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Biomedical subjects

M Hawkins

Publications and source records attributed to M Hawkins.

At least 109 records · Page 6Linked to original sources
PubMed1987

Inhibition of protein cross-linking in Ca2+-enriched human erythrocytes and activated platelets.

Treatment of human erythrocytes with Ca2+, in the presence of ionophore A23187, causes the formation of high molecular weight (greater than 10(6)) membrane protein polymers. This phenomenon, known to involve cross-linking of essentially all of the band 4.1 and 2.1 (ankyrin) proteins, as well as some spectrin, band 3, and hemoglobin molecules, could be prevented by preincubating the cells with a noncompetitive inhibitor of intrinsic transglutaminase, 2-[3-(diallylamino)propionyl]benzothiophene, at concentrations of about (3-6) X 10(-4) M. The compound also eliminated the proteolytic breakdown of the two major transmembrane proteins band 3 and glycophorin, which would otherwise occur during the Ca2+ loading of fresh human red cells. In addition, the inhibitor effectively blocked the formation of a cross-linked protein polymer in thrombin-activated human platelets.

Blood Platelets↗
PubMed1986

Platelet behaviour in non-insulin-dependent diabetes--influence of vascular complications, treatment and metabolic control.

Platelet-rich plasma was prepared from 47 patients with non-insulin-dependent diabetes treated with glibenclamide and metformin, and 21 controls. The release of radio-labelled 5-hydroxytryptamine in response to aggregating agents (adenosine diphosphate, adrenaline and sodium arachidonate), and the effects on release of a selective thromboxane inhibitor (UK-34787) were investigated. Subsequently, 20 of the diabetic subjects were chosen at random for treatment with insulin; the remainder continued to take tablets. Platelet studies were then repeated, in all patients, after 4 and 6 months. The results showed an association between platelet behaviour and the presence of vascular complications, and were consistent with previous observations of reduced platelet reactivity in patients taking sulphonylureas. There was no correlation of platelet reactivity with blood glucose, glycosylated haemoglobin or lipid levels.

Adenosine Diphosphate↗
PubMed1986

Inhibition of platelet aggregation in whole blood by dipyridamole and aspirin.

We have examined the effects of dipyridamole on platelet aggregation in whole blood both in vitro and after administration to man. The effects of dipyridamole ex vivo were compared with those of aspirin and a combination of dipyridamole and aspirin. In vitro dipyridamole was most effective as an inhibitor of platelet aggregation induced by platelet activating factor (PAF) and low concentrations of arachidonic acid (AA). Its inhibitory effect was always potentiated by adenosine suggesting that its effect on aggregation may be via inhibition of adenosine uptake into blood cells. Ex vivo, dipyridamole, aspirin and the combination of these drugs inhibited the platelet aggregation induced by PAF and AA. Again, adenosine increased the degree of inhibition. These results stress the importance of measuring platelet aggregation in the natural whole blood environment for detection of the inhibitory effects of dipyridamole and suggest a mode of action for the drug.

Aspirin↗
PubMed1986

Alcoholism treatment outcomes among career soldiers.

An 18-month follow-up study was performed on 210 career soldiers treated for alcoholism. The goal of the investigation was to determine treatment effectiveness and predictors of success. Success rates were 63% or 77% dependent on the utilization of either clinical or occupational criteria. Findings indicated that lower-ranking soldiers were more likely to be treatment failures. Other findings are also discussed.

Adult↗
PubMed1986

Treatment of multiple myeloma with recombinant alpha-interferon.

Thirty-two patients with multiple myeloma were treated with recombinant alpha-interferon clone A (rIFN alpha A) daily by intramuscular injection with an initial dose of 12 X 10(6) U/m2. Of 27 patients evaluable for response, tumor responses were obtained in seven of 14 previously untreated patients (50%) and two of 13 who had relapsed or failed prior chemotherapy (15%). In all patients who had tumor response, there was restoration from subnormal levels of serum immunoglobulins, an effect infrequently observed with chemotherapy. The median duration of tumor responses exceeded 14 months (range, 6 to 20). Moderate-to-severe fatigue was the predominant side effect and necessitated dose reductions in all patients. We conclude that treatment of early stages of multiple myeloma with rIFN alpha A is beneficial because of the substantial response rate and the improvement in the synthesis of serum immunoglobulins. rIFN alpha A has a potential role in combination with other agents in the treatment of multiple myeloma.

Female↗
PubMed1985

Effective dietary intervention in hypertensives: sodium restriction and weight reduction.

A Dietary Intervention Study of Hypertension (DISH) was undertaken to determine whether patients whose high blood pressure had been controlled pharmacologically for a period of more than 5 years could maintain that control with sodium restriction or weight reduction instead of drugs. Four hundred ninety-six patients, classified by degree of overweight, were randomly assigned into one of seven groups. Included were those who would be withdrawn from antihypertensive medication and receive intervention for either sodium restriction or weight reduction. After 8 weeks of intervention, an average reduction of 24-hour urinary sodium output from a baseline of 158 mEq to 106 mEq (p less than .001) and from 130 mEq to 96 mEq (p less than .01) was achieved for the overweight and nonoverweight groups, respectively. That decline was still maintained at 56 weeks. Dietary estimates, obtained by analysis of 3-day food records, underestimated urinary output by an average of 12%, with blacks more likely to underestimate than whites, and the overweight more likely to underestimate than the nonoverweight. An average 10-lb weight loss was achieved, with no difference between men and women. Weight declined for 32 weeks, then leveled off and was maintained up to 56 weeks, indicating that sodium intake modification can be accomplished faster than weight reduction. Modest sodium restriction and weight reduction are feasible and achievable in a free-living population and have a positive effect on control of hypertension.

Clinical Trials as Topic↗
PubMed1985

Phase I evaluation of a synthetic mutant of beta-interferon.

A synthetic mutant of beta-interferon, produced by recombinant DNA technology, was prepared with serine substituted for the naturally occurring cysteine at amino acid 17. This molecule, after purification to homogeneity, was evaluated in 23 patients with cancer for tolerated doses, safety, and pharmacokinetics. Each patient was begun on twice weekly administration, one dose i.m., then an identical dose i.v. Doses, escalated weekly, were tolerated by 9 of 12 patients at 100 X 10(6) units i.m., 11 of 14 patients at 100 X 10(6) units i.v., and 8 of 10 patients receiving i.v. doses of 200 X 10(6) units. Fever (greater than or equal to 38.9 degrees C), the commonest cause for ceasing dose escalation, occurred in 11 of 13 patients who developed limiting i.v. toxicity and 6 of 11 who developed limiting i.m. toxicity. Patients who did not have progressive cancer after completion of dose escalation received five consecutive daily doses at their maximum tolerated single dose by each route, i.m. and i.v. These two 5-day treatments were given without difficulty. All patients treated with 300 X 10(6) units or less, i.m. (n = 13) or i.v. (n = 10), were able to receive five daily doses without limiting toxicity. Peak serum titers occurred immediately after i.v. administration and declined in an exponential manner thereafter. Despite absence of measurable titers in serum after i.m. injection, fever and significant (P less than 0.05) depression of WBC and platelet counts, serum calcium, and serum cholesterol occurred (prestudy to maximum tolerated dose). An immunoglobulin antibody to beta-interferon, detected by enzyme-linked immunoabsorbent assay, developed in 17 of 23 patients. Neutralizing activity (titer 10(2] was found in only 1 of 23 patients. No immune-mediated sequelae (symptomatic or renal) were identified. Further Phase I and II trials with this molecule will determine whether it will prove to have a better therapeutic index or different spectrum of therapeutic activity from alpha-interferon or gamma-interferon.

Adult↗
PubMed1984

Collaborative phase I-II study of recombinant DNA-produced leukocyte interferon (clone A) in metastatic breast cancer, malignant lymphoma, and multiple myeloma.

Fifty-two patients with advanced cancer received sequentially escalating doses of 3 to 50 million units of recombinant DNA-produced alpha interferon by daily intramuscular injection. There were 23 patients with metastatic breast cancer, 17 patients with nodular poorly differentiated lymphocytic lymphoma, and 12 patients with multiple myeloma. Complete and partial remissions were obtained in 35 percent of patients with nodular poorly differentiated lymphoma, whereas rare activity was found in breast cancer and multiple myeloma. Dose-limiting toxicity occurred in patients receiving 36 million units or more and consisted of fatigue/asthenia, weight loss, and elevation of transaminase levels, requiring frequent interruption, reduction in dose, or cessation of treatment. Hematologic toxicity was rarely a limiting factor, but myelosuppression was severe in some patients with multiple myeloma. All toxicities were reversible on discontinuation of treatment. Antibodies to recombinant leukocyte A interferon were seen infrequently but may adversely affect therapy.

Adult↗
PubMed1984

Erythrocyte sodium content, sodium transport, ouabain binding capacity and Na+, K+-ATPase activity in lean and obese subjects.

Erythrocyte sodium content, sodium transport (ouabain-sensitive efflux rate of sodium, and ouabain-sensitive efflux rate constant of sodium) 3H ouabain binding capacity and sodium-potassium-activated ouabain-sensitive adenosine triphosphatase (Na+-K+-ATPase) activity were measured in 18 lean subjects and 25 obese subjects. The mean erythrocyte sodium content, sodium transport and ouabain binding capacity of obese subjects were the same as in lean subjects. There was no relationship between obesity index (wt/ht2) and sodium transport. We conclude that erythrocyte sodium transport in most obese patients is normal.

Adult↗
PubMed1984

Effects of methoxamine and alpha-adrenoceptor antagonists, prazosin and yohimbine, on the sleep-wake cycle of the rat.

A study was carried out on the effects of methoxamine, prazosin, and yohimbine on the sleep-wake cycle in rats prepared for chronic sleep recordings. Methoxamine (4-8 mg/kg), an alpha 1-adrenoceptor agonist, induced a dose-related increase in wakefulness (W) and a decrease in slow-wave sleep (SWS) and REM sleep (REMS). Prazosin (0.125-1 mg/kg), which selectively blocks alpha 1-adrenoceptors, modified only slightly the amount of time spent in W and SWS, and consistently decreased REMS values. Prazosin (0.5 mg/kg) reversed the effects of methoxamine, decreasing W and increasing sleep. Yohimbine (3 mg/kg), which blocks alpha 2-adrenoceptors, augmented W and diminished sleep. Methoxamine (4 mg/kg) in animals pretreated with yohimbine (3 mg/kg) induced a further decrease of SWS and REMS and an increase of W. Thus, pharmacological activation of alpha 1- or blocking of alpha 2-adrenoceptors appears to decrease sleep and increase W. Further, blocking of alpha 1-adrenoceptors decreases REMS. Rapid eye movement sleep depression by the alpha 1-agonist or the alpha 1-antagonist is tentatively ascribed to a critical change in noradrenergic transmission in the brain.

Animals↗
PubMed1984

Retrograde nephrostomy for stone removal: combined cystoscopic/percutaneous technique.

The retrograde percutaneous nephrostomy, a new technique for access to the urinary tract for stone removal, involves cystoscopic placement of a 9 French catheter into a selected minor calix, through which a sheathed 20- or 21-gauge needle is then advanced to exit at the skin. The tract is then dilated over this needle. This technique has been used successfully in 38 patients with only three complications. The technique is more reliable and less time-consuming than the standard antegrade percutaneous approach, particularly in the nondilated pelvicaliceal system. However, to avoid damage to the liver, spleen, or pleural cavity, care must be taken to ensure that the needle does not exit in a cranial direction.

Cystoscopy↗
PubMed1983

Degradation of transmembrane proteins in Ca2+-enriched human erythrocytes. An immunochemical study.

Apart from causing the formation of gamma-glutamyl-epsilon-lysine cross-linked polymers, exposure of human erythrocytes to Ca2+ and ionophore A23187 leads to a breakdown of the two major transmembrane proteins, i.e. the anion-transporting band 3 and glycophorin. This apparently proteolytic phenomenon was examined by crossed immunoelectrophoretic techniques. The main product of the cleavage of band 3 had a chain weight of about 55,000 and showed good precipitation with the antibody raised against the intact protein. The degradation of glycophorin was more rapid and, when complete, gave rise to small fragments which were barely precipitated with antiglycophorin antibody. Incubation of the cells with pepstatin or N-ethylmaleimide prior to and during Ca2+ loading prevented the breakdown of both transmembrane proteins. Histamine, a competitive inhibitor of the transglutaminase-catalyzed formation of gamma-glutamyl-epsilon-lysine cross-links in Ca2+-enriched erythrocytes, also provided some protection, suggesting that the breakdown of the two transmembrane proteins might in some manner be related to the transglutaminase-dependent polymerization process. Pathophysiological implications of the proteolytic event, which would distort the normal interaction of membrane proteins with the cytoskeleton, are discussed.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1983

Changes in erythrocyte sodium, sodium transport and 3H ouabain binding capacity during digoxin administration in the pig.

Time course of the changes in erythrocyte sodium content, sodium transport, 3H ouabain binding capacity and Na+, K+-ATPase activity were measured for 14 weeks, in 6 young pigs treated with digoxin and in 6 control pigs. After one week of treatment the erythrocyte sodium content increased from 5.4 mmol/kg cells to 6.9 mmol/kg cells and the efflux rate constant of sodium decreased. With prolonged treatment the erythrocyte sodium content returned to normal and the 3H ouabain binding capacity increased by week 5. The plasma digoxin concentration decreased from 1.1 ng/ml at week 5 to 0.6 ng/ml at week 8 probably due to the decline in dose (microgram/kg) of digoxin with age. The efflux rate constant of sodium and Na+, K+-ATPase activity were higher towards the end of treatment. It is concluded that with prolonged administration of digoxin there is an increase in erythrocyte sodium pump units.

Animals↗
PubMed1983

Hospitalization length of insanity acquittees.

Used step-wise multiple regression procedures to predict length of hospitalization of 225 defendants acquitted by reason of insanity in New York state. Of the 21 variables considered, only 9 (severity of offense, sex, marital status, days prior imprisonment, homicide offense, days previous civil hospitalization, educational level, race, number of victims) contributed to the significance of the regression equation. However, these accounted for but 11% of the observed variance.

Adolescent↗
PubMed1983

Characteristics of sodium transport in pig (Sus scrofa) erythrocytes.

Sodium content, sodium transport (ouabain-sensitive efflux rate of sodium, oMosNa; and ouabain-sensitive efflux rate constant of sodium, oKosNa), [3H]ouabain binding capacity, and Na+, K+-ATPase activity were measured in erythrocytes from young pigs (Sus scrofa). The sodium content, sodium transport, and the number of sodium pumps (assessed by ouabain binding capacity) were lower in the pig compared to the human erythrocytes. The efflux rate constant of sodium, oKosNa was 36% and the ouabain binding capacity was 60% of those in human, suggesting the degree of activation of sodium pump units is much lower.

Animals↗