Isolation and characterization of the mouse homolog of the preprodynorphin (Pdyn) gene

We have isolated and sequenced the mouse preprodynorphin gene (Pdyn). The Pdyn gene can encode for six biologically active dynorphin peptides. The predicted mouse preprodynorphin has 90%, 67%, and 66% identity with the predicted rat, porcine, and human preprodynorphins, respectively. Using an RT-PCR technique, we show that the Pdyn gene starts being expressed at embryonic day 12.5, with a steep increase of expression by embryonic day 14.5; in the adult mouse it is expressed in the brain, but not in liver, heart, spleen, or kidney.     

FK506-associated thrombotic microangiopathy: report of two cases and review of the literature

BACKGROUND: FK506 is a recently developed immunosuppressant that has been useful in improving the survival of transplanted organs. Among the numerous adverse side effects of FK506, thrombotic microangiopathy (TMA) stands out as an infrequent but severe complication. METHODS: We report two cases of FK506-associated TMA and review the 19 previous reported cases. RESULTS: From these 21 cases, the reported incidence of FK506-associated TMA is between 1% and 4.7%. It is more frequent in females, and the mean age at presentation is 47 years. Eighty-one percent of the cases occurred in patients with kidney allografts, and the remaining patients had liver, heart, or bone marrow transplants. Clinically, TMA was diagnosed at an average interval of 9.3 months from the time of transplantation. Patients may be asymptomatic or may present with the full-blown picture of hemolytic uremic syndrome. All patients had an elevated serum creatinine level but did not always show signs of hemolysis. Trough levels of FK506 were not predictive for the development of TMA, but generally a reduction of drug dose correlated with kidney function improvement and disappearance of the hemolytic picture. The renal allograft biopsy provided a conclusive diagnosis in all 17 cases in which this procedure was performed. Treatment, which mainly consisted of reduction or discontinuation of FK506, anticoagulation, and/or plasmapheresis with fresh-frozen plasma exchange, resolved TMA in most patients (57%). However, in one of these patients (5%), the graft was subsequently lost due to causes unrelated to TMA, such as acute or chronic rejection. Despite treatment, one patient (5%) lost the graft due to acute rejection and persistent TMA, and three other patients (14%) who had bone marrow, heart, and liver transplants, died of multiple organ failure, probably unrelated to TMA. In the remaining four patients (19%), response to treatment was not reported. CONCLUSIONS: TMA must be considered in organ transplant patients treated with FK506 whenever kidney function deteriorates, even in the absence of microangiopathic hemolytic anemia. Although TMA usually responds to treatment, it may, in rare cases, lead to loss of kidney function or even the patient's death.     

Immunogenicity of peptides derived from a fibronectin-binding protein of S. aureus expressed on two different plant viruses

The D2 peptide derived from an S. aureus fibronectin-binding protein (FnBP) was expressed on the surface of the icosahedral cowpea mosaic virus (amino acids 1-30 of D2) or on the rod-shaped potato virus X (amino acids 1-38 of D2), termed CPMV-MAST1 and PVX-MAST8, respectively. Mice and rats were immunized subcutaneously with CPMV-MAST1 and mice with PVX-MAST8 in adjuvant and high titres of FnBP-specific antibody were obtained. The mouse IgG was predominantly of the IgG2a and IgG2b isotypes, which strongly bound complement component C1q, suggesting a TH1-bias in the peptide-specific responses. Sera from mice and rats immunized with CPMV-MAST1 and from mice immunized with PVX-MAST8 were shown to completely inhibit the binding of fibronectin to immobilised recombinant FnBP and rat sera against CPMV-MAST1 were able to block adherence of S. aureus to fibronectin. These studies demonstrate that the D2 peptide is highly immunogenic when expressed on 2 different plant viruses and highlight the potential of plant virus-based vaccines to protect against S. aureus infections.     

An outbreak of Salmonella typhimurium RDNC A045 at a wedding feast in South Australia

In April 1998 an outbreak of salmonellosis amongst guests at a wedding feast was investigated. Of the 58 attendees interviewed 38 (66%) subsequently developed gastrointestinal symptoms. Stool cultures from 7 cases grew Salmonella Typhimurium RDNC A045. Food samples were culture-negative for Salmonella spp. A cohort study implicated spatchcock (RR 2.5, 95% CI 1.09-5.77) and scampi (RR 2.0, 95% CI 1.05-3.89). Temperature abuse and cross-contamination within the kitchen during preparation and cooking are likely to have been the main contributing factors to this outbreak. Control measures included staff education in safe food handling and improvements in poultry processing methods to minimise carcass contamination.     

Computed tomography in the diagnosis of Creutzfeldt-Jacob disease.

Creutzfeldt-Jacob disease manifests clinically as a form of presenile dementia. It is now known to be caused by a transmissible agent, probably a "slow virus". Rapidly progressive atrophic changes on serial computed tomograms of the brain are highly suggestive of the disease. Neuroradiographic and pathological findings in two cases of Creutzfeldt-Jacob disease are documented.     

Integrating providers into quality improvement: a pilot project at one hospital

Brigham and Women's Hospital initiated a study of the quality of care centering on self-reporting of potential medical injuries by providers. The goal of the study is to decrease the incidence of such injuries through a continuous quality methodology that integrates providers into the identification phase and incorporates all hospital employees in the development of new practices. This article provides an overview of the investigation methodology and discusses the conceptual relationships between clinical epidemiological analyses and industrial quality improvement.     

Inability to demonstrate hydroxylation of tyrosine by murine melanoma "tyrosinase" (L-DOPA oxidase), using the tritiated water assay technique.

Validity of the tritiated water assay technique for tyrosine hydroxylase activity as a qualitative method was demonstrated with mushroom tyrosinase. Using this method, isolated murine melanoma "tyrosinase" (L-dopa oxidase) showed no tyrosine hydroxylase activity. This finding supports previous studies in our laboratory which used a variety of histochemical and biochemical methods. The nonenzymatic production of tritiated water caused by tritium exchange with hydrogen peroxide complicates the use of the tritiated water assay technique with crude systems, since hydrogen peroxide is generated by a variety of oxidase reactions. For this reason, previous studies using the tritiated water assay technique with crude systems are ambiguous.     

Assessment of maternal nutrition.

A booklet, "Assessment of Maternal Nutrition," has been published by the American College of Obstetricians and Gynecologists in cooperation with The American Dietetic Association as a useful guide for physicians, nurses, dietitians, and nutritionists. Nutritional risks during pregnancy are clearly outlined. Clinical, dietary, and biochemical factors, as well as medical, obstetric, and social factors, are delineated as components of nutritional assessment. An A.D.A. Liaison Committee had major responsibility for the development of the "Eating Habits Questionnaire," a tool to screen dietary intake for major deficits and excesses, which is included in the booklet. It should be useful also as a starting point for nutrition education. Additional evaluation of the use and reliability of the screening tool is recommended.     

"Right" stay in hospital after sugery: randomised controlled trial.

A randomised controlled trial was carried out on 100 patients to compare the effects of discharge after certain pre-specified clinical criteria had been fulfilled--"right" stay--with those of discharge at an arbitrary 10 days after surgery--"fixed" stay. The operations concerned (cholecystectomy and vagotomy) were more hazardous than those previously included in studies of early discharge. Patients in the right-stay group were discharged, on average, 7-6 days after operation--that is, two days earlier than those in the fixed-stay group. In terms of clinical progress, social factors such as return to work, and the acceptability to patients and relatives of the implications of right stay, patients in this group fared as well as those in the fixed-stay group, and in some respects slightly better. Right stay entailed the transfer of some work from hospital to community medical and nursing staff, but this also was acceptable. The concept and use of the right-stay principle is of value in planning the postoperative discharge of suitable patients.