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R Smith

Publications and source records attributed to R Smith.

At least 775 records · Page 43Linked to original sources
PubMed1993

Solution structure of the toxic octapeptide, lophyrotomin.

Lophyrotomin is a toxic octapeptide, first isolated from larvae of the sawfly Lophyrotoma interrupta, which causes the death of cattle and sheep. It appears to act principally on the liver, however very little is known about the cellular site and mechanism of action. In the present study lophyrotomin was synthesized using solid-phase peptide synthesis, and the structure examined with two-dimensional nuclear magnetic resonance (NMR) spectroscopy. Two-dimensional correlation experiments (COSY and TOCSY) enabled the assignment of many of the resonances. Conventional NOESY experiments did not produce inter-residue information, however the alternative rotating frame NOE experiment (ROESY) resulted in intra-residue alpha N, and sequential alpha N and NN NOEs, permitting the sequence-specific assignment of all resonances. The presence of few additional shortage NOEs and the absence of any long-range NOEs in the ROESY spectra indicated a lack of persistent secondary structure. The results from circular dichroism (CD) spectroscopy experiments were consistent with the NOE data, as addition of high concentrations of the denaturant urea produced no changes in the lophyrotomin CD spectrum. This conclusion was further supported by 13C spin-lattice relaxation studies, which indicated that the peptide is a flexible molecule, by examination of the alpha-carbon chemical shifts, and by amide proton exchange rate measurements. Consequently it appears that if this peptide has to adopt a well defined structure to exert its biological activity, it must do so on interaction with other molecules, such as a receptor.

Circular Dichroism↗
PubMed1993

Corticotropin-releasing hormone in baboon pregnancy.

During human pregnancy, plasma CRH immunoreactivity (CRH-IR) rises progressively, peaking during labor and falling after delivery. Among animal species, only higher primates have elevated CRH-IR during pregnancy. This study examines whether changes in plasma CRH-IR in the baboon (Papio hamadryas) are similar to those in the human. CRH-IR was determined by RIA in 16 baboons at different stages of gestation (44 samples) and in 3 males. Assays were performed on Vycor extracts of plasma and CRH-IR diluted in parallel to synthetic human (h) CRH-41 standard. Reverse phase high pressure liquid chromatography and size-exclusion chromatography with Sephadex G-50 showed that baboon CRH-IR eluted in a position similar to that of hCRH-41. Regression analysis revealed a cubic association between plasma CRH-IR and gestational age, with peak concentrations occurring at 60 days gestation (term = 182 days). Although greatly elevated concentrations persisted throughout pregnancy, concentrations in the first half (1-91 days) were significantly higher (mean +/- SEM, 1.9 +/- 0.3 nM/L; n = 27) than in the second half (92-182 days; 1.0 +/- 0.2 nM/L; n = 11; P < 0.003 by t test). CRH-IR fell to low levels by day 1 postpartum. The concentration of total cortisol in nonpregnant animals was 1370.9 +/- 134.9 nM/L (n = 5), which was similar to pregnancy levels (1346.3 +/- 356.1 nM/L; n = 28); there was no gestational age-related pattern evident. Plasma corticosteroid-binding globulin was estimated by RIA, and plasma free cortisol was calculated to be 73 +/- 14 nM/L in pregnant animals and showed no gestational age-related changes. The mean progesterone concentration in the pregnant baboon was 12.5 +/- 2.2 nM/L (7-169 days; n = 27). There was no significant change in progesterone levels during the period of gestation studied; however, they were higher than nonpregnant levels. Baboon and human plasma (0.1 mL each) were incubated with [125I]Tyr-hCRH in Tris-HCl buffer (pH 7.5) and chromatographed with Sephadex G-75, using the same buffer. The radioactivity of fractions was determined, and no CRH-binding protein was identified in baboon plasma. This study indicates that gestational changes in CRH-IR in the baboon are different from those observed in humans. There is a dissociation between maternal plasma CRH and cortisol. The apparent lack of bioactivity of baboon plasma CRH is not due to a circulating binding protein, which is absent in this species.

Animals↗
PubMed1993

Preoperative evaluation of cardiac failure and ischemia in elderly patients by cardiopulmonary exercise testing.

Major surgery in the elderly continues to have a high mortality rate. Preoperative myocardial ischemia is a known risk factor. Cardiac failure is also a risk factor, but is difficult to quantify objectively. One hundred eighty-seven elderly surgical patients were evaluated for cardiac failure by cardiopulmonary exercise testing (CPX). The overall mortality in these patients was 7.5 percent. If three deaths secondary to surgical causes are excluded, mortality was 5.9 percent. There were 55 patients in whom the anaerobic threshold (AT) was less than 11 ml/min/kg; of these, 10 died, a mortality rate of 18 percent. There were 132 patients with an AT of greater than 11 ml/min/kg and of these, 1 patient died, giving a mortality rate of 0.8 percent (p < 0.001). A low AT associated with preoperative ischemia resulted in the death of 8 of 19 patients, a mortality rate of 42 percent. When the ischemia was associated with the higher AT, then 1 patient out of 25 died, a mortality rate of 4 percent (p < 0.01). Both preoperative ischemia and preoperative cardiac failure are independent risk factors for perioperative mortality in the elderly.

Aged↗
PubMed1993

Plasma corticotropin-releasing hormone, beta-endorphin and cortisol inter-relationships during human pregnancy.

To investigate the dynamic relationships among corticotropin-releasing hormone (CRH), beta-endorphin (beta EP), cortisol and obstetric events during pregnancy, blood samples were collected from 193 women at 28 weeks, 38 weeks, during labour and on the second postnatal day. Cord blood at delivery was also obtained. We found that: (1) Maternal plasma CRH, beta EP and cortisol rose from 28 to 38 weeks. (2) During the third trimester maternal plasma CRH and beta EP were correlated (r = 0.30, p < 0.001). (3) During labour, no correlations were found among maternal plasma CRH, beta EP and cortisol. (4) Maternal CRH at labour and the duration of labour were not correlated. (5) Maternal plasma CRH tended to be higher in women who delivered early (more than seven days prior to estimated date of confinement [EDC]) relative to those who were on time (within seven days' EDC) or late (greater than seven days after EDC). (6) CRH in maternal plasma at labour and cord blood were correlated (r = 0.29, p < 0.05) as were maternal and fetal beta EP (r = 0.43, p < 0.001). (7) Fetal obstetric difficulty was correlated with fetal beta EP (r = 0.54, p < 0.001). Our findings support the hypothesis that maternal plasma CRH regulates maternal beta EP during the third trimester, but other factors are involved during labour and in response to maternal obstetric stress.

Adult↗
PubMed1993

Recognizing illicit drug use by pregnant women: reports from Oregon birth attendants.

OBJECTIVES: This study was undertaken to determine the prevalence of recognized prenatal illicit substance abuse and the characteristics of women being identified as illicit drug users in a statewide population-based cohort. METHODS: During a 1-month period, birth attendants of all singleton births in Oregon (n = 3200) were surveyed regarding their knowledge of prenatal illicit drug use by women who gave birth. Birth certificates were linked to surveys after removal of personal identifiers. RESULTS: Illicit drug use was recognized in 5.2% of delivering women. Nearly half had used cocaine, methamphetamine, or heroin. Recognized users were significantly more likely than nonusers to be unwed and to have used tobacco or alcohol, have received inadequate prenatal care, and have public assistance as a source of payment. Drug use was recognized twice as frequently by practitioners who routinely questioned their patients about it compared with those who relied on clinical judgment or the occurrence of complications during pregnancy. Birth certificate reporting identified only 41% of recognized users. CONCLUSIONS: Oregon practitioners are identifying seven times as many drug-using women as can be accommodated by available treatment programs for this population. Increased efforts are needed to ensure the adequacy of resources necessary to cope with the problem as already recognized.

Adult↗
PubMed1993

Retinoic acid receptor, cytosolic retinol-binding and retinoic acid-binding protein mRNA transcripts and proteins in rat insulin-secreting cells.

To define the mechanism of vitamin A action at the beta-cell level, we tested for the presence of messenger RNA for retinoic acid receptors alpha, beta, and gamma; cytosolic retinol-binding protein; and cytosolic retinoic acid-binding protein in RINm5F cells, an insulin-secreting cell line, and determined whether cytosolic retinol-binding protein and cytosolic retinoic acid-binding protein are present in isolated purified normal rat beta-cells. Northern blot analyses showed two transcripts of retinoic acid receptor alpha messenger RNA (3.8 and 2.4 kb), one transcript of retinoic acid receptor messenger RNA (3.8 kb), and one transcript of cytosolic retinol-binding protein (0.9 kb) in RINm5F cells. Ribonuclease protection assays also showed the presence of cytosolic retinol-binding protein and cytosolic retinoic acid-binding protein in RINm5F cells. Quantitatively, cytosolic retinol-binding protein levels were 0.10 +/- 0.02 pg/micrograms total RNA. Using specific radioimmunoassays, normal isolated purified rat beta-cells contained CRBP (19.2 +/- 2.38) and cytosolic retinoic acid-binding protein (16 +/- 0.53 ng/10(6) cells). The presence of message for retinoic acid receptors alpha and gamma, cytosolic retinol-binding protein, cytosolic retinoic acid-binding protein, and the gene products of cytosolic retinol-binding protein and cytosolic retinoic acid-binding protein in insulin-secreting cells support a mechanism of vitamin A action and role for cytosolic and nuclear receptors at the beta-cell level similar to that suggested in nonendocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Functional gastrointestinal disorders in unselected patients with non-cardiac chest pain.

Patients with non-cardiac chest pain (NCCP) (n = 387) and cardiac chest pain (CCP) (n = 93) were compared with community controls (n = 81), using a symptom questionnaire that assessed the presence of irritable bowel syndrome (IBS), functional dyspepsia, and oesophageal dysfunction and chest pain characteristics. A significantly (p < 0.05) increased prevalence of symptoms compatible with IBS occurred in NCCP patients when compared with those with CCP and with controls. Dysphagia was more frequent in both those with non-cardiac and cardiac chest pain than in controls; this was not apparent, however, when patients with concomitant IBS were excluded. The presence of oesophageal or gastrointestinal symptoms did not enable discrimination with regard to the chest pain characteristics. We conclude that unselected referred patients with documented NCCP are more likely to have IBS and that the presence of oesophageal symptoms such as dysphagia may merely reflect the spectrum of the 'irritable gut'.

Angina Pectoris↗
PubMed1993

Chromosome 11q13 abnormalities in human breast cancer.

Amplification of markers centred on band q13 of human chromosome 11 is a consistent feature in a subset of oestrogen receptor positive breast cancers. Although the amplification was initially scored via FGF3/INT2, which has strong credentials as a mammary oncogene, current data suggest that some other gene on 11q13 provides the driving force for amplification. Here we have reviewed our understanding of the amplified DNA, the genes it encompasses and the evidence in favour of two candidate oncogenes, CCND1 and EMS1. As well as being among the most frequently amplified markers in the region, these genes are expressed at elevated levels as a consequence of amplification, and their predicted functions would be consistent with a role in tumorigenesis. Irrespective of the final conclusions regarding their biological relevance, the overexpression of CCND1 or EMS1 should provide a more amenable assay for the amplification and help to clarify its clinical significance.

Animals↗
PubMed1993

Treatment of social phobia with clonazepam and placebo.

Clonazepam and placebo were administered in a double-blind pilot study to 75 outpatients with social phobia. The mean maximum dose of clonazepam was 2.4 mg/day at endpoint (range, 0.5 to 3 mg). Treatment was continued for up to 10 weeks. The results of an intent-to-treat analysis indicated superior effects of clonazepam on most measures. Response rates for clonazepam and placebo were 78.3 and 20.0%. Drug effects were apparent on performance and generalized social anxiety, on fear and phobic avoidance, on interpersonal sensitivity, on fears of negative evaluation, and on disability measures. Significant differences were evident by week 1, 2, or 6, depending upon the rating scale used. Clonazepam was well tolerated in general, although unsteadiness and dizziness were more severe and persistent than was the case for placebo subjects.

Adult↗
PubMed1993

Needlestick injuries: the shock and reality.

It has been a typically busy Saturday night in the emergency department. Then, near midnight, a trauma casualty was admitted and an incident occurred that would occupy Suzanne Smith's thoughts for months to come. When starting an intravenous line on this patient, Suzanne spiked herself with a needle. Later the patient was taken to the intensive care unit and placed on a ventilator. Suzanne was overcome with fear that she might have contracted AIDS. Her fears intensified when she learned that the patient, Mr. Norman, was a heroin addict.

Fear↗
PubMed1993

Lung cancer.

Explore the source record for details and available documents.

Cadmium↗
PubMed1993

The elderly agoraphobic: a hidden problem.

This is a fascinating history of an untreated and undiagnosed patient with agoraphobia. The limitations to her lifestyle have been extreme. Improvement has been impressive and Mrs B is now enjoying her life considerably. The cognitive behavioural strategies have been useful and her improvement maintained at follow up. Asking elderly patients routine questions to elicit evidence of anxiety, phobias, and panic attacks will enable the physician to detect similar cases.

Aged↗
PubMed1993

Clozapine shows promise in schizophrenia treatment.

Clozapine represents the first significant advance in the pharmacotherapy of schizophrenia since development of phenothiazine antipsychotic drugs in the 1950s and 60s, yet only about 10% of potential patients nationwide are taking the medication.

Clozapine↗
PubMed1993

Mechanism of death in heart failure. The Vasodilator-Heart Failure Trials. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: The Vasodilator-Heart Failure Trial (V-HeFT) data base provides information on the mechanism of death of male veterans entered into two trials that evaluated the effect of vasodilator therapy on survival in heart failure. METHODS AND RESULTS: Men aged 18-75 years with heart failure were recruited at 13 Department of Veterans Affairs Medical Centers. In V-HeFT I, 283 of 642 patients (44%) died during follow-up (average, 2.3 years), and in V-HeFT II, 285 of 804 randomized patients (35.5%) died during follow-up (average, 2.5 years). Mechanism of death was established centrally using a standardized classification. In V-HeFT I, 124 of the 283 deaths (43.8%) were sudden with no worsening of symptoms; in V-HeFT II, 104 of the 285 deaths (36.5%) were sudden. An average of 31.5% of the deaths (31.4% and 31.6%, respectively) in the two trials was due to pump failure. The proportion of sudden deaths that occurred without worsening of symptoms was similar in patients with and without ischemic heart failure. Sudden deaths tended to occur earlier and pump failure deaths later in both V-HeFT studies. There was a trend for a lower percentage of cardiac deaths from pump failure and a higher percentage from sudden death in subgroups with higher peak exercise oxygen consumption (VO2), higher ejection fraction, and lower plasma norepinephrine levels. The proportion of deaths that occurred suddenly was similar in placebo, prazosin, and hydralazine plus isosorbide dinitrate treatment groups but was significantly lower in the enalapril treatment group. In V-HeFT I, measures of cardiac function and VO2 predicted pump failure death and sudden death. In V-HeFT II, VO2 and cardiothoracic ratio were independent predictors of all-cause deaths and pump failure deaths; only ejection fraction was an independent predictor of both pump failure and sudden death. CONCLUSION: Although mechanistically distinct terminal events can be identified in patients with heart failure and physiological measurements can provide some insight into the risk of these disparate events, sudden death and pump failure death both appear largely to be linked to the severity of cardiac dysfunction and symptoms. Strategies to identify individuals for selective preventive therapy are not yet practical.

Cause of Death↗
PubMed1993

Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Recognition of the complex pathophysiology of heart failure and its high mortality has emphasized the need for prognostic markers that can be used in clinical assessment as well as in the design of mortality trials. Data from the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT I, 642 patients; V-HeFT II, 804 patients) were therefore examined to determine the influence of prerandomization measurements on subsequent mortality. METHODS AND RESULTS: Patients entered into these trials were men with cardiac dysfunction and reduced peak exercise capacity. Measurements included in this analysis were left ventricular ejection fraction (EF) measured by radionuclide angiography, peak bicycle exercise oxygen consumption (VO2), cardiothoracic ratio (CTR) measured on a chest x-ray, ventricular arrhythmias assessed in a core laboratory by short-term Holter monitoring, plasma norepinephrine and plasma renin activity measured in a core laboratory only in V-HeFT II, and a variety of diagnostic and demographic data. The variables related only weakly to each other. EF, VO2, and CTR were powerful independent predictors of all-cause mortality in both studies. Ventricular arrhythmia was a significant independent predictor in V-HeFT II but not in V-HeFT I. Plasma norepinephrine but not plasma renin activity measured in V-HeFT II also had independent prognostic value. Other variables did not exert an independent effect on mortality. CONCLUSIONS: Optimal assessment of the mortality risk in an individual or a group of individuals with heart failure uses measurement of EF, peak VO2, CTR, plasma norepinephrine, and the presence of ventricular arrhythmias.

Arrhythmias, Cardiac↗
PubMed1993

Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Hospitalization of persons with congestive heart failure for recurrent heart failure or other complications is common. METHODS AND RESULTS: Male patients aged 18-75 with chronic heart failure were randomized in two sequential trials designed to study the efficacy of vasodilator therapy. Patients were evaluated every 3 months, and information regarding hospitalizations between visits was obtained from the patient, his family, and/or hospital records. Hospitalization data also were obtained for patients who had died between scheduled clinic visits. Hospitalizations were not recorded if a patient died during transit to the hospital or in the hospital emergency department before admission. In Vasodilator-Heart Failure Trial (V-HeFT) I, no significant difference in number of patients hospitalized or number of hospitalizations was noted among the treatment groups, although there was a trend for fewer and delayed cardiac hospitalizations in the hydralazine plus isosorbide dinitrate arm in which the survival was greater. In V-HeFT II, no difference in hospitalizations was apparent between the enalapril and hydralazine plus isosorbide dinitrate arms. Univariate predictors of hospitalization for all causes were reduced peak oxygen consumption (VO2) during exercise (p < 0.0001), reduced exercise duration (p < 0.0001), increased cardiothoracic ratio on chest radiograph (p < 0.0001), increased age (p < 0.03), and use of antiarrhythmic drugs (p < 0.013), whereas multivariate predictors were reduced peak VO2 (p < 0.0001), use of antiarrhythmic drugs (p < 0.015), and increased cardiothoracic ratio (p < 0.03). Univariate predictors of hospitalization for heart failure were peak VO2 (p < 0.0001), LVEF (p < 0.0001), reduced exercise duration (p < 0.0001), elevated cardiothoracic ratio (p < 0.0001), and elevated plasma norepinephrine (p < 0.0001). Multivariate predictors were exercise duration (p < 0.0001), LVEF (p < 0.04), elevated cardiothoracic ratio (p < 0.03), plasma norepinephrine (p < 0.0005), and coronary artery disease (p < 0.02). Time to first hospitalization, cause specific or overall, was considerably shorter for patients with baseline peak VO2 < 10 mL.kg-1 x min-1 compared with those with peak VO2 > 15 mL.kg-1 x min-1. CONCLUSIONS: Despite better survival in patients randomized to hydralazine plus isosorbide dinitrate compared with placebo and better survival in patients randomized to enalapril compared with hydralazine plus isosorbide dinitrate, no significant differences between the treatment groups were apparent in the incidence of hospitalization or time to first hospitalization for congestive heart failure, for cardiac reasons other than congestive heart failure, or for other causes. V-HeFT I and V-HeFT II data demonstrate no treatment effect on hospitalization, perhaps reflecting in part the effectiveness of the Veterans Affairs special heart failure clinics in dealing with worsening heart failure on an outpatient basis. Identification of predictors of hospitalization were similar in both studies.

Drug Therapy, Combination↗