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Biomedical subjects

P Smith

Publications and source records attributed to P Smith.

At least 19 recordsLinked to original sources

Acute and long-term effects on myocardial ischemia of intermittent and continuous transdermal nitrate therapy in stable angina.

The aim of this study was to compare the efficacy and safety of continuous and intermittent transdermal nitrate therapy using ambulatory electrocardiographic (Holter) monitoring. Eighty-five patients with stable angina pectoris and positive exercise test results participated during their concomitant antiischemic medication in a randomized open trial lasting 12 weeks. After a 3-week run-in period with continuous therapy (10 mg/24 hours), patients were randomized to either continuous- or intermittent-therapy groups. In the intermittent-therapy group the patients removed their patch at night (the mean patch-off period was 10 hours). Forty-eight-hour Holter monitoring was performed in each patient after randomization, and again after 2 and 12 weeks. Eighteen patients withdrew, 9 in each group. A total of 11,194 hours of electrocardiography were recorded and 607 ischemic episodes were detected, of which 79% were asymptomatic and 95% appeared during daytime. The number of ischemic episodes per 48 hours with intermittent therapy was 3.1 +/- 0.7 (mean +/- SEM) after randomization, 1.8 +/- 0.4 at 2 weeks and 2.0 +/- 0.6 at 12 weeks. With continuous therapy the respective numbers were 3.8 +/- 1.1, 3.5 +/- 0.9 and 4.2 +/- 1.2. The differences were not statistically significant because a large number of patients (30%) had no ischemic episodes on Holter recording. However, when examining 47 patients with episodes during the study, the number of episodes was significantly reduced in the intermittent-therapy group (p less than 0.05 at 12 weeks). The changes in asymptomatic and symptomatic episodes were concordant. No changes and differences between the treatment groups were seen in nighttime episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous

Effects of long-term treatment with warfarin on fibrinogen, FPA, TAT, and D-dimer in patients with coronary artery disease.

Sixty-four patients undergoing aorto-coronary bypass surgery were randomized to receive antithrombotic treatment with acetylsalicylic acid (ASA), 300 mg/d (n = 30) or warfarin, INR = 2.5 - 4.2 (n = 34). The levels of fibrinogen, thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA) and D-dimer were assessed before surgery and 9 months postoperatively. In the warfarin treated group the fibrinogen levels were increased after 9 months, while the levels of TAT, FPA and D-dimer were decreased. In the ASA group TAT levels were increased at 9 months, whereas no significant changes in fibrinogen, FPA or D-dimer from baseline were noted. Thus, a reduced activation of the coagulation system has been demonstrated during long-term treatment with warfarin in patients with coronary artery disease.

Adult

Antiphospholipid antibodies after myocardial infarction and their relation to mortality, reinfarction, and non-haemorrhagic stroke.

Antiphospholipid antibodies have been suggested as markers for a high risk of recurrent cardiovascular events in young survivors of an acute myocardial infarction. However, there are few data to confirm or refute this hypothesis. In a cohort study, we have measured anticephalin (aCEPHA) and anticardiolipin (aCL) antibodies in a group of patients surviving an acute infarct. Of 597 patients studied, 13.2% were IgG or IgM aCEPHA positive compared with 4.4% of a reference population (n = 158; p = 0.002). In a multivariate analysis, adjusted for major cardiovascular risk factors, neither aCEPHA (IgG or IgM) nor a CL (IgG or IgM) was an independent risk factor for mortality, reinfarction, or non-haemorrhagic stroke. Although an increased proportion of survivors of a myocardial infarction have antiphospholipid antibodies, the presence of such antibodies is not a risk factor for subsequent coronary or cerebrovascular thrombosis.

Adult

Mitotic instability of integrated plasmids in Penicillium chrysogenum transformants.

Transformation vectors based on the Streptoalloteichus hindustanus phleomycin-resistance gene placed under the control of either the Penicillium chrysogenum trpC or pcbC promoters were constructed (plasmids pGS1 and pGS7 respectively). Up to 100 transformants per microgram of DNA were obtained with pGS7 in P. chrysogenum strain P2. In order to follow the expression of additional penicillin biosynthetic genes introduced by transformation, a pcbC::lacZ gene fusion was introduced into pGS1, generating pGS6. Southern analysis of three pGS6 transformants indicated that the plasmid was integrated in tandem arrays. Revertants which had lost the exogenous beta-galactosidase activity, were detected for each transformant after several cycles of subculture on non-selective medium. Southern analysis indicated that the different phenotypes obtained resulted from the loss of part or all of the integrated plasmid copies.

Blotting, Southern

Long-term anticoagulant treatment after acute myocardial infarction. The Warfarin Re-Infarction Study.

High levels of fibrinogen and clotting factor VII are associated with an increased risk for subsequent death and cardiovascular disease in apparently healthy individuals. Furthermore, pathoanatomic studies and coronary angiography have confirmed a relationship between coronary thrombus formation and acute Q-wave infarction. Effective antithrombotic agents may prevent or limit thrombus formation and events related to thrombosis. The Warfarin Re-Infarction Study (WARIS) studied the effect of warfarin in survivors of acute myocardial infarction. Patients aged 75 years or less were randomized in a double-blind, placebo-controlled study to test whether long-term treatment with warfarin reduces the risk of death, reinfarction, and thromboembolic morbidity. A total of 1918 patients were screened for participation; 1214 were recruited. The mean follow-up was 37 months. Analyzed on an intention-to-treat basis, 123 (20%) in the placebo group died, versus 94 (15%) in the warfarin group, a risk reduction of 24% (P = 0.026). Considering patients on treatment or within 28 days after discontinuing the test medication, 92 in the placebo group died, as compared with 60 of the warfarin-treated patients, a risk reduction of 35% (P = 0.005). Relapsing myocardial infarction (fatal and nonfatal) was reduced by 43% (P = 0.0001). The incidence of cerebrovascular attacks was lower in the warfarin group (16 patients) than the placebo group (41 patients), a highly significant reduction of 61% (P = 0.0003). Serious bleeding occurred in 11 patients taking warfarin, an incidence of 0.6% per year. In conclusion, long-term anticoagulant therapy may be recommended after acute myocardial infarction.

Aged

Expression of the ERBB3 gene product in breast cancer.

Abnormalities of the EGF receptor and/or the related ERBB2 receptor occur in a significant proportion of cases of human breast cancer and are important influences in the behaviour of this tumour type. In this report we demonstrate by nucleic acid analysis and immunohistochemistry that the recently recognised third member of this gene family, ERBB3, shows a wide range of expression in breast cancer, and shows stronger immunoreactivity than that observed in normal tissue in 43 out of 195 cases (22%) of primary breast cancer. Overexpression of ERBB3 appears to result from increased levels of gene transcription since in none of the cell lines or primary cancers analysed did we find evidence of gene amplification. High expression of ERBB3 is positively associated with the presence of lymph node metastases, but there was no demonstrable relationship with patient survival in this series.

Blotting, Southern

The ability to 4-hydroxylate debrisoquine is related to recurrence of bladder cancer.

Oxidative metabolism by cytochrome P450 enzymes is often involved in the activation of environmental procarcinogens. Debrisoquine, mephenytoin, and dapsone were used as in vivo probes for the activities of P4502D6, 2CMP, and 3A4, respectively, as well as dapsone for N-acetyltransferase, in order to assess the relationship between such activities and the relative risk of recurrence of bladder cancer. Urinary recovery ratios of debrisoquine and dapsone and the R/S ratio of mephenytoin were measured in an 0-8 h urine sample after simultaneous administration of debrisoquine (10 mg) and racemic mephenytoin (100 mg), and the administration of dapsone (100 mg) one week later, to patients undergoing local surgical resection of transitional cell bladder cancer of G-I, G-II, or G-III histopathology. In addition, plasma levels of dapsone and mono-acetyldapsone were determined in an 8 h plasma sample to determine the N-acetylation phenotype. Patients were followed for 3 years, to the time of tumour recurrence, or death. Three patients were lost to follow-up; of the remaining 95 patients, 55 had tumour recurrence. The debrisoquine recovery ratio was significantly greater in patients with recurrence than in individuals who remained disease-free. Among the 65 patients with non-aggressive (G-I and G-II) histopathology, two patients were lost to follow-up and 32 had tumour recurrence. In this subgroup, the debrisoquine recovery ratio was again found to be significantly greater in those individuals with tumour recurrence (p < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Dual chamber rate responsive pacing to allow sotalol therapy for ventricular tachycardia.

In order to allow the use of sotalol to control ventricular tachycardia (VT), dual chamber rate responsive (DDDR) pacemakers were implanted in ten patients aged 6 to 73 years (mean 50 years). Nine presented with monomorphic VT (seven inducible at baseline electrophysiological study [EPS]) and one with syncope (monomorphic VT at EPS). On sotalol, VT was initiated in only one. This patient received sotalol in the absence of an effective alternative agent. The mean dose was 468 +/- 269 mg/day. Indications for pacing were symptomatic sotalol induced bradycardia (7), sinus node dysfunction (1), postoperative complete heart block (1), and infra-His block at baseline EPS (1). At least five of these patients would have been candidates for an implantable cardioverter defibrillator had sotalol required discontinuation. Initially, nine patients were paced in DDDR mode and one, with normal AV conduction on sotalol, in AAIR. One patient was unable to tolerate sotalol despite pacing. One patient died suddenly after 35 months of symptom-free follow-up. There was a significant improvement in symptomatic status (P = 0.03) after pacing among the other eight patients with no recurrence of VT. The implantation of a DDDR pacemaker may be indicated in selected patients with serious cardiac arrhythmias. With such a device programmed to an appropriate mode, sotalol can be used successfully where otherwise contraindicated by bradycardia or preexisting conduction disease. For some patients this may obviate the expense, inconvenience, and attendant risks of implantable cardioverter defibrillator implantation.

Bradycardia

Recurrent respiratory obstruction from a mediastinal bronchogenic cyst.

A large mediastinal bronchogenic cyst presented acutely with paroxysmal atrial fibrillation and severe airflow obstruction. The patient had experienced identical symptoms on two other occasions over the previous 24 years. These had been previously misdiagnosed as due to a mediastinal lymphoma. Percutaneous extrapleural aspiration successfully decompressed the cyst with substantial improvement in lung function. Recurrent swelling of the cyst occurred that could not be relieved surgically. After repeat aspiration percutaneous instillation of bleomycin and alcohol has been used to prevent further increase in the size of the cyst.

Adult

Implementing nurse case management in a community hospital.

A nursing case management system was implemented on the medical-surgical unit of an 86-bed community hospital using a four-phase process. The development and implementation processes are described. Program evaluation indicated that the application of the model resulted in benefits for patients, care providers, and the institution.

Hospitals, Community

Nodules resembling arachnoid villi in pulmonary venules in plexogenic pulmonary arteriopathy.

We have found nodules histologically resembling arachnoid villi adjacent to pulmonary venules in a woman of 30 years with primary pulmonary hypertension. Such lesions have been reported previously in cases of mitral stenosis and pulmonary thromboembolism and we believe them to absorb excess water from the interstitial tissues of the alveolar walls, thus protecting the lung from the development of edema. In this way they seem to have a similar function to that of cerebral arachnoid villi and granulations which transport cerebrospinal fluid into the dural sinuses.

Adult

Structural and antigenic studies of an idiotype-bearing murine antibody to the arsonate hapten.

Mice of strain A/J responded to repeated intraperitoneal injection of Limulus hemocyanin derivatized with arsanilic acid by producing large quantities (approximately 5 mg/mL of ascites fluid) of IgG antibodies specific for this hapten. The antibodies possessed a characteristic idiotypic determinant and exhibited restricted heterogeneity as demonstrated by isoelectric focusing and primary N-terminal amino acid sequence analysis of isolated light and heavy polypeptide chains. Both light- and heavy-chain sequences were comparable to those of myeloma proteins in lack of heterogeneity. The N terminus of the light chain exhibited V KI sequence and only one position in the first 30 residues showed more than one amino acid. No variability was observed in the first 10 N-terminal residues of the heavy chain. Rabbit antiserum to the idiotype blocked binding of hapten by the purified antibody. The presence of both light- and heavy-chain antigenic determinants was required for optimal formation of the idiotypic determinant.

Amino Acid Sequence

Electron microscopy of the plexiform lesion.

Pulmonary arteries from a case of plexogenic pulmonary arteriopathy were studied with the electron microscope. Many muscular pulmonary arteries showed intimal fibrosis of concentric or "onion-skin" type. The cells embedded within this fibrosis resembled smooth muscle but since they also possessed some features of fibroblasts we refer to them as myofibroblasts. Myofibroblasts also occurred in plexiform lesions together with fibroblasts and "fibrillary cells". These fibrillary cells contained numerous, prominent filaments with a random orientation. They lined the vascular channels of the plexiform lesions as well as being present within the stroma. They appeared to phagocytose fibrin and then to organise the plexiform lesion into a fibrous scar. Fibrillary cells closely resemble vasoformative reserve cells and the cells of the cardiac myxoma and so-called "papillary tumour" of heart valves. They may, therefore, be primitive multipotential cells found throughout the entire cardiovascular system.

Adult