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Biomedical subjects

B Todd

Publications and source records attributed to B Todd.

At least 19 recordsLinked to original sources

Prognostic significance of changes in prostate-specific markers after endocrine treatment of stage D2 prostatic cancer.

BACKGROUND: The prognostic value was determined of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) measured before and after endocrine treatment in 57 patients with newly diagnosed Stage D2 prostatic cancer. METHODS: Therapy included orchiectomy or administration of luteinizing hormone releasing hormone analogues or an antiandrogen. RESULTS: The absolute pretreatment PSA (elevated in 100% of patients) but not PAP (abnormal in 93%) predicted disease progression (P < 0.0011), i.e., a poor response to therapy. Fifty-three patients responded to androgen deprivation with a decrease in PSA level. This declined to normal at 3 and 6 months in 25% of patients. Forty-nine percent had a greater than 90% decrease in their PSA level. By 1 year, 58% of patients had progressive disease. Both the nadir PSA level and the percent decline from the pretreatment level at 3 and 6 months predicted the progression-free interval (P < 0.001). Patients with a 90% or greater decline in PSA had a prolonged progression-free survival. Serial PAP levels were similarly prognostic. CONCLUSION: It was concluded that PSA was better than PAP in evaluating patients before and after androgen-deprivation therapy. The nadir level of both markers was an important tool to predict progression-free survival in patients with metastatic prostatic cancer.

Acid Phosphatase

Effect of venous support on edema and leg pain in patients after coronary artery bypass graft surgery.

The purpose of this study was to assess the effect of external venous support on edema and pain in the saphenous graft leg of patients who had coronary artery bypass graft surgery (CABG) 5 days and 1 month after surgery. Fifty-six patients who had CABG surgery were randomly assigned to the experimental (n = 24) or control (n = 32) group. Subjects in the experimental group wore graded compression support hose. Edema was assessed by using ankle, calf, and thigh circumference measurements. Pain was measured on a visual analog scale. Hose were effective in preventing edema during hospitalization, but results at 1 month were inconclusive. There was no difference in leg pain for experimental and control subjects. That a number of patients in the experimental group were unable to complete the study suggests that off-the-shelf, thigh-high support hose may not be useful for individuals with disproportionately large thighs. Further investigation of the long-term effects of support hose is warranted.

Adult

Interleukin-2 enhances production in 24 hours of infectious human immunodeficiency virus type 1 in vitro by naturally infected mononuclear cells from seropositive donors.

When peripheral blood mononuclear cells from HIV-1 seropositive patients were treated with rIL-2 in vitro a rapid increase of 2-12 fold in production of extracellular infectious HIV-1 occurred, in 6 of 9 experiments. Overall, the increase in the 9 experiments was significant (p less than 0.01) and provides more direct evidence for an enhancing role of IL-2 in naturally infected cells.

Cells, Cultured

Computer-aided localisation of peripheral nerve lesions.

The clinical localisation of peripheral nerve lesions can sometimes be difficult, particularly following injury to the brachial plexus when multiple lesions are often present. In this situation, computers may be of assistance in interpreting the complicated patterns of clinical findings. This paper describes the evaluation of a computer program that uses a simulation model of the consequences of nerve injury, based on a representation of the relevant anatomy. A retrospective study of 26 patients with upper limb nerve lesions was carried out. The computer program compared favourably with three clinicians in interpreting the findings correctly. It is suggested that this approach may be transferable to other applications.

Arm

Mechanism of glucocorticoid regulation of alkaline phosphatase gene expression in osteoblast-like cells.

In the rat osteosarcoma cell line ROS 17/2.8, glucocorticoids increase the activity of the plasma membrane enzyme, alkaline phosphatase. To determine the mechanisms responsible for this effect, we have studied the actions of dexamethasone on alkaline phosphatase activity, immunoreactive protein, and steady-state mRNA levels. Dexamethasone treatment increased both specific activity of alkaline phosphatase and the cell surface expression of immunoreactive protein in a dose-dependent manner, with a half-maximal increase at 2 nM. Steady-state alkaline phosphatase mRNA levels were also increased in a dose-dependent manner. The time course of dexamethasone induction occurred relatively slowly, with a lag period of 12 h before any discernable effect on alkaline phosphatase mRNA levels. The rise in alkaline phosphatase mRNA levels was attributable entirely to changes in gene transcription, with no effect on message stability. Treatment of ROS 17/2.8 cells with actinomycin D completely abolished the dexamethasone-induced rise in alkaline phosphatase mRNA levels. Measurement of alkaline phosphatase mRNA degradation, by incubation of cells with the transcriptional inhibitor 5,6-dichloro-ribofuranosylbenzimidazole, indicated an apparent half-life of 24 h in both untreated and dexamethasone-stimulated cells. The protein synthesis inhibitors cycloheximide and puromycin blocked the dexamethasone induction of alkaline phosphatase mRNA. These data suggest that the dexamethasone-induced rise in alkaline phosphatase gene transcription requires the synthesis of an unknown mediator protein.

Alkaline Phosphatase

Intraoperative management of patients with heparin-induced thrombocytopenia.

For 11 patients with confirmed heparin-induced thrombocytopenia, we used reversible platelet inhibition with iloprost, a stable prostacyclin analogue, to permit safe heparin administration for cardiac (n = 9) or vascular (n = 2) operations. In vitro, iloprost (0.01 mumol/L) prevented both heparin-induced platelet aggregation and 14C-serotonin release in all patients. Therefore, intraoperatively, a continuous infusion of iloprost was started before administration of heparin and was continued until 15 minutes after administration of protamine. For cardiac patients, after heparin administration, the whole blood platelet count did not change (171,000 +/- 29,000/microL versus 174,000 +/- 29,000/microL, mean +/- standard error of the mean); no spontaneous platelet aggregation was observed, and plasma levels of the alpha-granule constituents platelet factor 4 and beta-thromboglobulin increased from 38 +/- 14 and 140 +/- 18 ng/mL to 591 +/- 135 and 235 +/- 48 ng/mL, respectively. Fibrinopeptide A levels actually decreased from 287 +/- 150 to 27 +/- 6 ng/mL. Furthermore, adenosine diphosphate-induced platelet activation was preserved, postoperative bleeding times were unchanged, and no heparin-related deaths occurred. Similar results were obtained in both vascular patients. We conclude that temporary platelet inhibition with iloprost now permits safe heparin administration in all patients with heparin-induced thrombocytopenia who require a cardiac or vascular operation.

Adult

Complications of cholecystectomy in district general hospitals.

The aim of this retrospective study was to determine the incidence of the complications in one thousand consecutive cholecystectomies performed in three district general hospitals. Major post-operative complications occurred in 63 patients (6.3 per cent) and were responsible for 12 deaths (1.2 per cent operative mortality) and 31 reoperations. The incidence of retained stones was 5.8 per cent (10 patients) for those who underwent exploratory choledochotomy, and 10.9 per cent in those who were managed by common bile duct exploration and stone extraction. There were four cases of iatrogenic biliary trauma (0.4 per cent), all in cases operated by junior registrars. All (except one) occurred during elective 'non-complicated' cholecystectomy.

Adult

Prognostic factors in patients with advanced prostate cancer.

One hundred ten patients with metastatic prostate cancer (Stage D2) were analyzed to determine the associations among time until progression and the pretreatment testosterone level, extent of bone metastases as indicated by a semiquantitative grading scale for extent of disease, performance status, race, age, and the pretreatment level of prostatic acid phosphatase (PAP). The median follow-up period was twenty-one months, with a range of four to eighty-nine months. All patients received androgen deprivation at the time metastases were identified. A multivariate analysis demonstrated that pretreatment serum testosterone was the most significant variable associated with time until progression (P less than 0.01) and that the extent of bone metastases observed on the bone scan was the second most important variable (P less than 0.05). The following factors did not significantly correlate with progression-free intervals: age, race, and PAP. The performance status was significantly correlated, but was nonsignificant in the multivariate analysis when the model already included the testosterone level and the extent of bone metastases. Patients with a pretreatment testosterone level of less than 300 ng/dL and with more than six areas of increased uptake on the bone scan progressed more rapidly.

Acid Phosphatase

Prognostic factors in survival free of progression after androgen deprivation therapy for treatment of prostate cancer.

We analyzed 110 patients with metastatic prostate cancer (stage D2) to determine the associations between interval until progression and the pretreatment testosterone level, extent of bone metastases, performance status, race, age and pretreatment level of prostatic acid phosphatase. The median followup was 21 months (4 to 89 months). All patients received androgen deprivation therapy when metastases were identified. This multivariate analysis demonstrated that the pretreatment serum testosterone was the most significant variable (p less than 0.01) associated with interval until progression and the extent of bone metastases observed on the bone scan was the second most important variable (p less than 0.05). Age, race and prostatic acid phosphatase were not significantly correlated with the interval free of progression. Performance status was significantly correlated but it was nonsignificant in the multivariate analysis if the model already included testosterone level and extent of metastasis. Patients with a pretreatment testosterone level of less than 300 ng. per 100 ml. and more than 6 areas of increased uptake on the bone scan had the most rapid progression. We conclude that serum testosterone and extent of bone metastases are the most important of the analyzed factors in terms of interval to progression in patients with prostate cancer following androgen deprivation.

Acid Phosphatase

Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan.

Most patients with metastatic prostate cancer will have metastasis to bone. Such patients are best monitored by serial radionuclide bone scans. One hundred sixty six men with bone metastasis from prostate cancer who received androgen deprivation therapy had their pretreatment bone scans reviewed using a semiquantitative grading system based upon the extent of disease (EOD) observed on the scan. The EOD on the scan correlated with survival. The 2-year survival rates for EOD I to IV were 94%, 74%, 68%, and 40%, respectively. The survival of patients in categories EOD I and IV significantly differed from the other categories. Men with metastatic prostate cancer entered into trials designed to evaluate the impact of treatment on survival should be stratified based upon the EOD on the bone scan. This analysis also indicates that patients in the EOD IV category have a particularly poor prognosis and may be candidates for alternative treatments.

Bone Neoplasms

Buserelin treatment of advanced prostatic carcinoma. Long-term follow-up of antitumor responses and improved quality of life.

The safety and efficacy of buserelin, a luteinizing hormone-releasing hormone (LH-RH) agonist, was tested in 33 evaluable patients with Stages C or D adenocarcinoma of the prostate. With a minimum follow-up duration of 10 months, there was one complete response and 22 partial responses (69%) by National Prostatic Cancer Project criteria, with a median duration greater than 18 months. Six patients (18%) had stable disease, median duration greater than 25 months, and only 12 patients have progressed. Performance status improved in 67%, patient-scored pain improved in 75%, and quality of life improved in 58%. Symptoms occurring during treatment consisted of hot flashes, loss of libido, and impotence. Buserelin produces a high frequency of durable objective and subjective responses in patients with advanced prostatic carcinoma.

Adenocarcinoma