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Biomedical subjects

B Todd

Publications and source records attributed to B Todd.

At least 37 records · Page 2Linked to original sources
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

Radiographic assessment of knee joint rotation.

A radiographic technique for measuring conjunct rotation at the knee joint is described. Conjunct rotation was demonstrated to occur over a greater range of values of flexion than conventionally believed. Rotation increased progressively as the knee extended, and was not confined to the last phase of extension. Consideration of such rotatory movement is relevant to the design of knee arthroplasties and also to possible mechanisms of non-bony injury of the knee.

Adult↗
PubMed1986

Pre-treatment testosterone levels: significance in androgen deprivation therapy.

From June 1982 to February 1985, 53 patients with stage D2 carcinoma of the prostate confirmed by tissue biopsy, elevated prostatic acid phosphatase and a positive bone scan were initiated on androgen deprivation therapy. Before commencement of treatment all patients underwent determination of serum testosterone levels at 8 a.m. Of the patients 23 received 200 mcg. buserelin per day, 17 received 1 mg. diethylstilbestrol 3 times daily, 6 received 40 mg. megestrol acetate 4 times daily, 2 received 1 mg. leuprolide per day and 5 underwent bilateral orchiectomy. Evaluation of the best response in each patient revealed 3 (6 per cent) complete and 17 (32 per cent) partial responses, while 22 patients (41 per cent) remained stable and 11 (21 per cent) had progression. Pre-treatment serum testosterone levels ranged from 150 to 879 ng. per dl. The mean serum testosterone level in patients having a complete response was 524 +/- 18.04 ng. per dl. The mean in the progression group was 279.4 +/- 110.1 ng. per dl. This difference was not statistically significant owing to the large standard deviation in the progression group. However, of the 15 patients who had a pre-treatment serum testosterone level of more than 500 ng. per dl. only 1 (7 per cent) had progression. None of the patients whose pre-treatment testosterone level was less than 200 ng. per dl. had objective tumor regression. Our study suggests that pre-treatment serum testosterone levels may predict the probability of a satisfactory response to androgen deprivation therapy.

Aged↗
PubMed1980

Some endocrine changes associated with the post-partum period of the suckling beef cow.

Seven Hereford cows with single calves were bled by jugular venepuncture, daily from parturition until 63-79 days post partum; 6 of the cows were also bled through jugular cannulae every 15 min for 8 h every 10 days. The average post-partum interval to first oestrus was 59.8 +/- 3.7 days for 5 of the cows. In cows returning to oestrus, plasma concentrations of progesterone were low until 55.5 +/- 3.0 days post partum, rose to exceed 0.5 ng/ml plasma for 4.0 +/- 0.4 days, declined for 5.0 +/- 0.5 days and then rose again to normal luteal-phase levels. First oestrus preceded the initial rise in progesterone in 1 cow and followed it is 4. Ovarian palpation revealed considerable follicular development before the initial rise in progesterone, but no clearly discernable corpus luteum until normal luteal-phase progesterone levels were detected. Plasma concentrations of oestradiol-17 beta fell after parturition and, although very variable, showed no apparent trend thereafter. Plasma concentrations of LH varied in an episodic manner, with an apparent increase in frequency and magnitude of peaks up to 10-33 days before the first elevation in plasma progesterone. Subsequently there was little change, except for a decline in peak LH concentrations after the initial elevation in plasma progesterone.

Animals↗
PubMed1973

Halophilic bacteria susceptibility to peracetic acid vapor and ethylene oxide.

Extremely to slightly halophilic bacteria were tested for susceptibility to two sterilizing agents, peracetic acid (PAA) and ethylene oxide (ETO). PAA susceptibility was explored by two methods: an agar plate (constant pH of 7.2) and a filter strip (constant incubation period of 37 days); 100% susceptibility was obtained by both methods. The dosage (0.5 ml/min) was applied to a filter pad in a petri dish cover. Glove box experiments with ETO (input 1.5 lb. [ca. 680.4 g]/24 hr, the only constant) yielded 100% susceptibility for all halophiles tested. These experiments demonstrated the efficacy of two lethal agents for extreme halophiles, PAA and ETO. Variation in pH did not affect susceptibility.

Acetates↗