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Biomedical subjects

M Parker

Publications and source records attributed to M Parker.

At least 199 records · Page 11Linked to original sources

The effect of clonidine on the cessation of cigarette smoking.

The effect of clonidine on smoking cessation was studied by randomly assigning 186 smokers in a double-blind fashion to either placebo or clonidine. Abstinence from smoking was reported more frequently by subjects receiving clonidine, but the difference was statistically significant only at the end of the first week (34.4% vs 21.5%; p less than 0.05). Bothersome side effects were common and resulted in the early discontinuation of the study medication by 23 of the subjects taking clonidine and eight taking placebo (p less than 0.05). Although this study did not demonstrate a significant effect of clonidine on smoking cessation, a beneficial trend was detected and therefore further trials with transcutaneous delivery of this agent in combination with behavior modification techniques are warranted.

Adult↗

Intestinal obstruction in patients with gynaecological malignancies.

Bowel obstruction developing in patients with gynaecological malignancies may present as a therapeutic dilemma. The causes, and results of surgical and conservative management of 92 patients are analysed. The causes of obstruction in the 64 patients who were treated surgically were: tumour recurrence in 42, adhesions in 12, radiation stricture in 9 and pelvic abscess in 1. Surgical palliation was effective in 45 patients in this group, with another 12 patients being palliated initially but subsequently developing further obstructive symptoms. Surgical palliation was ineffective in 7. Conservative management was effective only in 12 of the 41 patients, and even in this group 8 developed further obstructive episodes within the first month of discharge. The median survival in the surgically treated group for benign and malignant causes is 57 and 10 weeks respectively; while it is 4 weeks for those treated conservatively.

Female↗

Role of heparin after intravenous thrombolytic therapy for acute myocardial infarction.

The optimal approach to management of patients after thrombolytic therapy for acute myocardial infarction (AMI) is unclear. The role of anticoagulation with heparin was evaluated in 75 consecutive patients who received intravenous streptokinase for AMI. Heparin therapy was titrated to keep the partial thromboplastin time (PTT) between 90 and 120 seconds. Seventeen episodes of definite myocardial ischemia (associated with reversible electrocardiographic changes) were observed in 13 patients. When episodes of probable myocardial ischemia are included (typical chest pain relieved by nitroglycerin or associated with more than a 15-mm Hg change in blood pressure but without electrocardiographic changes), 52 episodes occurred in 28 patients. Four episodes of definite and 4 of probable myocardial ischemia occurred within 24 hours of discontinuation of heparin. Analysis of the level of anticoagulation as assessed by PTT at the time of the ischemic events shows that ischemia occurred more often at lower PTTs. Nine hemorrhagic complications occurred, all within 24 hours of streptokinase infusion. In 4 patients bleeding was believed to be major and heparin administration was discontinued; 2 patients with gastrointestinal bleeding required blood transfusions. Our data suggest that after thrombolytic therapy for AMI, the level of anticoagulation is inversely related to the frequency of recurrent ischemic events; that discontinuation of heparin is frequently associated with ischemia; and that administration of heparin is associated with a low incidence of hemorrhagic complications.

Female↗

Cloning of partial cDNA encoding differentiation and tumor-associated mucin glycoproteins expressed by human mammary epithelium.

Human mammary epithelial cells secrete and express on their cell surfaces complex mucin glycoproteins (Mr greater than 250,000) that are developmentally regulated, tumor-associated, and highly immunogenic. Studies using monoclonal antibodies directed to these glycoproteins suggest that their molecular structures can vary with differentiation stages in the normal gland and in malignancy. To analyze the molecular nature of these glycoproteins, milk mucin was affinity-purified and deglycosylated with hydrogen fluoride, yielding bands at 68 and 72 kDa on silver-stained gels. Polyclonal and monoclonal antibodies to the stripped core protein were developed and used to screen a lambda gt11 expression library of cDNA made from mRNA of the mammary tumor cell line MCF-7. Seven cross-reacting clones were isolated, with inserts 0.1-1.8 kilobases long. RNA blot analysis, using as a probe the 1.8-kilobase insert subcloned in plasmid pUC8 (pMUC10), revealed transcripts of 4.7 and 6.4 kilobases in MCF-7 and T47D mammary tumor cells, whereas normal mammary epithelial cells from pooled milks have additional transcripts. The expression of mRNA correlates with antigen expression as determined by binding of two previously characterized anti-mucin monoclonal antibodies (HMFG-1 and HMFG-2) to seven cell lines. Restriction enzyme analysis detected a restriction fragment length polymorphism when human genomic DNA was digested with EcoRI or HinfI.

Antibodies, Monoclonal↗

The bone pencil and the bone surgeon.

While helpful for preoperative skin markings, methylene blue is washed away by irrigation and tissue fluids during bony reconstruction. The bone pencil is an ideal marker for hard tissue because it is indelible to irrigation. Further, the surgeon may draw with ease in areas of limited access (i.e., sagittal split and intraoral vertical ramus osteotomies). The pencil can be obtained from most art suppliers. No adverse effects from use of the pencil have been noted in any of our patients.

Bone and Bones↗

Structural organization and expression of the mouse estrogen receptor.

Complementary DNA clones corresponding to the mouse uterus estrogen receptor mRNA have been isolated and characterized. Nucleotide sequence analysis predicts that full-length cDNA has the potential to code for a polypeptide of 599 amino acids, and comparison with the protein sequences of the rat, human, and chicken estrogen receptors reveals overall homologies of 97%, 88% and 77%, respectively. Genomic clones for the mouse estrogen receptor have been isolated from a cosmid library and used in conjunction with the cDNA clones to study the expression of the receptor in vivo by RNase mapping, primer extension, and Northern blotting. These analyses demonstrate that transcription initiates at multiple sites which span a region of at least 62 base pairs and that the estrogen receptor is encoded by mRNA of approximately 6.5 kilobases in size. There are 10 major starts in total, one of which is situated 31 nucleotides downstream from a TATA box-like motif and coincides with the start of the cDNA clone pMOR8. The ability of the cDNA clone to produce a functional protein was verified by transfection into COS-1 cells which lack endogenous estrogen receptor. The mouse estrogen receptor, in a SV40-based expression vector, was cotransfected with a chimeric marker plasmid consisting of an estrogen response element from the vitellogenin A2 gene linked to the thymidine kinase promoter and the chloramphenicol acetyl transferase gene. In the presence of estradiol chloramphenicol acetyl transferase activity is stimulated by up to 80-fold, while tamoxifen and 4-hydroxytamoxifen act primarily as antiestrogens in this in vitro assay.

Amino Acid Sequence↗

Chronic clonidine treatment and its withdrawal: effects on blood pressure and catecholamine synthesizing enzymes in brain-stem nuclei.

We have studied the effects of withdrawal from chronic clonidine treatment in the adult male spontaneously hypertensive rat (SHR). SHR received clonidine, 0.1 mg X kg-1 X day-1 i.v. for 10 days. Clonidine was delivered via osmotic minipumps. After 7 days of treatment there was a 16.5 +/- 2.5 mm Hg fall in mean arterial pressure. This was accompanied by a decrease in the dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase activities of the A1/C1 region. Withdrawal from clonidine was characterized by tachycardia and an increase in mean arterial pressure and heart rate lability. Phenylethanolamine-N-methyl transferase of the the dopamine-beta-hydroxylase activity remained diminished. The dopamine-beta-hydroxylase activity of the A2/C2 region was also diminished during withdrawal. We suggest that the blood pressure lowering effect of clonidine is accompanied by a decreased capacity to synthesize adrenaline in the A1/C1 region where adrenaline could mediate a pressor effect. Increased blood pressure lability during withdrawal is accompanied by a restoration of synthesis of adrenaline in the A1/C1 region. There is also a decrease in the capacity of synthesis of noradrenaline in the A2/C2 region where adrenaline may mediate a vasodepressor effect.

Adrenal Medulla↗

Frequency of pericardial effusion as determined by M-mode echocardiography in acute myocardial infarction.

A pericardial friction rub occurs in 6 to 16% of patients after acute myocardial infarction (AMI), but the incidence of pericardial effusion (PE) is not known. M-mode echocardiography was done 1, 3 and 5 days after AMI in 43 consecutive patients admitted within 24 hours of AMI, and PE was detected in 16 (37%). The PE was small in 7 patients, moderate in 6 and large in 3. A pericardial friction rub developed in 8 (19%), of whom only 4 had PE. Pleuritic chest pain diminished by sitting up and relieved by antiinflammatory agents developed in 12 (28%), of whom only 5 had PE. The peak creatine kinase level was significantly higher in patients with PE (1,769 +/- 1,003 U) than in those without (1,181 +/- 838 units). More patients with PE were in Killip classification II, III or IV (11 of 16 [69%] vs 9 of 27 [33%]). The presence of PE was not associated with age, site of AMI, development of Q waves, use of heparin or previous AMI. In conclusion, PE as detected by M-mode echocardiography is frequently present after AMI, and its presence is not closely associated with the occurrence of a pericardial friction rub or typical pericardial pain.

Aged↗

Association of methemoglobinemia and intravenous nitroglycerin administration.

Significant elevation of arterial methemoglobin levels has been reported with the administration of intravenous (i.v.) nitroglycerin (NTG). To determine the incidence and clinical significance of this side effect of i.v. NTG, serial arterial methemoglobin levels were determined in 50 consecutive patients receiving i.v. NTG for 48 hours or longer. The mean i.v. NTG infusion rate was 290 +/- 13 micrograms/min (4.1 +/- 0.2 micrograms/kg/min) and the mean duration of infusion was 7.1 +/- 0.5 days. The mean methemoglobin level for the 141 samples was 1.57 +/- 0.08%, which differs from the control mean value in our laboratory of 0.44 +/- 0.01%. Although no patient had clinical symptoms from methemoglobin, 20 patients had elevated (greater than 1%) levels on at least 1 measurement. Seventy-eight of the 141 samples analyzed were in the normal range; 63 determinations were between 2 and 5%. Patients with normal methemoglobin levels differed from those with abnormal levels in the dose of i.v. NTG (mean infusion rate 244 +/- 16 vs 351 +/- 17 micrograms/min; total cumulative dose 1,612 +/- 153 vs 3,398 +/- 308 mg). Age, weight, renal and hepatic function, and arterial oxygen saturation were not different between the groups. In conclusion, clinically significant methemoglobinemia is uncommon with i.v. NTG infusion; however, when large doses of NTG are administered, this complication is more likely.

Aged↗

Prophylaxis of supraventricular tachyarrhythmia after coronary bypass surgery with oral verapamil: a randomized, double-blind trial.

This study investigated the efficacy of oral administration of verapamil, started 24 hours after coronary artery bypass grafting (CABG), in reducing the incidence of postoperative supraventricular tachyarrhythmia (SVT). Two hundred patients were randomly assigned in a double-blind fashion to receive a one-week course of either a placebo or 80 mg of verapamil every 6 hours. Overall, SVT developed in 23 control and 14 verapamil-treated patients, a 39% reduction in incidence (p less than 0.10). Of the patients who received at least four doses and continued to receive the study drug, 17 in the control and 7 in the verapamil group experienced SVT, a 53% decrease in incidence (p less than 0.06). Atrial fibrillation constituted 34 of the 37 SVT episodes and was associated with a slower ventricular response in the group given verapamil (115 +/- 8 versus 156 +/- 4 beats per minute; p less than 0.001). No evidence was found linking postoperative SVT with the withdrawal of beta-blocking drugs. Adverse effects required that 20 patients in the verapamil and 6 in the placebo group be removed from the study. Hypotension or pulmonary edema or both developed in 13 of the patients receiving verapamil, but in only 1 of the control patients (p less than 0.001). We conclude that although verapamil has potential merit for the prophylaxis of SVT after CABG, its use in this setting is associated with a high incidence of unacceptable hemodynamic side effects.

Administration, Oral↗