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J Godwin

Publications and source records attributed to J Godwin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Behavioural sex change in the absence of gonads in a coral reef fish.

It is an axiom of vertebrate behavioural endocrinology that full expression of a male behavioural phenotype depends on testicular influences during development, in adulthood, or both. Sex change in fishes challenges this necessity: behavioural changes are often rapid and greatly precede gonadal changes. However, steroid hormones can have fast actions on the nervous system, so gonadal influences on behavioural sex change cannot be excluded based solely on the speed of these changes. We report that surgical gonad removal does not prevent or discernibly alter female-to-male behavioural sex change in a protogynous coral reef fish. Male behaviour assumption is instead purely dependent on attaining social dominance. This is the first example of a vertebrate fully expressing a male behavioural phenotype without current or previous exposure to a functioning testis or testicular products.

Animals↗
PubMed1996

Intrahypothalamic implantation of progesterone in castrated male whiptail lizards (Cnemidophorus inornatus) elicits courtship and copulatory behavior and affects androgen receptor- and progesterone receptor-mRNA expression in the brain.

A primary tenet of behavioral neuroendocrinology is that gonadal steroid hormones act on limbic nuclei to activate mating behavior in vertebrates. Traditionally, research has focused on the regulation of male-typical sexual behavior by testicular androgens and female-typical sexual behavior by ovarian estrogen and progesterone. Indeed, progesterone generally is regarded as an antiandrogen, acting centrally to inhibit sexual behavior in males. However, experiments with lizards, and more recently with rats, have challenged this paradigm. For example, exogenous progesterone induces mating behavior in some, but not all, castrated male whiptail lizards. The present study determined that implantation of progesterone into the anterior hypothalamus preoptic area of castrated, progesterone-sensitive males completely restored sexual behavior but failed to elicit sexual activity in castrated, progesterone-insensitive males. Further, androgen receptor -and progesterone receptor-mRNA expression in specific brain regions was significantly different in progesterone-sensitive versus progesterone-insensitive animals. Progesterone-sensitive males showed significantly higher relative abundance of androgen receptor-mRNA in the preoptic area, amygdala, and lateral septum, as compared with progesterone-insensitive animals receiving the same treatment. In contrast, progesterone receptor-mRNA abundance was lower in preoptic area of progesterone-sensitive males than in progesterone-insensitive males. No differences were found in the baseline abundance of androgen receptor-or progesterone receptor-mRNA in these nuclei between control groups of progesterone-sensitive and progesterone-insensitive males who were castrated but not implanted. This suggests that progesterone differentially regulates its own receptor as well as androgen receptor in areas of the brain involved in the control of sexual behavior of males and that the nature of this regulation shows individual variability.

Amygdala↗
PubMed1996

Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer reinfarctions per 1000 (2P = 0.04) and 1 (0.5) fewer pulmonary emboli per 1000 (2P = 0.01), but there was a small non-significant excess of stroke and a definite excess of 3 (1) major bleeds per 1000 (2P < 0.0001). CONCLUSIONS: The clinical evidence from randomised trials dose not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardial infarction (irrespective of whether any type of fibrinolytic therapy is used).

Anticoagulants↗
PubMed1996

Leukemogenic risk of hydroxyurea therapy in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

In polycythemia vera (PV), treatment with chlorambucil and radioactive phosphorus (p32) increases the risk of leukemic transformation from 1% to 13-14%. This risk has been estimated to be 1-5.9% with hydroxyurea (HU) therapy. When compared with historical controls, the risk with use of HU does not appear to be statistically significant. The leukemogenic risk of HU therapy in essential thrombocytosis (ET) and in myelofibrosis with myeloid metaplasia (MMM) is unknown. HU remains the main myelotoxic agent in the treatment of PV, ET, and MMM. We studied 64 patients with these three disorders, seen at our institution during 1993-1995. The patients were studied for their clinical characteristics at diagnosis, therapies received, and development of myelodysplasia or acute leukemia (MDS/AL). Forty-two had PV, 15 ET, and 6 MMM, and 1 had an unclassified myeloproliferative disorder. Of the 42 patients with PV, 18 were treated with phlebotomy alone, 16 with HU alone, 2 with p32, 2 with multiple myelotoxic agents, and 2 with interferon-alpha (IFN-alpha). Two patients from the phlebotomy-treated group, one from the HU-treated group, and 1 from the multiple myelotoxic agent-treated group developed MDS/AL. In the larger group, 11 received no treatment or aspirin alone, 18 were treated with phlebotomy alone, 25 with HU, 5 with multiple myelotoxic agents, 2 with p32, 2 with IFN-alpha, and 1 with melphalan. Study of the entire group of 64 patients showed that only one additional patient (total of 5 out of 64) developed MDS/AL. This patient had been treated with HU alone. Statistical analysis did not show any association between clinical characteristics at diagnosis, or HU therapy, and development of MDS/AL (P=0.5). Thus, our data provide no evidence suggestive of increased risk of transformation to MDS/AL with HU therapy in PV, ET, and MMM. Larger, prospective studies are needed to study this issue further.

Acute Disease↗
PubMed1996

Progesterone inhibits female-typical receptive behavior and decreases hypothalamic estrogen and progesterone receptor messenger ribonucleic acid levels in whiptail lizards (genus Cnemidophorus).

Female-typical sexual behavior in tetrapods is mediated primarily by estrogen and progesterone acting through intracellular receptors at specific sites in the mediobasal hypothalamus. Progesterone exerts both faciliatory and inhibitory actions on female sexual behavior and in well-studied rodent models, the inhibitory actions are exerted through downregulation of progesterone and estrogen receptors. This study examined progesterone effects on both female-typical sexual behavior and hypothalamic estrogen and progesterone receptor mRNA expression (ER- and PR-mRNA) in a sexual and parthenogenetic species of whiptail lizard. Progesterone capsules administered to ovariectomized female Cnemidophorus inornatus and Cnemidophorus uniparens following a receptivity-inducing dosage of estradiol benzoate (EB) strongly inhibited receptive behavior as compared to blank implanted controls. Progesterone capsules administered either before or after an EB injection also strongly downregulated ER- and PR-mRNA abundance in the ventromedial nucleus of the hypothalamus relative to blank implanted controls. The correlated decrease in both EB-induced receptive behavior and ER- and PR-mRNAs following progesterone administration are similar to findings in rats and guinea pigs, suggesting that this is an evolutionarily conserved mechanism in the regulation of female sexual behavior.

Animals↗
PubMed1995

Reptilian sex steroid receptors: amplification, sequence and expression analysis.

Sex steroid hormones secreted by the gonads play a central role in the reproduction of all vertebrates. In addition to direct effects on gametogenesis, sex steroid hormones are important in sexual development, brain organization, and sexual behavior. The actions of sex steroid hormones are mediated primarily by ligand-dependent transcription factors, or receptors which bind to specific sequences of the DNA and alter the transcription rates of nearby genes. We have used the polymerase chain reaction to amplify cDNA fragments of the estrogen receptor, progesterone receptor and androgen receptor from the unisexual whiptail lizard, Cnemidophorus uniparens. The lizard steroid hormone receptors share a high degree of sequence homology to the steroid hormone receptors of other vertebrates. Ribonuclease protection assays demonstrate that both estrogen receptor mRNA and progesterone receptor mRNA are increased in the oviduct during vitellogenesis and after estrogen treatment. This report demonstrates the utility of the polymerase chain reaction to generate species specific probes for comparative molecular studies and provides the first report of cDNA sequences for reptilian steroid hormone receptors.

Amino Acid Sequence↗
PubMed1995

Sex differences in estrogen and progesterone receptor messenger ribonucleic acid regulation in the brain of little striped whiptail lizards.

Sex differences in the regulation of steroid hormone receptors in brain areas controlling female- and male-typical sexual behavior may be important in determining sex differences in the display of these behaviors. This study examined sex differences in estrogenic effects on the relative abundance of messenger RNA for estrogen receptor (ER) and progesterone receptor (PR) in discrete brain areas of whiptail lizards, Cnemidophorus inornatus, by in situ hybridization with radiolabeled riboprobes. Gonadectomized females and males received an estradiol benzoate (EB) injection (0.5 microgram) which effectively induces receptive behavior in females; controls received vehicle alone. Sex and regional differences in estrogenic effects on ER- and PR-mRNA abundance were found. Females responded to EB treatment with increases in ER- and PR-mRNA relative abundance in the ventromedial nucleus of the hypothalamus (VMH). Males had similar relative mRNA abundances to females in gonadectomized controls, but did not exhibit increases with EB treatment. EB treatment increased ER-mRNA abundance in the dorsal hypothalamus of females, but not males. ER-mRNA decreases in the lateral septum and PR-mRNA increases in the posterior hypothalamus with hormone treatment were also found, but did not differ by sex. Neither sex nor treatment effects were definitively shown for ER- or PR-mRNA abundance in the anterior hypothalamus-preoptic area. The VMH controls female-typical receptive behavior in this species. Sex differences in the response to estrogen in this nucleus may therefore underlie sex differences in the display of receptive behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Design and conduct of a double-blind, placebo-controlled trial of daunorubicin and cytarabine with or without granulocyte colony-stimulating factor in elderly patients with acute myeloid leukemia: a Southwest Oncology Group study.

From the public health standpoint, acute myeloid leukemia (AML) is an important problem for both young and older adults. AML is the leading cause of cancer death in men aged 15-34 years and the second leading cause of cancer death in women in this age group. This clearly has an impact on loss of life in the productive years. But in terms of the population most affected and of the biology of the disease, the impact is even greater for the elderly patient. Age has been established in many AML treatment trials as a poor prognosis factor. Although ther is no consensus as to what age defines an elderly AML patient, those older than 45 years have a lower complete remission (CR) rate than those who are younger. In patients younger than 50 years, the average CR rate is 60%-75%; in contrast, in patients older than 70 years, the CR rate is 35%-40%. Long-term disease-free survival ranges from 25% to 50% in adult AML, depending on the post-remission therapy used and the age of the patient. In November 1991, the Southwest Oncology Group began a study to address the problems of treating AML in the elderly. Many previous treatment trials of AML have included elderly patients as a subgroup of the study analysis, with a larger proportion of young patients. This trial was designed to test the hypothesis that a myeloid growth factor used as supportive care could improve the outcomes in elderly patients with AML.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Medical assessment of bleeding in the surgical patient.

The key to avoidance of hemostatic failure during surgery is to be able to identify the high-risk patient and make a diagnosis and treat the defect before surgery. A thorough history and physical examination are mandatory in this regard. A screening coagulation profile is not a substitute for the history and physical examination. Selected presurgical tests are useful in major surgical cases and in certain high-risk cases. Otolaryngologists have advised presurgical testing for patients undergoing tonsillectomy, but the subject of presurgical testing is still a matter for investigation in view of the necessity for cost containment. Knowledge of the hemostatic system combined with a knowledge of the tests available to diagnose coagulation defects permits a rational approach to therapy of the bleeding surgical patient.

Blood Coagulation Disorders↗
PubMed1994

Acute myeloid leukaemia in a patient with Seckel syndrome.

We report a female patient with Seckel syndrome who developed acute myeloid leukaemia at the age of 26 years. Analysis of bone marrow chromosomes showed an abnormal clone with abnormalities involving multiple chromosomes, including monosomy 7, trisomy 8, trisomy 11, and loss of the long arm of chromosome 5. After treatment with chemotherapy, the patient experienced severe toxicity with profound bone marrow aplasia and died of pneumonia two months later. We suggest that patients with Seckel syndrome may be at risk of developing myelodysplasia and acute myeloid leukaemia. They may also have poor tolerance to cytotoxic therapy.

Abnormalities, Multiple↗
PubMed1993

Dietary fish oil supplementation reduces myocardial infarct size in a canine model of ischemia and reperfusion.

OBJECTIVES: This study was conducted to determine whether the long-term administration of fish oil attenuates myocardial necrosis in an occlusion-reperfusion model of myocardial ischemia. BACKGROUND: Omega-3 fatty acids found in fish oil have various biologic properties that may modify myocardial injury caused by severe ischemia and reperfusion. METHODS: Of 21 dogs fed an identical diet, 10 were given supplemental fish oil containing 0.06 g/kg per day of eicosapentaenoic acid for 6 weeks. Under anesthesia and open chest conditions, the left circumflex coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Regional myocardial blood flow was measured with 15-microns spheres before and during occlusion and during reperfusion. The area at risk and infarct size were measured using standard staining techniques. RESULTS: In the dogs receiving supplemental fish oil, the platelet cell membrane content of eicosapentaenoic acid increased from 0.9 +/- 0.56% to 7.1 +/- 4.0% (p < 0.001). Infarct size was 29 +/- 7% in the control group and 13 +/- 3% in the fish oil group (p < 0.05). There was no significant difference in the myocardial area at risk or rate-pressure product between the control and fish oil groups. There was no difference in regional myocardial blood flow between the groups at baseline study or during coronary occlusion and reperfusion. CONCLUSIONS: Dietary fish oil supplementation significantly reduced myocardial infarct size in this model. The difference in infarct size did not appear to be related to dissimilarities in regional myocardial blood flow or determinants of oxygen consumption. Further investigation is needed to determine the nature of the protective mechanisms of omega-3 fatty acids on myocardial infarct size.

Animals↗
PubMed1991

The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results.

From 1979-85, 2435 patients with a transient ischaemic attack or minor ischaemic stroke were randomly allocated to receive long term "blind" treatment with aspirin 600 mg twice daily (n = 815), aspirin 300 mg once daily (n = 806) or placebo (n = 814). No patient was lost to follow up. The "intention to treat" comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986. There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin, but the lower dose was undoubtedly less gastrotoxic. Also, there was no definite difference in the response of males and females to aspirin. The odds of suffering a major stroke, myocardial infarction or vascular death were 15% less in the combined aspirin groups compared with the placebo group (95% confidence interval 29% reduction to 3% increase in odds) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25%. There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring.

Aged↗
PubMed1990

Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context.

There are 14 unconfounded randomised trials of antihypertensive drugs (chiefly diuretics or beta-blockers): total 37,000 individuals, mean treatment duration 5 years, mean diastolic blood pressure (DBP) difference 5-6 mm Hg. In prospective observational studies, a long-term difference of 5-6 mm Hg in usual DBP is associated with about 35-40% less stroke and 20-25% less coronary heart disease (CHD). For those dying in the trials, the DBP difference had persisted only 2-3 years, yet an overview showed that vascular mortality was significantly reduced (2p less than 0.0002); non-vascular mortality appeared unchanged. Stroke was reduced by 42% SD 6 (95% confidence interval 35-50%; 289 vs 484 events, 2p less than 0.0001), suggesting that virtually all the epidemiologically expected stroke reduction appears rapidly. CHD was reduced by 14% SD 5 (95% CI 4-22%; 671 vs 771 events, 2p less than 0.01), suggesting that just over half the epidemiologically expected CHD reduction appears rapidly. Although this significant CHD reduction could well be worthwhile, its size remains indefinite for most circumstances (though beta-blockers after myocardial infarction are of substantial benefit). At present, therefore, a sufficiently high risk of stroke (perhaps because of age, blood pressure, or, in particular, history of cerebrovascular disease) may be the clearest indication for antihypertensive treatment.

Antihypertensive Agents↗
PubMed1990

Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.

The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.

Adult↗
PubMed1986

Can acute cholecystitis produce obstructive jaundice in the absence of choledocholithiasis?

A case is presented of acute cholecystitis that produced extensive ascending, intrahepatic acute cholangitis (sufficient to produce obstructive jaundice of significant degree) without evidence of choledocholithiasis or ductal dilatation.Questions are raised concerning the present accepted clinical classification of both cholangitis and obstructive jaundice.

Acute Disease↗
PubMed1980

Toxic nephropathy during continuous rifampin therapy.

A relatively mild nonoliguric acute renal failure developed early in the course of daily rifampin treatment in a 54-year-old man who was receiving concomitant steroid therapy. The renal lesion was an acute interstitial nephritis characterized by tubular dysfunction:inability to concentrate urine, increase in fractional excretion of sodium and uric acid, and glycosuria with normal blood glucose values. All abnormalities resolved promptly upon withdrawal of rifampin while steroid therapy was gradually reduced. The documents the fact that rifampin-induced nephropathy can occur in the course of a continuous daily regimen and may be favorably influenced by steroid administration.

Acute Kidney Injury↗