AIDS minus HIV?
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Biomedical subjects
Publications and source records attributed to J Moore.
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Vasovagally mediated cardiac asystole has been proposed as a potential cause of sudden cardiac death. To assess this possibility and identify characteristics that define patients with vasovagally mediated asystole, head-upright tilt-table testing was performed in 50 consecutive patients (26 women and 24 men, mean age 42 +/- 10 years) with recurrent unexplained syncope. The upright tilt-table test was performed in the fasting state for 30 minutes, with or without the use of intravenous isoproterenol (1 to 3 micrograms/min). The production of ventricular asystole lasting greater than 4 seconds was considered a positive result. All patients with tilt-induced asystole received therapy with either beta blockers, disopyramide, transdermal scopolamine or atrioventricular permanent pacing, the efficacy of which was evaluated with serial tilt-table tests. Reproducible tilt-induced asystole occurred in 10 patients (7 men and 3 women, mean age 23 +/- 12 years) (7 patients during baseline tilt, and 3 during isoproterenol infusion). Analysis of this group revealed that they had significantly more frequent and severe syncopal episodes (3 patients had episodes needing bystander cardiopulmonary resuscitation) than did those patients with tilt-induced syncope without asystole. All patients who had tilt-induced asystole eventually became tilt-table negative with therapy (4 with beta blockers, 2 with disopyramide, and 4 with atrioventricular permanent pacing), and over a mean follow-up of 21 +/- 6 months no further syncopal episodes occurred. It is concluded that patients with recurrent tilt-induced asystole represent a distinct subgroup that has recurrent severe syncope that may mimic or result in sudden cardiac death. Thus, the predischarge electrophysiologic study could predict late outcome with recurrence of preexicitation or supraventricular tachycardia in patients who had undergone surgical ablation of the accessory pathway with an overall predictive accuracy of 95% (107 of 113 patients), negative predictive value of 96% (103 of 107), and positive predictive value of 67% (4 of 6).
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Laboratory data suggest a synergistic interaction between carmustine (BCNU) and tumour necrosis factor (TNF) in melanoma. We therefore studied the activity of 200 mg/m2 BCNU given alone or in combination with 88 micrograms/m2 recombinant human TNF-alpha (rhTNF alpha) as a daily i.v. infusion for 5 days at 48-day intervals to patients with metastatic melanoma. In this randomised phase II trial, the rate of response to BCNU alone was 20% [95% confidence interval (CI), 2%-38%], and this was not improved by the addition of TNF (response rate, 10.5%; 95% CI, 1.3%-33%). Toxicity was higher in the combination arm, and there was no difference in survival.
A 10-year-old girl with uncorrected tetralogy of Fallot with pulmonary atresia presented with fevers of unknown origin and left lung infiltrates. At autopsy, necrotizing vascular changes resembling those of severe pulmonary hypertension (grade VI in the Health-Edwards classification) were confined to the left lung. Pulmonary blood flow and pressure were greater in the left lung and were provided by an enlarged collateral artery arising directly from the descending thoracic aorta. To our knowledge, this is the first report of necrotizing arteritis of the pulmonary arteries in uncorrected tetralogy of Fallot with pulmonary atresia.
We examined the distribution of colonic mucosal mast cells in 25 patients with active ulcerative colitis, with a clear line of demarcation separating active inflammation from normal mucosa. Biopsies, at least one adjacent to the line of demarcation, one in inflamed mucosa, and one above were obtained during colonoscopy. Eight patients had elevated mast cells throughout the colon, and 12 had increased numbers at the line of demarcation of disease. Mean numbers of mast cells from these patients were 6.3 (+/- 2.1 SD) in active inflammation, 19.5 (+/- 7.1 SD) at the line of demarcation, and 15.8 (+/- 8.4 SD) in normal mucosa. Histologic inflammation decreased as mast cells increased. The accumulation of mast cells at the visible line of demarcation between normal and abnormal mucosa suggests mast cells play a critical role in either accelerating the process of inflammation or in suppressing continued extension of the disease.
The purpose of this study was to determine the effect of manipulating the interdose interval (IDI) on the suppression of milk intake induced by haloperidol (HAL). Groups of rats were given chronic injections of either HAL (0.625 mg/kg) or saline at IDIs of 1, 2, 7, or 14 days. Dose-response curves were determined at the conclusion of the chronic phase. The results indicated that injections of HAL given at IDIs of 1 or 2 days produced neither tolerance nor sensitization, whereas injections given at intervals of 7 or 14 days produced sensitization. Sensitization was also observed in the control groups, perhaps as a result of the intermittent schedule of HAL injections given during the dose-response tests. Sensitization to HAL was not accompanied by changes in sensitivity to amphetamine. The results of this experiment are consistent with those of other studies in showing that the behavioral effects of neuroleptics are strongly influenced by the schedule of injections. In addition, evidence is presented that sensitization to HAL-induced hypophagia is contingent on behavioral experience under the drug.
Ten microsatellite DNA polymorphisms located on human chromosome 10 were regionally mapped using subchromosomal somatic cell hybrids and linkage analysis. The resulting order of the markers from pter-qter was [D10S89, D10S111], D10S107, D10S109, [D10S91, D10S110, D10S108, D10S88, D10S168], and D10S169. Order of the markers within brackets was uncertain, although the order given was most likely. The microsatellites were distributed along the chromosome from the proximal p arm to near qter, with an unlinked gap between D10S168 and D10S169.
A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment.
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The adult with nephrotic syndrome presents diagnostic and treatment challenges for the primary care physician. Early consultation with a nephrologist is advisable to assist in choosing between empirical therapy or renal biopsy to identify the specific causative lesion. Some patients respond to treatment of either the specific disorder or the underlying cause. All patients should be afforded specific therapy, where available, and nonspecific therapy to minimize the severity of the nephrosis and attenuate the incidence and severity of complications. Although the cause of most disorders resulting in nephrotic syndrome remains unclear, active research into the syndrome's pathogenesis and treatment options should prove fruitful.
We have assessed the use of clonidine and bupivacaine for postoperative analgesia. Both drugs were administered via the extradural route, and were given both alone and in combination. The analgesia produced by clonidine was superior to that of bupivacaine; a combination of the drugs resulted in significantly better and longer duration of analgesia than each drug administered alone. Cardiovascular changes and the incidence of side effects were similar in all three groups. The sedative effects of clonidine were not marked.
We measured gastric emptying (by paracetamol absorption) and duration of analgesia in 30 women in labour after extradural injection of 0.375% bupivacaine 10 ml either alone or combined with fentanyl 100 micrograms. Treatment was administered double blind by random allocation after the first request for analgesia. The median (range) times to maximal serum concentration of paracetamol were 60 (15-90) min and 75 (30-180) min after administration in the control and fentanyl groups, respectively (P = 0.026), and corresponding mean (95% confidence interval) maximal concentrations of paracetamol were 27.3 (18.8-35.8) micrograms ml-1 and 18.0 (15.1-20.9) micrograms ml-1 (P = 0.020). Mean duration of analgesia, from the first extradural bolus until return of pain in those given bupivacaine alone was 113 (87-139) min and 154 (131-176) min when fentanyl was added to the local anaesthetic (P = 0.016). These results confirm the prolongation of analgesia after fentanyl supplementation of lumbar extradural analgesia, but indicate that it results in delayed gastric emptying.
We have examined the effectiveness of extradural clonidine infusions for postoperative analgesia and the effect of clonidine on extradural morphine. In a double-blind, controlled study, patients, undergoing total hip replacement were allocated randomly to receive one of two doses of extradural clonidine (25 micrograms h-1 or 50 micrograms h-1), low dose extradural morphine or a combination of morphine and clonidine. Pain scores in the morphine group were significantly greater than in the clonidine groups (P less than 0.01) and the combination group (P less than 0.05) during the first 1 h after surgery. The requirements for systemic analgesia were least in the combination and larger dose clonidine group, and the duration of effect of the initial bolus dose was significantly longer compared with the morphine and low dose clonidine groups (P less than 0.05). Arterial pressure was reduced in the clonidine groups, although the incidence of clinical hypotension was low. There were no significant differences between the groups in emetic symptoms or urinary retention.
We investigated the effect of bacterial lipopolysaccharide (LPS) on phospholipid (PL) turnover in human monocytic leukaemia U937 cells. Cells were pre-labelled with [3H]choline, [14C]ethanolamine and [3H]inositol for 24 h. By monitoring the radiolabel association with cellular PL, the data indicated that LPS (10 micrograms/ml) drastically altered the catabolism of choline-containing PL; it induced their breakdown by 50% within 20 min. The reutilization of choline or its phosphates for PL synthesis was also suggested as a result of regaining radiolabel in the next 40 min. Choline-containing PL then underwent a second degradation after 60 min; 50% decline in radiolabel was detected at 120 min. In contrast, LPS did not induce the breakdown of phosphatidylethanolamine and phosphatidylinositol through phospholipase C/phospholipase D (PLC/PLD). No significant redistribution of the radiolabel in PL was detected in any cases during chasing. The data clearly indicate that LPS stimulates phosphatidylcholine breakdown, implying that the liberation of phosphatidic acid or diacylglycerol via PLC/PLD reaction may be relevant to the initiation of LPS-induced monocytic activation.
The Drosophila gene pumilio is expressed maternally, and its function is essential during early embryogenesis for the formation of abdominal segments. Our molecular analysis reveals that pumilio is a large gene that encodes a protein of 160 kD whose RNA is enriched at the posterior pole of the egg. As with pumilio, the maternal effect gene nanos is specifically required for abdomen formation. The Nanos protein is expressed in a posterior-to-anterior concentration gradient in the developing embryo. Previous experiments demonstrated a genetic interaction between pumilio and nanos, and led to the suggestion that pumilio is required for the proper spatial distribution of the Nanos protein. Here, we show that the expression and distribution of nanos RNA and protein in embryos derived from pumilio mutant females are indistinguishable from wild type. We conclude that abdomen formation depends both on Nanos activity, spreading from the localized posterior source, and on Pumilio activity, present throughout the embryo.
Recurrent syncope in an otherwise healthy child or adolescent is a common anxiety provoking disorder. Vasovagally mediated hypotension and bradycardia are believed common, yet difficult to diagnose, causes of syncope in this age group. Upright tilt table testing has been suggested as a potential method to test for vasovagal episodes. This study evaluated the utility of this technique in the evaluation and management of recurrent syncope in children and adolescents. Thirty patients with recurrent unexplained syncope were evaluated by use of an upright tilt table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/min given intravenously), in an attempt to produce hypotension, bradycardia, or both. There were 15 males and 15 females, mean age 14 +/- 6 years. Each of the tilt positive patients received therapy with either fluorohydrocortisone, beta blockers, or transdermal scopolamine. Syncope occurred in six patients (20%) during the base line tilt and in 15 patients (50%) during isoproterenol infusion (total positives 70%). All initially positive patients were rendered tilt negative by therapy. Over a mean follow-up period of 20 months, no further episodes have occurred. We conclude that tilt table testing is a useful and effective test in the evaluation of unexplained syncope in childhood.