Laparoscopic Nissen fundoplication in children: 2-5-year follow-up.

PURPOSE: This study aims to document the current status of a cohort of children who underwent laparoscopic fundoplication at a single centre between 1996 and 1998. METHODS: Parents were contacted and a questionnaire regarding preoperative and current symptoms completed. Case notes were reviewed for results of postoperative investigations. RESULTS: Forty-five laparoscopic Nissen fundoplications were performed. The median age was 5 years. Twenty-eight children were neurologically impaired. Five died of underlying medical problems during follow-up. Two were lost to follow-up, leaving 38 parents interviewed. Median follow-up was 36 months. Twenty-five children were asymptomatic, and 13 reported upper gastrointestinal symptoms. In ten, symptoms were less severe than preoperatively. Nine of the 13 children were taking acid suppressing drugs. No children reported problems with dysphagia. Twelve of the 13 symptomatic children had investigations for recurrent reflux. In no case was there evidence of reflux or wrap disruption. One of the children who died had been demonstrated to have recurrent reflux on barium swallow. CONCLUSIONS: Sixty-six percent of patients reported complete relief, and a further 26% reported considerable improvement of their symptoms. There was a high degree of parental satisfaction with the outcome of the operation. The results suggest that laparoscopic fundoplication is a durable procedure with documented recurrent reflux in only 2% of children at a median follow-up of 3 years.

Hyperphagia as a mediator of renal disease initiation in obese Zucker rats.

OBJECTIVE: We sought to determine whether prevention of overeating would block the very earliest manifestations of renal injury in young obese Zucker rats (OZRs). RESEARCH METHODS AND PROCEDURES: Three groups of rats were studied, obese (fa/fa) Zucker rats and lean (Fa/Fa). Zucker controls were allowed to feed ad libitum, whereas a group of obese (fa/fa) Zucker rats was pair-fed to the lean group. Urine albumin and serum lipids were studied weekly from 6 to 10 weeks of age. Renal pathology and renal glomerular gene expression were examined when the rats were killed at 10 weeks of age. RESULTS: Obese rats fed ad libitum developed significant albuminuria by 6 weeks of age, increasing at each subsequent time-point. This increase was completely blocked by pair-feeding. Serum triglycerides were significantly increased in obese rats fed ad libitum vs. the other groups. Urine albumin correlated significantly with both body weight and serum triglyceride level. Renal histopathology was normal in all groups. Analysis of gene expression of glomerular proteins by reverse transcriptase-polymerase chain reaction revealed that pair-feeding attenuated the increased expression of glomerular desmin, fibronectin, and the 92-kDa collagenase that was seen in obese animals fed ad libitum. DISCUSSION: Prevention of overeating in young OZR normalizes albuminuria and attenuates the pathogenic alterations in glomerular gene expression seen at the initiation of renal disease in obese animals allowed to feed ad libitum. This model may be relevant for studying the early end-organ effects of obesity.

Calorie restriction in obesity: prevention of kidney disease in rodents.

The incidence of end-stage renal disease (ESRD) has risen considerably in the past two decades. This trend is partly due to the alarming rise in the incidence of type 2 diabetes over the same period, which in turn might be linked to the staggering increase in overweight and obesity. If these trends continue, ESRD can be expected not only to cause suffering of ever growing numbers of patients, but also to become an increasing financial as well as logistical burden on the health care system. Therefore, it is imperative not only to gain a better understanding of the molecular, cellular and metabolic mechanisms involved in renal pathology, but also to uncover treatment modalities, including lifestyle changes, that can help prevent and/or slow the progression of kidney pathogenesis. Insights into both of these aspects are provided by animal models of obesity and diabetes. It has long been known that food restriction, more so than restriction of any particular dietary component, can greatly enhance longevity in laboratory rodents. These findings are being extended into a variety of other mammals, including nonhuman primates. These studies have indicated that caloric restriction in nonobese laboratory animals does not primarily affect specific disease processes but rather nonspecifically slows the aging process. In contrast, a growing body of evidence suggests that in genetically obese animals, food restriction can prevent or greatly delay the onset of specific degenerative lesions, in particular glomerulonephritis associated with obesity and diabetes.

Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat.

BACKGROUND: The obese Zucker rat (OZR) is a model of glomerulosclerosis and renal failure in the setting of hyperlipidemia, hyperinsulinemia, and obesity. Our prior work in OZRs has shown that ovariectomy attenuates glomerulosclerosis, while added estrogen worsens it. To investigate the mechanism of estrogen's effects on glomerular disease in this model, we evaluated the effects of ovariectomy and estrogen supplementation on seven-week peripubertal OZRs. At this time point, rats exhibit no overt histologic glomerular disease, but are just beginning to show elevated urinary albumin excretion. METHODS: Female OZRs fed ad libitum were ovariectomized at four weeks, with or without estrogen supplementation to raise estrogen levels to just below those of preoestral adults (mean 16.5 pg/mL). Sham-operated controls were included. RESULTS: Ovariectomy normalized albuminuria, lowered total and very low-density lipoprotein triglycerides, and reduced glomerular fibronectin expression. Estrogen supplementation worsened albuminuria and raised total/very low-density lipoprotein triglycerides and total cholesterol. Estrogen-supplemented rats exhibited enhanced glomerular deposition of apo A-IV and apo B, increased glomerular expression of desmin and type IV collagen, and increased interstitial macrophage deposition. CONCLUSION: Estrogen may be permissive for the early development of renal disease in OZRs and may act by increasing triglyceride-rich lipoproteins, which then bind to glomerular cells and initiate or accelerate glomerulosclerosis.