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Biomedical subjects

M L Smith

Publications and source records attributed to M L Smith.

At least 307 records · Page 17Linked to original sources
PubMed1990

Radon-222 levels in New York State homes.

Results are presented from a statewide survey that measured annual 222Rn concentrations in over 2000 single-family, owner-occupied homes in New York state. The participants were selected by a random-digit-dialing telephone interview approach developed by Mitofsky-Waksberg which allows inferences to be made from the sample to the statewide population. After completing a telephone questionnaire and agreeing to have their homes monitored, eligible households were mailed alpha-track detectors with instructions to place one detector in the main living area for 2 mo (during the winter heating season), a second in the main living area for 1 y, and a third in the basement (if applicable) for 1 y. The statewide median concentration for the heating-season, living-area readings was 31.6 Bq m-3, with a median of 24.0 Bq m-3 for the annual living-area readings and 51.8 for the annual basement readings. For the state, approximately 95% of the living-area concentrations and 86% of the basement concentrations were below 148 Bq m-3 (4 pCi L-1). In addition, only 1.4% of the readings in the basement were above 740 Bq m-3 (20 pCi L-1).

Heating↗
PubMed1990

Three-dimensional comparison of peripheral benzodiazepine binding and histological findings in rat brain tumor.

Experiments were undertaken to determine the in vivo utility of the mixed benzodiazepine ligand [3H]flunitrazepam and the selective peripheral benzodiazepine ligand [3H]PK 11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] to outline the borders of rat C6 glial tumors in three dimensions. Intravenous injection of [3H]flunitrazepam resulted in a tumor/cortex ratio of radioactive densities between 2.7 and 1.5 within the first 60 minutes after injection. [3H]PK 11195 demonstrated a higher tumor/cortex ratio (5.3) than [3H]flunitrazepam. For three-dimensional studies, images were generated from thionin-stained histological sections and autoradiograms. The mixed type benzodiazepine ligand [3H]flunitrazepam was superior in showing some of the normal anatomical structures surrounding the tumor, whereas [3H]PK 11195, a specific peripheral ligand, demonstrated higher tumor/brain contrast and superior topographical correlation between histological and autoradiographic images. Implications of peripheral benzodiazepine receptor ligands for positron emission tomography are discussed.

Animals↗
PubMed1990

Effects of bilateral oophorectomy on lipoprotein metabolism.

The effects of surgical menopause on lipoprotein levels and their time course were studied in 31 premenopausal women who were undergoing hysterectomy and bilateral oophorectomy for non-malignant conditions. Lipoprotein levels were measured before oophorectomy and afterwards at 6 and 12 weeks, then at intervals of 3 months for 18 months. Low density lipoprotein (LDL) cholesterol levels rose significantly (P less than 0.05) in the 6 weeks after operation from a mean of 3.57 (SD 0.66) mmol/l to 4.21 (SD 0.84) mmol/l with no significant changes thereafter. There were no significant changes in cholesterol in the other density fractions or in triglyceride levels. High density lipoprotein (HDL) subfractions were measured in 10 of the women to assess any change in the relative amounts of cholesterol carried on HDL2 and HDL3, since the protective effect of HDL is believed to be conferred by the HDL2 fraction only. No significant change was found in either fraction. The increase in LDL cholesterol would be expected to result in an appreciable increase in the risk of developing coronary heart disease, but cannot wholly account for the increase in cardiovascular disease associated with oophorectomy.

Adult↗
PubMed1990

Photochemotherapy of dominant, diffuse, cutaneous mastocytosis.

Diffuse, cutaneous mastocytosis is a rare variant of cutaneous mast cell infiltration that can arise in neonates or infants as a generalized bullous eruption. The mode of transmission is suggested as autosomal dominant. We report four infants from two unrelated families with diffuse cutaneous mastocytosis whose cutaneous disease was not controlled by initial therapies. Treatment of the four infants with photochemotherapy dramatically reduced or eliminated symptoms. One course of therapy resulted in improvement, and retreatment has not been required two to six years later.

Child↗
PubMed1990

Analysis of the mouse Dhfr/Rep-3 major promoter region by using linker-scanning and internal deletion mutations and DNase I footprinting.

The mouse dihydrofolate reductase (Dhfr) promoter region is buried within a CpG island (a region rich in unmethylated CpG dinucleotides), has a high G+C content, and lacks CAAT and TATA elements. The region contains four 48-bp repeats, each of which contains an Sp1-binding site. Another gene, Rep-3 (formerly designated Rep-1), shares the same general promoter region with Dhfr, being transcribed in the direction opposite that of Dhfr. Both genes appear to be housekeeping genes and are expressed at relatively low levels in all tissues. The 5' termini of the major Dhfr transcripts are separated from the 5' termini of the Rep-3 transcripts by approximately 140 bp. This curious structural arrangement suggested that the two genes might share common regulatory elements. To investigate the promoter sequences driving bidirectional transcription, a series of promoter mutations was constructed. These mutations were assayed by a replicating minigene system and by promoter fusions to the chloramphenicol acetyltransferase gene. Linker-scanning mutations that spanned the four repeats produced a variety of mRNA transcript phenotypes. The effects were primarily quantitative, generally reducing the abundance of transcripts for one or both genes. Some mutations affected Dhfr in a qualitative manner, such as by changing the startpoint of one of the major Dhfr transcripts or changing the relative abundance of the two major Dhfr transcripts. Additionally, protein transcription factors that bind to sequences in the mouse Dhfr/Rep-3 major promoter region, potentially affecting expression of either or both genes, were investigated by DNase I footprinting. The results indicate that multiple protein-DNA interactions occur in this region, reflecting potentially complex transcriptional control mechanisms that might modulate expression of either or both genes under different physiological conditions.

Animals↗
PubMed1990

Autonomic pathophysiology in heart failure: carotid baroreceptor-cardiac reflexes.

We evaluated reflex cardiac responses mediated by carotid baroreceptors in 14 patients with treated congestive heart failure and 14 age-matched healthy subjects. We used a neck chamber to deliver two types of pressure change: 5 s of continuous 50-mmHg suction and an R wave triggered, ramped neck pressure-suction sequence. Reflex latencies (functions of baroreflex arc duration) were comparable in heart failure patients and healthy subjects. However, the average maximum baroreflex slope (gain) was less in heart failure patients than healthy subjects (2.0 vs. 3.5 ms/mmHg, P less than 0.010), the R-R interval response range was smaller (91 vs. 188 ms, P = 0.002), and the resting R-R interval position on stimulus-response relation (operational point) was significantly (13 vs. 40%, P = 0.001) closer to threshold. Stepwise regression analysis suggested that baseline R-R interval variability, used as an index of ongoing vagal-cardiac nerve traffic, and the inverse of antecubital vein plasma norepinephrine level, used as an index of sympathetic nerve activity, contributed significantly to the prediction of abnormal carotid baroreceptor-cardiac reflex responses. Thus our results suggest that in heart failure patients, carotid baroreceptor-cardiac reflex abnormalities are related significantly to ongoing abnormalities of vagal and sympathetic cardiovascular outflow.

Adult↗
PubMed1990

Preservation of brain temperature during ischemia in rats.

Our objectives were to study the loss of heat from ischemic brain and to devise a method of maintaining brain temperature. Reversible forebrain ischemia was induced by carotid clamping and exsanguination in 30 anesthetized and artificially ventilated rats. Rectal, skull, and brain temperatures were measured, confirming previous findings that brain temperature falls by 4-5 degrees C during 15 minutes of ischemia unless measures are taken to maintain head temperature by external heating. Temperature gradients developed within the ischemic brain, superficial tissues being cooler than deep ones. These temperature gradients were reversed when skull temperature was maintained at core body (rectal) temperature by external heating. With rectal and skull temperatures maintained at 38 degrees, 37 degrees, 35 degrees, or 33 degrees C, brain temperatures nonetheless decreased by approximately 1 degree C during ischemia. This decrease in brain temperature could be prevented by placing the rat in a Plexiglas box with circulating air at temperatures close to that of the body core and a relative humidity of approximately 100%. We also found that, unless special precautions are taken, a temperature gradient develops between the brain and body core during recirculation.

Animals↗
PubMed1990

Coronary angioplasty in emergency treatment of myocardial infarction in a community-hospital setting.

From July 1986 through June 1988, 135 consecutive patients with myocardial infarction, including 23 in cardiogenic shock, were treated with percutaneous transluminal coronary angioplasty in a community-hospital setting. In 109 (81%) of the cases, angioplasty was successful, resulting in brisk anterograde flow and in residual stenosis of less than 50%. The success rate was 88% (99/112) for patients not in cardiogenic shock and 43% (10/23) for those in shock. During the term of hospitalization, clinically evident total reocclusion occurred in 5 (4%) patients not in shock on presentation (2 of these experienced anterior infarction, and 3 inferior infarction); repeat angioplasty was performed successfully in all 5. No clinical reocclusion was detected in the smaller group of patients admitted in shock. Eleven patients (8%) underwent emergency coronary artery bypass grafting following the coronary angioplasty procedure: 4 for failed angioplasty in the infarct-related artery, and the other 7 for severe triple-vessel disease. Hospital mortality was 0.9% (1/112) for patients not in cardiogenic shock and 52% (12/23) for those admitted in shock, for an overall rate of 10% (13/135). Among patients whose balloon angioplasty was successful, hospital mortality was 0% for those not in shock and 30% (3/10) for those in shock. Among patients whose angioplasty failed, however, mortality was 8% (1/13) for those not in shock and 69% (9/13) for those admitted in shock.

Journal Article↗
PubMed1990

Quality assurance in drug testing laboratories.

Drug testing is currently regulated for Department of Defense and other federal agency programs and many of the QA actions listed in this article are mandated in the regulations cited. This trend will probably continue in an effort to ensure high-quality test results and may expand into private sector testing. Also, more drugs may be added to the list of the five currently mandated for federal agencies. It remains to be seen if the certified DTLs avoid the pitfalls of past programs. A good QA program will undoubtedly be the key to success.

Government Agencies↗
PubMed1990

Postmortem forensic toxicology.

After all of the analytic data have been accumulated, the final step in the toxicologic process is to assess the meaning of the results. In suspected drug intoxications, one must determine if the amount of toxicant or toxicants present in the appropriate specimens is consistent with producing lethality. This decision ultimately must be made by the medical examiner or coroner, who must also consider the history, scene investigation, and gross and microscopic autopsy findings in reaching this decision. Once the cause of death has been determined, the manner of death needs to be decided. This can produce another group of questions to be addressed by the toxicologist. Items such as route of administration, acute versus chronic dose, and consistency between drug concentrations and behavioral effects may be critical factors in assessing the manner of death. These questions may arise even if the cause of death is ruled not to be drug related.

Autopsy↗
PubMed1990

Cardiac rupture following acute myocardial infarction: a case with successful surgical treatment.

This report involves a patient who sustained an acute lateral wall myocardial infarction complicated by cardiogenic shock. Cardiac catheterization revealed diastolic equilibration of all intracardiac pressures. Cardiac angiography revealed only acute occlusion of a small branch of the left circumflex coronary artery with good left ventricular systolic function. Since these findings could not explain the degree of cardiogenic shock, an immediate echocardiogram revealed a moderate pericardial effusion with an echo-dense mass suggestive of subacute cardiac rupture. Emergency cardiac surgery confirmed the diagnosis and successful surgical correction resulted in survival of the patient.

Cardiac Catheterization↗
PubMed1989

Construction of linker-scanning mutations using a kanamycin-resistance cassette with multiple symmetric restriction sites.

We demonstrate how a kanamycin-resistance (KmR) cassette flanked by polylinkers with multiple restriction sites can be used to introduce nucleotide (nt) sequence replacements into a region of interest. This method differs in two significant ways from traditional methods of linker mutagenesis. First, the presence of the KmR gene allows for selection of the polylinker, greatly facilitating formation of linker-containing molecules. Second, the polylinker with multiple restriction sites allows a given linker insertion to be combined with a second linker insertion in a variety of different ways and makes possible a range of novel nt to remain in the resulting linker replacement. The result of this flexibility is that fewer different molecules are needed to cover a region, and that relatively large replacements (greater than 40 nt) are possible. We have used this method to introduce a series of sequence replacements that span the mouse dihydrofolate reductase promoter region.

Animals↗
PubMed1989

Effect of etidronate disodium on bone turnover following surgical menopause.

A longitudinal study was performed to document the effect of surgical menopause and postmenopausal etidronate disodium therapy on several nonhistomorphometric indices of bone turnover. Twenty healthy, premenopausal women undergoing oophorectomy for nonmalignant conditions were studied preoperatively and at 3 monthly intervals postoperatively. Sequential measurements of serum calcium (Ca), alkaline phosphatase (AP), bone Gla protein (BGP), and urinary calcium and hydroxyproline excretion, expressed as a ratio of urinary creatinine (UCa/Cr and UOHp/Cr, respectively) were obtained. Twenty-four-hour whole body retention of diphosphonate (WBR) and radial bone density were also measured. When a postoperative increase in bone turnover was observed, patients were randomized to receive either 400 mg etidronate disodium daily or placebo for 3 months. Oophorectomy was associated with a significant increase in WBR, Ca, AP, and BGP and an insignificant rise in UCa/Cr. A variable pattern of UOHp/Cr was seen. Patients on placebo maintained these elevated levels of Ca, BGP, and UCa/Cr. WBR and AP continued to rise. Etidronate disodium therapy resulted in a fall towards premenopausal levels in WBR, Ca, and UCa/Cr. AP and BGP were unchanged. Three months after stopping etidronate, BGP fell significantly and the decrease in Ca was maintained; however, WBR and UCa/Cr had returned towards pretreatment values. Bone density measurements did not change significantly. An increase in several of the indices of bone turnover was seen following oophorectomy. Etidronate disodium suppressed this increase, affecting indices of both resorption and formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗