Search PubMed⌕ Search

Biomedical subjects

P Kelly

Publications and source records attributed to P Kelly.

At least 235 records · Page 13Linked to original sources
PubMed1989

The smaller human VH gene families display remarkably little polymorphism.

We report the nucleotide sequence of 30 distinct human VH gene segments from the VHIV, VHV and VHVI gene families. When these sequences were compared to previously published sequences from these smaller human VH families a surprisingly low level of polymorphism was noted. Two VHIV gene segments from unrelated individuals were identical to two previously published VHIV sequences. Five VHV sequences were identical and seven VHVI gene segments were identical. Where differences were found between the sequences, allele specific oligonucleotide probes were used to verify the germline nature of the change and to test for segregation in several large kindreds. These data provide evidence that at least some human VH gene segments are remarkably stable.

Alleles↗
PubMed1989

Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer.

Sections of formalin-fixed, paraffin-embedded tissue from 185 primary breast carcinomas were stained immunohistochemically using a polyclonal antibody against the c-erbB-2 oncoprotein. Positive staining, which is known to correlate with gene amplification, was associated with earlier relapse, shorter postrelapse survival, and shorter overall survival. Lymph node, epidermal growth factor receptor, and estrogen receptor status, tumor size, and histological grade also had prognostic significance but, applying multivariate analysis, only lymph node status was a more important predictor of relapse-free and overall survival than staining for the oncoprotein. Positive staining was correlated with negative estrogen receptor status and high histological grade, but there was no association with either lymph node or epidermal growth factor receptor status or tumor size. Expression of the c-erbB-2 oncoprotein appears to be an important independent indicator of prognosis in human breast cancer.

Analysis of Variance↗
PubMed1989

Muscle strength, physical fitness, and weight but not age predict femoral neck bone mass.

Hip fractures are the most serious complication of osteoporosis. Although low proximal femoral bone mineral density (BMD) does not cause hip fractures directly, it is clearly a prerequisite for the increased risk associated with aging. To investigate the mechanism of the age-related decline in proximal femoral bone mineral density, we have examined the relative importance of muscle strength, physical fitness, and body mass index (BMI) in addition to age in the determination of proximal femoral BMD in 73 healthy female volunteers age 20-75 years. Muscle strength was an independent predictor of BMD at all three sites in the proximal femur as well as in the lumbar spine and forearm; proximal femur BMD was also predicted by physical fitness. BMI was a positive predictor of bone mass at all sites. In the proximal femur, age was not an independent predictor of BMD at any site. In postmenopausal women muscle strength was a significant predictor of bone mass in the femur and forearm, but not in the spine. However, BMI remained predictive of bone mineral at all sites. Muscle strength, physical fitness, and weight appear to exert independent effects upon bone mass. Age effects may be mediated indirectly through associated changes in these factors. The integrated physical load on the skeleton may be a final common pathway.

Adult↗
PubMed1989

Is measurement of type III procollagen amino propeptide useful in primary biliary cirrhosis?

We have examined the value of serum type III procollagen amino propeptide (PIIINP) measurement both in evaluation of disease activity and in estimation of prognosis in primary biliary cirrhosis (PBC). 55 paired sera from 32 PBC patients not receiving treatment known to affect PIIINP levels not with non-hepatic inflammatory conditions were used to estimate serum PIIINP by radioimmunoassay. Significant correlations were found between serum PIIINP and serum albumin (P less than 0.001), bilirubin (P less than 0.002) and aspartate transaminase (P = 0.01). The mean serum PIIINP level rose with advancing histological stage (P less than 0.001). In 18 patients in whom more than 1 serum was assayed (mean follow-up 42 months) PIIINP often fell, particularly in patients with established cirrhosis and advanced disease. The independent prognostic value of PIIINP was examined using Cox's proportional hazards model with three other prognostic co-variables (bilirubin, albumin, patient age). Stepwise regression analysis selected albumin (P less than 0.001) and bilirubin (P = 0.002) as the most important prognostic factors. PIIINP did not give independent prognostic information. We conclude that PIIINP is another marker of disease activity in PBC which confers no benefit over existing conventional measurements in routine management of this disease.

Adult↗
PubMed1989

Assessment of regional myocardial blood flow with myocardial contrast two-dimensional echocardiography.

It was hypothesized that regional myocardial blood flow could be measured using myocardial contrast echocardiography. Accordingly, arterial blood was perfused into the coronary circulation in 16 dogs. In Group 1 dogs (n = 8), blood flow to the cannulated left circumflex artery was controlled with use of a roller pump, whereas in Group 2 dogs (n = 8) blood flow to the left anterior descending coronary artery was controlled by a hydraulic occluder placed around it. Sonicated microbubbles (mean size 4 microns) were used as the contrast agent. In Group 1 dogs the microbubbles were injected subselectively into the left circumflex artery, whereas in Group 2 dogs they were injected selectively into the left main coronary artery and two-dimensional echocardiographic images were recorded. Computer-generated time-intensity curves were derived from these images and variables of these curves correlated with transmural blood flow measured with radiolabeled microspheres. A gamma-variate function (y = Ate-alpha t) best described the curves, and alpha (a variable of curve width) correlated well with transmural blood flow at different flow rates in all Group 1 and Group 2 dogs (mean r = 0.81 and 0.97, respectively). Other variables of the curve width also correlated well with myocardial blood flow, but peak intensity had a poor correlation with myocardial blood flow in both groups of dogs (r = 0.39 and r = 0.63, respectively). When data from all dogs were pooled, Group 1 dogs still showed good correlation between variables of curve width and myocardial blood flow (r = 0.81); Group 2 dogs did not (r = 0.45). The difference between the two sets of dogs was related to the site of contrast agent injection. It is concluded that measurement of the transit time of microbubbles through the myocardium with two-dimensional echocardiography accurately reflects regional myocardial blood flow. Although injection of contrast agent selectively into the left main coronary artery only allows measurement of relative flow, it may be feasible to measure absolute flow by injecting contrast agent subselectively into a coronary artery. Myocardial contrast echocardiography may, therefore, offer the unique opportunity of simultaneously assessing regional myocardial perfusion and function in vivo.

Animals↗
PubMed1989

Evaluation of a simplified method for estimation of early childhood mortality in small populations.

The provision of simple health technologies in less developed countries has far outpaced the capabilities to evaluate their impact on health in general, and early childhood survival in particular. In rural Haiti, attempts to monitor the impact of health care delivery programmes have been frustrated by some of the same problems encountered elsewhere; ie lack of practicable yet scientifically sound methodologies that interface well with ongoing service delivery programmes. The 'preceding birth' technique, originally advanced by Brass and Macrae, holds promise as just such a method. Its practical appeal derives largely from simple data requirements. In its simplest form, the method requires only responses to a single question put to mothers at delivery regarding the survival status of her previous child. They have shown that the proportion of immediately preceding births dying before the 'index' birth date provides a good approximation of the standard life table probability of death before the second birthday. Given that in rural Haiti, as in much of the less developed world, few women deliver in clinic or hospital where such data could be systematically obtained, exploitation of the preceding birth method would require identification of a convenient and unobtrusive point of contact between questioner and mothers who have recently delivered. In Haiti, two options arose: (1) interview women at home after childbirth, and (2) interview women when they bring the 'index' child seeking vaccination or some other child survival intervention. Both of these deviate from the original technique of Brass and Macrae with respect to the timing and method of data collection, and could therefore introduce serious complications to the interpretation of trends in child mortality. To study this, we examined the effects of adapting the preceding birth method to a rural less developed country setting in Mirebalais, where since 1983 primary health care activities have been administered by MARCH (Management and Resources for Community Health), a private voluntary health organization. The Mirebalais study used a pregnancy register, originally developed for targeting of services, to identify women who were expected to have given birth during the 12-month period before each of two survey rounds. Brief interviews with these women would provide direct life table estimates of child mortality level and trend with which to compare estimates produced from use of the preceding birth method in modified form. Direct estimates of the probability of dying before the second birthday were 138/1000 from first round data and 134/1000 from second round data, indicating a 3% decline.(ABSTRACT TRUNCATED AT 400 WORDS)

Data Collection↗
PubMed1989

STRETCH: a rehabilitative program for patients with breast cancer.

Participants in an exercise-based rehabilitative program for women with breast cancer were evaluated for physical disability. Of 114 women who were evaluated initially, there was almost universal evidence of restriction of range of motion or abnormal posture. Of the 47 women who were available for evaluation after completion of the eight-week program, 42 showed increases in one or more movements with no concomitant decreases. Five patients had a decrease in a single measurement. Of 96 participants evaluated for psychosocial benefits, two thirds reported positive psychologic effects.

Adult↗
PubMed1989

Isoproterenol-induced alterations in myocardial blood flow, systolic and diastolic function in conscious dogs with heart failure.

The effects of isoproterenol were examined in 10 conscious, chronically instrumented adult dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by aortic banding at 8-10 weeks of age (LV free wall plus septum-to-body weight ratio, 8.6 +/- 0.5 g/kg) and also in eight control dogs (LV free wall plus septum-to-body weight ratio, 5.1 +/- 0.3 g/kg). Baseline values of heart rate, LV end-diastolic pressure, LV end-diastolic stress, and LV systolic wall stress were greater in the LV failure dogs (p less than 0.01), whereas the ejection phase index, rate of change of LV short-axis diameter, LV dD/dt, was depressed compared with control animals. In the control animals, isoproterenol infusion increased Vcf and LV dD/dt significantly (p less than 0.05), whereas LV systolic wall stress did not change. In the LV failure dogs, the increases in Vcf and LV dD/dt were less (p less than 0.01), and LV systolic wall stress increased (p less than 0.01). In the control animals, LV end-diastolic pressure, LV end-diastolic stress, LV end-diastolic stress-dimension ratio, diastolic radial myocardial stiffness, and the time constant of isovolumic relaxation decreased (p less than 0.05), whereas in the LV failure dogs, LV end-diastolic pressure, LV end-diastolic stress, diastolic radial myocardial stiffness, and the LV end-diastolic stress-dimension ratio increased. In the LV failure group, the endocardial to epicardial blood flow ratio fell to 0.59 +/- 0.06 during isoproterenol infusion, that is, significantly lower than in control dogs (0.93 +/- 0.06). These data support the concept that potent sympathomimetic amines exert deleterious effects on systolic and diastolic function in the failing heart, potentially related to subendocardial hypoperfusion.

Animals↗
PubMed1989

Short course chemotherapy for pulmonary tuberculosis. A randomised controlled trial of a six month versus a nine month oral regimen.

We report on the first trial in the Republic of Ireland to look at chemotherapy for TB. This management trial, carried out in single unit, which treats a third of all TB cases in the Republic of Ireland compared to effectiveness of a three drug/nine month regimen (Rifampicin (R), Isoniazed (R), supplemented with Ethambutol (E) for the first two months = RHE9) with a four drug six months regimen (R, H supplemented with E and Pyrazinamide (Z) for the first two months = RHEZ6). Two hundred and eighty eight patients (288) were entered into the study. A total of 143, (76 were in the RHE9 group and 67 in the RHEZ6 group) completed the trial as planned. At the end of the third month, significantly more patients in the RHEZ6 regimen (98%) were culture negative compared to the RHE9 regimen (88%). All were culture negative at the end of chemotherapy. Drug intolerance was seen in 35 (12%) patients with no significant difference in hepatitis between the two regimens. Toxicity from Pyrazinamide was minimal. One hundred and forty five (145) patients were invalid for analysis for the following reason:- bacteriologically negative TB (41), drug intolerance (35), death (23), non-compliance (19), diagnosis not TB (10), drug resistance (7), extrapulmonary disease (4), consent withdrawn (3), Mycobacteria other than tuberculosis (3). All patients are being followed to monitor relapse rates.

Administration, Oral↗
PubMed1988

Grading of astrocytomas. A simple and reproducible method.

This study determines the effectiveness and reproducibility of a previously published method of grading gliomas. The method under study is for use on "ordinary astrocytoma" cell types, i.e., fibrillary, protoplasmic, gemistocytic, anaplastic astrocytomas and glioblastomas, and is based upon the recognition of the presence or absence of four morphologic criteria: nuclear atypia, mitoses, endothelial proliferation, and necrosis. The method results in a summary score which is translated into a grade as follows: 0 criteria = grade 1, 1 criterion = grade 2, 2 criteria = grade 3, 3 or 4 criteria = grade 4. The histologic material and clinical data were derived from a previously reported series of patients with astrocytomas, radiotherapeutically treated at Mayo Clinic between the years 1960 and 1969. From this series, initially graded 1 to 4, according to the Kernohan system, 287 "ordinary astrocytomas" were entered into the study; 51 pilocytic astrocytomas and microcystic cerebellar-type astrocytomas also were included for comparison. Among ordinary astrocytomas, the grading method under study distinguished 0.7% of grade 1, 17% of grade 2, 18% of grade 3, and 65.3% of grade 4. A 15-year period of follow-up was available on all surviving patients. Statistical analysis showed that in ordinary astrocytomas, each of the four histologic criteria, as well as the resultant grade, were strongly correlated to survival (P less than 0.0001). Median survival was 4 years in grade 2, 1.6 years in grade 3, and 0.7 years in grade 4 tumors. Of the two patients with grade 1 ordinary astrocytomas, 1 had 11 years of survival, and the other was alive at 15 years. Furthermore, based upon the Cox Model, grade was found to be the major prognostic factor, superceding the effects of age, sex, and location. Among ordinary astrocytomas, the grading system under consideration clearly distinguished four distinct grades of malignancy, whereas, the Kernohan grading system accurately distinguished only two major groups of patients. Survival curve of patients with our grade 2 tumors coincided with the grade 1 and 2 Kernohan survival curves. Similarly, our grade 4 survival curve coincided with the Kernohan grade 3 and 4 survival curves. As a result, our proposed grading method generated an individualized curve corresponding to grade 3 tumors. Double-blind grading between two independent observers was concordant in 94% of ordinary astrocytomas; reproducibility was 81% in low-grade (grades 1 and 2) and 96% in high-grade (grades 3 and 4) astrocytomas of ordinary type.(ABSTRACT TRUNCATED AT 400 WORDS)

Astrocytoma↗
PubMed1988

Characterization of the mouse SPARC/osteonectin gene. Intron/exon organization and an unusual promoter region.

Two overlapping cosmids have been isolated containing the entire murine gene for SPARC (osteonectin), a Ca2+-binding, phosphorylated glycoprotein associated with extracellular matrix synthesis and remodeling. The gene contains 10 exons and covers 26.5 kilobase pairs of DNA. Exon analysis shows that the two N-terminal glutamic acid-rich sequences which are predicted to undergo conformational change upon binding of calcium, as well as the C-terminal EF-hand Ca2+-binding domain are each encoded by a single exon. Comparative analysis of the exon sequence does not support the idea that the SPARC gene has evolved by shuffling of exons from other Ca2+-binding proteins. The 5' flanking region of the SPARC gene, which promotes transcription when placed in front of the bacterial chloramphenicol acetyltransferase gene, contains neither "TATA" nor "CAAT" box sequences. However, unlike most other genes lacking these motifs, mapping of the 5' end of the SPARC gene by RNase protection and primer extension analysis reveals only a single major and one minor transcription start site. The upstream region to -120 includes six repeats of the sequence GGAGG, two repeats of the sequence 5' GGAGG A/C GGAGGG 3', and a potential transcription factor AP-2 binding site.

Acetyltransferases↗