Glaucoma, capillaries and pericytes. 3. Peptide hormone binding and influence on pericytes

To test the potential for vasoactive neuropeptide receptors to affect capillary resistance, we have begun to study the plausibility that pericytes might be equipped to respond to a representative peptide vasoconstrictor and a representative peptide vasodilator. Pericytes cultured from the bovine retinal vasculature specifically bind the angiotensin II (Ang II) antagonist saralasin (1 nM125I-saralasin bound at 2.2 +/- 0.41 fmol/mg protein) and 125I-vasoactive intestinal peptide (VIP; Kd of 0.5 nM with a population of 30 fmol/mg protein). Incubation with 100 microM Ang II induced minimal cAMP synthesis, while VIP (1 microM, 10 microM) did not induce any change in cAMP concentration. Ang II (10 microM and 100 microM) caused contraction of pericytes cultured on an elastic silicone surface. Circulating or locally produced vasoactive neuropeptides might affect pericyte contractile tone via several intracellular pathways, moderated by indirect effects of these peptides through endothelial stimulation, with the net effect on local blood flow resulting from the effects on arteries and veins as well as capillaries.     

Estrogen receptors, progesterone receptors, and cell proliferation in human breast cancer

We grafted fetal thymi from wild-type mice into immunodeficient RAG-2-/- or class II-/-RAG-2-/- (class II MHC-) recipients and followed the fate of naive CD4+ T cells derived from the grafts. In both types of recipients, newly generated CD4+ T cells proliferated to the same extent in the periphery and rapidly filled the empty T cell compartment. However, CD4+ T cells in class II- recipients gradually decreased in number over 6 months. These results show that interactions between the TCR and class II molecules are not required for newly generated CD4+ T cells to survive and proliferate, but are necessary to maintain the size of the peripheral T cell pool for extended periods.     

Treatment of infection with débridement and retention of the components following hip arthroplasty

Forty-two patients (forty-two hips) who had an infection following a hip arthroplasty were managed with open débridement, retention of the prosthetic components, and antibiotic therapy. After a mean duration of follow-up of 6.3 years (range, 0.14 to twenty-two years), only six patients (14 per cent) -- four of nineteen who had had an early postoperative infection and two of four who had had an acute hematogenous infection -- had been managed successfully. Of the remaining thirty-six patients, three (7 per cent of the entire group) were being managed with chronic suppression with oral administration of antibiotics and thirty-three (79 per cent of the entire group) had had a failure of treatment. All nineteen patients who had a late chronic infection were deemed to have had a failure of treatment. Débridement had been performed at a mean of six days (range, two to fourteen days) after the onset of symptoms in the patients who had been managed successfully and at a mean of twenty-three days (range, three to ninety-three days) in those for whom treatment had failed. Débridement with retention of the prosthesis is a potentially successful treatment for early postoperative infection or acute hematogenous infection, provided that it is performed in the first two weeks after the onset of symptoms and that the prosthesis previously had been functioning well. In our experience, this procedure has not been successful when it has been performed more than two weeks after the onset of symptoms. Retention of the prosthesis should not be attempted in patients who have a chronic infection at the site of a hip arthroplasty as this approach universally fails.     

Reducing healthcare costs through co-op care

The crisis of rising consumer costs in healthcare has its roots in the history of medicine combined with the public's perceived right to healthcare. To reduce costs, many institutions have reduced staff which, according to some critics, threatens quality of care. A true solution may be quite complex, requiring movement from the current paternalistic approaches typical of acute-care settings toward a cooperative model of illness care with an emphasis on wellness behavior. The concepts of efficacy and negotiated levels of health in the cooperative model care triad have been shown to reduce the cost of illness care while increasing satisfaction, client compliance and quality of care.     

Metformin inhibits ganglionic neurotransmission in renal nerves

Intravenous administration of the antihyperglycemic agent metformin decreases arterial pressure and sympathetic nerve activity (SNA). To test the hypothesis that metformin inhibits SNA by interrupting ganglionic neurotransmission, we compared the actions of intravenous administration of metformin and the ganglionic blocker trimethaphan on postganglionic renal and preganglionic adrenal sympathetic nerves in pentobarbital-anesthetized male Sprague-Dawley rats. Intravenous metformin elicited dose-dependent decreases in postganglionic renal SNA (1 mg/kg: 0 +/- 0%; 10 mg/kg: -20 +/- 4%; 100 mg/kg: -92 +/- 3%; n = 7). Conversely, only the maximal dose of metformin affected preganglionic adrenal SNA (100 mg/kg: delta adrenal SNA = -14 +/- 6%; n = 8). Ganglionic blockade with intravenous trimethaphan (5 mg/kg) produced a differential sympathoinhibitory response similar to the response observed after high-dose metformin (delta renal SNA = -100 +/- 3%; delta adrenal SNA = -17 +/- 7%; P < .001). Preganglionic renal neurons were electrically stimulated in the spinal cord, before and during the peak of the sympathoinhibitory response to intravenous metformin, and the magnitude of the stimulus-evoked increases in postganglionic renal SNA were compared. Metformin dose-dependently attenuated the magnitude of the increase in postganglionic renal SNA elicited by stimulation of the spinal cord (30 mg/kg: -23 +/- 8%; 90 mg/kg: -65 +/- 11%; 270 mg/kg: -91 +/- 8%; n = 6 per dose). We conclude that high-dose intravenous metformin interrupts ganglionic neurotransmission in renal nerves.     

Pediatric pyeloplasty: outcome analysis based on patient age and surgical technique

OBJECTIVES: To analyze our experience with open pyeloplasty, with specific emphasis on procedural outcome on the basis of patient age, surgical technique, complication rate, and complication management. METHODS: All patients from 1974 to 1994 who underwent pyeloplasty at our institution were included in our review. Charts were analyzed for age at presentation, presenting signs and symptoms, type of surgical reconstruction, complications and treatment, and final outcome. RESULTS: From 1974 to 1994, 234 pyeloplasties were performed in 227 patients (108 less than 1 year old, 119 more than 1 year old). The percentage of children less than 1 year old increased throughout: 24% for 1975 to 1980, 37% for 1981 to 1990, and 69% for 1991 to 1994. Presenting signs and symptoms varied according to the age of the child at pyeloplasty. For children less than 1 year old, these were prenatal ultrasound in 86 (79%), urinary tract infection (UTI) in 9 (8%), and abdominal mass in 5 (4.6%). For children more than 1 year old, these were pain in 57 (48%), UTI in 29 (24%), hematuria in 12 (10%), and prenatal ultrasound in 3 (2.5%). Reconstruction was a dismembered pyeloplasty in all cases. The majority of patients in both age groups underwent a nonintubated repair (less than 1 year old, 99 of 114; more than 1 year old, 102 of 120). Postoperative results were evaluated by ultrasound or intravenous urography, with improvement or stable results in 95% of children less than 1 year old and in 96% of children more than 1 year old. Complications included UTI in 18 patients (7.7%), recurrent obstruction in 5 (2.1%), and persistent leak in 4 (1.7%). The complication rate was not related to age. CONCLUSIONS: The nonintubated, dismembered pyeloplasty is an excellent technique for all age groups and has a low complication rate.     

Incidence of photosensitive epilepsy: a prospective national study

We undertook a prospective nationwide study to determine the incidence of photosensitive epilepsy (PE). Virtually all EEG departments in Great Britain (providing approximately 90% coverage of all EEGs performed on people with newly diagnosed seizures) screened cases referred to them over a 3 month period and identified all new cases of epilepsy (defined as one or more recognised seizures) whose first EEG showed a photoparoxysmal response (PPR) on intermittent photic stimulation (IPS). 191 cases were identified, 143 of whom had type 4 PPRs (generalised spike and wave on IPS) on their first EEG. The annual incidence of cases of epilepsy with type 4 PPRs on their first EEG was conservatively estimated to be 1.1 per 100,000, representing approximately 2% of all new cases of epilepsy. When restricted to the age range 7-19 years, the annual incidence rose to 5.7 per 100,000-approximately 10% of all new cases of epilepsy presenting in this age range. To ascertain if there was a significant seasonal variation in PE, 5 EEG departments (which together contributed 15% of cases in the first study period) were visited during a second 3 month study period to identify all new cases of epilepsy with type 4 PPRs on their first EEG. No significant seasonal variation in incidence between summer and winter was found.     

Development of invasive adenocarcinoma in a long-standing Kock continent ileostomy: report of a case

The first case of adenocarcinoma developing in a continent ileostomy is reported. A healthy, 39-year-old man with a continent ileostomy for 17 years developed subacute obstructive symptoms and was found on endoscopy to have a large adenocarcinoma involving the intussusception valve. At operation, he was found to have a large tumor originating in the valve, extending through the reservoir, and involving the afferent ileal limb. A number of metastatic lymph nodes were identified in the mesentery of the small bowel. He underwent excision of the pouch and formation of an end ileostomy. He is currently undergoing adjuvant chemotherapy. Biochemical and morphologic changes in the ileal pouch, both in the pelvis and the continent ileostomy, are discussed. The implications of this apparent de novo cancer arising in an ileal pouch are discussed.