Physicochemical aspects of drug release. XV. Investigation of diffusional transport in dissolution of suspended, sparingly soluble drugs

The dissolution rates of sparingly soluble, fine particulate, suspended drugs have been studied using a Coulter Counter Model TAII. For two sieve fractions of oxazepam the dissolution rates were monitored in media with varying viscosities brought about by the addition of glycerol, while for griseofulvin the change in the medium's viscosity was induced by changing the temperature. By calculating the dissolution rate, and compensating for differences in particle surface area and media solubility, it was shown that the dissolution rate was diffusion controlled. After additional normalization for the diffusion coefficient, it was suggested that the so-called apparent diffusional distance decreased substantially with particle size. The effect of particle size was more limited above approx. 15 μm.     

Trust, but verify. The accuracy of references in four anesthesia journals.

To determine the accuracy of bibliographic citation in the anesthesia literature, we reviewed all 1988 volumes of ANESTHESIOLOGY, Anesthesia and Analgesia, British Journal of Anaesthesia, and Canadian Journal of Anaesthesia and sequentially numbered all references appearing in that year (n = 22,748). One hundred references from each of the four journals were randomly selected. After citations to nonjournal articles (i.e., books or book chapters) were excluded, the remaining 348 citations were analyzed in detail. Six standard bibliographic elements--authors' names, article title, journal title, volume number, page numbers, and year--were examined in each selected reference. Primary sources were reviewed, unless our institution did not own the source or could not obtain it through interlibrary loan, in which case standard indexes, abstracting services, and computerized databases were consulted. Each element was checked for accuracy, and references were classified as either correct or incorrect. A reference was correct if each element of the citation was identical to its source. Of the examined references, more than half (50.3%) contained an error in at least one element. The elements most likely to be inaccurate were, in descending order, article title, author, page numbers, journal title, volume number, and year. No significant differences (P = 0.283) existed in the error rates of the four journals; the percentage of citations containing at least one error ranged from 44% (Anesthesia and Analgesia) to 56% (British Journal of Anaesthesia). The citation error rate of anesthesia journals is similar to that reported in other specialties, where error rates ranging from 38% to 54% have been documented.     

Cost-effectiveness of inpatient substance abuse treatment.

OBJECTIVE: To identify the characteristics of cost-effective inpatient substance abuse treatment programs. DATA SOURCES/STUDY SETTING: A survey of program directors and cost and discharge data for study of 38,863 patients treated in 98 Veterans Affairs treatment programs. STUDY DESIGN: We used random-effects regression to find the effect of program and patient characteristics on cost and readmission rates. A treatment was defined as successful if the patient was not readmitted for psychiatric or substance abuse care within six months. PRINCIPAL FINDINGS: Treatment was more expensive when the program was smaller, or had a longer intended length of stay (LOS) or a higher ratio of staff to patients. Readmission was less likely when the program was smaller or had longer intended LOS; the staff to patient ratio had no significant effect. The average treatment cost $3,754 with a 75.0% chance of being effective, a cost-effectiveness ratio of $5,007 per treatment success. A 28-day treatment program was $860 more costly and 3.3% more effective than a 21-day program, an incremental cost-effectiveness of $26,450 per treatment success. Patient characteristics did not affect readmission rates in the same way they affected costs. Patients with a history of prior treatment were more likely to be readmitted but their subsequent stays were less costly. CONCLUSIONS: A 21-day limit on intended LOS would increase the cost-effectiveness of treatment programs. Consolidation of small programs would reduce cost, but would also reduce access to treatment. Reduction of the staff to patient ratio would increase the cost-effectiveness of the most intensively staffed programs.     

Serological heterogeneity of the IgM components of mixed (monoclonal IgM–polyclonal IgG) cryoglobulins

Mixed IgG–IgM cryoglobulins were isolated from the sera of seven patients with macroglobulinaemia or cryoglobulinaemia. The IgM components of all seven cryoproteins were monoclonal, containing κ light chains only, whereas the IgG components were polyclonal, containing both κ and λ light chains. Despite their apparent immunological homogeneity, the IgM components showed a wide range of antiglobulin activity. The data indicate that serological specificity may vary from one mixed cryoglobulin to another and that the monoclonal IgM components of different mixed cryoglobulins represent a heterologous group of antiglobulins.     

Precipitating antibodies to DNA induced by heat-denatured DNA-albumin conjugates in the rabbit

(1) Antibodies reactive with purified DNA in the complement fixation system and induced by active immunization of rabbits with methylated bovine serum albumin—DNA aggregate (MBSA—DNA) have been previously described. The present study demonstrates their reactivity in the quantitative and double diffusion preciptin systems. In these systems they have shown preferential reactivity with heat denatured DNA and great cross-reactivity with denatured DNA from various sources.

(2) Methylated rabbit serum albumin—DNA aggregate (MRSA—DNA) is an effective immunizing antigen resulting in the production of antibodies similar to those produced by MBSA—DNA.

(3) The precipitating antibodies in this system are 19S immunoglobulins and appear to be identical to the complement fixing antibodies.

(4) The precipitin reaction is not significantly inhibited by mono-nucleotides.

     

Effect of enzymes on rotavirus infectivity.

The infectivity of a bovine rotavirus was enhanced 140-, 8-, and 3-fold, respectively, by trypsin, protease, and lactase. Ficin, carboxypeptidases A and B, lysozyme, and beta-galactosidase had little effect on the infectivity. Chymotrypsin caused a threefold decrease in the infectivity. Trypsin acts directly on the rotavirus and not on the host cell.     

Effect of pulse dose cyclophosphamide on the anamnestic immune response in NZB/W mice

Mice exhibiting a spontaneous SLE-like lethal autoimmunity (female NZB/W hybrids) were given monthy doses of cyclophosphamide (CPA) 240 mg/kg p.o. starting at four months of age. Antibodies to DNA and sheep red blood cells (SRBC) were measured as well as general well being of the mice. The CPA-treated group demonstrated a marked increased in survival compared to the untreated controls with reduction of anti-DNA antibody levels but only a slight inhibition of the anamnestic response to SRBC immunization.Supported in part by USPHS Grant No. GM 15759.     

Cystic fibrosis: Synthesis of ciliary inhibitor by amniotic cells

The presence of a ciliary inhibitor in media of cultured amniotic cells obtained from a fetus heterozygous for cystic fibrosis has been observed by the oyster gill cilia assay. The chromatographic fraction containing the inhibitor corresponded to eluted fractions chromatographed from cystic fibrosis fibroblast media and serum. An analogous chromatographic fraction from media of cultured amniotic cells from two proportedly normal fetuses did not inhibit cilia. The chromatographic fraction from media of cultured amniotic cells of a fetus at high risk for cystic fibrosis did not inhibit ciliary activity. Serum was collected from this baby seven weeks after birth and also did not inhibit ciliary action, indicating a homozygous normal genotype. These observations may lead to the development of an antenatal test for cystic fibrosis.     

Watermelon mosaic virus-Morocco is a distinct potyvirus

Summary The relationship of the Morocco isolate of watermelon mosaic virus (WMV) to WMV 2, soybean mosaic virus (a virus closely related to WMV 2) and the W strain of papaya ringspot virus (PRSV-W), formerly WMV 1, was examined by comparing tryptic peptide profiles using high performance liquid chromatography. The profiles indicated that the coat protein sequence of WMV-Morocco differed substantially from those of the other potyviruses. This conclusion was supported by sequence data from five tryptic peptides from the coat protein of WMV-Morocco, which showed only 61–68% identity to equivalent sequences in PRSV-W, WMV 2 and zucchini yellow mosaic, another potyvirus infecting cucurbits. Based on the above data, and on known correlations between coat protein sequence similarities and potyvirus relationship, it is concluded that WMV-Morocco should be regarded as a distinct potyvirus.     

Coat protein of potyviruses 7. Amino acid sequence of peanut stripe virus

Summary The amino acid sequence of the 287-residue coat protein of peanut stripe virus (PStV) was determined from the sequences of overlapping peptide fragments. Results indicated that the amino terminus was blocked by an acetyl group, as has previously been found for the coat protein of Johnsongrass mosaic potyvirus. Comparison of the PStV sequence with coat proteins of 20 distinct potyviruses gave sequence identities of 47–57%, except for zucchini yellow mosaic virus (ZYMV), passionfruit woodiness virus (PWV), and the related strains watermelon mosaic virus 2 (WMV 2) and soybean mosaic virus-N, which showed sequence identities of 70–76%. Several amino acid residues which were common to the core sequences of these coat proteins were at positions previously found to be invariant among potyvirus coat proteins. The degree of these similarities suggests that although PStV, WMV 2, ZYMV, and PWV are distinct potyviruses, they share a common ancestor in their evolutionary development.