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Biomedical subjects

J A Wilson

Publications and source records attributed to J A Wilson.

At least 19 recordsLinked to original sources

Hepatic cytochrome P-4503A (CYP3A) activity in the elderly.

Elderly patients exhibit decreased clearance of multiple drugs biotransformed by the hepatic cytochromes P-450. The cytochromes P-450 are a superfamily of enzymes, which comprise a central component of phase I drug metabolism. Distinct isoforms metabolize specific drugs. In human liver microsomes, the glucocorticoid-inducible cytochrome P-450IIIA, CYP3A, catalyzes the N-demethylation of erythromycin. To examine the activity of hepatic CYP3A in elderly males and females, erythromycin N-demethylation was examined, as reflected by the recently described [14C]erythromycin breath test in 24 healthy volunteers, age 70-88. The [14C]erythromycin breath test was measured in normal elderly males and females to: (a) determine persistence of the gender-related dimorphism (evident in younger subjects) of CYP3A activity in the elderly population, (b) examine the effect of % ideal body weight, age, diet, and medication use on the activity of human hepatic CYP3A, and (c) compare breath test results obtained in normal geriatric volunteers with published results obtained in younger subjects, to determine aging-related alterations in CYP3A enzyme activity. Erythromycin N-demethylation varied fivefold among these patients. Similar to earlier studies examining erythromycin N-demethylation in younger subjects, CYP3A activity was found to vary with gender in the geriatric cohort. [14C]Erythromycin N-demethylation at 60 min was 3.14% +/- 0.75 (n = 13) in females and 2.15% +/- 0.77 (n = 11) in males (P = 0.005). In evaluating the role of % ideal body weight and % dietary fat using multivariable linear regression analyses, [14C]erythromycin N-demethylation, was found to decline significantly as % ideal body weight increased (P = 0.001). This was not confounded by gender. [14C]Erythromycin N-demethylation was not related to dietary fat intake (P less than 0.13). [14C]Erythromycin N-demethylation in the elderly volunteers was similar to values reported for subjects aged 20-60. Performance of a new non-invasive test of the human hepatic glucocorticoid-inducible CYP3A in a geriatric cohort suggests that: (a) the gender-related heterogeneity in function of the glucocorticoid inducible human CYP3A persists during normal aging, (b) that the activity of CYP3A may decrease in obesity, and (c) that the activity of CYP3A is stable throughout normal ageing.

Aged

Bacillus cereus meningitis in two neurosurgical patients: an investigation into the source of the organism.

Two patients developed Bacillus cereus meningitis following neurosurgery. During the subsequent investigation into the source of the organism, linen was discovered to be heavily contaminated with B. cereus. No other prolific source of the organism was found. It seems probable that lint from contaminated fabric was the vehicle of transmission of the organism during extended surgery. Linen should be considered as a possible source of B. cereus infection.

Adult

Phase I trial of a cisplatin-albumin complex for the treatment of cancer of the head and neck.

1. A phase I trial of a cisplatin-albumin complex for the treatment of end-stage squamous cell carcinoma of the head and neck is reported. The complex was prepared by overnight incubation of cisplatin with human albumin at 37 degrees C. This resulted in more than 98% of the drug being bound to protein at the start of treatment. The patients were either unable to continue with or had refused conventional therapy with cisplatin. 2. The trial began at a dose of 100 mg cisplatin m-2 and was increased in 25 mg m-2 increments to 650 mg m-2. Despite the absence of the customary protective measures of pre-hydration and anti-emetic treatment no serious toxicity was encountered. 3. Unbound plasma platinum concentrations were lower than after conventional cisplatin treatment but total plasma platinum and tumour platinum concentrations were much higher. Urinary excretion of platinum was low and the incidence of nephrotoxicity was greatly diminished. Two responses were seen (one complete and one partial) in 38 patients treated and the median survival time was 109 days, compared with 151 days for patients treated conventionally with cisplatin and 56 days for untreated patients. 4. The complex is not as effective as conventional cisplatin therapy but is much less toxic, offers improved quality of life during treatment and may prove to be of benefit in patients who could not otherwise be treated.

Carcinoma, Squamous Cell

Globus sensation.

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Conversion Disorder

What do parents know about vitamins?

Parents of 120 children attending child health clinics answered a questionnaire on their understanding of vitamins. Fifty four children (45%) were taking vitamins; 12 (22%) were given the wrong dose. Only 19 parents (35%) knew when to stop supplements and 25 (46%) did not realise overdosage was potentially harmful. Only six children (11%) were receiving professional supervision. This indicates a need to improve parental understanding and professional supervision.

Awareness

The evaluation of dizziness in elderly patients.

Twenty-one elderly patients with dizziness underwent a comprehensive medical and otoneurological evaluation. The majority had vertigo, limited mobility and restricted neck movements. Poor visual acuity, postural hypotension and presbyacusis were also frequent findings. Electronystagmography revealed positional nystagmus in 12, disordered smooth pursuit in 18, and abnormal caloric responses in nine. Magnetic resonance imaging showed ischaemic changes in six out of eight patients. Although dizziness in the elderly is clearly multifactorial, the suggested importance of vertebrobasilar ischaemia warrants further consideration as vertigo has been shown to be a risk factor for stroke.

Aged

Clinical correlates of sway in elderly people living at home.

Postural sway has been noted to increase with advancing age and to correlate with a wide variety of clinical features. The relationships between sway and various clinical features were explored in a group of elderly subjects living at home and free from neurological illness and severe incapacity. Each subject underwent a thorough physical examination and sway was measured in the anteroposterior and lateral planes with eyes open and closed using a modified Wright's ataxiameter. Vibration sense was the only clinical feature to show a consistent relationship with all 4 measurements of sway in men. Age showed only a weak and inconsistent relationship to sway in both men and women. Weak but inconsistent relationships were noted between sway and mental function, tone, passive joint movement, antidepressant and tranquilliser therapy. This suggests that dorsal column function is of prime importance in the maintenance of balance and that the previously noted increase in postural sway with advancing age may have been exaggerated by the presence of disease processes.

Aged

Depression and 'hassles' in globus pharyngis.

A group of 25 patients (16 women, 9 men) attending an ENT department with globus sensation and 25 matched ENT controls were assessed using the Beck Depression Inventory and scales for daily stressful events ('hassles'). Globus patients of both sexes were significantly more depressed than controls and had Beck scores suggestive of significant depression. Thirteen patients, but only two controls, had an independent life event within two months of disease onset, and patients had higher hassles scores than controls.

Adult

Intraoperative angiography and temporary balloon occlusion of the basilar artery as an adjunct to surgical clipping: technical note.

The direct surgical treatment of intracranial aneurysms is not always possible, especially in posterior circulation aneurysms. This is usually because of their complex anatomy and location next to the skull base and brain stem, where proximal vascular control is usually not attainable. Four patients at our institution underwent intraoperative transfemoral catheterization of the basilar artery with a nondetectable endovascular balloon for proximal control of the basilar artery. The flow control in the basilar artery was excellent and facilitated the surgery. Before surgery, each patient underwent the placement of a 10-cm 8-French femoral introducer sheath and were taken to the operating room where they were placed in a supine position and a subtemporal or pterional craniotomy was performed. After the initial exposure and before aneurysm manipulation, a nondetachable silicone balloon catheter was passed through an introducer catheter and was placed into the rostral basilar artery, using flow direction, microguidewires, and angiographic "road-mapping" techniques. In two patients, temporary basilar occlusion was used to collapse the aneurysm and to facilitate clip placement. In the third patient, intraoperative aneurysm rupture occurred and was controlled by temporary basilar artery occlusion. Using intraoperative angiography, complete aneurysm obliteration and vessel patency was confirmed in all four patients. All patients made a complete recovery except for initial postoperative third nerve palsies in three patients. This technique achieves intraoperative control of the basilar artery proximal to an aneurysm by the use of a nondetachable occlusive balloon in the basilar artery. An added benefit is the ease with which intraoperative angiography can be obtained in this context.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Clinical evaluation of the NBD-PC fluorescence polarization assay for prediction of fetal lung maturity.

OBJECTIVES: 1) To examine a fluorescence polarization (FP) assay with an independent set of data that contained more cases of respiratory distress syndrome (RDS) than a previous study, 2) to determine whether the same reference ranges are applicable to infants born to diabetic women, and 3) to evaluate whether adding the lecithin-sphingomyelin ratio (L/S) would substantially improve the prediction of RDS among women with an intermediate FP value (between 0.26-0.289). METHODS: We identified 389 women who had FP analysis performed at the University of Washington Medical Center from February 1986 to October 1988 and who delivered within 3 days of amniocentesis. We reviewed the medical records of these women and their infants to extract information for our study. RESULTS: For FP values of 0.26 or greater, the sensitivity and specificity for prediction of RDS were 90.2 and 84.6%, respectively, compared with 100 and 82.0% in the previous study. For FP values of 0.29 or greater, the sensitivity and specificity were 62.8 and 94.2%, respectively (80.8 and 96.2% in the previous study). Among diabetics, an FP result below 0.26 was associated with the same low risk of RDS as among non-diabetics. Among the patients with FP between 0.26-0.289, the addition of L/S did not provide a clinically useful improvement in the prediction of fetal lung maturity. CONCLUSION: The NBD-PC FP assay can be used as the sole test of fetal lung maturity in most clinical circumstances.

Amniotic Fluid

Operation Desert Storm: clinical experiences at the 13th Evacuation Hospital, a Wisconsin National Guard unit.

The 13th Evacuation Hospital, a National Guard unit, was deployed to the Persian Gulf Jan 11, 1991. We set up a 400-bed hospital and became fully functional 11 days before the ground war started. From Jan 11 to March 8, 1991, the hospital took care of 3,907 out-patients and admitted 435 patients. Approximately half the patients were admitted before the ground war began, while 88 of the 125 operations were performed after the ground war started. We admitted 61 patients for war-related injuries, and 28 required operations in our hospital. Since the ground war lasted only 100 hours, we took care of many more patients with non-war related injuries or illness. The various complaints and reasons for admission to the hospital are presented in detail.

Hospitals, Military

Electrolyte and acid-base changes with massive blood transfusions.

The case records of 471 patients with massive transfusions of ten or more units of bank blood within 24 hours were reviewed to analyze the electrolyte and acid-base changes. The patients who lived had a less severe acidosis (7.23 +/- 0.15 vs 7.11 +/- 0.17) and the HCO3 was higher (19.8 +/- 15.2 vs 13.4 +/- 6.8) (P less than 0.001). The mean anion gap, despite the low HCO3, was 11.8 +/- 7.8 mEq/L. A combined metabolic and respiratory acidosis, often following bicarbonate therapy, was fetal in 83 per cent (39/47). Serum potassium values (K) were high in 22 per cent and low in 18 per cent of patients. If potassium levels were "corrected" by subtracting 0.5 mEq/L for each 0.1 pH of metabolic acidosis, only 5 per cent of patients were hyperkalemic. Patients dying within 48 hours of the massive transfusions had higher potassium levels (4.9 +/- 1.1 vs 4.4 +/- 0.9; P less than 0.001). Ionized calcium levels (Ca++) were less than normal (1.13-1.32 mmol/L) in 94 per cent of patients and were very low (less than 0.70 mmol/L) in 46 per cent (108/234). The mortality rate with severe ionic hypocalcemia was 71 per cent (vs 40% in patients with more normal values); P less than 0.0001. pH, PCO2, K, and Ca++ must be followed closely with massive transfusions. Rapid correction of volume and pH, without overcorrection, is essential.

Blood Gas Analysis

Cricopharyngeal dysfunction.

The aim of the study was to determine the manometric patterns in dysphagic patients with radiologic evidence of upper esophageal sphincter (UES) dysfunction. Nineteen patients with radiographic abnormalities of the UES underwent measurement of several parameters of UES tonic pressure and pharyngoesophageal water swallow dynamics. At least two UES tonic pressures were elevated in six subjects, compared with a control group of 67 healthy volunteers. No patients had UES achalasia. The cricopharyngeal impression in the remaining patients may represent muscular hypertrophy or deficiency of UES opening, despite manometric relaxation, but its relationship to the patient's symptoms remains unknown. Cricopharyngeal myotomy appears to be a reasonable treatment for patients with manometric UES hypertonicity.

Adult

Phylogeny of the Whipple's-disease-associated bacterium.

Efforts to culture and identify the intracellular bacteria associated with Whipple's disease have been unsuccessful. Nucleotide sequencing and amplification by the polymerase chain reaction was done on the bacterial 16 S ribosomal DNA present in a small-bowel biopsy specimen taken from a patient with Whipple's disease. A search by computer for similar rRNA sequences filed in databases showed the Whipple's-associated organism to be most similar to bacteria of the Rhodococcus, Streptomyces, and Arthrobacter genera, and more weakly related to mycobacteria. The biopsy specimen was estimated to contain around 10(7) cells of the organism. The probable aetiological agent for our patient's illness has not been identified previously in a patient with Whipple's disease.

Aged

Intracellular response of caudate neurons to variable frequency stimulation of motor cortical areas in dog.

The intracellular response to electrical stimulation of motor cortex was studied in 77 neurons recorded in the head of the caudate (Cd) nucleus of dog. Single pulse stimulation of either medial, intermediate or lateral precruciate cortex produced a response in 69 neurons, 59% of which responded to more than one cortical area. Most intracellular responses were complex potentials consisting of an initial depolarization (E) followed by a longer duration hyperpolarization (I) or E-I response complex. When stimulated with trains of low frequency pulses (10 Hz), the stimulus-generated I potentials reduced the absolute amplitude of the evoked E's, often to a level below resting potential. However, at higher frequencies (50 Hz), the I potentials were attenuated and the E potentials summated into a prolonged depolarization lasting the duration of the stimulus train. A computer model of the response to multiple stimuli was generated assuming that the E-I response to each stimulus pulse in the train should temporally summate with previous responses. As the frequency of stimulation was increased, this model consistently predicted greater summation of the I potentials than was experimentally observed. These data suggest that inhibition of Cd neurons is input frequency dependent such that as the frequency of cortical input increases there is a decrease of input-generated inhibition of Cd neurons. Thus, inhibition may modulate the response of Cd neurons such that cortical input must reach a critical firing frequency before being relayed through the Cd nucleus.

Animals

The action of MPTP on synaptic transmission is affected by changes in Ca2+ concentrations.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a disruption of nigrostriatal dopaminergic function which resembles parkinsonism. On the cellular level, the disruption involves a Ca2+ independent release of dopamine, depletion of nigral and striatal dopamine, and the death of dopaminergic neurons. We have previously reported that MPTP can cause a non-reversible inhibition of neostriatal synaptic transmission. In this study we investigated the effect of altering Ca2+ concentration on MPTP's actions in the mouse nigrostriatal brain slice. We report finding that the MPTP induced non-reversible decrease in N-2 amplitude did not occur if synaptic transmission had been blocked using a low Ca2(+)-high Mg2+ artificial cerebrospinal fluid (ACSF) during MPTP application. Low Ca2(+)-high Mg2+ ACSF did not however alter the decrease in slice dopamine content caused by MPTP. These data provide initial support for the hypothesis that MPTP's ability to alter functional synaptic transmission is Ca2+ dependent whereas its releasing action on dopamine is Ca2+ independent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

The effect of laryngeal irradiation on pharyngoesophageal motility.

The upper esophageal sphincter (UES) receives the full radiation dose during external beam radiotherapy to the adjacent larynx. The aim of the study was to assess the effects, if any, of radical laryngeal radiotherapy on motility patterns in the pharyngoesophageal segment. A strain gauge assembly and a digital manometric recorder were used to assess 19 patients 13 to 71 months after irradiation of T1 to T3 glottic cancer to a central dose of 52.5 to 55.7 Gy in 20 daily fractions. Results were compared with those of 23 healthy controls. Tonic lower esophageal sphincter (LES) pressure, distal peristaltic contraction, tonic UES pressure, and eight parameters of pharyngoesophageal dynamics during water and bread swallows were studied. No difference was found between the two groups in tonic LES pressure, peristaltic amplitude, or tonic UES pressure. Water swallow pharyngoesophageal wave velocity was significantly lower in patients than in controls, and the irradiated group also showed a trend toward increased duration of the distal esophageal peristaltic wave. The reduction in upper esophageal wave velocity was associated with the interval following irradiation. The post-treatment interval was also inversely related to the amplitude of UES after-contraction, and associated with an increase in wave duration throughout the pharyngoesophageal segment. A study of 23 laryngectomy specimens, 5 of which had been removed following radiotherapy, failed to identify pathological features in nerves or muscle which characterised previous laryngopharyngeal irradiation. We conclude that laryngeal irradiation has no effect on upper or lower esophageal sphincter tone but causes an increase in wave duration and a reduction in wave velocity in the pharyngoesophageal segment. These changes are independent of age and sex and are not associated with pathological features like the neural degeneration described in the myenteric plexus of irradiated rectum.

Aged