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Biomedical subjects

W Jacobs

Publications and source records attributed to W Jacobs.

At least 55 records · Page 3Linked to original sources

Immunoreactivity for p53 protein in malignant mesothelioma and non-neoplastic mesothelium.

The presence of p53 protein in non-neoplastic pleural mesothelium (40 cases) and in human malignant mesothelioma (36 cases) was assessed immunohistochemically using the antibodies DO7, CM-1, and PAb240. In a quarter of the malignant mesotheliomas, there was nuclear immunoreactivity for p53 protein with both the DO7 and CM-1 antibodies. There were no statistically significant differences between the various mesothelioma subtypes (P > 0.05). No immunoreactivity was found with the PAb240 antibody, suggesting absence of mutant-type p53 protein. Nonneoplastic mesothelium was not immunoreactive with any of the antibodies. We conclude that there is immunoreactivity for p53 protein in some mesotheliomas. p53 protein immunoreactivity could be used to discriminate between neoplastic and reactive mesothelium.

Epithelium↗

[Lingual nerve injury during extraction of lower wisdom teeth].

A lingual nerve injury is an infrequent but unpleasant complication of the removal of lower third molars. The nerve stays at risk even with a correct technique. The classifications of nerve injuries of Seddon and Sunderland give insight in the complexity and give guidelines for prognosis and treatment. Degeneration and regeneration as in other peripheral nerves occur also here and knowledge of these phenomena is crucial for the success of the microsurgical repair. Confronted with the problem, an attempt to a correct evaluation of the extent of the injury should be done, and transfer to a specialist is necessary when the dysesthesia is still persistent after more than 2 months.

Humans↗

Transformation of BCG with plasmid DNA.

Pasteur 1173P2 and Japanese 172 BCG substrains were transformed with plasmid pAL5000::plJ666 by electroporation and assessed by the growth of kanamycin-resistant colonies. From the transformants pYUP plasmids were isolated containing plJ666 inserted into pAL5000. The introduction, persistence and the identity of the plasmid were monitored by reisolation from consecutive subcultures and restriction analysis. The effect of variables--age, viability, glycine pretreatment of BCG cultures, electroporation parameters--on transformation frequencies were analyzed. Consecutive transformation of BCG with plasmid DNA isolated from a BCG transformant increased the efficiency from the level of 10(1)-10(2) obtained with the initial library to 10(3)-10(4) colonies/micrograms DNA with the pYUB plasmids. Maintenance of plasmid and expression of kanamycin resistance in continuous subcultures were stable for 100 generations from the first successful transformation to the present. The introduction and stable expression of foreign DNA in BCG on a plasmid vector establishes a basis for the construction of polyvalent recombinant BCG vaccine vehicles expressing not only putative protective mycobacterial antigens, but also antigens for other infectious and malignant diseases.

BCG Vaccine↗

Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure: influence of prerandomization variables on the reduction of mortality by treatment with hydralazine and isosorbide dinitrate.

The Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure was designed to determine whether vasodilator drugs could alter the survival of patients with chronic congestive heart failure treated with digoxin and diuretics. Among the 642 patients entered into the study, 273 were randomly assigned to placebo, 186 were randomly assigned to the combination of hydralazine and isosorbide dinitrate, and 183 patients were randomly assigned to prazosin; all patients were followed for periods ranging from 6 months to 5.7 years. Treatment with hydralazine-nitrate produced a 28% reduction in mortality compared with that in patients receiving placebo (95% confidence interval, 3% to 46%), whereas prazosin exerted no apparent beneficial effect. Data were further examined to determine if any baseline variables had an impact on the response to treatment. Mortality in the placebo group was higher in those with coronary artery disease, with a history of antiarrhythmic drug use, and with values lower than the median for ejection fraction and exercise tolerance. A reduction in mortality with hydralazine-isosorbide dinitrate was observed in all of the above pairs of subgroups as well as in those above and below 60 years of age and those with and without a history of hypertension or excess alcohol ingestion. The benefit of hydralazine and isosorbide dinitrate was particularly prominent in younger patients with a lower ejection fraction and those with a history of hypertension and without an alcoholic history.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.

To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P less than 0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine--isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.

Clinical Trials as Topic↗

Multimodality approach to pericardial imaging.

In this chapter, three modalities--computed tomography, nuclear magnetic resonance imaging, and echocardiography--have been discussed. Each of these techniques offers unique advantages in the diagnosis of pericardial disease. Although echocardiography is the least expensive, most sensitive, and least invasive technique for the identification of pericardial effusion, false-positive and negative studies may be encountered. These are often resolved with the use of computed tomography and may be resolved with magnetic resonance imaging. Plain film radiography still has the advantage of identifying pericardial calcifications and will suggest the diagnosis of large pleural effusions at low cost and radiation dose. Exquisite portrayal of cross section anatomy using CT will aid in the diagnosis of multiple small tumor deposits and will clearly identify pericardial thickening. The value of magnetic resonance imaging awaits carefully controlled blinded studies, but its role in characterization of the content of pericardial effusions appears especially promising.

Cardiomyopathy, Restrictive↗

Beta-adrenoceptor blockade in stress due to oral surgery.

1 The effects of a single oral dose of 5 mg pindolol (P) and 100 mg metoprolol (M) were assessed in a double-blind study in 30 patients undergoing oral surgery. 2 Systolic and diastolic blood pressures and heart rate were reduced 90 min after oral medication and did not exceed initial values at rest during the procedure. 3 Noradrenaline, adrenaline and c-AMP concentrations did not differ at any time from the control values at rest after P, but were increased after local anaesthesia and during oral surgery after M as were the metabolic responses reflected by plasma concentrations of glucose and free-fatty acids. 4 Plasma levels of ACTH and cortisol showed the typical increase during the procedure, being independent of beta-adrenoceptor blockade. In contrast to the cardioselective antagonist M, prophylactic administration of the non-selective drug P prevented the sympathetic and metabolic responses to the stress of oral surgery. 5 Hypothalamic and adrenal stimulation were not reduced by either selective or non-selective beta-adrenoceptor blockade.

Adrenergic beta-Antagonists↗

Plasma luteinizing hormone in ovariectomized rats following pharmacologic manipulation of endogenous brain serotonin.

Ovariectomized rats were treated with pharmacologic agents to manipulate endogenous brain serotonin (5-HT). Neither the magnitude nor the timing of luteinizing hormone (LH) pulses in plasma were affected by drug-induced decreases in 5-HT. Acute increases in extraneuronal 5-HT resulting from fluoxetine administration to inhibit 5-HT uptake into neurons, decreased the magnitude of LH pulses, but did not affect the interval between successive LH pulses.

Animals↗

Echocardiographic practice in a large metropolitan area.

A survey performed concerning echocardiography in a metropolitan area. Of 110 hospitals in the area, 62 reported having echocardiographic facilities. Echocardiographic physicians and/or technicians from 41 of these hospitals responded to questionnaires designed to determine the following: (1) educational background and credentials of technicians, (2) average salaries of technicians, (3) role of the physician and technician in the performance and reporting of echocardiograms, (4) volume, cost, and method of storage of echocardiograms, and (5) number and type of echocardiographic units in use. Our data suggest various trends, including a lack of formal training among technicians, the prevalence of cardiologists-internists as directors of echocardiographic facilities, the performance of echocardiograms by cardiology fellows in only 46% of institutions with cardiology training programs, and the widespread projected availability of cross-sectional echocardiographic capability within the next two years.

Allied Health Personnel↗

Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. VIII. Expression and shedding of Fc gamma receptors on metastatic tumor cell variants.

The expression of receptors for the Fc portion of IgG immunoglobin molecules was studied on tumor cell lines with high and low metastatic capacity. Two tumor cell lines from DBA/2 mice that had high metastatic activity, ESb and MDAY-D2, contained a high percentage of Fc receptor positive cells, as detected in a rosette assay with IgG antibody-coated erythrocytes (EA). In contrast, the low metastatic parental line Eb, from which ESb was derived, contained only a low percentage of EA-rosette-forming cells. ESb ascites tumor cells adapted to tissue culture in the presence of 2-mercaptoethanol (2ME) had a high expression of Fc receptors, whereas a cell line adapted to tissue culture in the absence of 2ME had a low expression of Fc receptors. "Soluble" Fc receptors were detectable by their ability to bind to EA and to cause blocking of rosette formation. They were found to be present in fluids from tumor-bearing animals, such as serum and cell-free ascites. Even animals with an ascites tumor of the low-metastatic line Eb contained "soluble" Fc receptors. The results are discussed with regard to their possible significance for tumor metastasis.

Animals↗

Myopotential inhibition of demand pacemakers: etiologic, diagnostic, and therapeutic considerations.

Myopotential inhibition of demand pacemakers is a common phenomenon and is responsible for a greater degree of morbidity and possible mortality in patients with pacers. Significant electrical potentials generated by contracting muscle mass gain entry into the pacemaker circuitry causing inhibition of pacemaker activity. Intraoperative and bedside maneuvers can readily precipitate the problem and allow for accurate diagnosis. Holter monitoring frequently can also serve to establish the diagnosis. Pacemaker repositioning, replacement with a bipolar system, use of a fixed-rate pacemaker, and pacemaker "sleeves" are possible intraoperative therapeutic methods. External sensitivity adjustable pacemakers would seemingly allow for noninvasive solutions to the problem.

Action Potentials↗

On-line storage, retrieval, and evaluation of long-term electrocardiographic monitoring data.

A set of on-line computer programs has been designed and implemented for the acquisition and long-term storage, retrieval, and evaluation of Holter monitoring data. The physician interpreting Holter tapes enters his findings in the computer system using an on-line remote terminal located in the heart station. The programs are available practically around the clock and allow reviewing of individual cases, preparation of printed reports, and fast evaluation of the presence or absence of a number of common findings in the entire data base. Approximately 800 cases have been entered since the initiation of this project in early 1977.

Electrocardiography↗

Randomized sequential hormonal therapy vs adrenalectomy for metastatic breast carcinoma.

One hundred sixty-one postmenopausal and 65 premenopausal women, a total of 226 patients with metastatic breast carcinoma, were included in this randomized study to evaluate the merits of adrenalectomy as the primary mode of therapy as compared to the customary sequential hormonal manipulation. The 145 evaluable postmenopausal patients were randomized as follows: (1) primary additive hormone therapy first followed by adrenalectomy and (2) primary adrenalectomy followed by chemotherapy and/or additive hormone therapy. When 76 patients in group 1 were compared with 70 patients in group 2 regarding their survival time, there was no essential difference, but the response rate was 20% vs 38.6%, a significant difference. The 55 evaluable premenopausal women were randomized into two groups: (1) oophorectomy followed by adrenalectomy; (2) adrenalectomy-oophorectomy as primary mode of therapy. The response rate in group 1 was 17.4% as compared with 41.9% in group 2, but again there was no difference in the survival time among these two groups. When sequential hormonal manipulation was utilized, only one-third of these patients were subjected to adrenalectomy because of their rapidly deteriorating condition. Adrenalectomy performed as a secondary procedure showed a lower response rate but the total survival time was comparable with primary adrenalectomy patients.

Adrenalectomy↗

Stimulation of glucose release of the rat kidney in vivo by epinephrine and isoprenaline.

In anesthetized rats the glucose release of the kidneys was estimated from the glucose concentrations in the arterial and renal venous plasma, urinary glucose excretion and the total renal plasma flow. Net renal glucose release was found in control experiments. The glucose release of the kidneys decreased with rising arterial plasma glucose values. Epinephrine (220 mug/kg s.c.) and isoprenaline (10 mu/kg s.c.) enhanced arterial plasma glucose levels and increased mean renal glucose production significantly. The enhanced arterial plasma glucose levels and increased mean renal glucose production significantly. The enhanced glucose release after isoprenaline could be abolished by propranolol (1 mg/kg s.c.). The glycogen content of the kidney was found to be too small to account for the observed renal glucose release by glycogenolysis. Therefore, these in vivo data indicate enhanced renal gluconeogenesis after adrenergic stimulation. This effect is thought to be mediated by the beta-adrenergic receptors.

Animals↗