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Biomedical subjects

P Kelly

Publications and source records attributed to P Kelly.

At least 217 records · Page 12Linked to original sources
PubMed1990

Epidermal growth factor receptor expression in colorectal cancer.

Epidermal growth factor (EGF) receptor expression was estimated in 50 invasive human colorectal cancers using immunohistochemistry and the degree of expression was quantified from integrated optical density measurements on the stained sections. All tumours stained positively, but Dukes' C tumours exhibited significantly higher levels of receptor than either Dukes' A or B tumours. In addition, histologically high grade cancers expressed receptors more strongly than those of low grade. It is concluded that a high EGF receptor concentration is associated with poor prognostic factors in colorectal malignancy.

Aged↗
PubMed1990

Corticosteroid effects on proximal femur bone loss.

Prolonged high-dose corticosteroid therapy is known to result in an increased risk of osteoporotic fracture. Reductions in bone density have been demonstrated at the distal radius and lumbar spine in patients receiving corticosteroids; however there have been few studies of bone density in the hip (the most important site of osteoporotic fracture) in this context. To examine the effect of corticosteroids on the hip we measured bone mineral density (BMD) by dual-photon absorptiometry at three sites in the proximal femur as well as the lumbar spine in 32 patients aged 18-77 years who had been treated with corticosteroids (mean daily prednisone dose 12.7 mg) for up to 23 years. BMD was compared with the expected values using age regressions in normal subjects. BMD was significantly reduced in the femoral neck, Ward's triangle, and the trochanteric region (p less than 0.001 all sites). In the lumbar spine BMD was also significantly reduced (p less than 0.001). We also measured BMD serially in 29 patients receiving corticosteroids. BMD measurements were made in 12 patients who had already been treated with long-term corticosteroids at the time of first BMD measurement (chronic group) and from the commencement of corticosteroid therapy in 17 patients (acute group). The mean (+/- SEM) change in BMD (g/cm2 per year) in the lumbar spine and femoral neck were 0.006 +/- 0.006 and -0.021 +/- 0.007, respectively, for the chronic group and -0.02 +/- 0.005 and -0.039 +/- 0.006 for the acute group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Smooth pursuit eye tracking dysfunction and negative symptoms in schizophrenia.

This study examined the hypothesis that negative symptoms are associated with abnormalities of smooth pursuit in schizophrenic patients. The pursuit eye movements of 25 subjects with schizophrenia and 25 matched normal control subjects were recorded using an infrared eye tracking system and quantified using the log of signal-to-noise ratio (1n S/N). The severity of negative symptoms within the schizophrenic group was rated using the Scale for the Assessment of Negative Symptoms. Previous findings of pursuit abnormalities among schizophrenic patients as a group were replicated. There was, however, no significant association between the eye tracking dysfunction and the severity of negative symptoms.

Adolescent↗
PubMed1990

Surgical coronary revascularization in survivors of prehospital cardiac arrest: its effect on inducible ventricular arrhythmias and long-term survival.

In a selected subgroup of 50 survivors of cardiac arrest, the impact of surgical myocardial revascularization on inducible arrhythmias, arrhythmia recurrence and long-term survival was examined. The effects of several clinical, angiographic and electrophysiologic variables on arrhythmia recurrence and survival were also analyzed. All patients had a prehospital cardiac arrest and severe operable coronary artery disease and underwent myocardial revascularization. Preoperative electrophysiologic study was performed in 41 patients; 33 (80%) had inducible ventricular arrhythmias. Of 42 patients studied off antiarrhythmic drugs postoperatively, 19 (45%) had inducible ventricular arrhythmias. Thirty patients with inducible arrhythmias preoperatively underwent postoperative testing off antiarrhythmic drugs; arrhythmia induction was suppressed in 14 (47%). By multivariate analysis, the induction of ventricular fibrillation at the preoperative electrophysiologic study was the only significant predictor of induced ventricular arrhythmia suppression by coronary surgery (p less than 0.001). Inducible ventricular fibrillation was not present postoperatively in any of the 11 patients who manifested this arrhythmia preoperatively. In contrast, inducible ventricular tachycardia persisted in 80% of patients in whom preoperative testing induced this arrhythmia. Patients were followed up for 39 +/- 29 months. There were four arrhythmia recurrences; one was fatal. There were three nonsudden cardiac deaths and three noncardiac deaths. By life-table analysis, 5 year survival, cardiac survival and arrhythmia-free survival rates were 88%, 98%, and 88%, respectively. Depressed left ventricular ejection fraction and advanced age were predictive of death (p = 0.015 and 0.026, respectively) and cardiac death (p = 0.037 and 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1990

Pulmonary tuberculosis in the Republic of Ireland: an epidemiological profile from a single unit.

We present a retrospective epidemiological analysis of 1011 adults with a first time diagnosis of pulmonary TB seen between 1980-1985. Most (98.7%) were from the Republic of Ireland and 68.4% were male. Both males and females showed a bimodal age distribution with 37.6% of females and 18.8% of males aged younger than 30 years. More than half (58.6%) of patients smoked cigarettes and 63.7% consumed alcohol. Two patients indulged in the use of hard drugs. Only 5% of patients were asymptomatic and 0.9% of patients had symptoms for longer than 1 year. Radiologically, 54.7% of patients had bilateral disease; 58.5% had cavities and 10% had pleural effusions. Mantoux testing was positive to 1 tuberculin unit Mantoux in 76%; to 10 tuberculin units Mantoux in 15.3%; to 100 tuberculin units Mantoux in 3.7%; and negative to 100 tuberculin units in 5.0%. Primary drug resistance occurred in 0.9% of patients. Ninety (9.0%) of patients died before completing antituberculous treatment and in 40 patients tuberculosis was the principle or main cause of death.

Adolescent↗
PubMed1990

Cilofungin (LY121019) shows nonlinear plasma pharmacokinetics and tissue penetration in rabbits.

We studied the plasma pharmacokinetics and tissue penetration of cilofungin (LY121019), a new echinocandin antifungal compound, by intermittent and continuous infusion in rabbits. Following a single intravenous dose of 50 mg/kg of body weight, the maximum concentration in plasma was 297 +/- 39 micrograms/ml, the area under the curve was 30.1 +/- 6.7 micrograms.h/ml, clearance was 30 +/- 10 ml/min/kg, volume of distribution was 0.85 +/- 0.23 liters/kg, half-life in distribution phase was 3.7 +/- 0.2 min (first 12 min postdose), and half-life in elimination phase was 12.9 +/- 0.7 min. When rabbits received cilofungin by continuous infusion (CI) at 10 mg/kg/h over 6 days, sustained concentrations in plasma of 290 +/- 56 micrograms/ml were seen, more than 50-fold higher than predicted if kinetics were linear. Similarly, at 5 mg/kg/h, high levels were also obtained. Such elevated levels in plasma would not have been predicted from the pharmacokinetic characteristics of cilofungin given as a single intravenous dose. Further pharmacokinetic study at several rates of CI suggested that cilofungin elimination follows Michaelis-Menten kinetics. Simultaneous cilofungin levels in plasma and tissue were then determined for rabbits receiving six intravenous, intermittent doses (ID) of cilofungin at 15 mg/kg every 4 min and for rabbits receiving CI as described above. After ID, the mean of the ratios of cilofungin levels in tissue to those in plasma were highest for liver and bile but very low for cerebrum and cerebellum. After CI, ratios were as much as 89 times higher than for ID and significantly greater in the brain, choroid, kidney, and bile (P less than 0.05). We conclude that following a single dose of cilofungin, the compound is rapidly cleared via first-order kinetics and does not penetrate into the central nervous system, whereas following CI, cilofungin exhibits nonlinear saturable kinetics, is slowly cleared, and significantly penetrates into central nervous system tissues.

Animals↗
PubMed1990

SCH-39304 in prevention and treatment of disseminated candidiasis in persistently granulocytopenic rabbits.

To investigate the potential use of SCH-39304 for the prevention and treatment of disseminated candidiasis in granulocytopenic patients, we studied its in vivo antifungal activity as preventive, early, and late treatments in three models (acute, subacute, and chronic) of disseminated candidiasis in persistently granulocytopenic rabbits. SCH-39304 was an effective as amphotericin B alone and fluconazole alone for the prevention of disseminated candidiasis. SCH-39304 alone and fluconazole alone were as effective as amphotericin B plus flucytosine for early treatment of subacute disseminated candidiasis. When treatment was delayed for 5 days to establish chronic disseminated candidiasis, SCH-39304 was less effective than amphotericin B plus flucytosine. In comparison with different treatment regimens, SCH-39304 was more effective in early and preventive treatment. Thus, SCH-39304 was comparable to treatment control regimens in prevention and early treatment of subacute disseminated candidiasis. SCH-39304 also was most effective in granulocytopenic rabbits with disseminated candidiasis when used for prevention or early treatment.

Agranulocytosis↗
PubMed1990

Trichosporon beigelii, an emerging pathogen resistant to amphotericin B.

Trichosporon beigelii caused fatal disseminated infections that were resistant to amphotericin B in two granulocytopenic patients. In vitro susceptibility studies demonstrated that both index strains of T. beigelii were inhibited but not killed by amphotericin B at achievable concentrations in serum. The minimum lethal concentration for both isolates was greater than or equal to 18 micrograms/ml. Five of seven other isolates were found to have a similar pattern of amphotericin B resistance. The fact that the minimum lethal concentration of T. beigelii was many times greater than its MIC was consistent with a resistance pattern of tolerance. We concluded that T. beigelii may be resistant in vitro to amphotericin B and that this in vitro resistance was correlated with refractory, disseminated trichosporonosis in granulocytopenic patients. T. beigelii should be included in the expanding list of amphotericin B-resistant fungi.

Adolescent↗
PubMed1990

Exercise-induced subendocardial dysfunction in dogs with left ventricular hypertrophy.

The effects of treadmill exercise on regional myocardial blood flow and function were examined in 10 adult, conscious dogs with left ventricular hypertrophy (LVH) induced by aortic banding in puppies, which resulted in a left ventricular (LV) weight/body weight ratio of 8.5 +/- 0.3. Data were compared with results from eight control dogs with an LV weight/body weight ratio of 4.9 +/- 0.2. At rest, LV systolic and end-diastolic pressures were significantly greater (p less than 0.01), and mean arterial pressure was significantly less (p less than 0.05) in LVH dogs. Mean myocardial blood flow (control dogs, 0.98 +/- 0.11 ml/min/g; LVH dogs, 1.16 +/- 0.06 ml/min/g) and the transmural blood flow distribution at baseline, as assessed by endocardial/epicardial blood flow ratio (control, 1.35 +/- 0.12; LVH, 1.21 +/- 0.09), were similar in the two groups. During exercise to a target heart rate (240 beats/min), LVH dogs demonstrated greater (p less than 0.01) increases in LV systolic and end-diastolic pressures. In control dogs, as expected, exercise augmented velocity of circumferential fiber shortening (16 +/- 9%) and shortening fraction (15 +/- 5%), but in LVH dogs, exercise reduced the velocity of circumferential fiber shortening (-14 +/- 6%) and shortening fraction (-17 +/- 5%). Exercise also increased full wall thickening (35 +/- 5%), subendocardial wall thickening (66 +/- 10%), and subepicardial wall thickening (44 +/- 9%) in control dogs. In LVH dogs, exercise increased subepicardial wall thickening (31 +/- 9%) and reduced subendocardial wall thickening (-40 +/- 7%); full wall thickening did not change (-11 +/- 9%). This was associated with a fall in endocardial/epicardial flow ratio to 0.72 +/- 0.05 (p less than 0.01) in LVH dogs. The subendocardial dysfunction persisted late into recovery, at a time when the transmural blood flow distribution had returned to baseline; this occurrence suggested myocardial stunning. Thus, in dogs with LVH, selective subendocardial hypoperfusion and profound selective depression in subendocardial wall thickening are observed during exercise. The subendocardial dysfunction persisted into recovery despite resolution of the perfusion abnormality.

Animals↗
PubMed1990

The pathogenicity of Mycobacterium tuberculosis during chemotherapy.

We used the guinea pig as an experimental model to investigate the pathogenicity of Mycobacterium tuberculosis. Sputum samples were injected subcutaneously into guinea pigs and the animals were killed and an autopsy performed after eight weeks. The likelihood of the sputum samples producing tuberculosis in the guinea pig was related to culture positivity rather than to duration of chemotherapy. This study does not support the belief that a change in pathogenicity occurs during treatment of pulmonary tuberculosis.

Animals↗
PubMed1990

Raised PPD antibodies in active pulmonary tuberculosis.

Antibodies to purified protein derivative of tuberculin (PPD) were measured in 47 patients with active pulmonary tuberculosis and in various control subjects using an enzyme linked immunosorbent assay. Raised IgG anti PPD antibodies were found in 30 patients with active tuberculosis, in one of 28 patients with miscellaneous non tuberculous diseases and in one of 49 healthy control subjects. This gave the assay a sensitivity of 65% and a specificity of 98%. Antibodies were also measured in a further 20 patients with suspected tuberculosis but in whom microbiological evidence was absent. In eight of these patients active tuberculous disease was subsequently validated on the basis of clinical response to chemotherapy: raised PPD antibodies were found in six of this group but in none of the remaining 12 patients in whom the diagnosis of tuberculosis was considered doubtful. Further studies showed that patients' PPD antibody level fell over a one year period of successful therapy and that tuberculin skin testing and BCG vaccination did not cause a rise in antibodies in healthy subjects. These results suggest that the measurement of PPD antibodies is a useful adjunctive test in the diagnosis of tuberculosis.

Antibodies, Bacterial↗
PubMed1990

Fibreoptic bronchoscopy in the management of lone pleural effusion: a negative study.

In a retrospective review of 3,000 consecutive fibreoptic bronchoscopies, fifty were performed for investigation of lone pleural effusion. While 7 patients had bronchogenic carcinoma, in only one case was it visible endoscopically. In the absence of radiological or clinical features suggesting an endobronchial lesion, fibreoptic bronchoscopy is unlikely to aid in the diagnosis of lone pleural effusion.

Bronchoscopy↗