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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 829 records · Page 46Linked to original sources

Demonstration of two erythrocyte populations in young chickens by counter-current distribution of 59Fe-labelled cells in dextran-poly(ethylene glycol) two-phase systems.

The technique of fractionating cells by a counter-current distribution procedure in dextran-poly(ethylene glycol) biphasic systems was modified by increasing the settling time and decreasing the top/bottom two-phase volume ratio. Two sub-populations of 59Fe-labelled erythrocytes, namely definitive medullar cells and primitive embryonic cells, were present in the blood of young chicks until about day 8 of age. The primitive cells were progressively replaced by definitive red cells as age increased.

Aging↗

Malady and menopause.

Culver and Gert define 'malady' in their book Philosophy in Medicine. It is shown that this definition is sexist in its implication in that it either indirectly contributes to women's oppression or indirectly supports a policy that discriminates against women. This is because, on Culver and Gert's definition of 'malady', menopause, menstruation, and pregnancy become maladies. It is also argued that malady claims are normative in a way not recognized by Culver and Gert.

Age Factors↗

Therapeutic monitoring of chlorpromazine I: Pitfalls in plasma analysis.

Pooled plasma from healthy volunteers was spiked with pure, synthetic chlorpromazine (CPZ), chlorpromazine sulfoxide (CPZSO), or chlorpromazine N-oxide (CPZNO), and then made alkaline with either sodium hydroxide or sodium carbonate. The samples were allowed to stand at room temperature for various timed intervals before extraction with organic solvent. It was found that CPZNO was reduced to CPZ in plasma made alkaline with sodium hydroxide, but not in protein-free buffer solution at high pH nor in plasma made alkaline with sodium carbonate. The reaction appears to take place through reducing equivalents generated by the action of sodium hydroxide on plasma proteins. Thus, apparent concentrations of CPZ in plasma from patients were elevated by as much as 343% when sodium hydroxide was used compared with concentrations in aliquots of the same plasma samples alkalinized with sodium carbonate. The amount of CPZ produced from CPZNO depends on the type of extraction procedure employed as well as on the quantity of sodium hydroxide added to the plasma. By contrast, no interconversion between CPZ and CPZSO or CPZNO and CPZSO was observed in plasma alkalinized and extracted under any of the conditions tested.

Chlorpromazine↗

Therapeutic monitoring of chlorpromazine II: Pitfalls in whole blood analysis.

Pooled whole blood from healthy volunteers was spiked with pure, synthetic chlorpromazine, chlorpromazine sulfoxide, or chlorpromazine N-oxide and then made alkaline with either sodium hydroxide or sodium carbonate. The addition of alkali causes lysis of red cells, the contents of which spill into the plasma. The lysed samples were allowed to stand at room temperature for various timed intervals before extraction with organic solvents and analysis by high performance liquid chromatography. It was found that a portion (10-14%) of the chlorpromazine spike was oxidised to chlorpromazine sulfoxide, whether the blood was made alkaline with sodium hydroxide or sodium carbonate. Chlorpromazine N-oxide added to whole blood was entirely destroyed in the presence of alkali. The chlorpromazine N-oxide was rapidly reduced to chlorpromazine, a portion of which subsequently underwent oxidation to chlorpromazine sulfoxide. We have found that chlorpromazine N-oxide resides almost entirely in the plasma with only a small portion (less than 4%) distributed into the red cells. Hence, it is essential that red cells and plasma be separated before analysis. Chlorpromazine and chlorpromazine N-oxide can then be extracted from plasma by a method that does not lead to reduction of chlorpromazine N-oxide. Alkaline extraction methods must be avoided in the analysis of chlorpromazine in the red cell fraction.

Chlorpromazine↗

Reabsorption and secretion of alpha-ketoglutarate along the rat nephron: a micropuncture study.

The transport of alpha-ketoglutarate (alpha-KG) across the luminal membrane of the rat nephron was studied by micropuncture and microassay techniques. In normal and acidotic rats, approximately 75% of the filtered alpha-KG was reabsorbed in the proximal tubule and 20% in the pars recta and/or loop of Henle at endogenous plasma concentration of alpha-KG. A progressive elevation to steady-state levels of plasma alpha-KG resulted in a progressive reduction of the fractional reabsorption of alpha-KG in the proximal tubule as well as in a progressive increase in the fractional reabsorption of alpha-KG in the pars recta and/or loop of Henle. At plasma alpha-KG concentration 20-40 times above normal, reabsorption of alpha-KG was found to be limited by a maximal tubular capacity. In alkalotic rats, net secretion of alpha-KG in the early proximal convoluted tubule, net reabsorption in the remainder of the proximal convoluted tubule, and net secretion in the pars recta and/or loop of Henle were observed. These micropuncture data indicate that, depending on the acid-base conditions, net reabsorption or net secretion of alpha-KG may occur in at least two distinct sites along the rat nephron.

Acid-Base Equilibrium↗

Menstrual function and bone mass in elite women distance runners. Endocrine and metabolic features.

Bone mass and metabolic features were studied in 17 women distance runners. Eleven of the women had secondary amenorrhea for 1 to 7 years. Six women have maintained regular menses since menarche. Both groups were matched for aerobic capacity, body fat, exercise intensity, and age of menarche. Mineral density of lumbar spine in the amenorrheic runners was lower than that in the cyclic women and age-matched controls, but higher than that in runners with secondary amenorrhea who are less physically active. Mineral density of the radius was normal in both groups. Running-related fractures were more frequent in amenorrheic women. Metabolic assessment showed no differences between groups, except that serum triiodothyronine was lower in the amenorrheic group, perhaps reflecting low calorie intake. Intense exercise may reduce the impact of amenorrhea on bone mass; however, amenorrheic runners remain at high risk for exercise-related fractures.

Adolescent↗

Acute right ventricular failure is caused by inadequate right ventricular hypothermia.

The hypothesis of this study was that inadequate right ventricular hypothermia contributes to the right ventricular dysfunction occasionally observed after cardiac operations. Dogs were placed on cardiopulmonary bypass, and 60 minute periods of hypothermic myocardial ischemia were imposed. Left ventricular temperature was always maintained at 15 degrees C and right ventricular temperatures were maintained at 15 degrees C (Group I, n = 8), 25 degrees C (Group II, n = 8), and 35 degrees C (Group III, n = 8). These temperatures were produced by infusion of hypothermic crystalloid cardioplegic solution and appropriate topical cooling and heating of the left and right ventricles, respectively. Multiple indices of ventricular function were obtained 15, 30, 45, and 60 minutes after bypass and compared to prebypass control values. In all Group I animals (left ventricular temperature = 15 degrees C, right ventricular temperature = 15 degrees C), postischemic indices of right ventricular function were not different from control values (p = NS). In Group II (left ventricular temperature = 15 degrees C, right ventricular temperature = 25 degrees C), two animals died 30 and 45 minutes after bypass, respectively, of right ventricular failure. In the other six animals in Group II, all indices of right ventricular function were significantly reduced (p less than 0.05) except for right ventricular systolic pressure. In Group III (left ventricular temperature = 15 degrees C, right ventricular temperature = 35 degrees C), two animals could not be weaned from cardiopulmonary bypass because of right ventricular akinesia. Six animals were weaned from bypass, but two died 15 minutes, one died 30 minutes, and one 45 minutes after bypass. Two animals lived 60 minutes, but all indices of right ventricular function were decreased. Failure to maintain right ventricular temperatures below 25 degrees C during 1 hour of cardiac ischemia in the dog can result in fatal right ventricular failure.

Animals↗

[Inoperable lung epidermoid cancer non metastasizing. A phase II trial using radiotherapy and combined chemotherapy].

Thirty three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a Phase II study combining chemotherapy (Vindesine 1.5 mg/m2 dl; CCNU 50 mg/m2 d2, 25 mg/m2 d3; Cis-Platinum 100 mg/m2 d3; Cyclophosphamide 200 mg/m2 d3, 4, 5) (VCPC) and radical radiotherapy to the primary tumor, mediastinum and supraclavicular nodes. Responders to chemotherapy resumed four additional cycles following radiation therapy. Fourteen patients (42%) presented an objective response to the first two cycles of VCPC. On final evaluation, 18 patients (54.5%) obtained a complete remission and 6 patients (18%) a partial remission. Median survival of all patients was 15.9 months and toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.

Adult↗

Combined chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy in inoperable nonmetastatic squamous cell carcinoma of the lung.

Thirty-three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a phase II study combining chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy. Fourteen patients had an objective response rate of 42% (two complete responses and 12 partial responses) with the first two cycles of chemotherapy. All patients received radiation therapy to the primary tumor, mediastinum, and supraclavicular nodes, and responders to chemotherapy received four additional cycles. On final evaluation, 18 patients (54.5%) achieved complete response and six patients (18%) achieved partial response. The objective response rate was 73% with the combined therapy. The median survival was 15.9 months. Toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.

Adult↗

Synthesis and levels of organic phosphates in erythrocytes during avian development: specific formation of BPG and IP5 in two distinct populations from young chicks.

Two generations of red cells (embryonic and definitive), different types of haemoglobins, and special organic phosphates involved in the control of haemoglobin oxygenation (2:3-bisphosphoglycerate, BPG, and inositol-5-phosphate, IP5), have been found progressively during development of the chick. Levels of both organic phosphates, as well as activities of the enzymes involved in BPG synthesis (2:3-bisphosphoglycerate synthase, BPGM) and IP5 formation (phytase), were studied in the erythrocyte populations from embryo, young and adult chickens. Measurement of specific activities of BPGM and phytase in the two subpopulations present in young chickens showed that these phosphates could be specifically and predominantly formed in these two red cell populations.

6-Phytase↗

Dietary administration of 2(3)-t-butyl-4-hydroxyanisole elevates mouse liver microsome-mediated DNA binding and mutagenicity of aflatoxin B1.

Administration of the phenolic antioxidant 2(3)-t-butyl-4-hydroxyanisole (BHA) to mice resulted in a 2-3-fold increase in the liver microsome catalyzed irreversible binding of aflatoxin B1 (AFB1) to calf thymus DNA and up to a 5-fold increase in the ability to induce mutations in Salmonella typhimurium TA98. Maximum induction of AFB1 binding to DNA occurred after 2 days of BHA administration whereas cytosolic glutathione S-transferase was maximally induced (6-fold) only after 10 days of BHA feeding. The induction of a new cytochrome P-450 species was indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and an enhanced sensitivity to inhibition by metyrapone and alpha-naphthoflavone. Addition of control cytosol (containing glutathione S-transferase) + glutathione to control microsomes decreased AFB1 binding to DNA by 26%. However, replacement of control cytosol by BHA cytosol which contained 6 times more glutathione S-transferase only marginally enhanced the inhibition to 38%. These data suggest that BHA may exert its effect in the liver primarily through an alteration of the cytochrome P-450 dependent activation process although an increase in the conjugation of reactive metabolite may play a contributory role.

Aflatoxin B1↗

Radiosensitivity of swine lymphocytes: in vitro modifications of the cell cycle and kinetics of the appearance of chromosomal aberrations.

gamma-Radiation-induced modifications of the cell cycle of swine lymphocytes have been studied by the harlequin chromosome technique and by the uptake of tritiated thymidine. The radio-induced mitotic delay is 1 h per Gy. This delay occurs mainly in the lengthening of the initial phase prior to the first mitosis. The gamma-ray dose-response curve for dicentrics in first-division cells has been studied after different durations of culture. The radio-induced mitotic delay varied within the lymphocyte population: the mitosis commences much later as the cells exhibit a greater number of anomalies (dicentrics). The dose-effect relationships which can be established are thus closely conditioned by the duration of the culture. The mitotic delay observed in irradiated swine lymphocytes could amount to a restoration phase of duration varying with the importance of the induced damage.

Animals↗

The Kansas Family and Children's Trust Fund: funding prevention programs in the eighties.

The Kansas Family and Children's Trust Fund is an innovative approach to developing funding for community-based family violence prevention programs. Using a legislated trust fund which generates money from marriage license fees, the program has been developed based on three assumptions. First, funding at the federal level for programs to prevent family violence has probably reached its peak and has never been sufficiently secure as to allow for continuity in prevention programs from year to year. Second, there is a trend toward allowing local communities to assume a greater portion of the responsibility for developing social welfare programming. Third, in the long run more can be accomplished with a small amount of money given to a community-based organization which efficiently uses volunteer time than a larger amount of money given to an agency which has a large infrastructure to support. Information on the procedure utilized to enable passage of the Trust Fund legislation is included as well as a discussion of issues that arose in the legislation process. In addition, an explanation of the current funding procedures for accessing Trust Fund moneys is given along with examples of the types of programs that have received funding. Finally, examples are provided of similar approaches that have been used in other states as well as a call for additional innovative approaches to providing funding for child abuse prevention programs.

Child Abuse↗

Clinical pharmacokinetics of vindesine: repeated treatments by intravenous bolus injections.

Vindesine was administered intravenously to 12 patients with advanced cancer. Treatment was repeated after 2 weeks or more with a 1.5-to 2-fold increased dose of vindesine. Five patients received one or two additional injections at the higher dose level. One patient was given 0.4, 1 and 4 mg of vindesine on days 1, 3 and 6 and then 8 mg on days 19 and 34. Plasma samples and urine were collected over 3 days after injection and monitored for vindesine by radioimmunoassay. Significant time-dependence of vindesine plasma concentration decay kinetics at a constant dose was observed in four patients out of six. The comparison of the kinetics after administration of different doses to the same patient revealed frequent deviations from linearity with no obvious general trend. Urinary excretion was very low (1-12% of the dose), and urinary excretion rates correlated with plasma concentrations. Renal clearances were variable from one patient to another and also for the same patient from one injection to another. These data were interpreted in terms of time- and dose-dependence of vindesine pharmacokinetics.

Adult↗

Emergency phenytoin loading by constant intravenous infusion.

We evaluated the efficacy of constant intravenous (IV) phenytoin infusion. Thirty-eight patients were evaluated prospectively for complications of continuous-infusion phenytoin loading. A total dose of 18 mg/kg was administered as a solution of 500 mg phenytoin in 50 mL normal saline using a constant infusion pump. The initial delivery rate was 40 mg/min. Cardiac rhythm was monitored by telemetry, and rhythm strips and vital signs were obtained every 15 minutes during infusion. Therapeutic phenytoin blood levels (greater than 10 micrograms/mL) were achieved in 37 patients (97%). Infusion was discontinued in one patient because of IV site irritation shortly after initiation of the infusion. Phenytoin levels in the toxic range were seen immediately postinfusion in 22 patients and in the four-hour postinfusion samples of 16 patients. Thirteen of 18 levels drawn 12 to 24 hours after infusion were therapeutic. Phenytoin levels greater than 20 micrograms/mL were tolerated without significant change in rhythm, QRS interval, or QT interval. A small statistically significant (P less than .05) decrease in systolic and mean arterial pressure was noted during the infusion. Complications included burning at the IV infusion site in four patients; the discomfort was relieved in three cases by reducing the rate of infusion to 20 mg/min. Seizures occurred in two patients during the infusion, requiring the additional use of diazepam or phenobarbital. Administration of a loading phenytoin dose by constant IV infusion is an effective means for achieving therapeutic levels quickly.

Adolescent↗

Effects of cimetidine and indomethacin on the growth of dimethylhydrazine-induced or transplanted intestinal cancers in the rat.

The effects of cimetidine and indomethacin on the growth of dimethylhydrazine induced or transplanted intestinal tumours in the rat have been studied. Cimetidine is a histamine type 2 receptor antagonist and indomethacin is an inhibitor of prostaglandin synthesis. Two models of rat intestinal tumours were used: a colon carcinoma line transplantable in syngeneic animals and intestinal tumours induced by dimethylhydrazine treatment of Sprague-Dawley rats. Cimetidine and indomethacin were given in drinking water, alone or in combination. Cimetidine had no effect on the growth of transplanted colon cancer but significantly increased the incidence of chemically-induced tumours, with a tendency toward more invasive and metastatic tumours than in the control animals. Indomethacin did not significantly modify the incidence or other characteristics of the tumours in any of the models. This result is at variance with a protective effect of indomethacin on chemically-induced rat colon cancer previously reported by others.

1,2-Dimethylhydrazine↗