Pharmacokinetics of von Willebrand factor and factor VIIIC in patients with severe von Willebrand disease (type 3 VWD): estimation of the rate of factor VIIIC synthesis

Nine patients (10 infusions) with a confirmed diagnosis of type 3 VWD were infused with von Willebrand factor (human), a preparation of von Willebrand factor (VWF) with a very low factor VIII content. Each patient was infused with one dose of approximately 50 or 100 iu ristocetin cofactor activity (VWF:RiCoF) per kg body weight. Bleeding times were performed during the 24 h period after infusion. Plasma samples were obtained over the 96 h period after infusion and were analysed for factor VIII coagulant activity (FVIIIC), VWF:RiCoF, von Willebrand factor antigen (VWF:Ag), and multimers. The FVIIIC data were analysed by non-linear least-squares analysis assuming constant FVIIIC 'synthesis' and exponential decay. The VWF data were fitted for exponential decay. The average decay rates for FVIIIC, VWF:RiCoF and VWF:Ag were 0.041, 0.061 and 0.056 respectively. The average calculated 'synthesis' rate for FVIIIC was 6.4 u/dl/h. The synthesis of FVIIIC was slightly faster and the decay slightly slower following the infusion of 100 iu VWF:RiCoF/kg than of 50 iu VWF:RiCoF/kg. Correction of the bleeding time was strongly dose dependent. At 4 h post infusion the median bleeding time was 9 min following a dose of 50 iu VWF:RiCoF/kg versus 3 min with a dose of 100 iu VWF:RiCoF/kg. There was no decrease in the bleeding time until the level of VWF:Ag or VWF:RiCoF reached >100 u/dl.     

Comparison of beta-adrenergic agents delivered by nebulizer vs metered dose inhaler with InspirEase in hospitalized asthmatic patients

The present study was undertaken to determine if beta-agonists delivered by nebulizer provide better clinical responses than MDI therapy in status asthmaticus. We divided 28 hospitalized asthmatic patients into three groups. Group 1 received albuterol by MDI with InspirEase. Group 2 received nebulized albuterol. Group 3 received nebulized metaproterenol. Both nebulizer regimens resulted in significant improvements in both FVC and FEV1 by 30 min after initial hospital beta-agonist treatment. No significant improvement was noted in initial spirometry in the MDI with InspirEase group. In spite of the superiority of nebulizer therapy in the initial phase of hospitalization, the daily rates of spirometric improvement and duration of hospitalization were not significantly different among the three groups. Our results indicate that nebulizer therapy provides superior spirometric improvement in the initial phase of status asthmaticus. However, both MDI and nebulizer regimens provided similar rates of spirometric improvement and duration of hospitalization.     

The effects of season and alcohol intake on mineral metabolism in men

We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none-to-moderate intake had <8.4 oz/week of ethanol. Those with moderate or heavier intake had 8.4 oz or more of ethanol/week. Individuals with none-to-moderate SRAI had a significant seasonal increase in iPTH, osteocalcin, urine DPC/100 mg of Cr and a decrease in distal forearm bone mineral density, 25 hydroxyvitamin D (250HD), and urinary calcium/100 mg of Cr. Individuals with moderate or heavier SRAI only had significant seasonal decrease in 250HD. We have concluded that alcohol intake decreases seasonal change in serum iPTH. The biological effects of such alterations in parathyroid hormone levels include decreased seasonal loss of bone mineral density.     

Intestinal Dysmotility Syndromes in the Elderly: Measurement of Orocecal Transit Time

Altered bowel habits are common symptoms in the elderly, yet the pathophysiology of age-related gastrointestinal dysmotility syndromes is poorly understood. The present study was designed to correlate changes in orocecal transit time (TT) in healthy elderly subjects with or without gastrointestinal dysmotility complaints. Twenty-two geriatric facility resident volunteers, mean age 82 yr (range 65-94 yr) participated, of whom 16 had gastrointestinal dysmotility symptoms. Orocecal TT in the elderly subjects did not differ from that in younger adult controls (100 +/- 11 min vs 93 +/- 20 min). However, orocecal TT was longer in geriatric females (112 +/- 14 min) than in males (70 +/- 6 min, p less than 0.01). We conclude that age alone does not prolong orocecal TT, except when dysmotility symptoms have been present for a prolonged period.     

Identification of intervals on chromosomes 1, 3, and 13 linked to the development of lupus in BXSB mice

OBJECTIVE: To identify intervals containing systemic lupus erythematosus (SLE) susceptibility alleles in the BXSB strain of mice. METHODS: We analyzed 286 (B10 x [B10 x BXSB]F1) backcross mice for a range of phenotypic traits associated with the development of SLE in BXSB mice. The mice were genotyped using 93 microsatellite markers, and the linkage of these markers to disease was studied by extreme-phenotype and quantitative trait locus analysis. RESULTS: The disease phenotype in these backcross mice was less severe than that in BXSB mice. However, antinuclear antibody production was increased compared with the parental strain. We identified 4 areas of genetic linkage to disease on chromosome 1 (Bxs1-4), 1 on chromosome 3 (Bxs5), and another interval on chromosome 13 which were associated with various aspects of the phenotype. Bxs4 and Bxs5 are located in regions not previously linked to disease in other models of SLE. CONCLUSION: SLE in the BXSB mouse model has a complex genetic basis and involves at least 5 distinct intervals located on chromosomes 1 and 3. There is evidence that different intervals affect particular aspects of the SLE phenotype.     

Evaluation of Five Probiotic Products for Label Claims by DNA Extraction and Polymerase Chain Reaction Analysis

Label claims were evaluated for five probiotic products. Specific oligonucleotide primers were designed for 11 species from the Bifidobacterium, Lactobacillus, and Streptococcus genera. Polymerase chain reaction, gel electrophoresis, and amplicon excision with DNA sequencing were performed: Sequence analysis and DNA homology comparisons followed. Bifidobacterium bifidum was not detected in two of the five samples by PCR analysis. Also, Lactobacillus species were found in two of the five product samples for which the species was not listed as an ingredient. We conclude that (1) lack of B. bifidum in two probiotic products may be attributed to different preparation standards among probiotic manufacturers, and (2) indentification of additional Lactobacillus species may represent contamination of the samples due to manufacturers utilizing shared equipment to produce all probiotics.     

Divisions of general medicine

To evaluate caring for the poor and uninsured in divisions of general medicine (DGMs), and to document the impact of recent reimbursement changes on division ambulatory care activity, the authors conducted a survey of DGM directors. Questionnaires mailed to directors of 214 divisions or residency programs yielded 120 responses. DGMs staffed, on average, three ambulatory sites, with a median of 17,000 visits per site. Overall, 66% of visits were by poor, underinsured, and uninsured patients. The majority of directors (75%) considered care of the poor a goal of their divisions. The most commonly reported response to the cost containment environment was implementation of revenue-generating measures (66%); 19% reported reductions in care to the poor; and 20% reported increased service to this group. It is concluded that DGMs care for large numbers of poor and uninsured patients and therefore must carefully evaluate the impacts of current policy proposals on their future ambulatory care activities Received from the Task Force for Social Responsibility. Society for Research and Education in Primary Care Internal Medicine (Society of General Internal Medicine). Presented at the ninth annual meeting of the Society for Research and Education in Primary Care Internal Medicine, May 2, 1986, Washington, DC.     

Advancement of multiple myeloma from diagnosis through plateau phase to progression does not involve a new B-cell clone: evidence from the Ig heavy chain gene

The Ig heavy chain (IgH) gene was used as a marker to investigate clonal succession and the origin of the neoplastic cell in multiple myeloma. The polymerase chain reaction (PCR) was used to amplify a section of the rearranged IgH gene at diagnosis and at progression in 21 patients who had exhibited a plateau phase. A monoclonal PCR product was seen for 16 of the patients and the product present at progression was of the same molecular weight as that at diagnosis. This finding suggests that the IgH rearrangement present at diagnosis and progression was the same. This was confirmed by sequencing the IgH gene in 10 patients. The IgH genes were found to be hypermutated at diagnosis, but no further hypermutation occurred during the course of the disease. The results provide evidence that the neoplastic cell in myeloma may originate as a memory B cell, plasmablast, or plasma cell, and suggest that progression beyond the plateau phase is not caused by clonal succession.