Adaptive upregulation of gastric and hypothalamic ghrelin receptors and increased plasma ghrelin in a model of cancer chemotherapy-induced dyspepsia.

Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03+/-1.35% vs. 11.38+/-2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03+/-1.35% vs. 2.60+/-0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.

Induction immunotherapy in pediatric heart transplant recipients: a multicenter study.

BACKGROUND: The efficacy and safety of induction immunotherapy with antithymocyte antibody preparations (IND) in pediatric heart transplantation is controversial. Experimentally, recipient age is an important determinant of immune responses. The effects on induction immunotherapy were determined by an analysis of outcomes of 465 pediatric (age <18 years) heart recipients that either did or did not receive IND in the first week post-transplant. METHODS: The outcomes of 2 groups who received either OKT3 (n = 101) or rabbit polyclonal antithymocyte serum (N/R-ATS, n = 105) were compared with 255 recipients who did not receive antithymocyte antibodies. The study population were all heart recipients enrolled in the Pediatric Heart Transplant Study Group (PHTS) between January 1993 and December 1995 and followed up to 36 months. RESULTS: Overall mortality and death due to rejection were lowest with N/R-ATS IND (8/105 and 1/105, respectively) compared with the no-induction group (58/255 and 8/ 255, respectively) or the OKT3 group (22/101 and 7/101, respectively) with significance of p = 0.001 and 0.06 respectively. Late mortality beyond 30 days after transplant was lowest with N/R-ATS IND compared with the OKT3 and no IND (p = 0.01). Induction did not affect cumulative infections, deaths due to infection, or the frequency of malignancies. Patients excluded from N/R-ATS induction had the highest mortality (18/ 43), suggesting that the protocol's exclusion criteria identified a high-risk group. To minimize potential effect(s) of exclusion bias, patients transplanted at centers participating in the N/R-ATS induction trial were reanalyzed with a post hoc intent-to-treat analysis assigning patients by center (IND or no IND) irrespective of actual treatment. With this analysis overall mortality was 18% for N/R-ATS centers, 21% for OKT3 centers, and 26% for centers not using IND (p = 0.3). The mortalities of recipients <6 months old at transplant were lowest at centers using N/R-ATS and OKT3 IND compared to centers not using IND (p = 0.04). Cumulative rejection (0.8 vs 1.2 rejection/pt/year, p = 0.01) and freedom from rejection death (99% vs. 93% at year 1, p = 0.02) of the N/R-ATS centers were lower compared to OKT3 centers but were not different from centers not using IND. CONCLUSION: Following orthotopic transplantation, induction immunotherapy can exert the enduring benefit of reducing late deaths, a possible surrogate for rejection severity, in recipients less than 6 months of age, while not being associated with higher rates of infectious or malignant complications. Since polyclonal anti-T cell antibody preparations appears superior to OKT3 induction in pediatric recipients, the efficacy of ATS induction should be further evaluated in a randomized prospective study in pediatric heart recipients.

Improving physicians' preventive health care behavior through peer review and financial incentives.

We assessed improvement of preventive health care behaviors by physicians in an independent practice association-health maintenance organization. A before-after, 3-year study of a defined cohort measured changes through chart audit, accompanied by peer review, feedback, and financial incentives. Outcome measures consisted of rates of mump-measles-rubella (MMR) immunization, screening for cholesterol levels, and charting adequacy. Offices meeting MMR vaccination standards over 3 years increased from 78% to 96% (P < .05); those meeting standards for screening for cholesterol levels, from 92% to 95%. The average scores for charting adequacy rose from 87% to 92% (P < .05). The percentage of practices not in compliance with a standard of 90% decreased as follows: for MMR vaccination, from 57% to 12%; for screening for cholesterol levels, from 21% to 11%; and for charting adequacy, from 53% to 29% (P < .05).

Changes in fetal hemodynamics with terbutaline treatment and premature labor.

The aim of this study was to examine the fetal hemodynamic effects of terbutaline treatment and premature labor. Image-directed pulsed and continuous wave Doppler ultrasound studies, using 3.3-MHz and 5-MHz transducers (GE PASII and ATL echocardiographic machines), were used to assess fetal cardiac blood velocities in three groups of pregnancies matched for menstrual age (MA). Group 1: 13 normal pregnancies, mean MA 31 weeks. Group 2: 7 women in premature labor prior to tocolytic therapy, mean MA 32 weeks. Group 3: 8 women treated with terbutaline, average dose 18.8 mg daily, for previous premature labor, mean MA 31 weeks. Heart rate averaged 150 bpm, 135 bpm, and 127 bpm in the terbutaline, premature labor, and normal groups, respectively, and each were significantly different from each other. Products of time velocity interval and heart rate at the aortic valves were 1603 cm +/- 140 cm, 1413 cm +/- 190 cm and 1238 cm +/- 200 cm, and at the mitral valves 1102 cm +/- 170 cm, 812 cm +/- 110 cm, and 878 cm +/- 150 cm in the terbutaline, premature labor, and the normal groups, respectively. Aortic and mitral blood velocity products of time velocity integrals and heart rates were significantly higher (p = 0.01) in the terbutaline group relative to the normal group. In addition, the terbutaline group was significantly higher than the labor group at the mitral valve (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Tris (2,3-dibromopropyl) phosphate: human contact sensitization.

Liquid TBP caused delayed hypersensitivity in human subject maximization tests. It showed a dose/response relationship and is judged a weak to mild sensitizer. Patch testing a pre-sensitized subjects using fabrics containing TBP produced responses varying with the availability of the agent at the fiber surface. It appears improbable that treated textiles affording low TBP availability will cause sensitization.