Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort.

OBJECTIVES: HIV infection is associated with chronic systemic inflammation, with or without antiretroviral therapy. Consequences for foetal growth are not understood, particularly in settings where multiple maternal infections and malnutrition are common. The study was designed to examine maternal systemic circulating and umbilical cord blood cytokine concentrations in relation to birth anthropometry in a Tanzanian prospective cohort. METHODS: A 9-plex panel of maternal plasma cytokines in HIV-positive (n = 44) and HIV-negative (n = 70) mothers and the same cytokines in umbilical cord blood collected at delivery was assayed. Linear regression modelled associations between maternal or cord blood cytokines and birth anthropometry. RESULTS: Health indicators (haemoglobin, mid-upper-arm circumference, body mass index) in HIV-positive mothers without considerable immunosuppression did not differ from HIV-negative women. Despite this, HIV-exposed infants had lower birthweight and length. Subgroup analyses indicated that HIV management using HAART was associated with lower plasma TNF-α, as were longer durations of any antiretroviral therapy (≥2 months). Greater maternal plasma TNF-α was associated with earlier delivery (-1.7 weeks, P = 0.039) and lower birthweights (-287 g; P = 0.020), while greater umbilical cord TNF-α (-1.43 cm; P = 0.036) and IL-12p70 (-2.4 cm; P = 0.008) were associated with shorter birth length. Birthweight was inversely associated with cord IL-12p70 (-723 g; P = 0.001) and IFN-γ (-482 g, P = 0.007). Maternal cytokines during pregnancy did not correlate with umbilical cord cytokines at delivery. CONCLUSIONS: Systemic inflammation identified in maternal plasma or umbilical cord blood was associated with poorer birth anthropometrics in HIV-exposed and HIV-unexposed infants. Controlling maternal and/or foetal systemic inflammation may improve birth anthropometry.

Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries: importance of vessel size.

OBJECTIVES: To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels. METHODS: All 2314 BASKET-PROVE patients randomized to DES versus BMS were followed for 2 years with a primary endpoint of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, target-vessel revascularization). Cox proportional hazard models were used to evaluate the relative risk for women and men, respectively. All comparisons were adjusted for vessel size. RESULTS: Age, risk factors and complexity of coronary artery disease differed between women and men. DES reduced MACE rates at 2 years compared to BMS--in women: 4% vs. 15%, p<0.0001 with a hazard ratio (HR) of 0.27 (0.15-0.51), and men: 6% vs. 10%, p=0.003 (HR=0.60 (0.43-0.84)), respectively. The association persisted in both women (HR=0.25 (0.13-0.46)) and men (HR=0.60 (0.42-0.84)) following multivariable adjustments. A significant gender-treatment interaction was present (p=0.02). The reduced risk of MACE following DES vs. BMS implantation was present until 6 months in both women (HR=0.15 (0.06-0.36)) and men (HR=0.32 (0.17-0.59)) and remained significant until 2 years in women (HR=0.36 (0.15-0.87)), but not in men (HR=0.87 (0.49-1.55)). CONCLUSIONS: In women and men with similarly sized large coronary arteries, DES reduced 2-year MACE rates compared to BMS, but the significant gender-treatment interaction indicated a greater benefit of DES in women. Thus, factors other than vessel size seem to determine this gender difference.

Different cerebrovascular effects of medroxyprogesterone acetate and norethisterone acetate in the New Zealand White rabbit.

OBJECTIVE: The lack of a cardioprotective effect of hormone replacement therapy (HRT), as suggested by the Heart and Estrogen/progestin Replacement Study (HERS) and Women's Health Initiative (WHI) may in part be explained by the progestin used. The aim of this study was to elucidate the effect of different progestins on cerebrovascular reactivity in an animal model. METHODS: Fifty-six ovariectomized New Zealand White rabbits were randomized into seven groups receiving hormone treatment for 4 weeks: medroxyprogesterone acetate (MPA) (10 mg/day); norethisterone acetate (NETA) (3 mg/day); conjugated equine estrogens (CEE) (1.25 mg/day); 17beta-estradiol (E2) (4 mg/day); MPA + CEE (10 mg/day + 1.25 mg/day); NETA + E2 (3 mg/day + 4 mg/day); or placebo. Segments from the basilar and posterior cerebral arteries were mounted in myographs for tension recordings. Concentration-response curves to potassium, acetylcholine, sodium nitroprusside, L-NAME (N(omega)-nitro-L-arginine methyl ester), calcium and endothelin-1 were established. RESULTS: Treatment with MPA caused a significant increase in vasoconstriction, expressed as E(max) (mN/mm, mean +/- SEM; p < 0.05), in response to potassium (3.18 +/- 0.19 vs. 2.47 +/- 0.19) and calcium (4.00 +/- 0.22 vs. 3.34 +/- 0.14) in the posterior cerebral artery, and to endothelin-1 (6.88 +/- 0.69 vs. 5.22 +/- 0.30) in the basilar artery, when compared with NETA. This difference was neutralized in the groups receiving the combined treatment of MPA + CEE and NETA + E2. No overall differences were seen between CEE and E2. CONCLUSIONS: In rabbit cerebral arteries, MPA treatment causes a higher development in arterial tension compared with NETA, indicating that different progestins may display different cerebrovascular effects. However, when accompanied by estrogens, as in the case of HRT, this difference is eliminated.

Acute effects of tibolone on cerebral vascular reactivity in vitro.

OBJECTIVE: To evaluate the acute effects of tibolone and its metabolites on cerebral vascular reactivity in vitro. METHODS: Ring segments of the posterior cerebral artery from female rabbits were mounted in myographs for isometric tension recordings. Concentration-response curves with tibolone, 3alpha-OH-tibolone, 3beta-OH-tibolone, Delta(4) isomer and 17beta-estradiol were obtained before and after addition of the NO blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/l) or the potassium-channel blocker tetraethylammonium chloride (TEA, 10(-2) mol/l). Additionally, the effects of the hormones on the concentration-response curves with calcium were examined. RESULTS: Tibolone and its metabolites induced a concentration-dependent relaxation comparable to that of 17beta-estradiol (area under the curve (AUC); tibolone vs. 17beta-estradiol: 242 vs. 251; p < 0.05, analysis of variance). L-NAME increased the AUC for all substances compared with controls (p < 0.05, Student's t test), except for 17beta-estradiol. Preincubation with TEA induced no changes. The concentration-dependent contraction curves with calcium were shifted rightward by all hormones. CONCLUSIONS: The study demonstrates that the acute relaxation induced by tibolone and its metabolites in cerebral arteries in vitro is comparable to that with 17beta-estradiol, and seems to be mediated by inhibition of voltage-gated calcium channels and possibly partly by a nitric oxide-dependent mechanism.

ICD-10 criteria for depression in general practice.

BACKGROUND: The rate of recognition of depressive disorder in general practice is reported to be low. Current classification systems, i.e. ICD-10 and DSM-III-R, and DSM-IV with operational diagnostic criteria, have led to greater agreement concerning the diagnosis of depressive disorder. The aim of this study was to assess the applicability and validity of the ICD-10 criteria for depression in general practice in Denmark. METHODS: After a 1-day training course in the ICD-10 criteria for depression, ten general practitioners, during an 8-week period assessed all patients aged 18 or older for depressive symptoms in accordance with the ICD-10 criteria. RESULTS: Among a total of 3505 consultations, 116 patients (3.3%) met the criteria for a depressive episode. Of these, 80 (68.8%) accepted to be reinterviewed by a psychiatrist, who confirmed the diagnosis of depressive disorder in 57 of the 80 patients (71.3%). LIMITATIONS: The number of 'false negative' cases are unknown in the study. CONCLUSION: The ICD-10 criteria for depression seem to be appropriate and valid in general practice.

Pituitary adenylate cyclase-activating peptide stimulates acute progesterone production in rat granulosa/Lutein cells via two receptor subtypes.

Pituitary adenylate cyclase-activating peptide (PACAP) is transiently expressed in ovarian granulosa/lutein cells from eCG/hCG-treated rats, and in vitro immunoneutralization of endogenously released PACAP inhibits acute progesterone secretion and subsequent luteinization in such cells. This suggests that PACAP mediates locally some of the effects of the LH surge, but the putative PACAP receptor(s) involved in such an auto or paracrine activity is presently unknown. Reverse-transcription polymerase chain reaction with specific primers to the three cloned PACAP-binding receptors called PAC(1), VPAC(1), and VPAC(2) demonstrated both PAC(1) and VPAC(2) mRNA in extracts from preovulatory follicular cells. Radioligand-binding assays revealed the presence of high-affinity binding sites with characteristics of these two receptors on the intact cells, and autoradiography demonstrated that the binding was restricted to a minor proportion of the follicular cells as well as the oocytes. Pituitary adenylate cyclase-activating peptide and vasoactive intestinal peptide (VIP) dose-dependently stimulated cAMP accumulation and acute progesterone accumulation. Forskolin and db-cAMP also stimulated acute progesterone accumulation, and the protein kinase A inhibitor H89 dose-dependently inhibited peptide induced acute progesterone accumulation, suggesting involvement of cAMP and the protein kinase A pathway in the process. In conclusion, two of the three PACAP binding receptors are present on preovulatory follicular cells and are involved in the effects of PACAP on acute progesterone production. The data provide further evidence to establish PACAP as an auto- or paracrine regulator of LH-induced acute progesterone production in rat preovulatory follicles.

Late allergy-like reactions following vascular administration of radiography contrast media.

PURPOSE: To compare the frequency of allergy-like reactions in adults following vascular injection of iohexol and iopentol versus other contrast media (CMs), with emphasis on late reactions. MATERIAL AND METHODS: Thirty-two trials involving a total of 2,656 patients in the European clinical development programmes for iohexol and iopentol were retrospectively evaluated. The number of patients experiencing late allergy-like reactions, immediate allergy-like reactions, and both types of reaction were pooled separately. Late was defined as time of onset being 60 min or more after the first injection of CM. RESULTS AND CONCLUSION: After vascular administration of iohexol and iopentol, 0.52% (0.44% and 0.68% respectively) of the patients experienced a late allergy-like reaction. The same frequency was reported for immediate allergy-like reactions. After administration of ionic CMs, the frequency of late allergy-like reactions was in the same range (0.42%) as for non-ionic CMs, but the frequency of immediate allergy-like reactions was much higher (6.99% vs 0.52%). Our results are in the same range as those reported by other authors. No serious adverse reactions were reported in the 32-trial series.

Induction therapy with OKT3 in pediatric liver-transplant recipients.

The goal of any posttransplant immunosuppressive regimen is to prevent allograft rejection while minimizing infectious complications. We hypothesized that sequential induction immunotherapy using the monoclonal antibody ORTHOCLONE OKT3 (muromonab-CD3) would meet these objectives effectively. We have therefore used such a protocol since July 1988 for all pediatric patients undergoing liver transplantation at Children's Hospital Medical Center of Cincinnati. Initial immunotherapy consisted of OKT3, administered preoperatively and then QD, methylprednisolone, and azathioprine. Cyclosporine was begun on POD 3-5, and OKT3 was discontinued when therapeutic cyclosporine levels were achieved for 48 hours. Rejection has not occurred throughout the lifetime of the allograft in 55% of long-term survivors. In the 28 patients who experienced rejection episodes, 71% had a single episode, 21% had two episodes, and 7% had a single episode, 21% had two episodes, and 7% had more than two. Rejection occurring after more than 120 days was invariably associated with noncompliance or subtherapeutic cyclosporine levels. The use of an OKT3-based sequential induction protocol resulted in a decreased incidence of acute rejection. Renal function was preserved, and the incidence of infection was not increased. Long-term outcome analysis of this protocol shows excellent patient survival and the near absence of late or chronic rejection.

[Infertility and pregnancy outcome in women with insulin-dependent diabetes. An epidemiological study]. / Infertilitet og graviditetsforløb hos kvinder med insulinafhaengig sukkersyge. En epidemiologisk undersøgelse.

A questionnaire survey comprising an unselected group of 18-49-year old women with insulin-dependent diabetes mellitus and an age comparable control group was performed. Two hundred and forty-five (94%) of the diabetic women and 253 (88%) of the controls answered questions concerning fertility, pregnancy planning and pregnancy outcome. There was no difference in the cumulative rate of pregnancies in the two groups. The prevalence of involuntary infertility among the diabetic women was 17% and similar to that of controls. Compared to controls, diabetic women had significantly fewer pregnancies (mean 1.4 versus 1.7) and fewer births per pregnancy (70% versus 77%), and significantly more diabetic women were nulliparous (48% versus 38%). Only about half of all pregnancies were planned. In general the diabetic women reported that their diabetes had a negative influence on their attitude towards having children.

Accelerated surgical stay programs. A mechanism to reduce health care costs.

OBJECTIVE: To increase cost-efficiency while maintaining the standard of medical care, an accelerated surgical stay program for patients having breast surgery was instituted. SUMMARY BACKGROUND DATA: In the past 20 years, annual health care costs have soared and now comprise 12.2% of the United States gross national product. The annual inflation rate of almost 11% has prompted third-party payers to scrutinize hospital costs as hospitals now consume 38% of health care costs. METHODS: A multidisciplinary task force was formed to analyze and reduce lengths of stay for breast surgeries and to standardize clinical protocols to address ensuing issues. RESULTS: After 1 year, this prospective study found a 39% decrease in average length of stay and a 22% increase in patient volume. This was also accompanied by a low incidence of surgical complications. Through information obtained from 373 consecutive patients through telephone surveys and questionnaires, the Center for Cost-Effective Care reported high patient acceptance and satisfaction. CONCLUSIONS: As a management strategy, accelerated surgical stay programs increase operating efficiency and reduce medical care costs without compromising quality of patient care. Success of this program was attributed to support from senior management, expansion of available educational resources for patients, and to a carefully planned transition from the program's developmental to its operational phase.

The spectrum of bile duct complications in pediatric liver transplantation.

It has been noted that reduced-size liver transplants are associated with increased rates of biliary complications, and it has been suggested that some of these complications can be handled nonoperatively. In a 6-year period, 91 orthotopic liver transplants were performed in 77 children. The medical records were reviewed to analyze the effect of reduced-size grafts on the incidence of bile duct complications and to investigate the utility of interventional radiology techniques for treatment. Forty-two children received 47 whole-organ transplants, and 35 children received 44 reduced-size transplants. The median age and weight were greater for children receiving whole-organ transplants (age, 4.25 years; weight, 16 kg) than for those receiving reduced-size grafts (age, 1.0 year; weight, 8 kg). The overall incidence of bile duct complications was 19.5% (n = 15). The incidence was not different between the whole organ group (17%) and the reduced-size group (16%). Four of the children with bile duct complications had associated hepatic artery thrombosis, two of whom had another transplant. Complications included anastomotic stricture (n = 6), anastomotic leak (n = 5), intraparenchymal biloma (n = 3), and multiple strictures (n = 1). Twelve of 15 children presented within 3 months of transplantation. Six children had initial percutaneous drainage or placement of transanastomotic stents (external). Operative repair was eventually required for all 15 children, three of whom received a second transplant. There was a 40% incidence of cytomegalovirus infection involving the liver or extrahepatic bile ducts near the time of presentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequelae one year after meningococcal disease.

Of 99 consecutive patients with meningococcal disease, 6 died during the acute stage. The 93 survivors were examined one year after hospitalization. 21 (40%) of the adults and 6 (15%) of the children had definite sequelae, and an additional 27% and 11% possible sequelae. 6 adults (12%) and 1 child (2%) had definite neurological sequelae. Electroencephalography (EEG) abnormalities were observed in 7 adults (14%) and 2 children (5%). Epileptogenic activity was present in 3 of these, but none had experienced seizures. 8 adults (19%) and 5 children (14%) had sensorineural hearing loss or impaired vestibular function. Cerebral computerized tomography (CT) scan showed definite and possible abnormalities in 1 (3%) and 6 (18%), respectively, of the 34 patients tested. Neuropsychological tests were performed in 9 patients, 2 of these showed definite impairment. The frequency of neurological abnormalities was higher than in many previous studies, probably reflecting the more comprehensive examinations performed in the present study. However, only 3 patients had serious sequelae. The results suggest that the occurrence of sequelae after meningococcal disease is related to the severity of the acute disease. This may explain the higher rate of sequelae in adults, who have a higher proportion of seriously ill patients. The presence of meningitis is not required for the occurrence of neurological sequelae.

Growth and nutritional management of pediatric patients after orthotopic liver transplantation.

The overall results of pediatric liver transplantation continue to be increasingly encouraging and rewarding. The careful development of long-term follow-up protocols addressing nutrition and growth are vital components of the comprehensive care of this patient population.

Monoethylglycinexylide formation in assessing pediatric donor liver function.

Lidocaine metabolism to monoethylglycinexylide (MEGX) has been described as a novel method to assess liver function in adult transplant donors and recipients. While this assay appears to offer a number of advantages over existing liver function tests, limited work has been done to evaluate its potential in the pediatric population. This study evaluated MEGX formation in potential pediatric liver donors (n = 35) and a control group of children (n = 16). The mean MEGX formation was significantly higher in pediatric donors than in the control group (156 +/- 62 vs 106 +/- 33 ng/ml, p < 0.05). No correlation with age, total bilirubin, liver transaminases, or alkaline phosphatase could be made within each group. Significant differences in MEGX levels were noted when each group was compared to its adult counterpart. Both pediatric donors and controls had greater mean MEGX formation than has been reported for adult donors and controls (156 +/- 62 vs 127 +/- 61 ng/ml, p < 0.05 and 106 +/- 33 vs 72 +/- 36 ng/ml, p < 0.05, respectively). Drugs that alter lidocaine pharmacokinetics and their potential influence on MEGX formation were evaluated in the pediatric donor group. Donors exposed to hepatic enzyme-inducing drugs had a higher mean MEGX formation (187 +/- 60 vs 146 +/- 63 ng/ml). No significant differences were noted between donors receiving and not receiving vasopressors. In conclusion, the significant differences between pediatric and adult MEGX formation should be noted when establishing reference or normal ranges for this diagnostic test. Furthermore, concomitant drug therapy may significantly alter MEGX formation.

Hepatobiliary scintigraphy in pediatric liver transplant recipients.

The clinical usefulness of hepatobiliary scintigraphy was evaluated in pediatric liver transplant recipients. One hundred fifteen hepatobiliary scintigraphic studies were performed in 30 patients who received 22 whole liver and 16 segmental grafts. Parameters that were useful in predicting an adverse outcome were failure to visualize excreted radiopharmaceutical at or beyond the biliary anastomosis on a study performed within 24 hours after transplant, and persistent or increasing delay in the time of visualization of excreted radiopharmaceutical. Abnormalities of liver uptake and excretion were seen in rejection, but they were also seen in patients who remained well without rejection or parenchymal disease. Significant biliary leaks were identified in the three cases in which they were known to be present. In liver transplant recipients, hepatobiliary imaging is useful in predicting graft survival and identifying biliary leaks.

Liver transplantation in children.

Children with end-stage liver disease now have a greater chance of survival through treatment with hepatic transplantation. This article reviews the pediatric liver transplantation process, including selection and evaluation of candidates, operative procedures, postoperative complications, and long-term survival.

Current issues in profiling quality of care.

Profiling provider performance for the assessment of quality involves a number of issues related to selection of appropriate quality measures, subsequent data collection and analysis, and selection of standards of comparison. This article emphasizes the limitations of current data systems for this purpose and discusses hierarchical modeling as the optimal analytic approach for analyzing resulting data. Mention is made of the difficulties of achieving large enough sample sizes for statistical significance at the individual provider level. Finally, the article discusses feasible options for profiling quality.

[From psychiatric hospitals to local municipal departments. The county of Vejle 1973-1987]. / Fra psykiatriske hospitaler til amtskommunale afdelinger. Vejle Amt 1973-1987.

On April 1, 1976 the Danish State handed over the responsibility for treatment of psychiatric patients to the counties. None of the state hospitals were situated in the county of Vejle. The changes of the admission pattern of the inhabitants of Vejle county aged 15+ years during the years from 1973 to 1987 are described. The annual bed occupancy per 1,000 inhabitants decreased markedly during the period (from 829 in 1973 til 366 in 1986) while the admission rates were relatively stable. Vejle county has successfully reduced the number of admissions to mental hospitals in other counties, but was, however, still not self-sufficient in 1987. The decrease in bed occupancy was significant in the groups of schizophrenia, manic-depressive psychosis, organic states, neurosis, alcohol and drug addiction, while in the group of other psychoses and other conditions the decrease was not significant. In the group of personality disorder the bed occupancy increased, but not significantly.