"The Duesberg phenomenon": Duesberg and other voices.
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Biomedical subjects
Publications and source records attributed to M Delaney.
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We reinvestigated the effect of estradiol 17 beta on the responses of adrenergic and nonadrenergic vasoconstrictors characterized it in terms of steroid specificity, time course, and the role of classic estrogen receptors. We evaluated the effect of estradiol 17 beta on the pressor responses of isolated perfused rat mesenteric vascular bed (McGregor's preparation). Estradiol 17 beta (7-700 nM) significantly increased the pressor response to bolus applications of norepinephrine (NE) (p < 0.05). However, estradiol 17 beta did not significantly increase the responses to endogenous NE release induced by electrical field stimulation. Other steroids, testosterone, and the 17 alpha isomer of estradiol (7 and 700 nM) were ineffective. Estradiol 17 beta (700 nM) also significantly increased the maximum pressor response of rat mesenteric preparation to both the prostaglandin endoperoxide analogue U-46619 and to K+. The potentiation by estradiol 17 beta of mesenteric vasoconstriction elicited by NE, K+, and U-46619 was rapid (2-8 min), suggesting that a nuclear receptor may not be involved. This notion received further support in that significant potentiation of the NE-induced pressor response was also observed with estradiol 17 beta conjugated to albumin (700 nM), but not when electrical field stimulation was used. The conjugate increased the effect of all NE concentrations. Its effect was also more consistent (p < 0.01) than that elicited by free estradiol 17 beta. The dose-response curve was shifted to the left, and the maximum effect was increased. These data suggest that estradiol 17 beta may possess rapid nongenomic actions unrelated to nuclear receptor binding and gene transcription.
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Screening biological samples using the polymerase chain reaction (PCR) has obvious advantages compared with current molecular analytical methods based on gel electrophoresis and/or hybridisation, both of which are expensive and time-consuming, therefore the development of a PCR assay format that is applicable to large sample numbers and that can readily use equipment commonly found in diagnostic laboratories would be advantageous. This report describes the development of a colour amplified PCR detection system which is simple in design and could be universally applied to the detection of any DNA template. As an example, the system has been applied in the detection of the heat-stable toxin coding gene (ST-gene) from enterotoxigenic Escherichia coli (ETEC). The assay is sensitive, detecting 10 fg of a purified DNA template and 270 cfu of an ST-gene-positive ETEC strain.
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A retrospective review of all emergency department visits to a combat support hospital (one of four combining to support 150,000 troops) during Operations Desert Shield and Desert Storm was conducted, and all medical records of patients with ocular complaints were analyzed. Ocular injury and/or disease accounted for 14% (108/767) of these visits to the emergency department. Of 108 patients with ocular complaints, corneal foreign bodies (18), ocular burns (14), and traumatic iritis (eight) were the most common injuries treated, while blepharitis and conjunctivitis (16) were the most common diseases. Nineteen (18%) of the 108 patients with ocular complaints were treated during support of the ground war in Iraq (13 were Iraqi prisoners). Ophthalmic injuries accounted for 13% (19/149) of all ground war casualties; however, eight individuals had associated injuries deemed more significant than those of ocular concern. This incidence continues the trend of earlier wars, which has demonstrated a steady increase in ocular injuries. Most US Army troops were issued protective goggles, but only three of 92 American patients wore them at the time of their injury and/or disease.
The long-term objective is to understand the role of the adrenal in altering systemic arterial blood pressure. This paper summarizes research on genetic hypertension in the rat and bears a relationship to several forms of human hypertension in which defects of steroid hydroxylases lead to increased secretion of mineralocorticoids other than aldosterone in genetic and experimental hypertension in rats. We demonstrated that 19-nor-corticosteroids are produced in excess in genetic and experimental hypertension in rats and man. We studied the enzymatic alteration responsible for excessive production of 19-nor-deoxycorticosterone (19-nor-DOC) in the salt-sensitive hypertensive rat S/JR. Biosynthesis of 19-nor-steroids involves hydroxylation of the C-19 methyl group. We characterized the adrenal 11 beta, 18,19-hydroxylase enzyme system in inbred salt-sensitive and resistant rats (R/JR). This system is capable of all three hydroxylations. The Km for 19-hydroxylation was different from S/JR and R/JR but was much greater for 11 beta- and 18-hydroxylation in both. This suggested that the catalytic site for 19-hydroxylation is different from that for 11 beta and 18. The S/JR adrenal enzyme binds the substrate with higher affinity than does the R/JR adrenal enzyme. We were unable to distinguish the cDNAs of the S/JR from the R/JR adrenal enzyme from bovine 11 beta-hydroxylase cDNA by restriction mapping. We were unable to demonstrate restriction length polymorphism. 19-Acetylenic DOC is an inhibitor which preferentially inhibits the 19-hydroxylation of DOC, and does not interfere with the 18- and 11 beta-hydroxylation. This inhibition leads to a reduction in blood pressure in the S/JR Dahl rat. We suggest that an S/JR 19-nor-DOC is involved in the development of salt-sensitivity and hypertension and that inhibition of its formation by acetylenic DOC and other aromatase and non-aromatase inhibitors is associated with reversal of these phenomena.
Pigeon-breeder's lung should be included in the differential diagnosis when patients present with interstitial lung disease or intermittent cough and dyspnea. No single test confirms the diagnosis. Rather, careful attention must be given to results of history taking, physical examination, pulmonary function and precipitin testing, chest radiography, and, if indicated, lung biopsy. Symptoms usually resolve when exposure to suspected antigens is avoided.
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Two final year dental students spent an elective period in the HIV clinic of the Dental Hospital of the Freie University of Berlin. The oral manifestations and management of 50 HIV patients were observed.
Twenty-four hour ambulatory electrocardiographic recording using a Medilog tape recorder was attempted in 16 healthy pet dogs weighing between 18.4 and 34 kg, while they were living in familiar surroundings. Full 24-hour records were obtained from 10 of them and recordings of more than 10 hours duration from two others; and the findings in these recordings were similar. Maximum heart rates ranged between 110 and 300 beats/minute and the minimum rates ranged between 17 and 46 beats/minute. Intermittent ventricular premature complexes were recorded from these apparently healthy dogs and all but one dog demonstrated a sinus pause, longer than two seconds; the longest pause was 5.7 seconds. The pauses were associated with marked sinus arrhythmia and occurred in both brachycephalic and non-brachycephalic breeds.
Rats susceptible to the hypertensive effect of dietary salt (SS/Jr) have excess 18-hydroxydeoxycorticosterone (18-OH-DOC) and 19-nor-DOC compared to control rats (SR/Jr). This may be caused by an abnormal adrenal 11 beta-hydroxylase, which catalyzes the 11 beta, 18, and 19-hydroxylations of DOC. A comparison of the urinary products of this enzyme including 18-OH-DOC, 19-nor-DOC, corticosterone (B), and 18-OH-B have not been described in the SS/Jr. Therefore, these steroid products were measured at 7 and 12 weeks of age in 36 weanling male and female, SS/Jr and SR/Jr (n = 9 in each group), on a low-salt diet. In both the male and female SS/Jr urinary free levels of 18-OH-DOC, 19-nor-DOC, and 18-OH-B were elevated, while B was not different at 6 and 10 weeks of age. The largest increases were in 18-OH-B levels, and these levels correlated with 18-OH-DOC and B but not 19-nor-DOC. The high degree of correlation between these steroids probably reflects their closely related dependence on adrenal 11 beta-hydroxylase biosynthesis.
During an exchange programme at the "Freie Universität Berlin" the authors worked on the department of Oral Surgery. Their work consisted of treating HIV positive patients. A report on their experiences is given.
Trichosanthin, a ribosomal inhibitor protein, blocks HIV replication in lymphocytes and macrophages. This agent was used to treat 51 patients with advanced HIV disease in a dose-escalation study in which three injections were administered over a 9-21-day period in a dose range of 10-30 micrograms/kg per injection. The maximum tolerated dose was estimated to be 30 micrograms/kg. Reversible but severe fatigue and myalgias were the major dose-limiting side-effects; mild leucocytosis and elevations in serum transaminases were noted and were reversible. Non-dose-related reversible mental status changes were seen in six patients and were considered to be associated with the drug. This was usually manifest as dementia, but progressed to coma in two patients. This reversed, but the sequelae resulted in death in one patient. Decreases in serum p24 antigen levels were noted 1 month after the first infusion in 10 of 18 patients who entered the study with elevated levels; one converted to negative. Values usually remained low to the end of the study period (2 months). In those patients with CD4+ cell levels greater than 50 x 10(6) cells/l significant decreases in sedimentation rate and increases in CD4+ cell numbers were also noted. These changes were found at all dose levels but only in patients receiving three infusions.
Athletic preparticipation evaluations are among the most common routine health screening tools, yet no standardized approach to these evaluations has been adopted. This paper presents a focused preparticipation examination form developed by the authors with the assistance of the North Carolina Academy of Family Physicians' Task Force on Sports Medicine. After reviewing the major studies of preparticipation examinations, 11 basic questions that identify specific risks for sports participation were selected. Three specific components form the core of the physical examination: blood pressure measurement, a comprehensive orthopedic examination, and cardiovascular auscultation. Other portions of the physical examination may be included because of sport-specific risks or problems identified in the history, but are not routine. The rationale for this form and guidelines for the physician to make recommendations for sports participation and timing of reevaluation are discussed.
A prospective study was developed to examine whether personality factors predispose runners to injury. Forty runners who completed a type A behavior screening were followed for 1 year during which they documented their training mileage, injuries, and time lost from training because of injury. Runners with high scores on the type A behavior screening questionnaire experienced significantly more injuries, especially multiple injuries. Although not significant, high scorers lost nearly twice as much training time because of injury. No significant relationship was found between mileage and injury. The data suggest that a type A behavior score warrants consideration as a predictive risk factor when screening for potential running injuries.