Oenology: red wine procyanidins and vascular health.

Regular, moderate consumption of red wine is linked to a reduced risk of coronary heart disease and to lower overall mortality, but the relative contribution of wine's alcohol and polyphenol components to these effects is unclear. Here we identify procyanidins as the principal vasoactive polyphenols in red wine and show that they are present at higher concentrations in wines from areas of southwestern France and Sardinia, where traditional production methods ensure that these compounds are efficiently extracted during vinification. These regions also happen to be associated with increased longevity in the population.

Risk factors for mortality in infants and young children on dialysis.

The factors associated with a greater mortality risk in infants and young children undergoing dialysis have not been clearly determined. We report the results of a North American Pediatric Renal Transplant Cooperative Study designed to assess risk factors in patients aged younger than 6 years at initiation of dialysis therapy. Sixty-four nonsurvivors were matched with 110 survivors for age at dialysis initiation, primary renal disease, and year of entry onto the database. Questionnaires on 137 patients (51 nonsurvivors, 86 survivors) were completed by participating centers. Seventy-five percent (103 of 137 patients) of the patients were aged younger than 2 years at dialysis initiation; 42% (58 of 137 patients) had renal aplasia, dysplasia, and/or hypoplasia or obstructive uropathy; 62% were boys; and 62% were white. One-year patient survival rates were 83% in infants beginning dialysis at younger than 3 months of age, 89% in 3- to 23-month-olds, and 95% in 2- to 5-year-olds (P = 0.001). Comorbid nonrenal disease occurred in 37 of 51 nonsurvivors (74%) versus 46 of 84 survivors (55%; P = 0.027). Nonsurvivors had pulmonary disease and/or hypoplasia more often (14 of 37 nonsurvivors; 37.8% versus 8 of 46 survivors; 17.4%; P = 0.04). Oliguria or anuria was present in 23 of 33 nonsurvivors (70%) aged younger than 2 years versus 26 of 64 survivors (41%; P = 0.007). Infection accounted for 15 of 51 deaths (29.4%). In summary, these results suggest that age at dialysis initiation; presence of nonrenal disease, particularly pulmonary disease and/or hypoplasia; and oliguria or anuria in children aged younger than 2 years are identifiable as risk factors for mortality in these young patients.

Familial syndrome of progressive arterial occlusive disease consistent with fibromuscular dysplasia, hypertension, congenital cardiac defects, bone fragility, brachysyndactyly, and learning disabilities.

We report on 4 of 9 sibs with a syndrome of stenosis of the renal arteries and chronic hypertension, variable stenosis or occlusion of cerebral, abdominal and probably coronary arteries due to suspected fibromuscular dysplasia, congenital cardiac abnormalities, brachydactyly and syndactyly of the hands and feet, and increased bone fragility consistent with a mild form of osteogenesis imperfecta. Three affected individuals have had mild to moderate learning disabilities. The parents and the remaining 5 sibs have normal hands and feet and no history of excessive fractures. Individual components of this syndrome may appear as isolated conditions, including fibromuscular dysplasia, brachydactyly, syndactyly, and osteogenesis imperfecta, and are autosomal dominant traits in many cases. Explanations for this familial occurrence include autosomal recessive inheritance, autosomal dominant inheritance with decreased penetrance, or parental gonadal mosaicism for a mutation involving a single gene or several contiguous genes.

Expression of cyclooxygenase-2 in rat vascular smooth muscle cells is unrelated to nuclear factor-kappaB activation.

The promoter region of cyclooxygenase-2 (COX-2) gene contains binding sites for a number of important transcription factors including cyclic AMP response element, nuclear factor-IL6, nuclear factor-kappaB (NF-kappaB) and TGF-beta response element. Several reports have documented that the activation of NF-kappaB triggers the expression of COX-2 gene. In the present study, NF-kappaB was activated by TNF-alpha in rat aortic smooth muscle cells as demonstrated by electrophoretic mobility shift assay. The activity of NF-kappaB induced by TNF-alpha was blocked by calpain inhibitor I, a potent NF-kappaB inhibitor. However, the activation of NF-kappaB was not related to the expression of COX-2 induced by TNF-alpha since calpain inhibitor I blocked the activation of NF-kappaB but not the expression of COX-2 mRNA or protein. Mutation of rat COX-2 NF-kappaB-like sites in the promoter region did not significantly reduce the promoter activity. These results suggest that the transcriptional regulation of COX-2 expression by NF-kappaB depends upon the types of cells studied and that activation of this transcription factor alone does not play an important role in the expression of COX-2 in rat smooth muscle cells.

Molecular bending and networks in a basement membrane-like collagen: packing in dogfish egg capsule collagen.

Low-angle X-ray diffraction data have been obtained from three mutually perpendicular axes through sheets of the collagenous egg capsule of the dogfish Scyliorhinus caniculus, a collagen that resembles type IV collagen. The data are interpreted in the light of the body of knowledge of the structure derived from transmission electron microscopy by Knight and Hunt. A model to account for the X-ray data is proposed incorporating the main dimensions of the Knight and Hunt model which are confirmed by the diffraction data. Several features of the diffraction patterns are not explained by the existing model however, and a new model is proposed to account for these features. This consists of antiparallel packed pairs of two mutually parallel molecules, each kinked and rotated so as to produce a four-fold helix resembling a crankshaft. This has the advantage of conferring intermolecular linkage in three dimensions throughout the structure with tetragonal symmetry and unit dimensions a = b = 22.6 nm, c (fibre axis direction) = 39.3 nm. The result is a fairly rigid open polygonal network or sponge-like architecture that is capable of accommodating large quantities of water and other molecules.

Types of anterior cervical grafts.

Anterior cervical diskectomy and fusion provide satisfactory results in most instances of cervical disk herniation and cervical spondylosis. A variety of interpositioned grafts have been described for such problems at one or two levels. Multiple level anterior decompression and fusion for patients with spondylotic myelopathy produce satisfactory results in most instances and are particularly effective when a degenerative kyphosis is present. Appropriate patient selection and attention to technical aspects of exposure, neural decompression, and graft procurement and placement directly influence the surgical outcome.

Treatment of ipsilateral fractures of the distal femur and femoral shaft.

Thirteen patients with segmental fractures involving the distal femur and femoral shaft were treated with internal fixation. Nine of the distal femur fractures were intraarticular. Priority was given to restoration of the articular surface and the alignment of the distal femur. No single method of fixation could be used for all patients. Nine patients were treated using plate fixation with one or more plates. Three patients were treated with a combination of an interlocked intramedullary nail and lag screw fixation. One patient was treated with Ender nails. All the fractures eventually healed, but the recovery time was long. Although no patient was asymptomatic, 10 have resumed their preinjury level of function.

Outcome of infants on chronic peritoneal dialysis.

To assess the outcome of infants on chronic peritoneal dialysis (PD), we retrospectively reviewed 21 patients who began PD prior to one year of age. Mean age at first dialysis was 56 +/- 56 days with mean weight of 3.6 +/- 1.6 kg. Seventeen infants were male and 17 were Caucasian. The most common primary renal diagnosis was renal hypoplasia/dysplasia, occurring in 7 infants. Mean time on PD was 10 +/- 10 months. Eleven infants had oliguria, and 10 infants had adequate urine output. All but 1 infant received tube feedings; mean caloric intake was 453 +/- 92 kJ/kg/day. Despite nutritional management, weight, height, and head circumference was at or above the fifth percentile in only 10, 4, and 5 infants, respectively. Nonrenal abnormalities were present in 12 of 21 infants with lung, heart, and central nervous system abnormalities occurring most often. Outcome included 7 receiving renal transplants, 1 who recovered renal function, 4 who continued on PD, and 9 who died. Seven infants with oliguria died, while only 2 infants with adequate urine output died. No infant with isolated renal disease died, while 9 of 12 patients with renal plus nonrenal abnormalities died. Thus mortality in infants less than one year of age on PD appears to be associated with the presence of oliguria and nonrenal abnormalities.

Ultrafiltration using low volume peritoneal dialysis in critically ill infants and children.

Ultrafiltration (UF) using dialysate volumes of less than 20 ml/kg was assessed in 12 critically ill infants and children with hypervolemia as the primary indication for dialysis. Ten of the 12 required mechanical ventilation (O2 requirements 45-100%). Seven, all infants, received at least one pressor intravenously in attempts to maintain systolic blood pressure of 60. Age was 22 +/- 11.5 mos. (mean +/- SE) with weight of 11.1 +/- 4.3 kg (range 2.4-50 kg). Dialysis prescription was as follows: Volume of 10.1 +/- 1.3 ml/kg/exchange; dwell time 30-45 minutes; drain time 15-20 minutes. Glucose concentration ranged from 1.5-4.25%. Drained dialysate volume expressed as a percent of volume instilled was 133.5 +/- 3.4%. When calculated for body weight and time, UF was 3.0 +/- 0.3 ml/kg/hour. UF was not significantly different in patients requiring pressors versus those not requiring blood pressure support. Although minor ventilatory changes were required, significant deterioration of blood gases did not occur during the first 3-6 hours of PD, nor did significant changes in blood pressure develop. Hyperkalemia, present in 1 patient prior to PD, resolved using this regimen. Low volume PD was a viable alternative to hemodialysis or hemofiltration for control of hypervolemia in this small group of very ill infants and children.

Complications of nasogastric and gastrostomy tube feedings in children with end stage renal disease.

Twelve children with end stage renal disease requiring dialysis received enteral feedings via nasogastric (NG) or gastrostomy (G) tube between 1984 and 1989 for provision of adequate nutrition. Records were reviewed for frequency and types of complications seen. Six patients, ages 1 week to 16 months received NG feedings for a total of 32 months. Complications included persistent vomiting with recurrent aspiration (2), persistent vomiting with peritoneal dialysis (PD) exit site leak (1), sinusitis (1), and refusal to continue NG feeds because of patient/parental anxiety (1). Three of the 6 were changed to G tube feedings after 2 days to 3 months. The complication rate was 1 per 6.4 patient months. Nine patients, ages 4 days to 11 years, received G tube feedings for 64 months. The complication rate was similar, 1 per 7.1 months. Complications were PD fluid leak around G tube exit site (1), G tube infection (2), G tube obstruction requiring tube replacement (3), tube migration producing intestinal obstruction (1), and gastrocutaneous fistula (2). Both methods were associated with similar complication rates, although somewhat different types of complications were seen. The young dialysis patient may have certain unique risks in addition to the complications generally associated with enteral feedings.

Asymptomatic hematuria in childhood: a practical approach to evaluation.

The differential diagnosis of hematuria with or without proteinuria is extensive, and isolated hematuria is a common problem in children and adolescents. Extensive evaluation is often necessary for the child presenting with macroscopic plus microscopic hematuria including nonglomerular and glomerular etiologies, while children with only isolated microscopic hematuria can generally be followed after baseline evaluation to rule out infection, hypercalciuria, familial hematuria, sickle cell disease, post-streptococcal glomerulonephritis (GN), and structural abnormalities (cysts, stones, obstruction, Wilms tumor). Children with the combination of hematuria and proteinuria require rapid systematic evaluation, generally including renal biopsy, except in cases where post-streptococcal GN can be clearly documented. Post-streptococcal GN occurs 7-21 days after a streptococcal infection, is associated with an acute fall in C3 levels with return to normal by approximately 8 weeks, rarely causes acute renal failure, and in children has a pattern of gradual resolution of hypertension, hematuria, and proteinuria over a course of 6-12 months.

Strategic plan can start physician network on path to success.

Forming physician networks can improve the ability of healthcare organizations to attract managed care contracts. However, forming physician networks can be risky for organizations new to such affiliations. One way healthcare organizations can reduce the risk and improve the odds of success in network participation is to develop a strategic plan.

Type-specific antibody prevents platelet aggregation induced by group B streptococci type III.

Group B streptococci (GBS) type III organisms readily induced platelet aggregation and serotonin release in human platelet-rich plasma (PRP). In a system using a GBS/platelet ratio of 1.5, aggregation occurred after 2 to 9 minutes (maximum aggregation, 73% +/- 11%). Serotonin release began within the first minute, reaching 40% before aggregation was detected. Maximum release was 65% +/- 9%. The addition of type-specific rabbit antisera inhibited aggregation and release in a dose-dependent fashion, whereas rabbit antisera against GBS type II and a pneumococcus type 14 and 19 had no effect. To test the activity of different isotypes, monoclonal antibodies against the sialic acid determinant of the GBS type III antigens were used. IgG, IgM, and IgA antibodies were all effective in blocking aggregation and serotonin release. Although the significance of this phenomenon is not clear, it may represent a protective function of antibody that is not directly related to opsonization and phagocytosis.

A prospective study of group B streptococcal bacteriuria in pregnancy.

Bacteriuria in pregnancy was prospectively studied in 569 women, with specific reference to group B streptococcal infection. Forty-six patients (8%) had bacteriuria, including 14 with group B streptococcal infection; group B streptococci (GBS) were exceeded in frequency only by Escherichia coli. Two thirds of the bacteriuric patients remained asymptomatic. The outcome of pregnancy was studied in 41/46 bacteriuric patients, including all those with group B streptococcal infection. Two pregnancies ended in intrauterine fetal death, and one neonate developed group B streptococcal sepsis; all three complications occurred in the 14 women with group B streptococcal bacteriuria. Diabetes mellitus appeared to increase the risk of group B streptococcal bacteriuria. This study revealed that group B streptococcal bacteriuria is more common in pregnancy than was previously suspected and suggests that culture methods to detect GBS should be used in bacteriuria screening programs done in pregnancy. In terms of perinatal infection risk, screening for group B streptococcal bacteriuria at or near the time of delivery may be more meaningful than other group B streptococcal surveillance culture studies.

Spectrum of disease associated with anti-neutrophil cytoplasmic autoantibodies in pediatric patients.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are usually determined during the diagnostic evaluation of systemic vasculitis and glomerulonephritis syndromes in adult patients, but few pediatric patients with ANCA have been reported. We describe five pediatric patients with ANCA and glomerulonephritis, with and without upper or lower respiratory tract disease. We compared these five patients and six previously described patients to affected adults; the spectrum of ANCA-associated disease appears to be similar in adults and children, but a female predominance may exist in the pediatric patients. Pediatric patients often had end-stage renal disease within 1 year after onset. We conclude that ANCA is a useful diagnostic tool in both pediatric and adult patients with systemic vasculitis and glomerulonephritis.

Intravenously administered labetalol for treatment of hypertension in children.

Thirteen children (ages 9.2 +/- 3.7 years, mean +/- SD) received intravenous doses of labetalol, an alpha 1- and beta-adrenergic blocker, on 15 separate occasions for treatment of hypertension. In 12 of 15 episodes an initial dose of 0.55 +/- 0.34 mg/kg was given; in all 15 a continuous infusion of 0.78 +/- 0.39 mg/kg per hour was utilized for 67.3 +/- 57.1 hours. A significant decrease in systemic blood pressure occurred in all episodes (143/99.1 +/- 17.7/11.1 vs 115.6/72.4 +/- 7.7/9.5; p less than 0.01). A clinically unimportant yet statistically significant decrease in heart rate occurred during labetalol infusion (116.3 +/- 19.8 vs 107.8 +/- 11 beats/min; p less than 0.01). The episodes in children with creatinine clearances greater than 50 (n = 6) were compared with those with creatine clearances less than 20 ml/min per 1.73 m2 (n = 9); similar doses of labetalol were required for control of blood pressure. We conclude that infusion of labetalol is effective for control of blood pressure in children with hypertension, regardless of renal function.

Ovarian response to gonadotrophins, optimal method for oocyte retrieval and pregnancy outcome in patients with vaginal agenesis.

The aim of this study is to characterize the ovarian response to stimulation and the optimal method of oocyte retrieval in patients with vaginal agenesis (Mayer- Rokitansky-Küster-Hauser syndrome) in a gestational carrier programme. Twelve patients underwent gonadotrophin stimulation and hormonal monitoring. Forty-nine treatment cycles were initiated; seven cycles were cancelled secondary to poor stimulation. Five patients had undergone surgical neovagina construction; seven patients had utilized vaginal dilators. Oocyte retrieval was achieved in one cycle via transvesical ultrasound, in two cycles via transabdominal ultrasound, in nine cycles via laparoscopy and in 30 cycles via transvaginal ultrasound. Ten pregnancies were achieved which included two clinical pregnancies, two biochemical pregnancies, three singleton births and three sets of twin births. A live birth rate of 45.5% was achieved per patient. Hormonal response to gonadotrophin stimulation in this population was similar to that of patients with normal pelvic anatomy. Pregnancy outcome was comparable to other patients utilizing gestational carriers within the same program (i.e. surgically absent uterus, anatomically non-functioning uterus, etc.). The surgical creation of a neovagina makes transvaginal retrieval technically more difficult than when dealing with a dilator-created vagina, and may require laparoscopy or transabdominal ultrasound for oocyte retrieval.

Glomerular membranopathy in children with IgA nephropathy and Henoch Schönlein purpura.

We evaluated renal biopsies from 34 children with IgA nephropathy or Henoch Schönlein purpura to further characterize the ultrastructural features of the glomerular membranopathy that occurs in these disorders. Focal glomerular basement membrane damage was identified in 29 children and was severe in 4 of the children. Alterations included focal and segmental attenuation, splitting, duplications, and spike-like subepithelial protrusions of the lamina densa, along with saccular glomerular microaneurysms arising at the paramesangium. Those cases with extensive glomerular basement membrane lesions had either moderate or severe glomerular alterations apparent by light microscopy. Over half of the cases with glomerular membranopathy had immunohistological or ultrastructural evidence of focal peripheral glomerular capillary wall immune deposits and electron-dense deposits occurred at sites of glomerular basement membrane splitting. Despite the focal attenuation of the glomerular basement membrane, we did not identify any biopsy with findings of thin basement membrane disease. The glomerular basement membrane ultrastructural findings we describe are characteristic of IgA nephropathy and Henoch Schönlein purpura, are common in children with these disorders, and are similar to the ultrastructural alterations of the basement membrane that occur in other glomerulonephritides. These basement membrane injuries may be inflammatory cell or immune mediated but their pathogenesis requires further study.