Myofibroblasts and the progression of diabetic nephropathy

Background. The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study.Subjects and methods. We have studied by immunohistochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; &agr;-smooth-muscle actin (&agr;-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue for three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression renal cytoskeletal proteins. Results. In normal kidneys, cells expressing &agr;-SMA were confined to the vascular media and adventia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing &agr;-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial &agr;-SMA proved to be a predictor of progressive diabetic nephropathy (R² for 1/serum Cr slope=0.608, P=0.00001). This predictive parameters; tubular atrophy (R²=0.477, P=0.00004) and interstitial fibrosis (R²=0.28, P=0.001). Conclusion. We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.     

The Workup for Bariatric Surgery Does Not Require a Routine Upper Gastrointestinal Series

Background: Morbid obesity is a serious disease that afflicts over five million Americans, threatening their health with such co-morbidities as diabetes, arthritis, pulmonary failure and stroke. Surgery is the only effective therapy, providing long-term control of weight, diabetes, pulmonary failure, and hypertension for as long as 14 years. Because the operation presents a major expense, this study examined whether X-ray examination of the gut could be omitted safely as a cost-saving measure. Methods: The records of 814 consecutive morbidly obese patients who underwent gastric bypass were reviewed to determine: (1) whether these individuals had undergone an upper gastro-intestinal (GI) series, and (2) if these studies influenced therapy or caused cancellation or postponement of surgery. Results: Of the 814 patients, 657 (80.7%) underwent a preoperative GI radiography. Of these examinations, 393 (59.8%) were normal, with the following abnormalities in the remaining 264: hiatal hernia, 164; esophageal reflux, 39; Schatzki's ring, 18; small bowel diverticula, four; renal stones, four; malrotation, three; gall stones, two; pyloric ulcer, one; possible pelvic mass, one; calcified leiomyoma, one; and dysphagial lusoria, one. None of these findings resulted in cancellation or a delay in surgery. Conclusions: The upper GI series can be safely omitted from the routine preoperative evaluation of patients undergoing gastric bypass. At a cost of $741.00 per examination, this change represents significant potential savings. Similar evaluations of other routine preoperative tests may well provide a better basis for the evaluation of these complex patients.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:From oligonucleotide shapes to genomic SELEX: Novel biological regulatory loops

The SELEX method and oligonucleotide combinatorial chemistry discovery process yields high-affinity/high-specificity ligands for virtually any molecular target. Typically, the enormous starting libraries used in the SELEX process contain 10¹⁴–10¹⁵ sequences. We now ask if the smaller sequences, complexity of extant organisms, and evolutionary history provide useful interactions between oligonucleotides and at least some unexpected targets. That is, do organisms contain a robust “linkage map” between their oligonucleotides and proteins and/or small molecules that enriches life?     

Improving self-care among older patients with type II diabetes: the "Sixty Something..." Study.

A 10-session, self-management training program was designed specifically for persons over 60 years of age having Type II diabetes. It targeted social learning variables, especially problem-solving skills and self-efficacy, found to be related to diabetes self-care in earlier correlational research. One hundred two adults were randomized to immediate or delayed intervention conditions. At posttest, subjects in the immediate intervention condition showed significantly greater reductions in caloric intake and percent of calories from fat than control subjects. The intervention also produced greater weight reductions and increases in the frequency of glucose testing than did the control condition. Improvements among immediate intervention subjects were generally maintained at a 6-month follow-up. Intervention results from subjects receiving delayed intervention closely replicated those for immediate intervention subjects. We conclude that a relatively short-term program can improve self-management skills of older diabetic adults, and that there is an important need for such interventions.     

HELLP Syndrome: an Often Unrecognized Complication of Preeclampsia

We describe a case of preeclampsia with the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and highlight the delayed diagnosis due to its nonspecific presentation. This syndrome is associated with significant maternal and perinatal mortality and morbidity and we discuss the importance of early recognition of the condition, aggressive management and a multidisciplinary approach.     

Physiologic comparison and validation of Stairobic stepping with bench stepping.

To compare the oxygen cost of submaximal exercise on the Stairobic stepping (SS) machine with bench stepping (BS), 12 healthy men and women (mean age 23 years) underwent six different five minute exercise bouts that were randomly assigned. Tests were conducted using standard open circuit calorimetry. SS at 40 and 60 st/min was equal to BS at 20 st/min and SS at 80 st/min was equal to BS at 30 st/min for VE and RER. VO2 was equal at 20 st/min (BS) and 60 st/min (SS), and 30 st/min (BS) and 80 st/min (SS). Stairobic MET (SM) displayed values over-estimated actual MET (AM) values at the two lowest SS rates and under-estimated the AM value at the highest SS rate. Forty-eight observations of the MET response of SS were conducted and analyzed (BMDP2R) in a forward stepping solution. The multiple regression equation calculated for AM was: AM = -0.567 + -0.012 (WT) + 0.063 (rate) + 0.612 (SM) with an adjusted R2 of 0.82 and a SEE of 0.90. The physiologic cost of BS was approximately equal to SS at two to three times the BS rate of stepping.     

CNS mycosis fungoides: CT and MR findings.

Mycosis fungoides (MF) is a malignant T-cell lymphoma that primarily involves the skin, but may, in its advanced stages, metastasize to internal organs. From autopsy series, CNS involvement of MF can be seen in 14% of patients. We describe the CT and MR findings in three patients with CNS metastases. The images showed various manifestations of CNS MF, including parenchymal homogeneously intensely enhancing masses and ependymal enhancement. The CSF and biopsy results were eventually diagnostic in all three cases. One patient was treated prior to pathologic diagnosis, the other two were treated after diagnosis. The tumor improved following treatment in two patients. Although the imaging findings of CNS MF are nonspecific, they can be the first evidence of the disease.