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Biomedical subjects

R Cooper

Publications and source records attributed to R Cooper.

At least 19 recordsLinked to original sources

Survival of heart failure patients with preserved versus impaired systolic function: the prognostic implication of blood pressure.

The impact of impaired versus preserved systolic function on survival of patients with heart failure was investigated in 78 patients with decompensated heart failure. Patients were classified on the basis of their left ventricular systolic performance, as defined by fractional shortening (FS); group I (n = 56) had impaired systolic function (FS less than 24%) and group II (n = 22) had preserved systolic function (FS greater than or equal to 24%). Mean ejection fraction was 15 +/- 5% and 40 +/- 13% for these groups, respectively. By the end of 48 months, 36 patients in group I had died compared with only 22 patients in group II (p less than 0.05). Both systolic and diastolic blood pressure were significantly lower in the deceased patients compared with the survivors in group I (p less than 0.05). There was a trend for an opposite direction in the relationship of blood pressure to mortality in group II. We conclude that the prognosis of patients with heart failure and preserved systolic function is more favorable than that of those with impaired function, and that blood pressure may have a differential prognostic meaning in the two groups.

Blood Pressure

Effect of doxapram on the rate of recovery from atracurium and vecuronium neuromuscular block.

We have studied the effect of doxapram on the rates of spontaneous and neostigmine-induced recovery from neuromuscular block with atracurium and vecuronium, by measurement of the time to recovery of T1 (first twitch in the train-of-four) from 25 to 75% of control (recovery index, RI). After each neuromuscular blocking drug, RI was measured without administering either doxapram or neostigmine (control group), or after administration of doxapram 1 mg kg-1, neostigmine 50 micrograms kg-1 or a combination of doxapram and neostigmine, in groups of 10 patients. RI was significantly longer after vecuronium in the presence of doxapram compared with control (20.1 min vs 14.6 min). There was no significant difference in the RI after atracurium in the presence of doxapram compared with control (12.5 min vs 11.8 min) or when neostigmine was administered with or without doxapram (2.4 min vs 2.4 min, respectively after vecuronium; 3.3 min vs 2.9 min, respectively, after atracurium).

Adolescent

Comparison of intubating conditions after administration of Org 9246 (rocuronium) and suxamethonium.

We have assessed intubating conditions after administration of Org 9426 (rocuronium) 600 micrograms kg-1 at 60 or 90 s in groups of 20 patients anaesthetized with thiopentone, nitrous oxide in oxygen and small doses of fentanyl, and compared the data with those obtained after suxamethonium 1 mg kg-1 in similar groups of patients. The influence of prior suxamethonium administration on the potency of Org 9426 was studied also by constructing a dose-response curve. Intubating conditions after Org 9426 were found to be clinically acceptable (good or excellent) in 95% of patients at 60 s and in all patients at 90 s and in all patients at both times after suxamethonium. The average time for the onset of block following Org 9426 at this dose was 89 s (which is shorter than with any of the currently available non-depolarizing neuromuscular blocking drugs); the duration of clinical relaxation (25% recovery of twitch height) 30 min. Prior administration of suxamethonium did not appear to influence the potency of Org 9426.

Adolescent

Dose-response relationships for neostigmine antagonism of vecuronium-induced neuromuscular block in adults and the elderly.

We have studied the dose-response relationship for neostigmine in 36 adult (ages 18-50 yr) and 36 elderly (ages > 70 yr) subjects during antagonism of neuromuscular block induced by vecuronium. All patients received vecuronium 0.08 mg kg-1 and neuromuscular block was monitored mechanomyo-graphically using the train-of-four (TOF) mode of stimulation. Six patients of each age group were allocated randomly to receive neostigmine 5, 15, 25, 35 or 45 micrograms kg-1 or saline at 10% recovery of T1 (first response in the TOF). TOF ratios were recorded continuously over the next 10 min and the values at 1-min intervals from 5 min onwards were used to construct the dose-response relationships. There was a significant difference (P < 0.05) in the time to spontaneous recovery of T1 to 10% between the adults (24 (SD 5.5) min) and the elderly (33 (7.8) min). Dose-response curves for neostigmine were parallel in the two age groups, but those for the elderly were significantly to the right of the curves for the adults. This suggests an apparently lesser relative potency of neostigmine, or the requirement of a larger dose, in the elderly for attaining antagonism of a moderately intense vecuronium block at the same time as in adults.

Adolescent

A phase II study of recombinant interleukin-2 with or without recombinant interferon-beta in non-Hodgkin's lymphoma. A study of the Cancer and Leukemia Group B.

Interleukin-2 (IL-2) and interferon-beta (IFN-beta) have demonstrated activity against lymphoid malignancies, presumably mediated by the augmentation of lymphokine-activated killer (LAK) cell and natural killer (NK) cell activity. There is in vitro and in vivo evidence to suggest that the combination of IL-2 and IFN-beta is synergistic. The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II trial of IL-2 with or without IFN-beta in 49 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Overall toxicity was severe, with 17 patients experiencing life-threatening toxicity. Three patients had treatment-related deaths. Responses were noted in seven patients (17%). There were no meaningful differences between treatment arms in toxicity profile, response rate, or modulation of in vivo NK and LAK activity. We conclude that IL-2 with or without IFN-beta is not effective therapy for NHL in the doses and schedule used in this study.

Adult

Blood vitamin concentrations during the acute-phase response.

OBJECTIVES: To investigate the effect, if any, of the acute-phase response on blood vitamin concentrations and to test the hypothesis that these concentrations may change during stress. DESIGN: Open study, utilizing a volunteer sample of patients. SETTING: Tertiary care center. PATIENTS: Twenty-six healthy adult volunteers (14 female and 12 male); 25 volunteers underwent uncomplicated orthopedic surgery and one suffered traumatic limb fractures. INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: The presence of a systemic acute-phase response was documented by the determination of serum C-reactive protein concentrations. Blood vitamin concentrations were determined from sequentially collected blood samples over a 7-day period, and compared with entry values. RESULTS: The presence of the acute-phase response was documented by significant and transient increases in C-reactive protein values. This response was accompanied by significant and transient decreases in the concentrations of leukocyte vitamin C, and in plasma concentrations of vitamin A, retinol-binding protein, vitamin E, total lipids, pyridoxal-5'-phosphate, and albumin. Blood concentrations of pyridoxal-5'-phosphate, retinol-binding protein, and leukocyte vitamin C decreased to values below the respective normal ranges. These concentrations normalized without any therapeutic interventions. CONCLUSIONS: We demonstrated transient, but significant, decreases in blood vitamin concentrations during the acute-phase response. Recommendations regarding daily supplementation with these vitamins in clinical practice cannot be made on the basis of these results, as the functional importance of these observations is not, at present, clear. However, what is clear is that biochemical vitamin concentrations, determined during the acute-phase response, should be interpreted with care.

Acute-Phase Reaction

Clinical evaluation of doxacurium chloride.

Doxacurium was administered to 50 adult patients for determination of potency (n = 10), onset and duration of clinical relaxation (n = 40). Cumulative dose-response showed the ED95 to be 33.24 micrograms.kg-1 (95% confidence limits 27.4-39.3). Doxacurium 33 micrograms.kg-1 was then administered to four groups of 10 patients each who had anaesthesia maintained with either fentanyl-droperidol or halothane and nerve stimulation carried out with single-twitch stimulation at 0.1 Hz or train-of-four stimulation at 2 Hz every 12 s. The onset and duration showed wide individual variation. The mean (SD) times to occurrence of maximal block were 8.5 (4.6), 6.1 (1.9), 6.7 (1.8) and 4.7 (1.3) min in the single twitch-fentanyl, train-of-four--fentanyl, single twitch-halothane and train-of-four--halothane groups respectively, although it ranged from 3.4 to 13.1 min in individual patients. The mean (SD) durations of clinical relaxation (recovery of single twitch or first response in train-of-four to 25%) were 65 (22.8), 52 (21.7), 70 (33.4) and 72 (21.0) min respectively with individual values ranging from 31 to 103 min. Although halothane administration increased the duration of clinical relaxation and train-of-four stimulation accelerated the onset of effect, the changes due to these were not significant. There were no adverse effects on heart rate or indirectly measured arterial pressure.

Adult

Onset and duration of action of vecuronium in the elderly: comparison with adults.

The onset and duration of action of vecuronium were studied in young adult (n = 30; mean age 34 +/- 11.1 (s.d.) yr), middle-aged (n = 20; mean age 60 +/- 5.8 yr) and elderly patients (n = 30; mean age 80 +/- 4.6 yr) anaesthetised with thiopentone, nitrous oxide in oxygen and halothane. Neuromuscular block was monitored by applying the train-of-four (TOF) stimulation at 2 Hz to the ulnar nerve every 12 s. Half the patients in each group received 0.08 and the other half 0.12 mg kg-1 of the relaxant. The time to return of T1 (first response in the TOF sequence) to 25% of control was 28 +/- 5.2 (s.d.), 34 +/- 7.1 and 39 +/- 10.2 min following 0.08 mg kg-1 dose (P less than 0.05 between the elderly and young adults) and 45 +/- 9.2, 48 +/- 6.2 and 69 +/- 19.2 min following 0.12 mg kg-1 dose, respectively, in the three age groups (P less than 0.05 between the elderly and the other two groups). The recovery indices (time for 25-75% recovery of T1) after the 0.08 mg kg-1 was 9.6 +/- 3.4, 13.6 +/- 5.1 and 17.4 +/- 6.1 min, respectively (P less than 0.05 between the elderly and young adults). There was no significant difference in any of the parameters between the young adults and the middle-aged. The onset of block at each dose was not significantly different between the three age groups; however, the time to maximum effect was significantly shorter with the higher dose in the young and the middle-aged, but not in the elderly. Regression analysis of the data between age and the duration of action and recovery index suggested a significant prolongation (P less than 0.05) of these parameters in the elderly.

Adult

Intensive combination chemotherapy, concurrent chest irradiation, and warfarin for the treatment of limited-disease small-cell lung cancer: a Cancer and Leukemia Group B pilot study.

PURPOSE: In prior Cancer and Leukemia Group B (CALGB) studies, combined chemotherapy and thoracic irradiation was superior to chemotherapy alone in limited-disease (LD) small-cell lung cancer (SCLC). A combined modality pilot study was performed to test the feasibility of adding warfarin to aggressive chemoradiotherapy for LD SCLC. PATIENTS AND METHODS: Combination chemotherapy with doxorubicin 45 mg/m2 intravenously (IV) on day 1, cyclophosphamide 800 mg/m2 IV on day 1, and etoposide (ACE) 80 mg/m2 on days 1 to 3 was given every 21 days for the first three courses. The fourth and fifth courses substituted cisplatin 33 mg/m2 IV on days 1 to 3 for the doxorubicin, with concurrent chest irradiation to a total of 4,000 cGy given in 20 fractions during a 4-week period followed by a boost of 1,000 cGy in five fractions during a 1-week period. Prophylactic cranial irradiation, 3,000 cGy was given concurrently in 10 fractions during a 2-week period. Courses 6 to 8 again used ACE chemotherapy, but courses 4 to 8 were given on a 28-day schedule with dose adjustment for hematologic or renal toxicity. Warfarin was given throughout the treatment period titrated to achieve a prothrombin time (PT) of 1.5 to 2 times the control. Patients with histologically proven limited-stage SCLC, good performance status, and normal renal, hematologic, and hepatic functions were eligible. RESULTS: Sixty-one of 66 patients entered onto the study were eligible and assessable. Fifty-four (89%) (95%) confidence interval [CI], 78% to 95%) experienced an objective response, 35 (57%) achieved a complete response (CR) (95% CI, 44% to 70%), and 17 (28%) achieved a partial response (95% CI, 16% to 39%). Median durations were CR, 26.3 months; failure-free survival, 11.8 months; and survival, 18 months. Forty-one percent of the patients were alive at 2 years, 33% were alive at 3 years, and 25% were alive at 4 or more years. Median follow-up for survivors is 5 years (range, 3.5 to 5.9 years). Severe or life-threatening myelosuppression occurred in 90%, infection occurred in 34%, fever without documented infection occurred in 26%, and pulmonary toxicity occurred in 6%. Another 6% of patients experienced severe or life-threatening hemorrhages. There were four treatment-related fatalities. The pulmonary toxicities have been associated with the resumption of ACE chemotherapy after chest irradiation. CONCLUSIONS: These highly encouraging response and survival results compare favorably with any prior CALGB group study. Although they are somewhat more toxic, they are comparable to the best published results. A randomized study that examines the role of warfarin is underway.

Adult

Sch 42137, a novel antifungal antibiotic from an Actinoplanes sp. Fermentation, isolation, structure and biological properties.

A novel polycyclic xanthone, Sch 42137, related to the albofungin family of compounds was isolated from culture broth. Its structure was determined by detailed spectroscopic studies and comparison of circular dichroic studies to related compounds albofungin and simaomicin. Sch 42137 exhibited MIC values less than 0.125 micrograms/ml against yeasts and dermatophytes. Details are presented herein.

Actinomyces

Macrolactams: two novel homologous series of compounds produced by Actinomadura sp. SCC 1778.

Eight antifungal compounds were identified from the fermentation of Actinomadura sp. SCC 1778. This culture produces four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, mycosamine, and four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, 3,6-dideoxy-3-amino-L-talopyranose. Five of the compounds identified were novel macrolactams. All these compounds exhibit antifungal activity against Candida spp. with geometric mean MICs ranging from approximately 1.0 micrograms/ml for the higher homologs to 30 micrograms/ml for the lower homologs.

Actinomycetales

Campylobacter jejuni enteritis mistaken for ulcerative colitis.

Campylobacter jejuni is the most common bacterial cause of gastroenteritis and is often missed by routine stool cultures. Patients may present with a clinical syndrome and endoscopic findings that are similar to acute ulcerative colitis. Ciprofloxacin is currently the recommended antibiotic therapy.

Adult

Lupus nephritis. Part II. A clinicopathological correlation and study of outcome.

A 5-year retrospective study of lupus nephritis at Tygerberg Hospital was performed in an attempt to document the clinical and histological spectrum of the disease and to study the outcome of the illness. Activity and chronicity scores were used in addition to the World Health Organisation classification system. Of 55 biopsies from 51 patients reviewed, 6 were class II, 13 class III, 32 class IV and 4 class V. There were 19 deaths and in 15 of these the histological classification was IV. Renal failure and infections, often with uncommon pathogens, were the most important causes of death. Serum creatinine values and creatinine clearance at the time of biopsy or follow-up, and hypertension at follow-up showed a significant relationship with outcome. WHO class IV was associated with a poor outcome (P = 0.048) when compared with the other WHO classes combined. Activity scores showed a significant relationship to the outcome (P = 0.018). The anticardiolipin antibodies IgG and IgM were not associated with WHO class or outcome. The study revealed a spectrum of histological results similar to that of other studies, with a high mortality rate, particularly in class IV disease. Poor renal function, persistent hypertension, histological classification IV, and high activity scores were found to be important prognostic indicators.

Adolescent

Characterization of a candidate gene for GP72, an insect stage-specific antigen of Trypanosoma cruzi.

The Trypanosoma cruzi insect stage-specific antigen GP72 was purified from epimastigotes and the amino acid sequences of peptide fragments determined. Oligonucleotides derived from these data were used to amplify and clone a cDNA sequence, which was used to isolate a full-length gene. All the sequenced peptides were encoded within the gene. The characteristics of the encoded 62,600-Da protein, including a potential amino-terminal signal sequence, a hydrophobic carboxy-terminus, and a large number of potential O-glycosylation sites, are consistent with the properties of GP72. No sequence homologies were found in searches of DNA and protein data banks. GP72 is encoded by a single pair of non-telomeric allelic genes.

Amino Acid Sequence

The effects of the falling therapeutic and subtherapeutic barbiturate blood levels on electrocerebral silence in clinically brain-dead children.

In a retrospective study at a large children's hospital, we identified 92 children who had received barbiturates that were simultaneously discontinued at the time they were being evaluated for brain death in the presence of electrocerebral silence and clinical brain death by physical exam. Of these 92 children, 67 had barbiturate levels that were monitored from initial therapeutic or subtherapeutic levels. Repeat EEGs were obtained in 76 patients, and in all electrocerebral silence and clinical brain death (by exam) persisted despite the lower barbiturate levels. The study suggests that therapeutic and subtherapeutic barbiturate levels have no effect on the outcome of children who fulfill the criteria for brain death.

Adolescent

Socioeconomic status and cancer survival.

Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.

Adolescent

Elevated pulmonary artery pressure. An independent predictor of mortality.

Analyses in this study were based on hemodynamic and angiographic data obtained in a cohort of 1,371 predominantly black patients during right and left heart catheterization. All patients were followed up prospectively for a mean of 117 weeks, and 103 fatal events were recorded. In Cox survival analysis, three variables were found to be independently related to survival: pulmonary artery mean pressure (PAMP), number of stenosed vessels, and left ventricular (LV) ejection fraction (p less than 0.01); in multivariate stepwise analysis, PAMP entered the model first with the largest chi 2 value of the three prognostic variables (chi 2 = 33.4; p less than 0.0001). The PAMP was 32 percent higher in decedents compared with survivors (25 + 11 mm Hg vs 19 + 8 mm Hg, p less than 0.01 [mean, SD]) and a 10 mm Hg increase in PAMP was associated with a more than fourfold increase in the relative risk of dying; this finding was independent of pulmonary vascular resistance and therefore could not be attributed to primary pulmonary vascular or parenchymal disease. In both the subgroup of 1,118 patients with a normal LV ejection fraction (greater than 50 percent) and the 253 patients with a reduced ejection fraction (less than 50 percent), PAMP emerged as an independent predictor of mortality (p less than 0.0001 and 0.01, respectively), and is therefore a marker of cardiac disease beyond impairment of systolic contractile function. Among patients without obstructive coronary artery disease, PAMP alone provided prognostic information in the multivariate survival analysis.

Black People

Blood pressure and educational level among factory workers in Ibadan, Nigeria.

An epidemiological survey of blood pressure was carried out among men employed at a single factory in Ibadan, Nigeria. All available employees participated, with only four persons excluded at the time of analysis for missing data. Hypertension was uncommon (blood pressure greater than or equal to 160/95 = 8%) and little rise in mean blood pressure was observed with age. Obesity was likewise uncommon, although body mass index was related to blood pressure (r = 0.22; P less than 0.01). Contrary to reports from Western industrialised countries, education was found to have a significant positive association with blood pressure, and this finding was independent of age, body mass index, pulse, and alcohol consumption. The process of modernisation is associated with rising blood pressure in West Africa at the present time, but the absolute risk remains low.

Adolescent