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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 1,099 records · Page 61Linked to original sources

Postconception menses induction using prostaglandin vaginal suppositories.

Vaginal suppositories containing 15 methyl prostaglandin F2 alpha methyl ester in a high-melt base were administered to 60 women desiring early pregnancy interruption who were no more than 56 days' (eight weeks) pregnant as calculated from the first day of the last regular menstrual period (LMP). The purpose of this study was to evaluate the safety, efficacy, and patient acceptability of this mode of noninvasive early abortion. Some factors evaluated during the study included the time interval from insertion of the suppository to the onset of cramping and bleeding. Also measured were immediate and delayed blood loss, nausea, vomiting, and diarrhea. Of the 60 patients entered into the study, 55 procedures have been judged as successful by the prospective criteria set forth in the protocol. There were no deaths or serious complications. Four patients required hospitalization and follow-up dilatation and curettage (D&C). One patient withdrew from the study after receiving a suppository and subsequently delivered a preterm infant.

Abortion, Induced↗

Early changes in plasma and urinary potassium in diuretic-treated patients with systemic hypertension.

Two groups of patients with uncomplicated systemic hypertension were studied. Group 1 included 11 patients who had overt hypokalemia with diuretic drug treatment, and group 2 included 11 patients who remained normokalemic. After baseline studies without treatment were performed, both groups received hydrochlorothiazide, 50 mg twice daily. Plasma potassium (PK) was significantly reduced within the first day of treatment and stabilized by day 7 in both groups. The average decrease in PK was 1.0 +/- 0.1 mEq/liter (p less than 0.01) in the first group and 0.6 +/- 0.2 mEq/liter (p less than 0.01) in the second group. Cumulative losses of K were approximately 200 mEq in the hypokalemic group and were minimal in the normokalemic group as assessed by 24-hour urinary collections. Patients in the hypokalemic group also had a greater reduction in body weight and blood pressure. Supplementation with KCl, 96 mEq/day, or triamterene, 200 mg/day, in 9 hypokalemic patients resulted in an increase of PK to approximately 3.5 mEq/liter leveling off by day 7, and a cumulative K retention of approximately 200 mEq. Thus, overt thiazide-induced hypokalemia was associated with small and biologically unimportant losses of K from body stores. With replacement therapy the estimated amount of retained K was also small.

Blood Pressure↗

Metabolism of sodium pentosan polysulphate in man--catabolism of iodinated derivatives.

An iodinated derivative of the heparin analogue SP54 has been prepared and used in conjunction with unlabelled SP54 to study the catabolism and organ distribution of this potential antithrombotic agent in healthy human volunteers. As observed previously with 125I-heparin, we found that the 125I-SP54 was rapidly cleared from the circulation, returning later in a desulphated form. Organ distribution studies with 123I-SP54 suggested that the liver and spleen were major sites of desulphation. Gel filtration and Polybrene binding showed the presence of sulphated macromolecular SP54 and desulphated macromolecular and depolymerised SP54 in post-injection urines. No depolymerised material was present in plasma suggesting depolymerisation occurs in the kidney.

Adult↗

Monitoring response to chemotherapy of intact human tumours by 31P nuclear magnetic resonance.

10 kidneys bearing adenocarcinoma (hypernephroma), 1 ureteric tumour, 2 Wilms' tumour from patients undergoing nephrectomy, and normal human and animal kidneys were preserved and later tested to see whether normothermic blood perfusion restored glomerular filtration, oxygen consumption, and energy metabolism, as monitored by 31P nuclear magnetic resonance (NMR). NMR spectra of normal human kidney and of renal tumours were characteristic of kidney in other species (rat, rabbit, and dog), with six principal resonances assigned to adenosine monophosphate, inorganic phosphate (Pi), glycerophosphoryl choline, gamma, alpha, and beta adenosine triphosphate and an intrarenal pH 7.0-7.2. 7 out of 9 hypernephromas and 1 of the 2 Wilms' tumours produced an additional resonance at +4.2 ppm. This peak was absent from all normal kidney spectra and may represent Pi in a specific and highly acidic environment (pH 6.1-6.5) found in actively metabolising human tumours. Furthermore, in 1 tumour (out of 5 tested) the +4.2 ppm peak rose rapidly after the addition of chemotherapeutic agents to the perfusing blood. This observation may indicate drug sensitivity of this one tumour. The results suggest that 31P NMR imaging may be used to monitor therapeutic response during regional perfusion of malignant tumours in man.

Animals↗

In vitro generation of specific deletions in DNA cloned in M13 vectors using synthetic oligodeoxyribonucleotides: mutants in the 5'-flanking region of the yeast alcohol dehydrogenase II gene.

Deletion mutants are particularly useful in defining the boundaries of noncoding genetic functions. Such mutants can be precisely generated using synthetic oligodeoxyribonucleotides as mutagens. In this paper we describe the application of this method to recombinant DNA cloned in a phage M13-derived vector. The mutagenic oligodeoxyribonucleotides, 20 and 21 nucleotides in length, were used to delete a tract of 20 dA-dT base-pairs and an adjacent 22 base-pair perfect dyad from the ADR3 locus, the 5'-flanking regulatory region of the ADR2 gene, of Saccharomyces cerevisiae with high efficiency.

Alcohol Dehydrogenase↗

Out-of-hospital management of cardiac arrest by basic emergency medical technicians.

The outcome in 126 consecutive patients with nontraumatic out-of-hospital cardiac arrest was analyzed to determine the effectiveness of a standard ambulance system over 22 months. Therapy was limited to basic life support (that is, administration of oxygen by mask, i.v. fluids, closed-chest massage and artificial respiration) by emergency medical technicians in a community in which less than 1% of the population had been trained in cardiopulmonary resuscitation (CPR). Analyses of patient data were performed to determine the relations between survival to hospital admission or discharge and 6 variables; response time, prior CPR, initial rhythm, acute myocardial infarction, initial blood pressure and initial pulse. Of 126 patients, 28 (22%) survived to hospital admission and 11 (9%) to hospital discharge. Two patient subgroups had a higher discharge rate: those with an initial rhythm of ventricular tachycardia or fibrillation (7 of 50, 14%), and those with an initial blood pressure greater than or equal to 90 mm Hg and a pulse rate of greater than 50 beats/min (3 of 6, 50%). For patients in arrest before ambulance arrival, there was no difference in outcome between those who did or those who did not receive prior CPR. Results of this study can be used as a basis for evaluating and comparing interventions directed toward stabilization of patients during the prehospital phase of cardiac arrest.

Allied Health Personnel↗

Model system to study interaction of platelets with damaged arterial wall. I. Inhibition of platelet adhesion to subendothelium by aspirin and dipyridamole.

An experimental model system has been developed to study the interaction of platelets with a damaged vessel wall, in vivo, without deep surgical intervention. Endothelium of the central ear artery of an anesthetized rabbit is damaged by placing artery forceps on the ear directly over the vessel. Forceps are removed 30 min later and blood flow resumes. After 30 min, blood is washed out with Tyrode's solution and the vessel is perfused with 1% glutaraldehyde solution. Tissue containing the vessel is then removed and further prepared for scanning and transmission electron microscopy. Damage to the endothelium observed by scanning electron microscopy included separation of adjacent endothelial cells (EC); partial destruction and lifting up of some EC, exposing subendothelium; and denudation of larger areas of endothelium. Disc-shaped platelets were seen clinging to some damaged endothelial cells. Platelets adhered, formed pseudopods, and spread over the surface of some areas of exposed subendothelium. The extent of platelet adhesion to exposed subendothelium was estimated by eight "blind" evaluators and the average taken. Aspirin (8 mg/kg, ip) significantly inhibited adhesion (P less than 0.05) when compared to controls. No other agent tested gave significant inhibition after a single treatment. Dipyridamole (1.5 mg/kg, ip) given five times on 3 successive days, inhibited adhesion significantly (P less than 0.001). Heparin (800 U/kg, iv) or dipyridamole (0.7 mg/kg, ip) enhanced the inhibitory effect of aspirin (8 mg/kg, ip), with either combined treatment giving P less than 0.001.

Animals↗

The distal transcription signals of the herpesvirus tk gene share a common hexanucleotide control sequence.

The two distal transcription signals of the herpesvirus tk gene share a common hexanucleotide sequence and function in a mutually dependent manner. We examined their roles by introducing corresponding base mutations into each hexanucleotide. The effects of mutations in the hexanucleotide of the first distal signal match the pattern of effects of the corresponding mutations in the second distal signal. These concordant patterns suggest that the hexanucleotide repeats are functionally analogous. There is one difference between the two distal signals. Disruption of the second distal signal concomitantly inactivates the first distal signal; disruption of the first distal signal leads to only partial inactivation of the second distal signal. When the positions of the two distal signals are switched, the partial dependence of the second distal signal is alleviated. We suggest a model for positive transcriptional control analogous to activation of the cl maintenance promoter of bacteriophage lambda by repressor.

Alleles↗

Identification of functional regions in the transforming protein of Fujinami sarcoma virus by in-phase insertion mutagenesis.

A novel mutagenesis procedure based on the insertion of a hexameric nucleotide sequence into Rsa I restriction sites of cloned DNA has been applied to a copy of the Fujinami sarcoma virus (FSV) genome with the aim of identifying functional regions in the transforming protein. Mutations specifying peptide insertions in both the NH2- and the COOH-terminal fps-specific portions of the transforming protein reduce or abolish the capacity of the genome to induce transformed foci in rat-2 cells. Insertion of multiple copies of the hexamer into one central position in the oncogene results in dislocation of the NH2- and COOH-terminal regions in the primary structure, but has no inhibitory effect on focus induction. Taken together, the results imply that both the NH2- and COOH-terminal fps-specific portions of the FSV oncogene product possess determinants which function in fibroblast transformation, and that cooperation of these two regions is not sensitive to their separation in the primary structure.

Animals↗

Mutagenesis of Fujinami sarcoma virus: evidence that tyrosine phosphorylation of P130gag-fps modulates its biological activity.

The 130 kd transforming protein of Fujinami sarcoma virus (FSV P130gag -fps) possesses a tyrosine-specific protein kinase activity and is itself phosphorylated at several tyrosine and serine residues in FSV-transformed cells. We have used oligonucleotide-directed mutagenesis of the FSV genome to change the TAT codon for tyrosine (1073), the major site of P130gag -fps phosphorylation, to a TTT codon for phenylalanine that cannot be phosphorylated. This mutant FSV induces the transformation of rat-2 cells but with a long latent period as compared with wild-type FSV. The P130gag -fps protein encoded by the mutant retains the ability to phosphorylate tyrosine, but is five times less active as a kinase in vitro than wild-type FSV P130gag -fps. These data indicate that tyrosine phosphorylation stimulates the biochemical and biological activities of FSV P130gag -fps, and they set a precedent for the ability of this amino acid modification to modulate protein function.

Amino Acid Sequence↗

Preliminary findings on used cervical caps.

Rubber cervical caps (Lambert-Dalston), used for periods of time ranging from 1 month to 3 years, were collected and assessed for deterioration and contamination as part of a product safety and efficacy study. Examination at magnification of 10 to 30 times as well as evaluation of surface damage and bulk mechanical properties revealed significant deterioration on all caps used consistently for more than one year. Changes were also evident on caps worn for shorter periods. Potential for adverse reaction from rubber degradation products and contamination adsorbed from disinfecting agents does not appear negligible. This problem, in combination with the inability to satisfactorily clean the caps after use, further limits their clinical value. A rethinking of cap design and the choice of better cap materials appears necessary to minimize long-term user problems and to mitigate product-related aesthetic deficiencies of this fertility control method.

Consumer Product Safety↗

TRH test abnormalities in psychiatric disorders.

Blunted responses to thyrotropin-releasing hormone (TRH) stimulation have been found consistently in depressed patients, and have been reported in other affective disorders as well. In a smaller number of schizophrenic subjects, TRH tests have generally been normal. Thus, it has been suggested that this test may have diagnostic utility in distinguishing schizophrenia from affective disorders. In the present study the TRH test was performed upon a sample of 51 subjects that included 17 schizophrenics in order to further study the diagnostic or symptom specificity of this endocrine test. Abnormal TRH tests were present in both schizophrenic and affectively disturbed patients. There were no correlations with ratings of depression or other aspects of psychopathology. Factors which may have previously obscured abnormal TRH tests in schizophrenia are discussed.

Bipolar Disorder↗