Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial.

Several case reports have implicated Ginkgo biloba in clinically adverse bleeding disorders. Ginkgo biloba has been reported to increase pain-free walking distance among patients with peripheral artery disease (PAD). Standard PAD therapy includes 325 mg/day aspirin. The objective of this study was to examine potential adverse effects of concomitant aspirin and Ginkgo biloba on platelet function. Ginkgo biloba (EGb 761, 300 mg/day) was compared with placebo for effects on measures of platelet aggregation among adults consuming 325 mg/day aspirin in a randomized, double-blind, placebo-controlled, parallel design trial of 4-week duration. Participants were adults, age 69 +/- 10 years, with PAD or risk factors for cardiovascular disease. Outcome measures included platelet function analysis (PFA-100 analyzer) using ADP as an agonist (n = 26 placebo; n = 29 ginkgo), and platelet aggregation using ADP, epinephrine, collagen and ristocetin as agonists (n = 21 placebo; n = 23 ginkgo). Participants kept daily logs of bleeding or bruising episodes. There were no clinically or statistically significant differences between treatment groups for any agonists, for either PFA-100 analysis or platelet aggregation. Reports of bleeding or bruising were infrequent and similar for both study groups. In conclusion, in older adults with PAD or cardiovascular disease risk, a relatively high dose of Ginkgo biloba combined with 325 mg/day daily aspirin did not have a clinically or statistically detectable impact on indices of coagulation examined over 4 weeks, compared with the effect of aspirin alone. No adverse bleeding events were observed, although the trial was limited to a small sample size.     

Die Verwendung eines Nervenstimulators zur sicheren Platzierung von Ilisarov-Drähten

OBJECTIVE: Avoidance of potential iatrogenic nerve injury during insertion of Ilizarov fine wires into areas of high anatomic risk by using a modified nerve stimulation technique. INDICATIONS: Application of the Ilizarov ring fixator to areas of high anatomic hazard, in situations where anatomic topography may be distorted by previous surgery, trauma, or congenital anomalies. CONTRAINDICATIONS: Use of systemic muscle relaxants. Caution in patient with cardiac pacemaker. SURGICAL TECHNIQUE: Preliminary experiments showed that a standard nerve-stimulating device can deliver a negatively charged, monophasic square pulse of current through Ilizarov wires. During the application of an Ilizarov frame to potentially hazardous anatomic regions, providing no systemic muscle relaxants are used, a voltage field sufficient to cause nerves in close proximity to the Ilizarov wire to depolarize is produced. Identification of a distal muscle twitch provoked by the stimulation may indicate a potential for iatrogenic nerve injury. RESULTS: Results show that with the nerve stimulator set at 2.5 mA (pulsed at a frequency of 2 Hz), peripheral nerves are stimulated if they lie within 5 mm of the wires. Should a distal muscle twitch occur, wires should be repositioned so that equivalent stimulation produces no twitch. The technique was used during Ilizarov frame application in ten patients, with only a single occurrence of distal muscle twitches in a lower-leg frame. Following repositioning of the Ilizarov wire in this case, no further twitches were observed, indicating that no Ilizarov wire was inserted close to peripheral nerves. No neurologic impairment was present postoperatively.     

Psychiatric morbidity among people aged 85+ in 1987. A follow-up study at two and a half years: Associations with changes in psychiatric morbidity

This article reports findings from a longitudinal survey of very elderly people living at home in London. The research aimed to identify social, psychological and physical characteristics associated with positive ageing and successful survival in the community in later life and its converse—negative ageing—as well as the associated policy implications. Associations with psychiatric morbidity, measured using the General Health Questionnaire, among sample members without cognitive impairment between the baseline interviews in 1987 and at follow-up, two and a half years later in 1990, are reported. Twenty-five per cent of survivors scored over the threshold of the GHQ in 1987 and 30% scored over the threshold in 1990. Half of those with a score over the threshold in 1990 also scored over the threshold in 1987. Hierarchical regression (using residualized change analysis) was used to estimate the effects of the independent variables on changes in psychiatric morbidity. The most significant predictor of psychiatric morbidity (GHQ score) in 1990 was baseline GHQ score, followed by health and functional status scores. Health and functional status were also the strongest predictors of baseline (1987) GHQ scores. The uniqueness of the study lies in the collection of follow-up data on a sample of very elderly people, given that most surveys are corss-sectional and contain too few people aged 85+ to merit separate analysis. It contributes to the small body of literature on outcome of depression. The lack of consistent associations with recovery from psychiatric morbidity in the literature enhances the importance of studies aiming to identify factors associated with different outcomes.     

INGUINAL HERNIA REPAIR BY LAPAROSCOPIC SURGEONS: EARLY EXPERIENCE AND ATTITUDES

The introduction of laparoscopic inguinal hernia repair (LIHR) has been controversial. A questionnaire was sent to all general surgeons in New Zealand to document the early experience with LIHR and attitudes towards it. Of the 118 replies (response rate 55%). 74 were from laparoscopic surgeons. 26 of whom had performed 564 (201 public. 363 private) LIHR (23 bilateral) until January 1994. Only nine (35%) of these surgeons had assisted an experienced surgeon before performing an LIHR. and only four (15%) were supervised by an experienced surgeon during their first case. The transabdominal preperitoneal technique of LIHR was used by 14 (54%) surgeons. the extraperitoneal technique by eight (31%), and the tronsabdominal onlny technique by four (15%). There were 29 (5%) recurrences, 17 (3%) neuropathies. seven (1.2%) conversions, four (0.7%) miijor perforations. and one (0.17%) death. Of the 26 surgeons who performed LIHR, 20 (77%) were concerned about the absence of long-term results. 14 (54%) considered that the optimal technique had not been established. 13 (50%) were concerned about the unique complications associated with LIHR. 11 (42%) were less enthusiastic about performing LIHR than previously. 10 (38%) were doubtful about its advantages, and six (23%,) were uncertain about its future and considered that it should only be performed within the context of a controlled trial. This study highlights a number of issues that need to be addressed before the role of LIHR can be determined.     

Huntington disease-linked locusD4S111 exposed as the α-l-iduronidase gene

-l-Iduronidase (IDUA) has been intensively studied due to its causative role in mucopolysaccharidosis type I (Hurler, Scheie and Hurler/Scheie syndromes). The recent cloning of a human IDUA cDNA has resulted in a reevaluation of the chromosomal location of this gene. Previously assigned to chromosome 22, IDUA now has been localized to 4p16.3, the region of chromosome 4 associated with Huntington's disease (HD). The existence of a battery of cloned DNA, physical map information, and genetic polymorphism data for this region has allowed the rapid fine mapping of IDUA within the terminal cytogenetic band of 4p. IDUA was found to be coincident with D4S111, an anonymous locus displaying a highly informative multiallele DNA polymorphism. This map location, 1.1×10⁶ bp from the telomere, makes IDUA the most distal cloned gene assigned to 4p. However, it falls within a segment of 4p16.3 that has been eliminated from the HD candidate region, excluding a role for IDUA in this disorder.     

Monoclonal antibodies against membrane proteins of the rat glomerulus. Immunochemical specificity and immunofluorescence distribution of the antigens.

Monoclonal antibodies (MAbs) were generated to detergent-solubilized glomerular extracts to identify new epithelial and endothelial membrane proteins and to study the possible role of the corresponding antigens in the formation of immune deposits. Triton X-114 extracts of isolated glomeruli were subjected to phase separation, and the resultant detergent and aqueous phases were used to immunize mice. Monoclonal antibodies were prepared by standard techniques, and hybridomas secreting antibodies (IgGs) that recognize glomerular cell surface antigens were selected by enzyme immunoassay (EIA) and indirect immunofluorescence. The IgGs of 13 MAbs selected for study recognized antigens of different molecular weights (45-350 kd) by immunoprecipitation and immunoblotting and had different distributions in the glomerulus and in other renal structures by immunofluorescence. Several proved to recognize known antigens--ie, podocalyxin (MAbs 1A, 5A, 11A, and 20A), gp330 (20B), and dipeptidylpeptidase IV (26C). Others recognized antigens not previously characterized that fell into four groups: 1) those that were detected mainly in glomeruli; 2) those present in both glomeruli and peritubular capillaries; 3) those present in both glomeruli and tubule epithelia; and 4) those detected in all these sites. The pattern of glomerular staining also varied, but most of the antigens appeared to be expressed on either the endothelium or the epithelium, or on both. 27A IgG was specific for podocytes and weakly precipitated a 103-kd protein. 7A and 13A IgG precipitated a 120-kd protein and stained glomeruli as well as the basal aspects of distal tubules. 23A IgG recognized a more-than 350-kd antigen that appeared to be specific for endothelial cells in rat kidney and in all other organs studied. 14A IgG precipitated a 150-kd protein and stained glomeruli, proximal tubule brush borders, and endothelial and epithelial cells in rat kidney and in several other organs. 4B and 9B IgG gave a granular cytoplasmic staining in all cells. When injected intravenously into rats, all of the MAbs except 4B and 9B rapidly bound to glomeruli, demonstrating that the respective antigens are exposed at the cell surface and represent potential targets for antibody-mediated immune injury. It is concluded that selective detergent extraction of glomeruli is a useful approach for generation of antibodies that recognize native, nondenatured membrane components of glomerular endothelial and epithelial cells.     

Vitamin A Levels and Immunity in Humans

In animal studies, vitamin A deficiency induces a shift from type 2 (humoral) to type 1 (cellular) cytokines; there are no similar data for humans. Control of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections requires type 1 cytokine (cellular) immunity. These infections and vitamin A deficiency are highly prevalent in Africa. We therefore examined the interactions among serum vitamin A levels, immune parameters, HIV infection status, Mycobacterium bovis BCG vaccine scarring (as an indicator of a type 1 cytokine profile), and clinical findings for 70 hospitalized children in Malawi, Africa. Directly conjugated monoclonal antibodies and flow cytometry were used to assess cell-specific cytokine production by peripheral blood monocytes and lymphocyte subpopulations. The statistical techniques employed included nonparametric statistics and logistic regression analyses. Thirty percent of the participants had severe vitamin A deficiency (<10 μg/dl), 34% had moderate deficiency (10 to <20 μg/dl), and 36% had normal levels (≥20 μg/dl). Vitamin A levels were lower for HIV-positive than for HIV-negative children (median, 10 and 17 μg/dl, respectively). Vitamin A-deficient children (<20 μg/dl) were more likely than non-vitamin A-deficient children to have higher proportions of natural killer (NK) cells (median, 8.3 and 5.2%, respectively) and lower ratios of interleukin-10-producing monocytes to tumor necrosis factor alpha-producing monocytes after induction (median, 1.0 and 2.3, respectively). Vitamin A-deficient children were also more likely than non-vitamin A-deficient children to exhibit respiratory symptoms (47% versus 12%) and visible BCG vaccine scars (83% versus 48%), which are indicative of a type 1 response to vaccination. Vitamin A status did not vary with gender, age, incidence of malaria parasitemia, blood culture positivity, or rates of mortality (6% of vitamin A-deficient children died versus 20% of non-vitamin A-deficient children). Lower vitamin A levels were associated with a relative type 1 cytokine dominance and proportionately more NK cells, both of which may be somewhat beneficial to persons who are exposed to HIV, M. tuberculosis, or other type 1 pathogens.