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Biomedical subjects

R Townsend

Publications and source records attributed to R Townsend.

At least 37 records · Page 2Linked to original sources
PubMed1995

Methodological and conduct principles for pharmacoeconomic research. Pharmaceutical Research and Manufacturers of America.

In January 1995, the Pharmaceutical Research and Manufacturers of America (PhRMA) adopted a voluntary set of principles to provide guidance for its member companies on the conduct and evaluation of pharmacoeconomic research. The principles were prepared by a working group of pharmacoeconomic scientists from the PhRMA Task Force on the Economic Evaluation of Pharmaceuticals. The principles were reviewed by a panel of academic experts and outside reviewers at each stage of their development. The PhRMA document consists of a set of broad principles that will foster high quality pharmacoeconomic research without impeding further methodological development of the field. Specific recommendations are offered in those methodological areas for which general agreement exists. However, no attempt was made to force a consensus for those methodological issues which have yet to be resolved. The principles address methodology and reporting of research rather than sponsor-investigator relationships or conflict of interest issues, which have been addressed elsewhere. This approach is based on the belief that the scientific integrity of pharmacoeconomic research is best ensured through the soundness of the research methods used and the full disclosure and transparency of all methods, analyses and results.

Communication↗
PubMed1994

Both T cells and macrophages are targets of kappa-opioid-induced immunosuppression.

We have previously shown that antibody responses are inhibited following administration of kappa-opioid agonists. We found that the inhibition was blocked by either naloxone or the kappa-selective antagonist norbinaltorphimine. This inhibitory activity is apparent after short-term treatment with the kappa-opioid agonist. In an attempt to identify the cell populations which serve as the target for this immunosuppressive effect, we have carried out cell fractionation analyses to generate isolated T cells and macrophages. Using multiple cell fractionation methods, we have determined that short-term treatment of either T cells or macrophages with the kappa-opioid agonist U50,488H results in significant inhibition of in vitro antibody responses. We also find that the inhibition of both T cell and macrophage activity can be blocked by naloxone. These studies demonstrate that resting T cells and macrophages express kappa-opioid receptors and exhibit significant opioid responsiveness prior to activation by antigen.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Evaluation of cisplatin and DTIC in inoperable stage III and IV melanoma. A Southwest Oncology Group study.

The Southwest Oncology Group entered 62 patients with Stage IV or inoperable Stage III (one patient) melanoma into SWOG protocol 8804 and treated them with cisplatin 100 mg/m2 and DTIC 750 mg/m2 i.v. infusion over 15-30 minutes. There were 18 patients with brain metastases and four ocular primaries. Five patients, all without bain metastases, were ineligible. Responses of 8 patients could not be determined, and 11 patients received only one course of treatment. Of the eligible patients, 46 (81%) had some hematologic toxicities, with 31 of these (67%) having grade III or worse. There were 23 patients (40%) with renal toxicities. The miscellaneous toxicities were muscle weakness, flu-like symptoms, and fatigue. Five patients died while on treatment. There were no complete responses. Eight patients had partial responses ranging from 1.5 to 10.5 months, although two patients were still alive at 30.4 and 30.9 months. The estimated response rate for patients with brain metastases was 11%. The estimated response rate for patients without brain metastases was 13%. If one unconfirmed partial response is included, the overall response rate is 14% with a 95% confidence interval of 6% to 26%. It is concluded that DTIC and cisplatin have definite activity in melanoma, but, at least in this population, the toxicity is treatment-limiting and requires close attention to patient care.

Adult↗
PubMed1991

Walk-in refrigerators are key to proper cold storage.

Often overlooked as an important kitchen design element, properly sized refrigeration and freezing equipment is an important contributor to a kitchen's functionality. In many operations, particularly large-volume units, walk-in refrigerators are the anchors of a good cold-storage system. A walk through three different foodservice operations--a college, a hotel and a hospital--finds walk-ins at work.

Equipment Design↗
PubMed1991

Renin profile, race, and antihypertensive efficacy with atenolol and labetalol.

In this randomised double-blind parallel study, we compared the efficacy of labetalol and atenolol in a group of black (n = 33) and white (n = 34) hypertensives with uncomplicated essential hypertension after obtaining pretreatment renin profiles. After single-blind placebo (14-21 days), patients with standing diastolic BP between 105-119 mmHg were randomised to receive either labetalol (100-800 mg twice daily) or atenolol (50-100 mg once daily) to achieve a DBP less than 90 mmHg. Dosage titration occurred at weekly intervals for labetalol and biweekly for atenolol. The supine BP decrease with atenolol was -18/-14 vs. -6/-6 mmHg in whites vs. blacks respectively. With labetalol, it was -13/-12 in whites and -2/-7 mmHg in blacks. Standing BPs were: -19/-14 vs. -4/-5, whites vs. blacks with atenolol and -17/-17 vs. -19/-9 mmHg with labetalol. Neither labetalol nor atenolol was as effective in black compared with white hypertensives. The atenolol but not labetalol BP response was positively correlated with pretreatment renin values.

Atenolol↗
PubMed1990

Left ventricular filling in hypertensive blacks and whites following adrenergic blockade.

Left ventricular diastolic filling was investigated in 12 black and 15 white subjects before and after double-blinded randomized treatment of mild to moderate hypertension with combined alpha- and beta-adrenergic receptor blockade (labetalol) and beta-blockade alone (atenolol). At baseline (off medication), both groups were similar for age (46 +/- 8 years v 48 +/- 12 years), mean blood pressure (121 +/- 8 mm Hg v 115 +/- 8 mm Hg), left ventricular dimensions, left ventricular mass index (118 +/- 24 g/m2 v 113 +/- 13 g/m2), and left ventricular filling as reflected by transmitral flow velocity ratio A/E (0.97 +/- 0.33 v 0.92 +/- 0.19, normal age-matched control A/E ratio is 0.64 +/- 14). There were 6 blacks and 6 whites in the labetalol group; 6 blacks and 9 whites in the atenolol group. At six weeks of treatment, whites in the labetalol group showed a significantly greater drop in mean blood pressure (114 +/- 7/102 +/- 11, P less than .007 v 123 +/- 9/114 +/- 11, P = NS) and correspondingly greater improvement in A/E ratio (1.04 +/- 0.14/0.74 +/- 0.23, P less than .024 v 1.02 +/- 0.23/0.89 +/- 0.16, P = NS). However, this difference was no longer significant when controlling for age and blood pressure level. In the atenolol group, whites showed a significant increase in the rapid filling phase velocity E, while late filling phase velocity A significantly dropped only in blacks, without significant improvement in A/E ratio in either subgroup. In conclusion, greater improvement in left ventricular filling is seen with combined alpha-beta-blockade than beta-blockade alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension.

Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization.

Adult↗
PubMed1990

Evaluation of the interaction of lithium and alprazolam.

A potential pharmacokinetic interaction between lithium and alprazolam was studied in 10 normal subjects. Pharmacokinetic parameters were determined from the following regimens: single-dose alprazolam, multiple-dose lithium, and multiple-dose alprazolam with lithium. Steady-state alprazolam clearance during multiple dosing with lithium was not different from that with the single dose of alprazolam. Lithium renal clearance decreased when it was coadministered with alprazolam (31.2 vs. 22.4 ml/minute, p less than 0.05). There was a small but significant increase in the steady-state area under the curve for lithium in the presence of alprazolam (10.3 vs. 11.1 mEq/hour/liter). The small increase in the serum lithium concentrations and decrease in lithium renal clearance was probably the result of lower urine flow rates (1.46 vs. 0.98 ml/minute, p less than 0.05) with the combination of the drugs. This is supported by a weak but significant linear relationship between urine flow rates and lithium renal clearance (N = 57, r = 0.353, p = 0.007). The percent of daily lithium dose recovered at steady-state from the 24-hour urine collection decreased significantly from 93.6% to 78.2% in the presence of alprazolam. This suggests that alprazolam may decrease lithium absorption. The results of this study do not support a definitive interaction of lithium and alprazolam and there is little clinical significance to the small rise in serum lithium concentrations.

Adult↗
PubMed1989

The power of the Z statistic: implications for trauma research and quality assurance review.

The Z statistic can be used to test whether the observed number of survivors in a specific trauma population is significantly different from what would be expected based on the Major Trauma Outcome Study (MTOS) norms. However, as with any statistic, inferences based on the Z statistic should be made with care. This is particularly true when a non-significant Z statistic is observed. The purpose of this paper, using data from a large, urban trauma registry, is to illustrate how the power of the Z statistic, or its ability to detect a difference between observed and expected survival, is influenced by the magnitude of the difference, the direction of the difference, the survival probability distribution of the study population, and the sample size. The implications for trauma research and quality assurance review are discussed.

Craniocerebral Trauma↗
PubMed1989

Intravenous nicardipine for the treatment of severe hypertension. A double-blind, placebo-controlled multicenter trial.

A placebo-controlled, double-blind multicenter trial was conducted in 123 patients with severe hypertension to examine the efficacy and safety of intravenously administered nicardipine hydrochloride in controlling blood pressure. Seventy-three patients were initially randomized to receive nicardipine treatment. This group had an initial blood pressure of 213 +/- 3/126 +/- 2 mm Hg. Sixty-seven patients achieved the therapeutic goal (diastolic blood pressure less than or equal to 95 mm Hg; systolic blood pressure less than or equal to 160 mm Hg). Fifty patients were randomized to receive placebo solution. Blood pressure in these patients was 216 +/- 3/125 +/- 2 mm Hg. No patient in this group achieved the therapeutic goal during the "blinded" portion of the study. Forty-four of 49 patients who did not respond to placebo administration responded to subsequent treatment with nicardipine. Patients with end-organ damage were included in the study. These included patients with left ventricular hypertrophy, retinopathy, and renal insufficiency. Patients with and without end-organ damage responded equally well to nicardipine treatment. Serious adverse experiences were infrequent, the most common adverse reaction being headache in 24% of the patients studied.

Dose-Response Relationship, Drug↗
PubMed1988

Pharmacokinetics, toxicity, and short-term results of cisplatin hyperthermic isolated limb perfusion for soft-tissue sarcoma and melanoma of the extremities.

Fifty-nine patients with melanoma or soft tissue sarcoma of the extremities underwent hyperthermic isolated limb perfusion utilizing cisplatin and wide local excision. Doses of cisplatin ranged from 0.75 to 2 mg/kg. The mortality and morbidity rates were 0 and 6.8 percent, respectively. Pharmacokinetic studies indicate that cisplatin is rapidly bound to perfused tissues and remains bound for 1 month. Maximum tumor response in sarcomas occurs 1 to 2 weeks after perfusion, compared with 1 month after perfusions with l-phenylalanine mustard and actinomycin D. Local and regional recurrence rates were 0 and 3.4 percent, respectively, at 1 year. Further studies of hyperthermic limb perfusions with cisplatin are warranted.

Adult↗
PubMed1988

Left ventricular function in mild hypertension after adrenergic blockade.

We previously used the Doppler transmitral flow velocity ratio A/E (A = late ventricular filling peak velocity; E = early ventricular filling peak velocity) and the age-adjusted ratio A/E/Age to detect left ventricular filling abnormalities in untreated mild hypertension. This study is a double-blind assessment of the effect of combined alpha- and beta-blockade (labetalol) and beta-blockade alone (atenolol) on left ventricular filling in mild hypertension. Twenty-seven patients blindly randomized to labetalol (12 patients) and atenolol (15 patients) treatment completed the echocardiographic and Doppler studies. Clinical and echo-Doppler data obtained at baseline and 6 weeks after initiation of therapy showed no difference between the two groups for age (49 +/- 10 vs 46 +/- 10 years), mean blood pressure (before therapy, 118 +/- 9 vs 117 +/- 8 mm Hg; after therapy, 108 +/- 12 mm Hg), left ventricular dimensions, wall thickness, systolic function, and mean late filling velocity A. There was no significant change in left ventricular mass and mass index with labetalol (left ventricular mass, 211 +/- 36 vs 216 +/- 38; mass index, 110 +/- 17 vs 112 +/- 16) or atenolol (245 +/- 41 vs 271 +/- 65; 120 +/- 18 vs 130 +/- 35). The mean velocity E, A/E, and A/E/Age ratios significantly improved with labetalol (p less than 0.05) but did not change significantly with atenolol. The improvement in A/E and A/E/Age ratios was primarily due to an increase in early filling velocity E.(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol↗
PubMed1986

Infectious mutants of cassava latent virus generated in vivo from intact recombinant DNA clones containing single copies of the genome.

Intact recombinant DNAs containing single copies of either component of the cassava latent virus genome can elicit infection when mechanically inoculated to host plants in the presence of the appropriate second component. Characterisation of infectious mutant progeny viruses, by analysis of virus-specific supercoiled DNA intermediates, indicates that most if not all of the cloning vector has been deleted, achieved at least in some cases by intermolecular recombination in vivo between DNAs 1 and 2. Significant rearrangements within the intergenic region of DNA 2, predominantly external to the common region, can be tolerated without loss of infectivity suggesting a somewhat passive role in virus multiplication for the sequences in question. Although packaging constraints might impose limits on the amount of DNA within geminate particles, isolation of an infectious coat protein mutant defective in virion production suggests that packaging is not essential for systemic spread of the viral DNA.

DNA Viruses↗
PubMed1986

Synthesis of viral DNA forms in Nicotiana plumbaginifolia protoplasts inoculated with cassava latent virus (CLV); evidence for the independent replication of one component of the CLV genome.

Totipotent leaf mesophyll protoplasts of Nicotiana plumbaginifolia, Viviani were inoculated with cassava latent virus (CLV) or with full length copies of CLV genomic DNAs 1 and 2 excised from replicative forms of M13 clones. Virus specific DNAs began to appear 48-72h after inoculation with virus or cloned DNAs, coincident with the onset of host cell division. Infected cells accumulated supercoiled forms of DNAs 1 and 2 as well as progeny single-stranded (ss) virion (+) sense DNAs representing each component of the genome. Both supercoiled and ss molecules were synthesised by cells inoculated with cloned DNA 1 alone but DNA 2 failed to replicate independently.

Cell Division↗