Biomedical subjects

A D Dean

Publications and source records attributed to A D Dean.

29 records · Page 2Linked to original sources

PubMed1992

Liver disease associated with diclofenac, naproxen, and piroxicam.

Based on information derived from computers used by general practitioners in the United Kingdom, we identified all patients with any recorded diagnosis of a liver disorder within 90 days of a prior prescription for diclofenac, naproxen, or piroxicam, three nonsteroidal antiinflammatory drugs (NSAIDs). The follow-up cohort consisted of 102,644 persons who used one or more of these drugs. A case history was requested from the physician to provide a description of the liver disorder and its relation to NSAID exposure. One case of clinically important liver disease was likely to have been caused by a study drug and another appeared to be caused by use of numerous NSAIDs. In 10 additional patients a causal connection between a study NSAID and the liver disorder seemed unlikely but could not be fully ruled out. We conclude that serious liver disease caused by diclofenac, naproxen, or piroxicam appears to be uncommon.

Adolescent↗

PubMed1991

Effects of fetal bovine serum and serum-free conditions on white and dark axolotl neural crest explants.

Neural crest cells from both white mutant and dark (wildtype) axolotls (Ambystoma mexicanum) were cultured in increasing concentrations of fetal bovine serum (FBS; 2 to 20%). For each explant, the total number of cells that migrated and the percent of differentiated melanophores were recorded. At concentrations of FBS above 2% melanophore differentiation was essentially equivalent (32 to 59%) for both the white and dark neural crest cultures, but subtle differences in cell behavior and differentiation were found between the two phenotypes. By contrast there was a significant difference in the percent melanization of cells in serum-free control cultures, wherein melanophore differentiation in dark neural crest cultures was, on average, 18% compared to 5% in white cultures. Thus, contrary to all previously published work, white and dark neural crest cells are not intrinsically equivalent. Our culture results are discussed with regard to the probable in vivo conditions that cause the white phenotype.

Ambystoma↗

PubMed1990

A comparison of the risk of hypoglycemia between users of human and animal insulins. 1. Experience in the United Kingdom.

In a case-control study of 121 young insulin-dependent diabetics diagnosed as having an episode of hypoglycemia, the relative risk estimate comparing human with animal insulins was 0.8 (95% confidence interval 0.4, 1.6) controlling for age, general practice, and calendar time. We conclude that in this study population derived from general practices in the United Kingdom, the risk of hypoglycemia was no higher in users of human insulin than it was in users of animal insulins.

Adolescent↗

PubMed1985

Electrical stimulation of the ventral noradrenergic tract (VNAT) releases hypothalamic noradrenaline and stimulates prolactin secretion in ovariectomized female rats treated with oestrogen.

Electrical stimulation of the ventral noradrenergic tract (VNAT) caused a significant fall in the hypothalamic content of noradrenaline in ovariectomized female rats which had been treated with oestrogen. No similar effect was observed in the cerebral cortex, which implies that the stimulation did not affect the dorsal noradrenergic tract. In parallel experiments with groups of similarly treated rats, VNAT stimulation was found to increase release of prolactin from the pituitary gland, and this increase was significantly enhanced in animals which had been stressed by fasting for 3 days.

Animals↗

PubMed1985

Fasting impairs LH secretion in female rats by activating an inhibitory opioid pathway.

Two experiments were undertaken to investigate the way that fasting impairs LH secretion and to assess whether endogenous opioid mechanisms might be responsible for the impairment. In the first experiment, pulsatile LH secretion was measured in a total of 51 chronically ovariectomized female rats. Initially 29 rats were subjected to food withdrawal for 24, 48, 72 or 120 h before the experiment. When compared with data collected from eight unfasted control rats, the 120-h fast was found to reduce significantly the mean peak and trough values of the LH pulses measured. However, in a subsequent study, the inhibition of pulsatile LH secretion by a 120-h fast was prevented in a group of eight rats given the opioid antagonist naloxone hydrochloride before the start of the blood-sampling period. Naloxone was without effect on pulsatile LH secretion in eight unfasted control rats. In the second experiment, plasma LH concentrations were measured before and after unilateral electrical stimulation of the ventral noradrenergic tract (VNAT) in ovariectomized female rats pretreated with oestradiol benzoate. In 17 rats VNAT stimulation caused a significant rise in plasma LH, but after a 72-h fast this rise was significantly less than in unfasted control rats. However, pretreatment of fasted rats with naloxone (n = 9) significantly enhanced the VNAT-stimulated release of LH to the control values. Naloxone did not potentiate VNAT-stimulated LH release in unfasted animals (n = 6) or LH release in control unstimulated rats (n = 12). The experiments indicate that both pulsatile LH secretion, and LH release caused by VNAT stimulation, are impaired by an acute fast.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

PubMed1985

Central opioids: a possible role in parturition?

Pregnant rats were implanted with subcutaneous minipumps to deliver either naloxone or saline. The time-course of subsequent parturition was different between the two groups: the interval between successive births was significantly shorter for the naloxone-treated rats. This supports the hypothesis that the opioid innervation of the neurohypophysis, which is known to influence oxytocin release profoundly, has a physiological role in parturition. To test the further hypothesis that this role is particularly important in a stressful environment, pregnant rats, again implanted with minipumps, were regularly transferred, at 15-min intervals beginning with the birth of the first pup, between their normal cage and the unfamiliar environment of a glass observation chamber. No difference was noted between the time-courses of parturition for the naloxone- and saline-treated groups, although the time-courses were markedly altered from those observed in rats not subjected to an unfamiliar environment. We conclude that opioid modulation of oxytocin release may play a role in 'spacing' the delivery of successive births during normal parturition.

Animals↗

PubMed1984

Relative effectiveness of naloxone and MR2266 in potentiating oestrogen-stimulated luteinizing hormone surges in ovariectomized female rats.

The oestrogen-stimulated surge of luteinizing hormone (LH) can be inhibited by opiates and potentiated when endogenous opiate pathways are blocked by naloxone. Experiments were undertaken to allow an assessment to be made of the opiate receptor category predominantly responsible for inhibiting LH secretion. Thus the effects of MR2266 (primarily a mu and kappa antagonist) and naloxone (primarily a mu and delta antagonist) on LH surges were compared. At a dose of 4.5 mg/kg, administered three times in the 6 h preceding the LH surge, naloxone significantly potentiated LH release whereas this dose of MR2266 was without effect. However at the lower dose of 0.5 mg/kg, administered three times also, the size of the LH surge was significantly increased by MR2266 but not by naloxone.

Animals↗

PubMedDate not supplied

The risk of sulfasalazine- and mesalazine-associated blood disorders.

Sulfasalazine (SASP) has often been reported to cause serious blood disorders, particularly agranulocytosis; however, little quantitative information is available to estimate the risk or to identify possible modifiers of the risk. We used comprehensive clinical information recorded on office computers by selected general practitioners in Britain to conduct a follow-up study of some 10,000 users of SASP and some 4000 users of mesalazine to estimate the risk of blood disorders associated with these drugs. Overall, the frequency of blood disorders attributable to SASP was 27/10,332 (2.6/1000 users). The risk for SASP users who were treated for arthritic disorders (6.1/1000 users) was some 10 times higher than that for users who were treated for inflammatory bowel disease (0.6/1000 users). There were no cases of blood disorders in users of mesalazine.

Adolescent↗

PubMedDate not supplied

A follow-up safety study of ciprofloxacin users.

We followed 37,233 outpatients for 45 days after receiving a prescription for ciprofloxacin to identify any newly diagnosed, important illnesses that might have been caused by the drug. For 29 users the role of ciprofloxacin in the etiology of the illness could not be confidently ruled out (7.79/10,000 persons; 95% CI 5.42-11.18). In only seven was a causal relation to ciprofloxacin considered likely: three skin reactions and one case each of thrombocytopenia, "headache, nausea, and shakes," hallucinations, and palpitations. No fatal illnesses occurred, and all patients recovered after discontinuing the drug. In addition, few cases of photosensitivity were associated with the agent. We conclude that important adverse reactions attributable to ciprofloxacin are uncommon.

Central Nervous System Diseases↗

PubMedDate not supplied

Nonsteroidal antiinflammatory drugs and certain rare, serious adverse events: a cohort study.

We performed a population-based study of over 100,000 users of diclofenac, naproxen, or piroxicam to identify cases of important blood, skin, central nervous system, kidney, pancreas, or pulmonary disorders caused by these drugs. In three cases a causal relation seemed likely; one of hemolytic anemia attributed to diclofenac, one of neutropenia attributed to naproxen, and one of pancreatitis attributed to piroxicam. In 13 additional cases a causal connection seemed unlikely but could not be fully ruled out. We conclude that such illnesses are uncommonly caused by the three agents studied.

Adult↗

PubMedDate not supplied

Liver disorders in patients receiving chlorpromazine or isoniazid.

Based on information derived from computers and clinical records obtained from general practitioners in the United Kingdom, we estimated the frequency of liver toxicity associated with two known hepatotoxins, chlorpromazine and isoniazid. Among the cohort of 10,502 users of chlorpromazine, 14 had illnesses compatible with drug-induced liver disease, a frequency of 1.3/1000 users (95% Cl 0.8, 2.2). Four presumed cases of the disorder occurred among 921 users of isoniazid, for a frequency of 4/1000 users (95% Cl 1.7, 11.1). This study provides population-based quantification of the frequency of liver disorders associated with the use of these two agents.

Adult↗