Reduction in acute rejections decreases chronic rejection graft failure in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Chronic rejection accounted for 32% of all graft losses in 7123 pediatric transplants. In a previous study acute, multiple acute and late acute rejections were risk factors for the development of chronic rejection. We postulated that the recent decrease in acute rejections would translate into a lower risk for chronic rejection among patients with recent transplants. We reviewed our data on patients transplanted from 1995 to 2000, and using multivariate analysis and a proportional hazards model developed risk factors for patients whose grafts had failed due to chronic rejection. A late initial rejection increased the risk of chronic rejection graft failure 3.6-fold (p < 0.001), while a second rejection resulted in further increase of 4.2-fold (p < 0.001). Recipients who received less than 5 mg/kg of cyclosporine at 30 days post-transplant had a relative risk (RR) of 1.9 (p = 0.02). Patients transplanted from 1995 to 2000 had a significantly lower risk (RR = 0.54, p < 0.001) of graft failure from chronic rejection than those who received their transplants earlier (1987-94). Since we were able to demonstrate that there is a decreased risk of chronic rejection graft failure in our study cohort, we would conclude that the goal of future transplants should be to minimize acute rejections.     

The impact of laparoscopic cholecystectomy on the treatment of symptomatic cholelithiasis

Background: There has been a debate about the cost-effectiveness of laparoscopic cholecystectomy (LC), as well as a concern regarding its possible overutilization and changes in the indication for surgery. Methods: A retrospective analysis of all cholecystectomies performed at UCDMC from 1988 to 1994 was done. The annual rate of cholecystectomy increased by 50% in 1990 when LC was introduced but has since stabilized at a rate 11% higher than the rate before LC. The disease status and severity did not change. Results: The incidence of nonelective surgery remained stable at 31.2% to 37.5%. Elective cholecystectomy had lower mortality (0.16% vs 1.8%, P=0.029), morbidity (2.6% vs 11.2%, P=0.0001), and conversion rate (2.6% vs 16%, P=0.0001) and a shorter length of stay (2.1 days vs 5.4 days), compared with nonelective procedure. Conclusions: The indication for surgery in cholelithiasis has not changed since the introduction of LC. In patients with symptomatic gallstones, early elective surgery is recommended and may be more cost-effective.Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Orlando, FL, March 12–14, 1995     

Cyclin E, p27 and mutant p53 do not predict the prognosis in AJCC stage II colorectal carcinomas.

BACKGROUND/AIMS: Carcinogenesis is characterized by the abnormal regulation of cell cycle. The abnormal expression of the regulators of cell cycle may be related to the prognosis. Since the clinical significance of the expression of the three proteins in colorectal carcinomas is still controversial, we evaluated the prognostic value of the expression of cyclin E, p27 and mutant p53 in stage II colorectal cancer. METHODS: The expression levels of cyclin E, p27 and mutant p53 proteins in 41 patients with stage II colorectal carcinomas were analyzed by immunohistochemistry. RESULTS: In the univariate analysis, the level of CEA at diagnosis was associated with disease relapse. In the multivariate analysis, the clinicopathological variables such as age, gender, site of primary tumor, tumor size, state of tumor differentiation and preoperative plasma CEA level were not associated with disease relapse. When Kaplan-Meier survival curves were constructed to determine the prognosis, cyclin E, p27 and mutant p53 expressions did not predict poor prognosis. CONCLUSIONS: Our results suggested that the expression of cyclin E, p27 and mutant p53 proteins did not predict the clinical outcome in the stage II colorectal carcinomas.     

Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure.

This is a retrospective analysis of 5037 patients with squamous cell carcinoma of the nasopharynx treated during the years 1976-1985. The stage distribution according to Ho's classification was 9% Stage I, 13% II, 50% III, 22% IV, and 6% Stage V. Only 4488 (89%) patients had a full course of megavoltage radiation therapy. The median equivalent dose to the nasopharyngeal region was 65 Gy and cervical region in node-positive patients 53 Gy. Seventy percent (906/1290) of the node-negative patients had no prophylactic neck irradiation. The overall actuarial 10-year survival rate was 43%, and the corresponding failure-free survival 34%. Altogether, 4157 (83%) patients achieved complete remission lasting more than 6 months, but 53% (2205/4157) of them relapsed after a median interval of 1.4 years. The 10-year actuarial local, regional, and distant failure-free rates were 61%, 64%, and 59%, respectively. Thirty-eight percent (338/891) of all patients with local recurrence achieved second local remission. The local complete remission rate with aggressive re-irradiation alone was 47% (333/706). But 37% (124/338) of the responders recurred the second time. The incidence of distant failure correlated significantly with both the N-stage and the T-stage, with the highest (57%) occurring in patients with N3 disease. The incidence of nodal relapse in node-negative patients was 11% (44/384) among those given prophylactic neck irradiation, but 40% (362/906) among those without. Therapeutic irradiation achieved a complete regional remission rate of 90% (306/339). However, despite successful salvage, these patients had a significantly higher distant failure rate than those without nodal relapse, even if they remained local-failure-free (21% vs 6%). Patients treated during 1981-1985 achieved significantly better treatment results than those treated during 1976-1980, especially in terms of the overall survival (57% vs 47% at 5-year), the overall failure-free survival (42% vs 35% at 5-year), and the local failure-free rate (70% vs 63% at 5-year). The possible contributing factors are discussed.     

Effect of dietary omega-3 and omega-6 fatty acid sources on PUVA-induced cutaneous toxicity and tumorigenesis in the hairless mouse

Because of concern about psoralen-induced phototoxicity and photocarcinogenesis, we investigated the effects of dietary lipids in a mouse model in which 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy has been shown to be carcinogenic. SKH-Hr-1 hairless albino mice were fed diets containing either omega-3 or omega-6 fatty-acid sources (menhaden oil and corn oil, respectively). After 2 weeks on the diets, the mice were treated topically with 8-MOP and then exposed to UVA (5 J/cm²). Mice receiving the omega-3 fatty-acid source exhibited a marked decrease in inflammatory response and a more rapid repair, as expressed both grossly and microscopically. In support of the latter response, i.e. repair, ornithine decarboxylase activity was about 20% greater in animals receiving the omega-3 fatty-acid source. The effects of the dietary fatty acid sources on PUVA tumorigenesis were examined in long-term studies in which animals were treated topically with 0.01% 8-MOP thrice weekly after which they were exposed to UVA (1 J/cm²). These studies indicated that a dietary lipid rich in omega-3 fatty acid and known to exhibit anti-inflammatory properties can markedly ameliorate the course of PUVA toxicity but does not impede the course of PUVA tumorigenesis     

Coexistence of autonomic and somatic mechanisms in the pressor areas of medulla in cats.

The effects of electrical stimulation and microinjection of sodium glutamate (0.5 M) in the sympathetic pressor areas of the dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular nucleus (PVC) on the knee jerk, crossed extension, and evoked potential of the L5 ventral root produced by intermittent electrical stimulation were studied in 98 adult cats anesthetized with chloralose and urethane. During electrical and glutamate stimulation of these pressor areas, in addition to the rise of systemic arterial blood pressure marked inhibition of the spinal reflex was produced, indicating presence of neuronal perikarya responsible for these actions. Mild to moderate augmentation of spinal reflexes was also observed during brain stimulation but only in a few cases. The magnitude of the somatic effects among the pressor areas of the VLM, DM, and PVC subsequent to glutamate activation was about the same. Induced spinal reflex inhibition, independent from the baroreceptor and vagal influence, remained essentially unaltered after acute midcollicular decerebration. The inhibition was also observed in cats decerebellated 8-10 days in advance. The inhibition was not affected after bilateral electrolytic- or kainic-acid-induced lesions in the paramedian reticular nucleus (PRN). On the contrary, PRN-induced spinal reflex inhibition was attenuated after bilateral lesions in the DM or VLM. Data suggest that there coexists neuronal subpopulations in the VLM, DM, and PVC that can affect both the sympathetic pressor systems and spinal reflexes.     

The effect of combinations of ampligen and zidovudine or dideoxyinosine against human immunodeficiency viruses in vitro.

The combinations of ampligen and zidovudine at ratios of 100:1, 25:1, 10:1, and 1:50 acted synergistically to reduce cytopathology caused by HIV in MT-2 cell cultures. Combination indices were less than 1 at all of these ratios representing different combinations of concentrations and at 3 effective doses (ED30, ED50, ED70). Combination of drugs which show synergism at a wide range of ratios of combinations suggest that they may be useful clinically, and that the antiviral efficacy of ZDV may be increased in combination with ampligen. Synergism was also found between ampligen and zidovudine by reduction of HIV-produced plaques in a HeLa cell line expressing CD-4 receptors. However the combination of ampligen and dideoxyinosine against HIV in MT-2 cells was only additive and not synergistic.