Measurement of gastric and duodenal mucosal protein turnover in humans

Conventional measurement of mucosal turnover is based on labeling cellular DNA with [³H]thymidine, but because of the risk of genetic damage, this technique is not suitable for studies in normal human subjects. Consequently, we have measured mucosal protein turnover by a primed/continuous intravenous infusion of tracer quantities of [1¹⁴C]leucine and measured its incorporation into mucosal protein at 4 hr in nine healthy adult volunteers. Mucosal samples were obtained by standard endoscopic techniques from the distal duodenum and gastric antrum. In addition, duodenal villous height and width were measured by microscopic micrometric techniques in order to calculate villous growth rate. Results demonstrated a mucosal protein turnover of 57±5%/day in gastric antrum and 39±2%/day in duodenum, suggesting a mucosal replacement rate of 1.8 and 2.6 days, respectively. Average duodenal villous height was 433±77 m, suggesting a villous growth rate of approximately 160 m/day. As our mucosal protein turnover rates are similar to epithelial turnover rates measured by cellular labeling techniques, our results support the intestinal proliferon theory that suggests all mucosal elements follow similar turnover characteristics. In conclusion, the technique should provide a practical alternative method of studying the effect of disease upon mucosal regeneration and repair.     

The Effect of Basic Fibroblast Growth Factor on the Reversion of Omental Adipocytes from Lean and Obese Patients

Background: this study was designed to characterize some of the biochemical and molecular genetic changes during reversion of human fat cells. Methods: mature adipocytes were isolated from greater omental fat tissue of eight lean and 14 massively obese persons by established methodology. Results: at day 7 of adherence to Leighton tubes, there was appreciable depletion of triacylglycerol, as well as assumption of an elongated contour. Relatedly, there was an increase in the expression of β-actin mRNA and a significant decrease in the specific activity of cytosolic glycerophosphate dehydrogenase. The decrement in the specific activity of glycerophosphate dehydrogenase, after 7 days in culture, was significant at p < 0.001. Basic fibroblast growth factor at 10 ngml^-1 accelerated significantly (p < 0.03) the decrease in the specific activity of glycerophosphate dehydrogenase in adipose cells from lean subjects. In contrast, basic fibroblast growth factor had no significant influence on cells from massively obese persons. Conclusion: such resistance may contribute to the intractability of massive obesity.     

Treatment of Vitamin B12 Deficiency after Gastric Surgery for Severe Obesity

Background: Vitamin B₁₂ deficiency after gastric surgery for obesity is due to a failure of separation of vitamin B₁₂ from protein foodstuffs and to a failure of absorption of crystalline vitamin B₁₂ in the presence of intrinsic factor. The purpose of this study was to determine which of four oral doses of crystalline vitamin B₁₂ was most effective in treating vitamin B₁₂ deficiency in 102 patients. Methods and Results: At time of entry into the study, the patients had a serum vitamin B₁₂ < 100 pmol L ⁻¹, were 29.9 ± 21.7 months post-op, were 37 ± 8 years old and had a body mass index of 30 ± 6 kg m⁻². Eight (8%) had had a vertical banded gastroplasty and 94 (92%) a gastric bypass. For the first 3 months all patients received 350 μg per day of crystalline vitamin B₁₂ and all increased their serum vitamin B₁₂ levels to over 100 pmol L⁻¹. The patients were then assigned to receive for a further 3 month period one of four oral doses of crystalline vitamin B₁₂-100 μg, 250 μg, 350 μg and 600 μg. Serum vitamin B₁₂ levels were greater than 150 pmol L⁻¹ after 6 months in 83.3% of patients who received 100 μg; 92.3% of patients who received 250 μg; 94.7% after 350 μg and 95.2% after 600 μg (p%0.525). Conclusion: At least 350 μg per day is the appropriate oral dose of crystalline vitamin B₁₂ after gastric surgery for obesity to correct low serum vitamin B₁₂ levels in 95% of patients.     

Epi-Inositol and inositol depletion: Two new treatment approaches in affective disorder

Inositol is a simple polyol precursor in a second messenger system important in brain myo-insitol, the natural isomer, which has been found to be therapeutically effective in depression, panic disorder, and obsessive-compulsive disorder in double-blind controlled trials. Recently, epiinositol, an unnatural stereoisomer of myo-inositol, was found to have effects similar to those of myo-inositol to reverse lithium-pilocarpine seizures. We measured the behavior of rats in an elevated plus maze model of anxiety after chronic treatment of 11 daily intraperitoneal injections of epi-inositol, myo-inositol, or control solution. Epi-inositol reduced anxiety levels of rats compared with controls, and its effect was stronger than that of myoinositol. Lithium has been hypothesized to alleviate mania by reducing brain inositol levels. Inositol in brain derives from the second messenger cycle, from new synthesis, or from diet via transport across the blood brain barrier. Because the first two are inhibited by lithium, we propose that an inositol-free diet will augment lithium action in mania by enhancing restriction of inositol.     

Computerized analysis of lesions in US images of the breast

RATIONALE AND OBJECTIVES: Breast sonography is not routinely used to distinguish benign from malignant solid masses because of considerable overlap in their sonographic appearances. The purpose of this study was to investigate the computerized analyses of breast lesions in ultrasonographic (US) images in order to ultimately aid in the task of discriminating between malignant and benign lesions. MATERIALS AND METHODS: Features related to lesion margin, shape, homogeneity (texture), and posterior acoustic attenuation pattern in US images of the breast were extracted and calculated. The study database contained 184 digitized US images from 58 patients with 78 lesions. Benign lesions were confirmed at biopsy or cyst aspiration or with image interpretation alone; malignant lesions were confirmed at biopsy. Performance of the various individual features and output from linear discriminant analysis in distinguishing benign from malignant lesions was studied by using receiver operating characteristic (ROC) analysis. RESULTS: At ROC analysis, the feature characterizing the margin yielded Az values (area under the ROC curve) of 0.85 and 0.75 in distinguishing between benign and malignant lesions for the entire database and for an "equivocal" database, respectively. The equivocal database contained lesions that had been proved to be benign or malignant at cyst aspiration or biopsy. Linear discriminant analysis round-robin runs yielded Az values of 0.94 and 0.87 in distinguishing benign from malignant lesions for the entire database and for the equivocal database, respectively. CONCLUSION: Computerized analysis of US images has the potential to increase the specificity of breast sonography.     

Breast Carcinoma in Childhood and Adolescence: Case Report and Review of the Literature

Secretory breast carcinoma is a rare tumor originally described in children and adolescent women with a characteristic morphology and a controversial choice of treatment. We report an additional case of a 4-year-old girl with a breast tumor diagnosed as a secretory carcinoma without involvement of the axillary lymph nodes. The therapy consisted of simple mastectomy and low axillary dissection. She presented with a local recurrence near the surgical scar 8 months later, and a wide elliptical excision of the scar and underlying tissue was performed with subsequent radiotherapy of the surgical bed. This tumor has a relatively benign behavior and rarely metastasizes. A literature review revealed only 22 cases of breast carcinoma in childhood and adolescence. ▪     

Supratentorial cavernous haemangiomas and epilepsy: a review of the literature and case series

OBJECTIVES: To characterise the clinical features and response to treatment of supratentorial cavernomas associated with epilepsy. METHODS: A systematic review of the literature was carried out and a retrospective case series of patients with cavernoma diagnosed by MRI and/or histology was compiled. Patient selection biases in the literature review were reduced as far as possible by selection of unbiased publications. RESULTS: In the literature, cavernomas were relatively less common in the frontal lobes. There were multiple cavernomas in 23% of cases. The main clinical manifestations were seizures (79%) and haemorrhage (16%). The annual haemorrhage rate was 0.7%. The outcome after excision was good with improvement in seizures in 92% of patients. In the case series the surgical outcome was less favourable, reflecting inclusion of a higher proportion of patients with intractable epilepsy. In both the literature review and the case series, outcome was poorer in cases with a longer duration of seizures at the time of surgery. CONCLUSIONS: The good surgical results, particularly in cases treated earlier, and the significant cumulative haemorrhage rate, suggest that excision is the optimum treatment. However, these factors have not been examined prospectively and, despite the availability of several retrospective studies, the optimum treatment, particularly for non-intractable cases, will only be determined by a prospective study.     

Borna disease virus-induced hippocampal dentate gyrus damage is associated with spatial learning and memory deficits

In neonatally inoculated rats, Borna disease virus (BDV) leads to a persistent infection of the brain in the absence of an inflammatory response and is associated with neuroanatomic, developmental, physiologic, and behavioral abnormalities. One of the most dramatic sites of BDV-associated damage in the neonatal rat brain is the dentate gyrus, a neuroanatomic region believed to play a major role in spatial learning and memory. The absence of a generalized inflammatory response to neonatal BDV infection permits direct effects of viral damage to the dentate gyrus to be examined. In this report, neonatally BDV-infected rats at various stages of dentate gyrus degeneration were evaluated in the Morris water maze, a swimming test that assesses the rats' capacity to navigate by visual cues. Our data demonstrate progressive spatial learning and memory deficits in BDV-infected rats that coincided with a gradual decline in the estimated hippocampal dentate gyrus neuron density.     

Inherent Abnormalities of Fat Cells from Massively Obese Individuals

In vitro investigations into adipose cell dynamics have revealed intrinsic characteristics of massively obese individuals' cells that could contribute to a relatively intractable expanded fat mass. Morbidly corpulent peoples' preadipocytes replicate to a greater degree than those from lean individuals. Coupled with exaggerated differentiation this enhanced growth would result in a greater number of fat cells which would increase adipose tissue mass. The relative resistance to de-differentiation that adipocytes from the massively obese demonstrate would contribute to stability of an increased number of adipocytes further exacerbating the problem. The increased message of an energy sensing protein, the obese gene product, suggests that the morbidly obese are insensitive to its action. Together these attributes provide a strong argument for a significant genetic role in the pathogenesis of obesity.     

Appendicitis: Higher risk in Mexican Americans?

Objectives. Mexican Americans (MAs), compared to white non‐Hispanics (WNHs), have higher rates of biliary disease, noninsulin dependent diabetes, and endstage renal disease but lower rates of lung cancer, hip fractures, and mortality from coronary heart disease. Relatively little research has been done to identify other ethnic differences in disease incidence. We used surgical procedure rates to confirm known ethnic differences and to explore our clinical suspicion that MAs have higher rates of appendectomy than WNHs.

Methods. We used a registry of surgical procedures at two teaching hospitals in South Texas to calculate proportional operation ratios (PORs) for MAs versus WNHs. These two hospitals are the primary source of acute hospital care for the indigent in the area. The POR is arithmetically identical to proportional incidence and mortality ratios.

Results. MAs underwent appendectomy proportionally more often than WNHs at both hospitals (POR = 1.41 and 1.75, p < 0.0001). Other significant PORs were consistent with known ethnic disease differences in biliary tract operations, vascular access for chronic hemodialysis, lung cancer, and coronary artery bypass.

Conclusions. These findings support the hypothesis that MAs may undergo appendectomy more often than WNHs and so may be at higher risk of appendicitis.