The effect of etophylline clofibrate on HDL subfractions

The effect of etophylline clofibrate on lipids and apolipoproteins of the high density lipoprotein (HDL) subfractions HDL2 and HDL3 as well as on very low density (VLDL) and low density lipoproteins (LDL) and the post heparin lipolytic activities (PHLA) of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) has been studied in 14 patients with type II hyperlipoproteinemia (HLP). The study was preceded by a 4-week washout phase, followed by a 6-week placebo period. During the next 12 weeks, the patients received 750 mg etophylline clofibrate per day. Then the drug was again replaced by placebo for another 6 weeks. During the study the patients were on a low fat diet poor in cholesterol with a P/S ratio over 1.0. HDL cholesterol and apoproteins increased significantly during treatment. In the first verum phase this effect was related to the rise in HDL2 components with minor changes in HDL3 concentrations, whereas in the second verum period a distinct increase of the HDL3 components could be detected. This development was accompanied by a significant increase of the LPL activities during the first 6 weeks of treatment, followed by a decrease to initially measured values after 12 weeks. The drug lowered plasma- and LDL-cholesterol levels by 19% and 22%, and plasma and VLDL triglycerides by 22% and 25%, respectively. VLDL-C apoproteins (C-I, C-II, C-III) declined by 31% with a percentage increase of apo C-II compared with apo C-I and apo C-III.     

Exogenous reinfection in experimental airborne tuberculosis

This study of experimental airborne tuberculosis in which guinea pigs were infected with tubercle bacilli of low and high virulence, provides no support for hypotheses suggesting that a second or third exposure to tubercle bacilli leads to an adverse effect on host response to the first infecting strain or to the reinfecting strain. The principal influence of the first infection was to protect against a subsequent infection. This protection was most evident as inhibition of the spread of bacilli from the lungs to the spleen. The first infection appeared to exert less influence on events at the site of reimplantation of organisms in the lungs.     

Evolution of primary Raynaud's phenomenon (Raynaud's disease) to connective tissue disease

Eighty-seven patients diagnosed as having primary Raynaud's phenomenon (Raynaud's disease) were reexamined after this symptom had been present for a mean of 8.8 years (range 2.0-34.5). One or more additional clinical feature(s) suggesting an underlying connective tissue disease were found in 12 patients (14%) at first evaluation, and in 23 (26%) by the last evaluation. The most frequent findings were puffy fingers (10 patients), digital tip pitting scars (8 patients), and digital tip ulcerations (6 patients). Distal esophageal hypomotility and/or decreased pulmonary diffusing capacity for carbon monoxide were found in 12 patients. Only 4 individuals (5%) developed clear evidence of a connective tissue disease, and in all cases, the diagnosis was the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome variant of systemic sclerosis. This condition became obvious 8-17 years after the onset of Raynaud's phenomenon. One or more serologic test values were initially abnormal in 2 of these CREST syndrome patients, as well as in 12 patients who continued to have primary Raynaud's phenomenon at the last evaluation. The combination of puffy fingers, digital pitting scars, and serum anticentromere antibody, all consistent with CREST syndrome, occurred in a small group of patients. None of the 78 patients whose serologic tests were repeated during followup had a change in the serologic profile. These results suggest that only a small proportion of patients with primary Raynaud's phenomenon develop one of the connective tissue diseases during the first decade after onset. When such a disorder does appear, systemic sclerosis with the CREST syndrome variant is the most likely eventual diagnosis.     

Obesity, But Not High-Fat Diet, Promotes Murine Pancreatic Cancer Growth

Background

Obesity accelerates pancreatic cancer growth; the mechanisms underlying this association are poorly understood. This study evaluated the hypothesis that obesity, rather than high-fat diet, is responsible for accelerated pancreatic cancer growth.

Methods

Male C57BL/6J mice were studied after 19?weeks of high-fat (60?% fat; n?=?20) or low-fat (10?% fat; n?=?10) diet and 5?weeks of Pan02 murine pancreatic cancer growth (flank).

Results

By two-way ANOVA, diet did not (p?=?0.58), but body weight, significantly influenced tumor weight (p?=?0.01). Tumor weight correlated positively with body weight (R ²?=?0.562; p?<?0.001). Tumors in overweight mice were twice as large as those growing in lean mice (1.2?±?0.2?g vs. 0.6?±?.01?g, p?<?0.01), had significantly fewer apoptotic cells than those in lean mice (0.8?±?0.4 vs 2.4?±?0.5; p?<?0.05), and greater adipocyte volume (3.7 vs. 2.2?%, p?<?0.05). Apoptosis (R ²?=?0.472; p?=?0.008) and serum adiponectin correlated negatively with tumor weight (R?=?0.45; p?<?0.05).

Conclusions

These data suggest that body weight, and not high-fat diet, is responsible for accelerated murine pancreatic cancer growth observed in this model of diet-induced obesity. Decreased tumor apoptosis appears to play an important mechanistic role in this process. The concept that decreased apoptosis is potentiated by hypoadiponectinemia (seen in obesity) deserves further investigation.     

Changes in C-reactive protein predict insulin sensitivity in severely obese individuals after weight loss surgery

The production of inflammatory mediators by abdominal adipose tissue may link obesity and insulin resistance. We determined the influence of systemic levels of interleukin-6 and C-reactive protein on insulin sensitivity after weight loss via Roux-en-Y gastric bypass surgery. Severely obese individuals (n 5 15) were evaluated at baseline and at 6 months after surgery. Insulin sensitivity was determined by frequently sampled intravenous glucose tolerance testing at the same time points. Visceral and subcutaneous adipose tissue volumes were quantified by computed tomography. Interleukin-6 and C-reactive protein were measured by enzyme-linked immunoassay in plasma and in adipose tissue biopsies. Correlation analysis was used to determine associations between insulin sensitivity and other outcome variables. Significance was set at P < 0.05. Plasma interleukin-6 concentrations were significantly correlated to the IL-6 content of subcutaneous adipose tissue (r = 0.71). At 6 months postsurgery, subcutaneous and visceral adipose tissue volumes were significantly reduced (34.7% and 44.1%, respectively) and insulin sensitivity had improved by 160.9%. Significant longitudinal correlations were found between insulin sensitivity and plasma C-reactive protein (r = 20.61), but not plasma interleukin-6 at 6 months. These findings offer insights that link obesity and insulin resistance via the activity of inflammatory mediators. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). Supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases 1R03 DK067167-01A1 (N.G.), the Emory University Research Committee Grant (N.G.), and the National Institutes of Health/National Center for Research Resources General Clinical Research Center Grant M01 RR00039 (N.G., E.L.).     

Current TNM classification of renal cell carcinoma evaluated: revising stage T3a

PURPOSE:: Recent studies of rare cases of pT3a renal cell carcinoma extending directly into the adrenal gland showed worse survival than in other pT3a cases and recategorization as stage pT4 was suggested. We assessed the prognostic validity of a stage pT3a diagnosis based on perirenal fat infiltration. MATERIALS AND METHODS:: The records of 1,794 patients with renal cell carcinoma who underwent surgical resection between 1975 and 2000 at our institution were analyzed retrospectively. Focusing on pT3a tumors, as defined by perirenal fat infiltration, numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods with cancer specific survival as the primary end point. RESULTS:: We identified 237 of 1,794 patients with perirenal fat infiltration, classified as having pT3a disease. In patients with pT3a tumors tumor size was a significant parameter predicting survival. The most significant cutoff value for tumor size in pT3a disease was 7 cm. Patients with distant metastasis had a worse prognosis independent of T classification. Therefore, to assess the prognostic value of the current T classification in regard to T3a tumors we excluded patients with tumor stage cM+ for further subgroup analysis. Survival comparison of pT1 pNall, cM0 (744 of 1,794 cases) and pT3a pNall, cM0 7 cm or less (100 of 237) as well as pT2 pNall, cM0 (265 of 1,794) and pT3a pNall, cM0 greater than 7 cm (93 of 237) yielded similar results. After splitting pT3a into a modified T1/T2 classification a significant difference in 5-year survival analysis for a modified T1/T2 stage was found (pT1 plus pT3a less than 7 cm 90% vs pT2 plus pT3a greater than 7 cm 73%, p <0.001). Subsequently multivariate analysis in all 1,794 patients showed that modified T stage was an independent significant predictor of cancer specific survival. CONCLUSIONS:: We suggest revising the current pT3a classification based on perirenal fat infiltration but rendering a modified pT1/pT2 classification, which resolves pT3a cases without the loss of prognostic validity. Perirenal fat infiltration should not be used to assign T category. Tumors directly infiltrating the adrenal gland should be reclassified as T4.     

Diagnostic of non-palpable testis in children: laparoscopy or magnetic resonance imaging?

Summary Laparoscopy and magnetic resonance imaging (MRI) are competetive tools in the diagnostic of non-palpable testis. Advantages and disadvantages of this methods will be demonstrate. 29 boys investigated for this indication with MRI. In case MRI failed to locate the testis laparoscopy was performed with a new miniaturized set of pediatric instruments (1.9 mm optic). The aim of laparoscopy was the identification of the spermatic duct and vessels and their topographic relation to the internal inguinal ring. All findings were verified by open surgical procedures. MRI revealed 10 inguinal and 7 abdominal testis. There was no false positive finding. In 12 boys MRI showed no testis. 4 cases were correct negative, 8 cases were false negative (32 %). In these 8 MRI-negative patients laparoscopy revealed 7 inguinal and 1 abdominal testis. The optical quality of the mini-telescope was sufficient for a 100 % correct diagnosis. Laparoscopy related complications did not occur. Laparoscopy proved to be a powerful low risk diagnostic method in non- palpable testis with high senitivity and specifity (100 % correct positive, 0 % false negative). Therefore lapraroscopy is recommended as primary diagnostic access for this indication. In the same anesthesia a optimal therapy is possible. Nevertheless a positive MRI-finding locates the testis reliably, whereas a negative finding always needs further exploration because testis might have been missed.      

Effect of open wedge high tibial osteotomy on the lateral compartment in sheep. Part I: analysis of the lateral meniscus

Purpose

To evaluate whether medial open wedge high tibial osteotomy (HTO) results in structural and biochemical changes in the lateral meniscus in adult sheep.

Methods

Three experimental groups with biplanar osteotomies of the right proximal tibiae were tested: (a) closing wedge HTO resulting in 4.5° of tibial varus, (b) open wedge HTO resulting in 4.5° of tibial valgus (standard correction) and (c) open wedge HTO resulting in 9.5° of valgus (overcorrection), each of which was compared to the contralateral knees with normal limb axes. After 6 months, the lateral menisci were macroscopically and microscopically evaluated. The proteoglycan and DNA contents of the red–red and white–white zones of the anterior, middle and posterior third were determined.

Results

Semiquantitative macroscopic and microscopic grading revealed no structural differences between groups. The red–red zone of the middle third of the lateral menisci of animals that underwent overcorrection exhibited a significant 0.7-fold decrease in mean DNA contents compared with the control knee without HTO (P = 0.012). Comparative estimation of the DNA and proteoglycan contents and proteoglycan/DNA ratios of all other parts and zones of the lateral menisci did not reveal significant differences between groups.

Conclusion

Open wedge HTO does not lead to significant macroscopic and microscopic structural changes in the lateral meniscus after 6 months in vivo. Overcorrection significantly decreases the proliferative activity of the cells in the red–red zone of the middle third in the sheep model.