Synthesis of two biologically active fluorescent probes of thymopentin

This study reports on the synthesis of two fluorescent analogues of thymopentin (TP-5; Arg-Lys-Asp-Val-Tyr). A fluorescein isothiocyanate labeled analogue (FITC-TP-5) and a stilbene isothiocyanate labeled analogue (SITS-TP-5) were extensively purified by ion-exchange and gel filtration chromatography. Characterization of the coupling site through amino acid analysis, dansylation and N-terminal cleavage of the fluorescent amino acid yielded results which indicated that both were mono-labeled analogues derivatized at the N-terminal. These analogues were shown to be TP-5-like in nature by their ability to induce the expression of the Thy 1.2 surface marker on nude mouse prothymocytes in both in vivo and in vitro assays. In addition, these analogues were able to inhibit the specific binding of radiolabeled TP-5 to human lymphocytes. Initial studies describing the interaction of FITC-TP-5 with human lymphocytes are shown.     

Nutrition and Health for Older Persons in Rural America: A Managed Care Model

Health care services and resources for older persons living in rural areas may be highly variable, and integrated service-delivery models are often lacking. This article presents a managed-care model of nutrition risk screening and intervention for older persons in rural areas. Nutrition risk screening was implemented by the Geisinger Health Care System, Danville, Pa, to target all eligible enrollees in a regional Medicare risk program. A single remote clinic site participating in the managed health care system was chosen for further study of a linked screening and case-management effort for undernourished persons. Screening and intervention at the clinic site selected for this study were guided by centralized expertise and resources. Individualized evaluation and intervention plans were developed with the aid of a dietitian and implemented by the clinic case manager. Of the 417 subjects who completed screening at the remote site, 68 met the risk criteria for undernutrition and were selected for case management. Many of the targeted persons received interventions that included evaluations by a physician or physician extender (eg, physician assistant, nurse practitioner) at the clinic and consultations with nutrition, mental health, or social services professionals. Twenty-six of the subjects who took part in the intervention completed a follow-up screening 6 months later. Ten of those persons no longer exhibited risk criteria. This demonstrates the feasibility of a linked screening and case management program for nutrition risk in the managed-care setting. J Am Diet Assoc. 1997; 97: 885-888.     

Short report: zinc sulphate supplementation corrects abnormal erythrocyte membrane long-chain fatty acid composition in patients with Crohn's disease

Patients with Crohn's disease may become zinc-deficient and, in such patients, an altered metabolism of radiolabelled long-chain fatty acids has been reported. We have investigated the possible reversal by zinc supplementation of altered long-chain fatty acid profiles of red cells in Crohn's disease. Twenty patients with long-standing Crohn's disease in clinical remission received 200 mg of zinc sulphate daily for 6 weeks. Phospholipid fatty acid profiles of washed red cells were analysed before and after zinc treatment and compared to those of 20 unsupplemented healthy controls. Plasma zinc levels in Crohn's were 72 ± 8 μg/dL before zinc treatment and increased to 114 ± 10 μg/dl after the therapy. Prior to zinc supplementation, the percentage of palmitic, stearic and oleic acids was significantly higher in Crohn's disease, while linoleic, arachidonic and n-3 fatty acids were reduced in Crohn's disease compared to healthy controls. Zinc supplementation abolished these pre-treatment differences in red-cell long-chain fatty acid profiles but did not affect plasma fatty acid values. Further studies are needed to clarify whether these fatty acid changes can be related to the clinical course of the disease.     

Bioavailability of single and multiple doses of a new oral formulation of 5-ASA in patients with inflammatory bowel disease and healthy volunteers

Aims: An oral multiparticulate coated formulation of 5-aminosalicylic acid (5-ASA; mesalazine) has been developed to provide a controlled release of the drug, in a pH-dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic availability of the drug and its metabolite, acetyl-5-ASA, following single (800 mg) and multiple (2400 mg for 56 days) oral dose administration. Methods: Three groups were investigated: six healthy volunteers, six patients with ulcerative colitis, and nine patients with Crohn's disease in remission. In the single oral dose study (800 mg) all three groups participated, whereas in the multiple oral dose study (2400 mg/day for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5-ASA and Ac-5-ASA were measured for 48 h. Results: In the single oral dose regimen, systemic absorption of 5-ASA and Ac-5-ASA were low and did not differ between the three groups. Only about 20% of the 5-ASA given was absorbed, with more than 80% of the drug being available in the terminal ileum and colon for therapeutic activity. The multiple oral dose regimen in patients with inflammatory bowel disease produced a significantly higher plasma concentration and urine excretion of both 5-ASA and Ac-5-ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher systemic absorption of 5-ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse event was reported and laboratory screening tests remained within normal ranges. Conclusions: The new oral 5-ASA formulation is gradually released throughout the small and large intestine, reflected by a low plasma concentration of the drug and its metabolite, with about 80% of the drug being available for ileum-colon therapeutic activity.     

Undergraduate medical education in obstetrics and gynaecology in the USA and Canada, 1985

Many factors have led to a movement from the emphasis of the 1960s and 1970s on departmental expansion towards an emphasis on cost-effective undergraduate medical education emphasizing the 'art' as well as the 'science' of medicine. In January 1985 a questionnaire was sent under the auspices of the Undergraduate Education Committee of the Association of Professors of Obstetrics and Gynecology to all chairmen of departments of obstetrics and gynecology in the USA and Canada seeking their opinions about these trends and information about the educational programmes in their departments. The information from this study indicates that the chairmen are aware of and responding to this new direction in medical education. A stabilization of teaching staff and clerkship sizes and the emphasis on clinical as well as cognitive evaluation, despite recognition of the cost of the former, shows active interventions towards these ends. An emphasis on education in 'basic' as compared to 'subspecialty' areas which is independent of the subspecialty of the academic chairman also supports this trend.     

Evaluation of the Crithidia assay to distinguish between auto-immune chronic active hepatitis and systemic lupus erythematosus

The aim of this study was to determine if the Crithidia luciliae assay for auto-antibodies to double-stranded DNA, often positive in systemic lupus erythematosus, is always negative in auto-immune chronic active hepatitis (CAH) as has recently been suggested. Twenty-five patients were identified as having auto-immune CAH. Mean duration of follow-up was 10.5 years. Antinuclear antibodies were detected in 92%, smooth muscle antibodies in 76% and antimitochondrial antibodies in 16%. Antibodies to double-stranded DNA were detected by the Crithidia assay in four patients (16%). Two of these patients had positive tests on only one occasion and no features of systemic lupus erythematosus. In the other two the assay was persistently positive. During follow-up both developed arthritis and serositis but the liver lesion remained the dominant clinical feature. It was concluded that there is significant serological overlap between auto-immune CAH and systemic lupus erythematosus making the Crithidia assay unreliable in distinguishing between them.     

Curative factors in alcohol and drug treatment: behavioral and disease model perspectives

Unlike the general psychotherapy field which has been subjected to extensive process analysis, there are no systematic studies of treatment processes in the alcohol and drug treatment literature. As a necessary first step to study treatment process, the alcohol and drug literature was culled for references to treatment processes. Thirty-five separate processes were identified and were broadly categorized as either disease model, behavioral or general psychotherapy processes. A national survey of treatment expert's views on treatment processes was conducted to determine whether certain processes would be considered as most important in the treatment of alcohol or drug problems. Results of this survey indicate that experts tend to rate certain processes as most important in the resolution of alcohol and drug problems. Results suggest that it is possible to identify core disease model and behavioral treatment processes. These processes might be used to assess the relative effectiveness of each therapeutic approach. Finally, results indicated that while disease model and behavioral experts tended to differ strongly on their ratings of the importance of some processes, there seems to be a trend toward integrating behavioral processes into a traditional disease model framework. The use of these results in constructing an instrument to measure processes used in alcohol and drug treatment is discussed.     

Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells

The vitamin D₃ derived hormone 1,25 (OH)₂ vitamin D₃ (1,25 D₃) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1,25 D₃ reduced proliferation as measured by ³H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D₃ 65% inhibition was achieved at 48 n M . The MC 1288 stereoisomer of 1,25 D₃ was more potent and had the same activity at 48 n M .
The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4.
The antiproliferative effect of liposomal 1,25 D₃ was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33.
When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)₂ vitamin D₃ may offer a novel approach to treatment of myelomonocytic leukaemia.     

Change in Nutrient Intakes, Number of Servings, and Contributions of Total Fat from Food Groups in 4- to 10-Year-Old Children Enrolled in a Nutrition Education Study

Objective To determine change in nutrient intakes, number of servings, and contributions of total fat from food groups in children who lowered their dietary fat intake.Design A research and demonstration study designed to lower plasma low-density lipoprotein cholesterol level. There were four study groups: two intervention and two control groups. All children had hypercholesterolemia except for those in one control group. Three 24-hour dietary recalls were collected on randomly assigned days over a 2-week period at baseline and 3 months after the intervention.Subjects Three hundred three 4- to 10-year old children from suburbs north of Philadelphia, Pa.Interventions One intervention involved a home-based, parent-child autotutorial program (PCAT group) with audiotaped stories and print materials for the children and their families; the other intervention involved one face-to-face counseling session with a registered dietitian (counseling group).Outcome measures Change in mean nutrient intakes compared with the Recommended Dietary Allowance (RDA); change in number of servings and mean grams of total fat contributed from 10 different food groups.Statistical analyses performed Analyses of variance and χ² analyses.Results Children in every study group had mean intakes of all nutrients (except vitamin D) greater than 67% of the RDA 3 months after the baseline measurement. Several food groups (ie, meats, dairy products, fats/oils, and desserts) provided less total fat to the diets of children who reduced their dietary lipid intake after 3 months (ie, PCAT and counseling groups). These children also reduced the mean number of servings selected from these food groups. Within these same food groups, some children consumed fewer servings of higher fat foods and more servings of lower fat foods.Applications/conclusions Children who lowered their dietary fat intake after intervention reported both quantitative and qualitative changes in food choices from several food groups. These choices did not significantly reduce their nutrient intakes. J Am Diet Assoc. 1996; 96:865-873.