Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia).

A canine model of glycogen storage disease Ia (GSD Ia), similar clinically, biochemically, and pathologically to the human disease, was established by crossbreeding Maltese and Beagle dogs carrying a mutated, defective glucose-6-phosphatase (G-6-Pase) gene. Ten puppies were born in three litters from these crossbreedings. Six were homozygous for the previously described M121I GSD Ia mutation. Of these six affecteds, two were stillborn, and one died at 2, 32, and 60 days of life, respectively (puppies A, B, C, D, E), while one is alive at age 15 months (puppy F). Affected puppies exhibited tremors, weakness, and neurologic signs when hypoglycemic. They had postnatal growth retardation and progressive hepatomegaly. Biochemical abnormalities included fasting hypoglycemia, hyperlactacidemia, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Microscopic examination of tissues from affected puppies showed diffuse, marked hepatocellular vacuolation, with distended clear hepatocytes and central to marginally located rounded nuclei. In the kidneys of puppies D and E, there was segmental glomerular sclerosis and vacuolation of proximal convoluted tubular epithelium. Biochemical analysis revealed increased liver glycogen content and isolated markedly reduced G-6-Pase enzyme activity in liver and kidney. The canine G-6-Pase gene was characterized by screening a canine genomic library. It spans approximately 11.8 kb and consists of five exons with >90% amino acid sequence homology to the derived human sequence. The first 1.5 kb of the 5' region was sequenced and contains several putative response element motifs homologous to the human 5' region. Establishment of this canine colony of GSD Ia that closely resembles human disease and isolation of the canine genomic gene provides an excellent model for studying pathophysiology and long-term complications and an opportunity to develop novel therapeutic approaches such as drug and gene therapy.

A patient acuity and staffing tool for stroke rehabilitation inpatients based on the FIM instrument.

We undertook to develop a tool based on the FIM instrument to predict the number of nursing hours required to care for stroke patients in an acute inpatient rehabilitation program. The initial study to evaluate the feasibility of using the FIM instrument revealed that the total FIM score had a strong inverse relation to the level of care indicated by the Patient Care Index (PCI) at days 1, 5, 7, 10, 15, and 20 of rehabilitation (rs = -.76 to -.87). The results warranted continued investigation of the FIM instrument as a guide for nurse staffing decisions. Based on data from the initial study, five categories of FIM score ranges were designated that demonstrated the most accuracy of placing patients at the correct level of care. Special care considerations unique to institutional settings were identified and incorporated into the tool's final format, as were the calculations to determine the amount of assistance needed. The study reported here was undertaken to evaluate the level of care indicated by the adapted tool, compared with that of the PCI, in a sample of 67 stroke admissions. Spearman correlations revealed a moderate relationship (rs = .49 to .54) between the amount of care determined by the Patient Acuity and Staffing tool and through the PCI at the first, second, and third team meetings. We conclude that the system is an effective, efficient guide for scheduling nurse staffing on the stroke rehabilitation unit.

Determining stroke rehabilitation inpatients' level of nursing care.

The purpose of this study was to evaluate the feasibility of using the Functional Independence Measure (FIM) to predict staffing needs of stroke patients in an acute inpatient rehabilitation program. The Patient Care Index (PCI) was concurrently administered with the FIM on all stroke admissions to a stroke rehabilitation unit over a 3-month period. One hundred fourteen patients 18 years of age or older admitted to the unit with a medical diagnosis of stroke were included in the sample. Total FIM score had a strong inverse relationship to the level of care indicated by the PCI at Days 1, 5, 7, 10, 15, and 20 of rehabilitation (r(s) = -. 76 to -.87). Total FIM score and the need for staff supervision for safety were the two factors predictive of the level of nursing care. The FIM has potential to guide nurse-staffing decisions.

Lupus nephritis: pathophysiology, diagnosis, and collaborative management.

Lupus nephritis (LN) is a complex disease. The pathophysiology involves the glomerulus and mesangium, and its manifestations are exhibited in extensive renal lesions. The World Health Organization (WHO) has developed a classification system to assist clinicians in understanding the severity of renal involvement. The diagnosis of systemic lupus erythematosus (SLE) and LN can be difficult because of their often vague symptoms and the long list of differential diagnoses. However, it is important to identify LN quickly to have an impact on a patient's prognosis. The 11 criteria established by the American Rheumatology Association provide a framework for identifying clinical manifestations of SLE. Management of LN, which may be guided by renal biopsy findings, includes pharmacologic therapy, management of drug toxicities, dialysis, transplantation, controlling symptoms (e.g., hypertension), patient education, and psychosocial support for the patient and family. This article focuses on the pathophysiology, diagnostic approach, and collaborative management of LN.

Pharmacodynamics and pharmacokinetics of DMP 728, a platelet GPIIb/IIIa antagonist, in healthy subjects.

DMP 728 showed a dose-dependent inhibition of platelet aggregation at doses of 0.05 to 0.9 mg per subject, with a maximal inhibition (> 90%) of platelet aggregation at doses of 0.9 mg per subject and higher. Minimal changes in bleeding time from baseline were observed at doses up to 0.6 mg per subject. At the 0.9 mg/subject dose level, bleeding time was prolonged by approximately twofold to threefold above the baseline. At higher doses (1.5 mg/subject to 3.9 mg/subject), bleeding time prolongation was > 30 minutes during the infusion. In all dose groups, bleeding times returned to the control value within 8 hours after cessation of the infusion. Maximum plasma concentration and area under the curve of DMP 728 increased linearly and proportionally to the dose. No clinical changes in vital signs, 12-lead electrocardiograms, physical examinations, coagulation tests, or stool hemoccult tests were observed at any of the doses. In conclusion, DMP 728 is a potent antiplatelet agent and well tolerated at doses ranging from 0.05 to 3.0 mg/subject.

The safety profile of naltrexone in the treatment of alcoholism. Results from a multicenter usage study. The Naltrexone Usage Study Group.

BACKGROUND: Naltrexone hydrochloride is the first medication approved in the United States for the treatment of alcohol dependence in almost 50 years. This study was designed to collect safety data in a setting that reflected the expected clinical use of naltrexone. METHODS: This was a 12-week, nonrandomized, open-label usage study conducted in 40 alcoholism treatment centers throughout the United States, including free-standing alcoholism treatment programs, university clinics, Veterans Administration hospitals, and office-based primary care practices. Eligible patients were assigned, at the investigators' discretion, to a naltrexone treatment group or to a reference group that did not receive study medication. At study entry, patients must have been abstinent from alcohol for 1 to 6 weeks and enrolled in a psychosocial treatment program for alcoholism. Patients often underrepresented in controlled clinical trials, including women and patients with comorbid medical and psychiatric illness, were eligible. Patients with polysubstance abuse or infection with the human immunodeficiency virus were not excluded. RESULTS: Of 865 patients enrolled, 570 received naltrexone and 295 were in a reference group. The most common new-onset adverse clinical events in the naltrexone group were nausea (9.8%) and headache (6.6%). Naltrexone was discontinued in 15.0% of patients because of adverse events, most frequently nausea. The results of liver function tests in the naltrexone group were similar to those in the reference group. No death occurred during the study. CONCLUSIONS: This is the largest study to date describing the safety of naltrexone in a heterogeneous population of persons with alcoholism. No new safety concerns were identified.

Treatment of congenital and acquired hemophilia patients by extracorporeal removal of antibodies to coagulation factors: a review of US clinical studies 1987-1990. Hemophilia Study Group.

This paper reviews the use of extracorporeal immunoadsorption with immobilized Staphylococcal Protein A in attempts to lower the inhibitor titer in 22 patients with either congenital hemophilia or with acquired inhibitors. Eighty-five immunoadsorption procedures were performed at 13 locations in the United States between June, 1987 and February, 1990. In general, immunoadsorption was shown to efficiently remove IgG and, in eight congenital hemophilia patients, it also produced a clinically significant lowering of inhibitors allowing effective conventional factor replacement therapy. Three of thirteen congenital hemophilia patients treated received factor concentrate prior to immunoadsorption and were anamnestic at the time of treatment. Although they experienced substantial lowering of their inhibitor titers, it was not sufficient to allow effective factor replacement. The effectiveness of immunoadsorption therapy in the 9 patients with acquired inhibitors was more difficult to evaluate due to the wide variety of concomitant medications which were employed, although in several patients serious bleeding episodes were substantially improved (or halted) following immunoadsorption. Side effects associated with immunoadsorption were slight. These findings suggest that immunoadsorption can be a significant benefit to patients with inhibitors, particularly if it is instituted prior to factor administration.