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Biomedical subjects

J Brennan

Publications and source records attributed to J Brennan.

At least 19 recordsLinked to original sources
PubMed1992

Gastrointestinal transit and systemic absorption of captopril from a pulsed-release formulation.

Captopril has been administered to eight healthy male subjects by means of a pulsatile delivery system that was designed to release the drug in the colonic region of the intestine. The gastrointestinal transit and pulsatile release were followed using gamma scintigraphy. A pulsatile capsule system with release after a nominal 5-hr period was found to perform reproducibly in vitro and in vivo. In six of the eight subjects, the drug was delivered to the colon, and in the remaining two subjects, to the terminal ileum. Measurable blood levels of free captopril were found in three subjects. Variable instability of the drug in the distal intestine is suggested as a possible reason for the lack of absorption of the drug in the majority of subjects.

Adult↗
PubMed1992

Radioimmunoassay for ceronapril, a new angiotensin-converting enzyme inhibitor, and its application to a pharmacokinetic study in healthy male volunteers.

Ceronapril is a member of a new chemical class of angiotensin-converting enzyme inhibitors being developed by The Bristol-Myers Squibb Pharmaceutical Research Institute. A radioimmunoassay (RIA) has been developed for the measurement of ceronapril in biological fluids. The RIA has a range of 0 to 500 ng/ml and has the sensitivity to detect 1.0 ng/ml of ceronapril. Satisfactory zero binding and sensitivity were obtained after a 2-h incubation at room temperature or overnight at 4 degrees C. Separation of the antibody-bound and free radiolabel was achieved by employing polyethylene glycol-goat anti-rabbit gamma-globulin separant. A quantitative recovery of the exogenous analyte was obtained at all concentrations of ceronapril tested. Intraassay coefficients of variance (CV's) were 3.9% and 4.6% for the low and medium controls, respectively. A highly significant statistical correlation between RIA and [14C]TLRC was observed for both plasma and urine samples. Clinical samples from the ascending dosage studies have been analyzed by the ceronapril RIA. The maximum concentration and the area under the plasma concentration-time curve did not increase in a dose-proportional manner for doses above 100 mg.

Adult↗
PubMed1992

Percutaneous transluminal coronary angioplasty in unstable and stable angina pectoris: a comparison of immediate success and complications.

To determine the success rate and the safety of percutaneous transluminal coronary angioplasty in patients with unstable angina pectoris (group 1) versus stable angina (group 2), we studied 299 consecutive patients who underwent coronary angioplasty of 373 consecutive lesions. Of these patients, 149 had unstable angina pectoris and dilation of 188 arteries. The success rate was high and similar in both groups (95 and 93%, respectively). The groups did not differ in regard to the lesion characteristics, vessels and number of sites dilated except for an increase in the presence of thrombus in the unstable angina group (p < 0.03). Although there was a higher incidence of coronary thrombus and more acute myocardial infarction in group 1, the major complication rate did not differ from that of group 2 and was low in both of them (3 and 2%, respectively). No deaths occurred. Six patients (3 in each group) needed urgent coronary artery bypass grafting while 3 additional patients developed acute Q-wave myocardial infarction (all of them in group 1). Thus, percutaneous transluminal coronary angioplasty is a safe and successful procedure in patients with unstable angina as well as in patients with stable angina pectoris.

Aged↗
PubMed1991

myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens.

We studied 107 specimens (38 tumors and 69 tumor cell lines) from 90 patients with small cell lung cancer to determine the characteristics and clinical situations of patients from whom tumor cell lines could be established and the myc family DNA copy number. The proportion of extensive stage small cell lung cancer patients from whom a tumor cell line could be established prior to the initiation of therapy increased during the 10 years of the study (P less than 0.001). Amplification of one of the myc family genes occurred in 3 of 40 (8%) of the untreated patient specimens compared to 19 of 67 (28%) of the treated patient specimens (P = 0.01). The myc family DNA amplification occurred in 17 of 54 (31%) of the specimens from patients treated with cyclophosphamide-based combinations and 2 of 13 (15%) of the specimens from patients treated with etoposide/cisplatin (P = 0.25). Both tumors and tumor cell lines were obtained from 17 patients with small cell lung cancer and the myc family DNA copy number was similar in 16 of the 17 patients. We conclude that: (a) myc family DNA amplification occurs more commonly in specimens from treated than untreated patients (b) there are no prominent differences in the frequency of amplification following treatment with different chemotherapy regimens; and (c) myc family DNA amplification is similar in tumors and tumor cell lines from the same patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Above-knee prosthetic grafts do not compromise the ipsilateral long saphenous vein.

Prosthetic graft materials are used preferentially by a number of surgeons for above-knee femoropopliteal bypasses. Using B-mode ultrasonography we have assessed the ipsilateral long saphenous vein in patients undergoing such bypasses to determine its suitability for future use in more distal bypasses. A total of 137 above-knee prosthetic grafts were performed over a 10-year period. Of the patients, 74 were available for further assessment. Overall, 97 per cent of veins were suitable for future bypass surgery if required. Above-knee prosthetic bypasses do not appear to jeopardize the ipsilateral long saphenous vein.

Arteriovenous Shunt, Surgical↗
PubMed1990

Infrainguinal bypass surgery: factors determining late graft patency.

The results of 373 infrainguinal bypass grafts, in a single centre, between 1980 and 1988 are reviewed. One hundred and thirty in situ vein (ISV), 47 reversed saphenous vein (RSV), 118 polytetrafluoroethylene (PTFE) and 78 human umbilical vein (HUV) grafts were used. The indications for surgery were disabling claudication in 25 per cent of patients and limb salvage in 75 per cent. In 36 per cent of operations the distal anastomosis was above the knee and in 64 per cent it was below the knee. Overall 5-year patency rates and limb salvage rates respectively were, for ISV (41 and 69 per cent), RSV (62 and 90 per cent), PTFE (31 and 67 per cent) and HUV (29 and 59 per cent). There was no significant difference in patency among these grafts at the above-knee level, but significant differences between vein and prosthetic grafts were evident below the knee (P less than 0.001). Using a proportional hazards model the three factors that consistently correlated with late graft patency were graft type (P less than 0.001), site of distal anastomosis (P less than 0.001) and distal run-off (P less than 0.001). Overall, the results suggest that prosthetic grafts are a suitable alternative to autogenous vein when the distal anastomosis is above the knee, but vein should always be used, if available, below the knee joint.

Adult↗
PubMed1990

Percutaneous transluminal angioplasty of occlusions of the femoral and popliteal arteries by subintimal dissection.

A technique for recanalization of femoral and popliteal arterial occlusions by intentional subintimal dissection is described. Recanalization with this technique was attempted in 71 occlusions of the femoro-popliteal segment with a mean length of 11.4 cm. Primary technical success was achieved in 54 (76%) cases, with complications occurring in 4 (5.6%). Of 44 successful cases reviewed at a mean follow up of 6 months, 37 (84%) were either asymptomatic or improved. The technique has proved to be an effective method of treating occlusions of the femoral and popliteal arteries with an acceptable complication rate. It may allow successful angioplasty where the standard intraluminal method fails, particularly when reconstructive surgery is the only option.

Aged↗
PubMed1990

An examination of defense style in parents who abuse children.

The study aimed to determine the predominant defense style in parents who abuse their children, at least as determined by a new defense style questionnaire. The scores of 32 parents who had physically abused their young children and had been assessed after court proceedings were compared with a normal population sample and with patients with anxiety disorders who were equally symptomatic. Parents who had abused their children identified themselves as being particularly likely to use projection, displacement, passive-aggressiveness denial, and splitting to a degree greater than normal persons or patients with anxiety disorders. We would caution that, although the differences remained after statistical control of age and sex differences, a firm conclusion that such defenses are germane to child abuse will have to await replication of these findings with a study using a control group of young parents who do not abuse their children matched for social class and family structure.

Adult↗
PubMed1990

A radioimmunoassay for SQ 27,519, the active phosphinic acid-carboxylic diacid of the prodrug fosinopril in human serum.

Fosinopril (SQ 28,555) is a member of a new chemical class of angiotensin converting enzyme inhibitors being developed by The Squibb Institute for Medical Research. During or following absorption, fosinopril, a prodrug, is hydrolyzed pharmacologically to the active diacid, SQ 27,519. A specific radioimmunoassay (RIA) for the measurement of SQ 27,519 in human serum has been developed. The assay utilizes a specific SQ 27,519 antibody, 125I-iodohistamine-SQ 27,519 radiolabel, and human serum standards. Satisfactory zero binding and assay sensitivity are achieved after a 2-h incubation at room temperature. Separation of the antibody-bound and free radiolabeled antigens is achieved by using polyethylene glycol-goat anti-rabbit gamma globulin separant. Recovery efficiencies ranged from 97.2 to 109.4%. The assay exhibited little or no cross-reactivity with captopril. Cross-reactivities for prodrug (SQ 28,555) and phenolic SQ 27,519 were 5 and 9%, respectively. Intra-assay variability (3.3-5.6%) and interassay variability (7.1-6.6%) were observed. Linear regression analysis indicates that RIA and [14C] thin-layer radiochromatography (TLRC) methods gave a highly significant correlation (RIA = 1.0 [14C]TLRC + 0.17, r = 0.991). Pharmacokinetic profiles of patient sera containing SQ 27,519 obtained by RIA and [14C]TLRC are identical. The RIA has been used routinely in support of the bioavailability and pharmacokinetic studies of fosinopril in humans.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Multi-cultural study of minor psychiatric disorders in Asia: symptom manifestations.

Patients with minor psychiatric disorders, including neuroses, situational adjustment reaction or acute emotional reaction, were investigated using symptom questionnaires at five research sites in Asia including: Chiang-Mai, Thailand; Bali, Indonesia; Kao-Hsiung, Taiwan, China; Shanghai, China; and Tokyo, Japan. The results revealed that the symptom profiles differ significantly among groups of different settings indicating that sociocultural background does contribute to the manifestation of neurotic symptomatology. It was also found that numerous and various subtypes of somatic scales were identified through factor analysis of symptoms for these Asian populations. It demonstrates that the spectrum of neurotic symptoms has a different focus for subjects in different sociocultural settings.

Adult↗
PubMed1990

The use of inert dehydration and glycol methacrylate embedding for immunogold localization of glomerular basement membrane components.

A protocol is described for the preparation of human pathology specimens without fixation, in order to perform immunocytochemistry at an ultrastructural level. Using the technique in conjunction with immunogold labeling, the basal lamina components type IV collagen, laminin, and heparan sulfate have been demonstrated in glomerular capillary loops in stored frozen human renal tissue. Tissue was thawed and immediately dehydrated with the inert cryoprotectant ethanediol (inert dehydration) followed by embedding in low-acid glycol methacrylate polymerized using the accelerator n,n-dimethylaniline. Tissue processed in this way retained superior antigenic activity when compared with tissue reprocessed from wax blocks and embedded in low-acid glycol methacrylate. Inert dehydration is a technique useful for the localization of processing sensitive epitopes in routine fresh or frozen archival pathologic material. Furthermore, high probe densities can be achieved without recourse to etching or enzyme treatments.

Acrylates↗
PubMed1988

On the expression of psychosis in different cultures: schizophrenia in an Indian and in a Nigerian community.

This sub-study of the WHO Determinants of Outcome of Severe Mental Disorders research project was aimed at characterizing the behavioral and expressive qualities of schizophrenia in two highly diverse cultures. Early research has indicated that the core elements involving affect, perceptual and cognitive dysfunction in schizophrenia are highly similar in form in most cultures of the world. Much of the cross-cultural literature emphasizes, however, strong differences in the ways in which schizophrenia is actually expressed and manifested in different settings. The basic methodology for psychiatric description and diagnosis in the WHO program was the Present State Examination. In five of the field centers a method for investigating the expressive quality and the social behavior of patients in their own communities through the eyes of significant others was applied. This method was then subjected to psychometric tests of cross-cultural applicability and found to be valid for comparing behavior across settings. The expressive patterns of the Indian and Nigerian patients were studied from two perspectives. Indian schizophrenics were described by family members as manifesting a more affective and "self-centered" orientation; the Nigerian patients presented with a highly suspicious, bizarre, anxious quality to the basic behavioral pattern. The main features of pathology were in general accord with the descriptions of indigenous psychiatrists. The special qualities of the psychosis in the two cultures were interpreted against the background of traditional psychopathological and anthropologic theories concerning the psychodynamics and the influence of differing social conflictual themes in the two cultures. Analysis of psychopathology in this manner was found to enhance understanding of underlying mechanisms and the role of cultural conflicts in its expression.

Adolescent↗