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Biomedical subjects

C Norris

Publications and source records attributed to C Norris.

At least 19 recordsLinked to original sources

Further studies of the effect of zinc on intestinal absorption of calcium in man.

In a previous study dietary supplementation with 140 mg zinc (Zn) as Zn sulfate (ZnSO4) per day significantly decreased absorption of calcium (Ca) during a low Ca intake (230 mg/day) but not during a normal Ca intake (800 mg/day). The purpose of the present study was to determine whether smaller doses of Zn would also inhibit Ca absorption during the 230 mg Ca intake, and whether the 140 mg dose of Zn would inhibit Ca absorption during a Ca intake less than 800 mg/day. To investigate the first aspect, 100 mg Zn as ZnSO4, was given daily during a low Ca intake (230 mg/day) in six studies, and in the second phase, 140 mg Zn as ZnSO4 was given during a Ca intake of of 500 mg/day in five studies. Intestinal absorption of Ca was determined with tracer doses of 47CaCl2 in control studies and in the two Zn supplementation studies. Results showed that 100 mg Zn/day during a low Ca intake (230 mg/day) did not inhibit Ca absorption and that 140 mg Zn given during the 500 mg Ca intake also did not affect the absorption of Ca.

Aged

Comparison of SCH 39304, fluconazole, and ketoconazole for treatment of systemic infections in mice.

SCH 39304 was compared with fluconazole and ketoconazole in a systemic Candida albicans infection in mice (10(6) CFU per mouse). Results were based on survival rates and CFU in kidneys following once-daily oral treatment of 2, 5, or 10 days duration. In normal mice, SCH 39304 (dose to reduce kidney counts by 4 log units, 0.5 mg/kg of body weight) was 3 and 200 times more active than fluconazole and ketoconazole, respectively. In immunocompromised mice (gamma irradiation, 600 rads), SCH 39304 (dose to reduce kidney counts by 4 log units, 1.3 mg/kg) was 35 and greater than 100 times more active than fluconazole and ketoconazole, respectively. In normal mice, when the infecting inoculum varied from 10(5) to 10(7) CFU, only a fivefold increase in the dose to reduce kidney counts by 4 log units was observed with SCH 39304. Excellent protection was also seen when mice were treated with a single oral dose of SCH 39304 up to 24 h prior to infection with C. albicans. Studies in a systemic C. albicans infection model indicated that SCH 39304 is equally efficacious following either oral or intravenous administration. In a systemic Aspergillus flavus infection, mice treated with SCH 39304 (5 mg/kg) survived twice as long (16 days) as those treated with fluconazole (50 mg/kg) or controls did.

Administration, Oral

In vitro and in vivo activities of SCH 42427, the active enantiomer of the antifungal agent SCH 39304.

SCH 39304, a new triazole antifungal agent, is a 50:50 racemic mixture of two enantiomers, SCH 42427 and SCH 42426. The activities of these three compounds were compared in a series of in vitro and in vivo experiments. SCH 42427 was twofold more active in vitro against a variety of yeasts and dermatophytes than SCH 39304, while SCH 42426 was inactive (MICs greater than 64 micrograms/ml). In a systemic Candida albicans infection in mice, SCH 42427 administered orally (p.o.) (50% protective dose [PD50], 0.17 mg/kg of body weight; 50% effective dose, [ED50], 0.47 mg/kg) had greater efficacy than SCH 39304 (PD50, 0.21 mg/kg; ED50, 0.62 mg/kg) and SCH 42426 (greater than 100 mg/kg for PD50 and ED50). In a pulmonary Aspergillus flavus infection in mice, SCH 42427 p.o. (PD50, 13 mg/kg) was also more effective than SCH 39304 (18 mg/kg) and SCH 42426 (greater than 250 mg/kg). In a C. albicans vaginal infection in hamsters, SCH 42427 p.o. (ED50, 3.5 mg/kg) was more active than SCH 39304 (8.5 mg/kg) and SCH 42426 (320 mg/kg). Following topical administration, against a Trichophyton mentagrophytes infection in guinea pigs, SCH 42427 was about 2-fold more active than SCH 39304 and about 100-fold more active than SCH 42426. These and other results indicated that SCH 42427 is the active enantiomer, responsible for all the antifungal activity observed with SCH 39304.

Animals

A permanent transvenous lead system for an implantable pacemaker cardioverter-defibrillator. Nonthoracotomy approach to implantation.

A transvenous lead system for implantable defibrillators would obviate a surgical thoracotomy and reduce the morbidity and mortality associated with implantation. We evaluated the clinical performance of a new nonthoracotomy lead system that included a defibrillation lead in the coronary sinus. At the time of defibrillator implantation, transvenous defibrillation leads were inserted percutaneously through the left subclavian vein into the right ventricular apex (RVA), superior vena cava (SVC), and distal coronary sinus (CS) under fluoroscopic guidance. A subcutaneous patch electrode (SQ) was also available if required. The first single- or dual-pathway electrode configuration that successfully terminated three of four ventricular fibrillation episodes using 18 J or less was implanted. Eleven men and three women aged 39-77 years (60.0 +/- 10.1 years) with left ventricular ejection fraction ranging from 16% to 63% (33.4 +/- 13.1%) were evaluated. Nine presented with ventricular tachycardia, three had ventricular fibrillation, and two had both. A totally transvenous lead system (RVA/CS/SVC) was implanted in seven patients (50%) with a mean defibrillation threshold of 15.6 +/- 2.9 J (10-18 J). Four patients received a partial transvenous lead system (RVA/CS/SQ). An effective nonthoracotomy lead system was not found in three patients; they received epicardial electrodes. After cumulative follow-up of 73 patient-months, nine patients remain alive and free of problems related to the implanted nonthoracotomy leads. One patient died of respiratory failure 3 months after defibrillator implant, and the leads from another patient were removed at 9 months because of bacterial infection. A transvenous lead system that includes a defibrillation lead in the coronary sinus is a safe, reliable, and, at least in the short term, effective nonthoracotomy approach for automatic defibrillator implantation.

Adult

Cyclic AMP modulates sensory-neural communication at the vestibular end organ.

Adenosine 3':5'-cyclic phosphate (cAMP) is a second messenger that plays an important role in mediating neuronal interactions in many systems. A possible role for cAMP in sensorineural communication at the vestibular end organ was studied. The putative roles for cAMP action investigated here were: the ability of cAMP to act as the second messenger for the efferent transmitter, acetylcholine, and the possible involvement of cAMP in modulating spontaneous or mechanically-evoked afferent nerve firing. Levels of cAMP were increased pharmacologically with forskolin, 3-isobutyl-1-methyl xanthine (IBMX) and dibutyryl cAMP. Changes in multiunit afferent nerve firing measured from the ampullar nerve of the semicircular canal, and the transepithelial potential measured across the neuroepithelium of the semicircular canal were recorded. At selected doses, all drugs produced a similar increase in spontaneous multiunit afferent nerve firing with a concomitant decrease in the transepithelial potential. Mechanically-evoked hair cell activity and the response to exogenously applied acetylcholine were unaffected by these drugs. We are suggesting that the excitatory aspects of the acetylcholine response are not mediated via a cAMP-dependent mechanism. However, cAMP does play an important role in modulating spontaneous afferent nerve firing in the semicircular canal. The finding that spontaneous afferent nerve firing can be biochemically modulated without altering mechanically-induced afferent firing is novel and deserves further investigation.

1-Methyl-3-isobutylxanthine

Effect of oat bran muffins on calcium absorption and calcium, phosphorus, magnesium and zinc balance in men.

Metabolic balance studies were conducted in adult human males to investigate the effect of oat bran on the nitrogen, calcium, phosphorus, magnesium and zinc balance, on the intestinal absorption of calcium and on the endogenous fecal calcium, using 47CaCl2 as the tracer. A 40-d control period preceded a 32-d experimental period in which subjects consumed four oat bran muffins daily as part of a constant metabolic diet. No significant changes in the calcium, magnesium or zinc balances were observed, but the nitrogen and phosphorus balances increased. The net or apparent absorption of nitrogen, magnesium and phosphorus expressed per milligram of intake increased significantly in the oat bran period due to the added content of these nutrients in the oat bran muffins. The intake of the oat bran muffins led to a significant increase in urinary phosphorus and significant decreases in urinary calcium and 47Ca excretions. The intestinal absorption of calcium, determined with 47Ca, did not change, whereas the endogenous fecal calcium increased slightly but significantly.

Adult

Feasibility of long-term electrocardiographic monitoring with an implanted device for syncope diagnosis.

Patients with infrequent recurrent syncope undiagnosed after extensive noninvasive and invasive testing pose a diagnostic and therapeutic dilemma. The purpose of this pilot study was to assess the feasibility of using an implanted, long-term monitor as an aid to diagnosis in these patients. This was done using commercially available pacemakers with monitoring functions. Sixteen patients (eight males and eight females), aged 59.7 +/- 17 years who had unexplained syncope despite a 12-lead electrocardiogram, repeated Holter monitoring, exercise testing, echocardiography, an electrophysiological study, and a tilt test (n = 6), were entered into the study. Patients had experienced a mean of 3.1 +/- 1 episodes of syncope in the 12 months prior to the study. All provided a history suggestive of Stokes-Adams attacks and were referred for consideration of pacemaker implantation. Two patients had ischemic heart disease and one patient had a long QT interval. Patients had an Intermedics Nova II or Medtronic Quintech DPG pulse generator capable of recording sensed and paced events implanted with a single right ventricular lead. Syncope or presyncope occurred in ten patients (62%) 4.9 +/- 4.2 months after pacemaker implantation. Bradycardia was detected in six patients and four patients had no arrhythmia. In addition to bradycardia, one patient also had tachycardia detected. Pacing therapy resulted in symptom relief in all six patients with syncope or presyncope due to bradycardia. Complications of pacemaker implantation (lead insulation failure) occurred in two patients. One of these patients subsequently had an infection of the generator pocket with associated systemic sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac

Evaluation of amino-oxyacetic acid as a palliative in tinnitus.

Amino-oxyacetic acid (AOAA) was evaluated as a palliative in tinnitus. Sixty-six patients with tinnitus presumed to be of cochlear origin were given either a placebo or 75 mg of AOAA four times a day for 1 week. Response was evaluated by both audiometric measurement of tinnitus loudness and subjective rating by patients of change or no change in tinnitus severity. Because loudness measurements and self-rating have not been shown to be independent, and since the aim of clinical treatment of tinnitus is the alleviation of subjective distress, greater weight was given to the patient's self-rating. A total of 21% of all patients reported a subjective decrease in tinnitus severity, usually within 3 to 4 days after the start of AOAA use. Patients with tinnitus caused by presbycusis or Meniere's disease were the most likely to respond to AOAA treatment with a reduction in tinnitus severity, whereas those with drug-induced tinnitus were the least likely to respond. Nausea and dysequilibrium were the most common side effects of AOAA use. Of the 21% of patients who responded to AOAA, 71% developed some type of side effect. Amino-oxyacetic acid produces a reduction in the severity of tinnitus in about 20% of patients; however, the incidence of side effects makes the drug unacceptable for clinical use.

Acetates

Use of the Million Clinical Multiaxial Inventory in evaluating patients with severe tinnitus.

The Million Clinical Multiaxial Inventory (MCMI) was evaluated as a diagnostic tool for personality disorder among 41 patients with severe tinnitus. Nearly 70 percent of the subjects demonstrated a personality disorder. Nearly half of the patients fell into one of two categories; dependent/submissive or the narcissistic category. Other important features include a high incidence (24%) of severe anxiety. One-third of the patients had a complaint tendency but 50 percent had a denial problem. We have found the MCMI to be easy to administer and evaluate and it provides the clinician with useful information. We believe that more routine use of this or similar instruments would improve the treatment outcome of tinnitus sufferers by bringing into focus the important psychological factors found in each patient.

Auditory Perceptual Disorders

Effect of a high protein (meat) intake on calcium metabolism in man.

The effect of a high protein (meat) intake of 2 g/kg on the calcium excretions and retention and on the intestinal calcium absorption was studied in man. In the control study the protein intake averaged 1 g/kg. The studies were carried out during a low calcium intake of 200 mg/day and a normal calcium intake of 800 mg/day. Two additional studies were carried out during a calcium intake of 1100 mg/day and one during a 2000 mg calcium intake. During the high protein-low calcium intake and during the 800 mg calcium intake the urinary calcium did not significantly increase. It increased moderately in two studies during the higher calcium intakes, however, these excretions decreased with time to control levels. The lack of a significant increase of the urinary calcium in the majority of the studies is probably due to the higher phosphorus content of the high protein intake. The calcium absorption, determined with 47Ca, the fecal calcium and calcium balances did not differ significantly during the high protein intake. In studies carried out during a low protein (meat) intake of 0.5 g/kg the urinary calcium changed little and the fecal calcium, the 47Ca absorption, and the calcium balance remained unchanged.

Adult