Effect of morphological abnormalities on blood retinal barrier permeability in diabetic retinopathy

The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (P_BRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lenstransmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the P_BRB by multiple regression analysis. The P_brb was not correlated to morphological abnormalities of non-proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p > 0.3]. The P_BRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (S_irma) and (2) new vessels (S_neo): p_brb = A – B.S_IRMA – C.S_neo with P_BRB in nm/sec, A = 1.5 ± 0.5, B = 0.9 ± 0.2 and C = 1.7 ± 0.4, R² = 0.65, p < 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities.     

Prenatal age-specific reference intervals for measuring all five digits of the fetal hand.

OBJECTIVE: To construct prenatal age-specific reference intervals for measurement of five digits in normal fetuses. PATIENTS AND METHODS: Prospective cross-sectional study of fetuses assessed at an antenatal ultrasound unit in a university-affiliated general hospital. The study cohort comprised 302 pregnant women attending our clinic for routine fetal biometry or anomaly scan between December 1997 and June 2000. They all fulfilled the study inclusion criteria: singleton fetuses with normal anatomy, accurate gestational age and no medical complications of pregnancy. Each fetus was scanned once only and the finger measurements of one hand were obtained. Electronic calipers were placed on the outer margin of the proximal phalanx to the outer margin of the distal phalanx level. Those measurements and the relevant gestational age were registered in a computerized database. RESULTS: The linear increase of size of each of the five fingers was plotted across the evaluated range of gestation (P < 0.001; r2 between 0.85 and 0.86 for fingers I to V). Tables showing the 5th, 50th and 95th centiles of finger lengths between 14 and 27 weeks' gestation were created based on the reference interval charts. CONCLUSIONS: Second-trimester measurement of all five digits of the fetal hand is feasible. This may assist in the evaluation of fetuses that are primarily suspected of having genetic abnormalities that might be expressed by deviation in finger length.     

Computer simulation of periacetabular osteotomy.

A simple static three-dimensional mathematical model of an adult hip in one-legged stance was used to evaluate the mechanical situation after periacetabular osteotomy. We found that the hip joint rotation center shifted as a consequence of the osteotomy. This may have considerable effects on the hip joint resultant force and therefore also on the pressure on the femoral head, which could cause the development of arthrosis.     

Flexible Sigmoidoscopy Screening in an Industrial Setting

Little is known about the yield of colorectal cancer screening programs in an industrial setting. We therefore established a flexible sigmoidoscopy screening program at a chemical manufacturing plant and offered testing to all employees over the age of 40. After a Fleet enema preparation had been administered, a digital rectal examination and sigmoidoscopy were performed on each volunteer worker in the medical office of the plant. The plant had an average census of about 650 workers; 202 were screened during a 2-yr period. The mean (+/- SEM) age of participants was 52 +/- 0.4. Sixty-four employees had polyps (31.7%); data on follow-up colonoscopy were available in 69%. Colonoscopy revealed adenomatous polyps in 23 workers (53.5%), hyperplastic polyps in 10 (23%), and no evidence of neoplasia in 10 (23%). Seven workers did not arrange for follow-up colonoscopy and 12 individuals could not be contacted. No cancers were detected. In the 40- to 50-yr age group, polyps were detected in 19.5% of employees (25% adenomatous). Incidental findings were common, and included prostatic nodules, hemorrhoids, diverticulosis, and proctitis, among others. We conclude that screening sigmoidoscopy can be conveniently and economically performed at the workplace, with a high yield and good worker acceptance. The high yield suggests a possible association between polyp formation and work in a chemical plant. The finding of adenomatous polyps in the younger patients suggests that the threshold for flexible sigmoidoscopy at age 50 needs to be reassessed.     

Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails.

Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine family of cytokines that mediate leukocyte chemotaxis. The potent and specific activation of monocytes by MCP-1 may mediate the monocytic infiltration of tissues in atherosclerosis and other inflammatory diseases. We have isolated cDNAs that encode two MCP-1-specific receptors with alternatively spliced carboxyl tails. Expression of the receptors in Xenopus oocytes conferred robust mobilization of intracellular calcium in response to nanomolar concentrations of MCP-1 but not to related chemokines. The MCP-1 receptors are most closely related to the receptor for the chemokines macrophage inflammatory protein 1 alpha and RANTES (regulated on activation, normal T expressed and secreted). The identification of the MCP-1 receptor and cloning of two distinct isoforms provide powerful tools for understanding the specificity and signaling mechanisms of this important chemokine.     

Effect of nitric oxide on mitogenesis and proliferation of cerebellar glial cells

In the brain, nitric oxide (NO) has been identified as a messenger molecule and a mediator of excitatory amino acid-induced neurotoxicity. In this study, the effects of NO on serum-induced mitogenesis and cell proliferation of the cerebellar glial cells were assessed. NO-generating agent, S-nitroso-N-acetylpenicillamine (SNAP) increased intracellular cyclic guanosine monophosphate (cGMP) levels. Furthermore, 2 chemically dissimilar NO-generating agents, SNAP and sodium nitroprusside (SNP) inhibited serum-induced thymidine incorporation and cell proliferation. The antimitogenic effect of NO was mimicked by 8-bromo-cGMP and blocked by hemoglobin, a known inhibitor of NO. The effect of NO was not cytotoxic, since the cells were not stained with Trypan blue and did not show increased release of lactate dehydrogenase in the culture supernatants. However, NO-treated cells showed decreased conversion of tetrazolium to blue formazan suggesting that NO inhibited mitochondrial activity in the glial cells. These results demonstrate that NO inhibits serum-induced mitogenesis and cell proliferation of cultured rat cerebellar glial cells.     

Incidence and Management of Chyle Leaks Following Pancreatic Resection: A High Volume Single-Center Institutional Experience

Background   No data on incidence, management, or natural history of chyle leaks following pancreatic resection have been published. We sought to identify possible risk factors associated with chyle leaks following pancreatic resection, as well as determine the natural history of this rare complication. Methods   Between 1993 and 2008, 3,532 patients underwent pancreatic resection at a single institution. Data on demographics, operative details, primary tumor status, and chyle leak were collected. To identify risk factors associated with chyle leak, a matched 3:1 paired analysis was performed. Results   Of 3,532 patients undergoing pancreatic resection, 47 (1.3%) developed a chyle leak (n = 34, contained chyle leak versus n = 13, diffuse chylous ascites). Chyle leak was identified at median 5 days following surgery. Median drain triglyceride levels were 592 ng/dl. After matching on tumor size, disease etiology, and resection type, the number of lymph nodes harvested and history of concomitant vascular resection predicted higher risk of chyle leak (both P < 0.05). Total parenteral nutrition (TPN) was required in more patients with chylous ascites (92.3%) than those with chyle leaks (44.1%) (P = 0.003). The median time to resolution was shorter for contained chyle leaks (13 days) versus chylous ascites (36 days) (P < 0.001). Patients with chylous ascites tended to have shorter overall survival (3-year, 18.8%) versus patients with no chyle leak (3-year, 46.9%) (P = 0.12). In contrast, patients with a contained chyle leak had a similar survival as patients with no chyle leak (3-year, 53.4% versus 46.9%, respectively) (P = 0.32). Conclusion   Chyle leak was a rare (1.3%) complication following pancreatic resection that was associated with number of lymph nodes harvested and concomitant vascular resection. In general, chyle leaks were successfully managed with TPN with no adverse impact on outcome. Patients with chylous ascites, however, had a more protracted clinical course and tended to have a worse long-term survival. Presented at the Society for Surgery of the Alimentary Tract, 49th Annual Meeting, San Diego, CA, May 18th, 2008 Support: Dr. Pawlik is supported by Grant Number 1KL2RR025006-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.