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Biomedical subjects

R Heath

Publications and source records attributed to R Heath.

At least 19 recordsLinked to original sources

Response-time dynamics: evidence for linear and low-dimensional nonlinear structure in human choice sequences.

Response time (RT) is a commonly used measure of cognitive performance, which is usually characterized as stochastic. However, useful information may be hidden in the apparently random fluctuations of RT. Dynamical systems analysis techniques allow an exploration of the alternative hypothesis that RT fluctuations are deterministic, albeit in a complex manner. We applied careful task construction and noise-reduction and surrogate series tests to show that RT series from a forced-pace serial response-time task have low-dimensional chaotic characteristics. In Experiment 1, 80% of subjects' filtered RT series had low dimensionality, sensitive dependence on initial conditions, spectra close to 1/f, and stable attractor geometry across sessions. In Experiment 2, we showed that the size of the inter-stimulus interval (ISI) determined the number of subjects with low-dimensional chaotic series. A small ISI caused 100% of subjects to respond in the chaotic regime, whereas only 25% had a low-dimensional chaotic RT component when the ISI was large. We argue that demanding task requirements cause a reduction in the dimensionality of the dynamics, producing RT fluctuations that may reflect a response strategy for controlling RT.

Adult↗

Agreeing goals.

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Aged↗

Recombinant Neisseria meningitidis transferrin binding protein A protects against experimental meningococcal infection.

To better characterize the vaccine potential of Neisseria meningitidis transferrin binding proteins (Tbps), we have overexpressed TbpA and TbpB from Neisseria meningitidis isolate K454 in Escherichia coli. The ability to bind human transferrin was retained by both recombinant proteins, enabling purification by affinity chromotography. The recombinant Tbps were evaluated individually and in combination in a mouse intraperitoneal-infection model to determine their ability to protect against meningococcal infection and to induce cross-reactive and bactericidal antibodies. For the first time, TbpA was found to afford protection against meningococcal challenge when administered as the sole immunogen. In contrast to the protection conferred by TbpB, this protection extended to a serogroup C isolate and strain B16B6, a serogroup B isolate with a lower-molecular-weight TbpB than that from strain K454. However, serum from a TbpB-immunized rabbit was found to be significantly more bactericidal than that from a TbpA-immunized animal. Our evidence demonstrates that TbpA used as a vaccine antigen may provide protection against a wider range of meningococcal strains than does TbpB alone. This protection appears not to be due to complement-mediated lysis and indicates that serum bactericidal activity may not always be the most appropriate predictor of efficacy for protein-based meningococcal vaccines.

Animals↗

Is outpatient laparoscopic cholecystectomy safe and cost-effective? A model to study transition of care.

BACKGROUND: There is increasing pressure to perform traditional inpatient surgical procedures in an outpatient setting. The aim of the current trial was to determine the safety and cost savings of performing laparoscopic cholecystectomy in an outpatient setting using a "mock" outpatient setting. METHODS: Patients who were scheduled for laparoscopic cholecystectomy by four attending surgeons and for whom operating time was available in the outpatient center were studied. All patients received a standardized anesthetic, including ondansetron, and were discharged from the outpatient postanesthesia care unit if appropriate. At discharge, all patients were admitted to a clinical research center where they were observed in a "mock home" setting and monitored for complications that would have necessitated readmission. A decision analysis was created assuming all patients underwent outpatient surgery with either direct admission or discharge to home and readmission if complications developed. RESULTS: Of 99 patients who were enrolled in this study, 96 patients would have met the discharge criteria for home. No major complications were observed in these 96 patients. Eleven patients experienced postoperative nausea and vomiting, 3 of whom required an additional 24 h of hospital observation. In the decision model, the optimal strategy would be to perform the procedure on an outpatient basis and readmit patients only for complications, with an average baseline cost savings of $742/patient. CONCLUSIONS: The results show that outpatient laparoscopic cholecystectomy is safe and cost-effective in selected patients, and that the mock home setting provides a means of studying the safety of transition of care.

Adult↗

Presence of antibodies to canine distemper virus, canine parvovirus and canine adenovirus type 1 in free-ranging jackals (Canis adustus and Canis mesomelas) in Zimbabwe.

A survey of free-ranging jackals (Canis adustus and Canis mesomelas) in Zimbabwe was conducted to determine the prevalence of serum antibodies to canine distemper virus (CDV), canine parvovirus (CPV) and canine adenovirus type 1 (CAV-1). Sera from 16 Canis adustus and 22 Canis mesomelas were collected from 1990 to 1993 from various regions of Zimbabwe and assayed by means of immunofluorescent techniques. Seroprevalence in C. adustus and C. mesomelas respectively were 50% and 63.6% for CDV, 12.5% and 18.2% for CPV and 37.5 and 9.1 for CAV-1. These results demonstrate that jackals are infected with these viruses and may act as reservoirs of them, although their susceptibility to the viruses is not known.

Adenoviruses, Canine↗

Valsartan, a new angiotensin II antagonist; blood pressure reduction in essential hypertension compared with an angiotensin converting enzyme inhibitor, enalapril.

OBJECTIVE: To compare the blood pressure reduction induced by valsartan, a new angiotensin II receptor antagonist, with that induced by enalapril, an angiotensin converting enzyme (ACE) inhibitor in essential hypertension. METHODS: In total 189 adult outpatients with uncomplicated essential hypertension participated in this double-blind study. Patients were allocated randomly in equal numbers to be administered 80 mg valsartan or 20 mg enalapril daily for 12 weeks. Patients whose blood pressure had not been controlled adequately despite 8 weeks of monotherapy were administered additional therapy with 12.5 mg hydroclorothiazide (HCTZ) daily thereafter. Patients were assessed aftger 4, 8 and 12 weeks of therapy. The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure (SDBP) after 8 weeks of therapy. Other variables analyzed included the change in sitting systolic blood pressure and percentage responses after 8 weeks of therapy. RESULTS: Valsartan and enalapril were both effective at lowering the blood pressure. Similar falls were induced in the two groups with a similar time course of blood pressure reduction. The mean decreases in SDBP after 8 weeks of therapy were 13.2 mmHg for valsartan and 12.0 mmHg for enalapril. There was no significant difference between the treatments [P = 0.475, 95% confidence interval of the estimated difference (SBP after therapy - SDBP before therapy) -3.5 to 1.6 mmHg]. After 8 weeks of therapy 60.6% had responded to valsartan and 52.6% to enalapril (P = 0.267). Both treatments were tolerated well. Three patients administered enalapril and one patient administered valsartan discontinued their treatment because it made them cough. CONCLUSION: The data show that 80 mg valsartan is as effective as 20 mg enalapril in the treatment of moderate hypertension and that it is tolerated well.

Journal Article↗

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril.

OBJECTIVE: To compare the antihypertensive efficacy and systemic tolerability of valsartan, a new angiotensin II receptor antagonist, with placebo and with an angiotensin converting enzyme (ACE) inhibitor, enalapril. DESIGN: A total of 348 adult outpatients with mild-to-moderate uncomplicated essential hypertension participated in this double-blind, parallel, study. Patients were allocated randomly in a ratio of 2:2:1 to receive 80 mg valsartan once a day, 20 mg enalapril once a day, or placebo for 8 weeks in general practice. Patients were assessed at 4 and 8 weeks of therapy. MAIN OUTCOME MEASURES: The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure (SDBP) after 8 weeks of therapy. Secondary variables included the change in sitting systolic blood pressure (SSBP) and response rates at 8 weeks. RESULTS: Valsartan and enalapril produced statistically significant reductions in diastolic and systolic blood pressures compared with placebo. Similar falls were found in both of the active treatment groups with mean changes in SDBP at 8 weeks of -9.5 mmHg for valsartan and -9.4 mmHg for enalapril (-4.5 mmHg for placebo). No significant differences between valsartan and enalapril were found for reductions in SDBP or SSBP. Response rates at 8 weeks were significantly greater for valsartan (54%) and enalapril (58%) than for placebo (20%), with no significant difference between the two active treatments. Both valsartan and enalapril demonstrated a consistent antihypertensive effect over time, with 90% of patients with a response at 4 weeks responding at 8 weeks. Both of the treatments were tolerated well. Although the incidence of coughing was generally low in the study, more cases were reported with enalapril (three) than with valsartan (one) or placebo (none). CONCLUSIONS: The data show 80 mg valsartan once a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension. Valsartan is tolerated well and does not appear to be associated with any increase in the incidence of coughing.

Adult↗

Increased unsaturated fatty acid production associated with a suppressor of the fabA6(Ts) mutation in Escherichia coli.

Plasmids that corrected the temperature-sensitive unsaturated fatty acid auxotrophy of strain M6 [fabA6 (Ts)] were isolated from an Escherichia coli genomic library. Subcloning and physical mapping localized the new gene (called sfa for suppressor of fabA) at 1,070 kb on the E. coli chromosome. DNA sequencing revealed the presence of a 227-bp open reading frame which directed the synthesis of a peptide of approximately 8 kDa, which correlated with the correction of the fabA6(Ts) phenotype. However, the sfa gene was an allele-specific suppressor since plasmids harboring the sfa gene corrected the growth phenotype of fabA6(Ts) mutants but did not correct the growth of fabA2(Ts) or fabB15(Ts) unsaturated fatty acid auxotrophs. Overexpression of the sfa gene in fabA6(Ts) mutants restored unsaturated fatty acid content at 42 degrees C, and overexpression in wild-type cells resulted in a substantial increase in the unsaturated fatty acid content of the membrane. Thus, the suppression of the fabA6(Ts) mutation by sfa was attributed to its ability to increase the biosynthesis of unsaturated fatty acids.

Alleles↗

Objective assessment for exercise treatment on the B-200 isostation as part of work tolerance rehabilitation. A random prospective blind evaluation with comparison control population.

The purpose of this study was to assess repeated exercise on the B-200 Isostation as part of rehabilitation work tolerance for nonsurgical patients with lumbar spine disorders. For a consecutive 7-month period, treatment subjects were randomly assigned according to birth date for participation in two groups: a standard work tolerance program only or standard work tolerance program plus inclusion of exercise on the B-200 Isostation. Each patient had similar referral diagnosis requiring conservative treatment. Treatment groups were compared with a control population of volunteers who had neither back pain nor known underlying spinal pathology. All study patients had objective measurement of range of motion, isometric strength, and velocity of motion, on the B-200 Isostation before treatment and at follow-up 3 weeks after treatment. The data showed no significant difference of percent improvement when comparing patients in either of the randomized assigned treatment groups. There was a higher percentage of improvement for each treatment group as compared with the control individuals, however. Based on our study using the B-200 Isostation, there is little objective justification for including exercise on the B-200 dynametric Isostation as part of the rehabilitation routine for improvement of functional physical capacity.

Analysis of Variance↗

Vincristine with high-dose etoposide in advanced breast cancer: a phase II trial of the Piedmont Oncology Association.

Vincristine (VCR) and etoposide (VP-16) have been shown to be synergistic in a murine model, and this combination was studied in a phase II trial. Eligibility required measurable disease, a performance status of 0-2, a life expectancy of > or = 2 months, an interval of at least 3 weeks since the receipt of previous radiation therapy or chemotherapy and recovery from related toxicity, no prior treatment with VCR or VP-16, and no more than two prior chemotherapy regimens (only one for treatment of metastatic disease). Treatment consisted of 0.5 mg i.v. (bolus) VCR followed by 200 mg/m2 VP-16 given over 2 h. Both drugs were given daily for 3 consecutive days every 3 weeks (total dose: VCR, 1.5 mg; VP-16, 600 mg/m2). A total of 18 patients with metastatic breast cancer were accured; 14 had adjuvant chemotherapy and 8 had chemotherapy for advanced disease. As judged by International Union Against Cancer (UICC) criteria, one complete response (CR) and three partial responses (PR) were obtained, for a CR + PR rate of 22% (95% confidence interval, 6%-48%). All responders had soft-tissue involvement only. Six patients had stable disease and 8 showed progression. The median time to treatment failure was 3.5 months, and the median survival from study entry was 8.3 months. The major toxicity was myelosuppression, with 9 patients (50%) experiencing a total WBC of < 1,000/mm3. Grade 2-3 neurologic toxicity was noted in 6 patients (33%) and grade 3 nausea and vomiting was noted in 5 (28%). The combination of VCR and VP-16 is active in advanced breast cancer but is not convincingly superior to either of these agents used alone.

Adult↗

Assessment of masticatory efficiency: new methods appropriate for clinical research in dental practice.

A new chewing test has been assessed in which the test food was contained in a chewable rubber bag. Six subjects chewed ten single 'unbagged' almonds and ten single 'bagged' almonds. The bagged experiments gave generally similar results to unbagged ones in terms of the particle size distribution; they also proved more acceptable to the subjects and eliminated the serious, undefinable loss of chewed particles that occurs intraorally in conventional (unbagged) tests. In this study an optical scanning method was used which provided a simple, fast measurement of individual particles.

Adult↗

Melanoma metastatic to the gastrointestinal tract.

Melanoma is increasing in incidence. An often-unsuspected complication is metastasis to the gastrointestinal tract, which leads to bowel obstruction or intussusception. The most common symptoms in patients with gastrointestinal metastasis are vomiting, abdominal pain and abdominal distention. Metastatic disease should be suspected in any patient with gastrointestinal symptoms and a history of cutaneous melanoma.

Female↗

The predictive value of progesterone receptor levels in endometrial cancer.

Recent reports have suggested that the presence of progesterone receptor correlates with other well known predictors of a favorable outcome for endometrial cancer patients. To test this hypothesis, we reviewed the records of 154 patients who had undergone a hysterectomy for adenocarcinoma of the endometrium, and pelvic irradiation if poor prognostic factors were present. The 3 year disease-free survival for all clinical Stage I patients was 80%. Patients with progesterone receptor levels greater than or equal to 100 had a 3 year disease-free survival of 93% compared with only a 36% 3 year disease-free survival for patients with progesterone receptor less than 100 (p less than .0001, log rank test). To determine whether elevated progesterone receptor was an independent prognostic factor for disease-free survival in endometrial cancer, or just correlated with the other well-known predictors, bivariate and multivariate analyses were conducted. Our results indicate the progesterone receptor levels are the single most important prognostic indicator of 3 year disease-free survival in clinical Stage I endometrial cancer, with only cervical involvement and peritoneal cytology being significant prognostic variables after adjusting for progesterone receptor levels.

Analysis of Variance↗

Peritoneal fluid cytology in endometrial cancer: its significance and the role of chromic phosphate (32P) therapy.

Between 1978 and 1986, 243 patients (all stages) had peritoneal fluid cytology performed while undergoing total abdominal hysterectomy for endometrial carcinoma; 39 (16%) were found to be positive. At 3 years (median follow-up of 30 months) the disease-free survival (DFS) for the 165 negative cytology clinical Stage I patients was 91% compared to only 56% for the 25 positive cytology patients (p less than .001). Of the 25 Stage I positive cytology patients, 14 with greater than one-third myometrial invasion had a DFS of 30% at 3 years as compared to 87% for negative cytology patients with comparable depth of invasion (p less than .001). There was no difference in DFS between the negative and positive cytology Stage I patients who had one-third or less myometrial invasion. Stage I patients with histologic Grade 2 and 3 had a lower 3 year DFS when cytology positive, 49% and 22%, versus 92% and 79% when cytology negative (p less than .001 and p = .03 respectively). In clinical Stage II patients the 3-year DFS was 21% for those with a positive cytology and 59% with a negative cytology. Fourteen of the 25 clinical Stage I positive cytology patients received 15 mCi of intraperitoneal 32P. At 3 years they had a 68% DFS as compared to 27% for those not receiving 32P (p = 0.01). All 11 patients with superficial myometrial invasion (9 received 32P) remained disease-free. The 4 Stage I patients with deep invasion who received 32P therapy had an improvement in abdominal/pelvic control and DFS when compared to 9 similar patients who did not receive 32P (p = .02). For histologic Grade 2 and 3 patients, there was a 64% 3-year DFS in the 32P treated group and 16% for those not receiving 32P (p = 0.02). Although 32P therapy improved DFS in Stage I positive cytology patients its use along with pelvic radiation therapy can lead to complications. Of 9 Stage I patients receiving 32P as well as pelvic irradiation, 4 experienced serious bowel complications requiring surgery. None of the 5 patients receiving 32P only had a complication.

Ascitic Fluid↗