile in chronic cardiac failure

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.     

Intrauterine devices: learning from the past and looking to the future

This paper reviews the historical development of the IUD, describing the challenges and successes, and attempts to offer a balanced perspective for family planning service workers today. Modern IUDs are an important component of family planning services and an excellent contraceptive choice for properly screened women, providing contraception that is safe, effective, long lasting and cost effective. Potential research strategies for the future are also discussed.