L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.      

Influence of sterilization, drying and oat bran enrichment of pasta on glucose and insulin responses in healthy subjects and on the rate and extent of in vitro starch digestion.

The effects of sterilization and oat bran enrichment of pasta on the glucose and insulin responses in healthy subjects were evaluated. Cooked and canned spaghetti and cooked fettucini without and with enrichment with oat bran (28%) were compared. Further, the effects of various low- and high-temperature drying conditions for spaghetti, cooking time and sterilization on the starch digestion rate and content of enzyme-resistant starch (RS) in vitro were also studied. Various cooking quality data were also determined to allow interpretation of results. The incremental glucose area (0-120 min) produced by canned spaghetti was twice the area of that produced by cooked spaghetti (69.03 vs 35.45 mmol/l x min, P less than 0.01). The incremental insulin area (0-120 min) was also significantly higher with canned spaghetti (17,500 vs 12,600 pmol/l x min, P less than 0.05). The rapid digestion was caused by excessive swelling of starch during sterilization that promoted a very soft texture of the spaghetti. Enrichment of fettucini with oat bran reduced slightly the incremental insulin area (15,600 vs 20,100 pmol/l x min, P less than 0.05, for 0-120 min), but did not significantly reduce the glucose area. Drying conditions and cooking times could be varied within broad limits without affecting the rate of starch digestion in vitro of cooked spaghetti. In sterilized spaghetti the content of resistant starch was higher than that found in cooked 'al dente' spaghetti (2.2-3.4 vs 0.5 mg/100 mg total starch). In conclusion, sterilization influences the nutritional properties of starch in pasta by substantially increasing the glucose and insulin responses and by formation of resistant starch. The effect of oatbran environment is restricted mainly to a slight decrease in the insulin response.     

Is there an association between periodontal condition and HIV infection?

Abstract Individuals in Tanzania who have limited access to medical and dental treatment provide an opportunity to study the natural association between periodontal condition and HIV infection and the stage of infection. 119 HIV infected adult individuals and 73 individuals with AIDS from the AIDS Clinical Trial Clinic at Muhimbili Medical Centre (MMC) in DaresSalaam participated as cases. Mean age was 35.3 and 35.1 years, respectively. 156 individuals with a mean age of 28.3 years, confirmed as HIV seronegative, served as controls. There were no significant differences in bleeding on probing, pocket formation or attachment loss among the HIV seronegative individuals. HIV seropositive and AIDS patients. We applied multiple logistic regression to calculate odds ratios for presence of periodontal conditions adjusting for age, gender and DMFT. Our odds ratios did not reveal any significant associations between bleeding on probing, pocket formation or attachment loss with regard to lymphocyte and CD4+ T cell counts among the HIV infected individuals and AIDS patients. When associations were investigated with regard to HIV serostatus (HIV seronegative. HIV seropositive or AIDS), our adjusted odds ratios were insignificant, too. In fact, most odds ratios were close to 1. Thus, our study supports recent views that the presence, extent and severity of periodontal disease among HIV infected individuals, may be less that hitherto thought.     

Brief report: Does fenfluramine treatment enhance the cognitive and communicative functioning of autistic children?

This project was supported by two separate research grants from the Trust Fund Board, Washington Association for Retarded Citizens to Richard Neel and Truman E. Coggins. The research was also supported by a training grant to the University of Washington entitled Comprehensive Training in Mental Retardation and Other Handicapping Conditions (MCH-000913, Clifford J. Sells, M.D., Principal investigator); and, a training grant to the University of Arizona entitled Doctoral and Post-Doctoral Leadership Training and Clinical Research, Teaching and Administration: Clinical Language Research Center (G008630088, Linda Swisher, Ph.D., principal investigator). We are indeed grateful to the parents of our five subjects for their patience, understanding, and commitment. Finally, we express our appreciation to Arelene Chaussee for her technical expertise and untiring spirit.     

Short- and long-term effectiveness, morbidity, and mortality of peritoneovenous shunt inserted to treat massive refractory ascites of nephrogenic origin analysis of 14 cases

The experience with 14 patients with end-stage renal disease (ESRD), 13 of them maintained on chronic hemodialysis (x 20.4 months +/- 2.9 SEM) and one following successful renal transplantation, underwent placement of a peritoneovenous shunt (PVS) for refractory ascites that had been present before insertion from two to 15 months (x 5.3 +/- 0.8 SEM). A "specific" cause for the ascites could not be identified in any of the 14 patients. The ascites was an exudate in every patient (protein content greater than 3.5 gm/dl). Twelve patients (86%) obtained significant relief of the discomfort and all effects of the ascites, and objective clinical improvement persisted for at least six months. Nine patients (75%) survived one year and six (50%) survived three or more years. Three patients (21%) had recurrence of ascites because of shunt malfunction; however, two of them were successfully treated with placement of a second shunt. Eight (57%) patients have died since the onset of their ascites (x 14.1 months +/- 3.5 SEM); one death was attributable to PVS placement, while the other seven deaths were due to complications of their ESRD. Insertion of a PVS is an effective therapeutic alternative to palliate the discomfort and ill effects of massive nephrogenic ascites that is often refractory to hemodialysis with ultrafiltration.     

Hydroxyurea potentiation of the antineoplastic activity of cyclophosphamide and 4′-(9-acridinylamino)methanesulfon-M-anisidide (AMSA) in the brown Norway rat myelocytic leukemia model

Summary The activities of hydroxyurea (HU), 4-(9-acridinylamino) methanesulfon-M-anisidide (AMSA) and cyclophosphamide (CY) were examined in the brown Norway rat myelocytic leukemia model in experiments designed to determine the synergy, optimal drug sequencing, and therapeutic index of combinations of these agents. A single dose of CY or four consecutive daily doses of AMSA produced increased survival in leukemic rats, with a positive-slope dose-response curve up to the maximum tolerated dose (MTD). HU at 1/2 MTD produced a minimal antileukemic effect but significantly potentiated the antineoplastic activity of 1/2 MTD of CY or AMSA with no significant toxic death rate. Drug-sequence experiments demonstrated that maximal synergy was achieved when HU was given immediately after CY but immediately before or during AMSA administration. No significant cure rate was seen with any CY/HU or HU/AMSA sequence. The three drugs given in the sequence of CY followed 3 days later by HU and AMSA simultaneously, however, was curative in the majority of rats with advanced leukemia, whereas other sequences were more toxic or less effective. Each of the drugs in these experiments was given at 1/2 of its single-agent MTD. HU significantly potentiates the antineoplastic effect of CY and AMSA in a drug-sequence-dependent manner in this model, apparently with an improved therapeutic index.Supported by the State of Nebraska Cancer and Smoking Disease Research Program Grant #87-10R     

Composition of the Essential Oil of Agastache foeniculum

AGASTACHE FOENICULUM contains 0.1-0.3% essential oil and the main components are limonene, beta-caryophyllene, methylchavicol, and germacrene B (92% altogether). In addition 35 components, each accounting for less than 1% of the total essential oil, were identified.     

In vitro studies of lymphocytes from patients with plasma cell myeloma. I. Stimulation by mitogens and cytotoxic activities

Highly purified blood lymphocytes from patients with plasma cell myeloma were tested in different in vitro systems. The patients were untreated or had received a standardized 4-day treatment with melphalan and prednisolone every sixth week. They were tested 5 weeks after the last treatment to minimize the acute toxic effects of the drugs. Lymphocytes from healthy controls were included in each experiment.

Stimulation of lymphocytes was measured by incorporation of ¹⁴C-thymidine into DNA after activation with phytohaemagglutinin (PHA), concancavalin A (Con A) and pokeweed mitogen (PWM). Their cytotoxicity was tested against Chang cells (human cell line) and chicken red blood cells in presence of PHA or heat-inactivated rabbit antibodies to target cell antigens. Lysis was quantitated as release of radio-activity from target cells labelled with ⁵¹Cr-chromate.

Antibody-induced cytotoxicity of lymphocytes from untreated patients was normal or slightly elevated while that of treated patients was severely depressed. Also, lymphocytes from treated patients were significantly less stimulated to DNA synthesis by PWM than were control lymphocytes. PHA-induced cytotoxicity and stimulation of lymphocytes by Con A or PHA were normal in all groups.

These results suggest that treatment of myeloma patients with melphalan and cortisone selectively impairs lymphocytes which respond to PWM by DNA synthesis and which participate in antibody-mediated cytolysis.

     

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome

Thirty-two women with polycystic ovary syndrome (PCOS) wereallocated to two antiandrogen treatment regimens; 28 women completedthe trial. Twenty women were treated with ethinyloestradioland cyproterone acetate (EO-CA) cyclically for 6 months andeight women were treated with the gonadotrophin releasing hormone(GnRH) analogue, goserelin for 6 months. Effects on hirsutism,insulin sensitivity (estimated by glucose clamp technique),blood lipids and hormones were measured. Women treated withEO-CA showed a reduction in hirsutism (P <0.05), and decreasedserum androgen concentrations (P <0.001) as well as reducedinsulin sensitivity (P <0.05). In women treated with goserelin,serum androgen concentrations also decreased (P <0.001),but there was no significant reduction of hirsutism. This group,however, showed an improved insulin sensitivity (P <0.05)despite an unchanged body mass index. Bone mineral density wasunaltered in both treatment groups. The reduction in androgenconcentrations caused by EO-CA was not paralleled by increasedinsulin sensitivity, most probably due to the effect of ethinyloestradiolper se. In contrast, the reduction in androgen concentrationsby goserelin was accompanied by an improved insulin sensitivity.