Biomedical subjects
Publications and source records attributed to T D Williams.
Application of computer digitizing methods to conventional kinetic visual field test data permits mathematical analysis of these data. In some cases this provides more information than is available by a simple inspection of the field charts. This is demonstrated by analysis of multiple isopter data for a patient with open-angle glaucoma and a patient with retinitis pigmentosa.
A 36-year-old male had been constantly wearing a patch to avoid diplopia since an operation on the right parietal area of the brain. Postsurgical visual field evaluation indicated a complete bilateral left hemianopia with macular splitting. The patient had a constant alternating comitant exotropia with no suppression. By terminating the patching, establishing the appropriate fixing eye, and applying relieving prisms, diplopia was removed. Once binocularity was thus established, it was found (over the course of 7 months) that binocular function was possible with diminishing amounts of prism power. During this 7-month period, measurements of the patient's heterophoria, motor fusion, and sensory fusion revealed that he adapted from his occlusion-induced exotropia toward an habitual heterophoria. Such vergence adaptation has been defined as orthophorization. The occurrence of vergence adaptation after sensory fusion indicates that sensory fusion plays an important role in the etiology of prism adaptation.
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Hormonal and cardiovascular responses to 1-desamino-8-D-arginine vasopressin (DDAVP) were investigated in six normal adult volunteers. After overnight fluid deprivation, an intravenous injection of either DDAVP (0.4 microgram/kg) or the same volume of normal saline was administered. One hour later an intravenous infusion of hypertonic saline was commenced and continued over two hours. Five minutes following the DDAVP injection, facial flushing, a fall in diastolic blood pressure by an average of 13% and a rise in pulse rate by an average of 18% were observed. There was a significant increase in plasma renin activity and plasma cortisol concentration, but no significant changes were observed in plasma concentrations of LH, FSH, TSH, prolactin or GH. Following osmotic stimulation by hypertonic saline plasma AVP rose to the same extent in both the DDAVP and control studies. DDAVP (0.4 microgram/kg) was also administered to five subjects with cranial diabetes insipidus. Again facial flushing, increased facial temperature, a fall in diastolic pressure and a rise in heart rate were all observed, suggesting that DDAVP exerts its cardiovascular actions by a mechanism other than antagonism of circulating endogenous AVP.
After dehydration, oral rehydration causes a fall in plasma arginine vasopressin (AVP) that precedes changes in plasma osmolality. To investigate further the stimulus for this effect, its specificity, and association with thirst, six volunteers were deprived of water for 24 h and given a salt load on two separate occasions. On each study day they then drank rapidly 10 ml/kg of either tap water or hypertonic saline (360 mosmol/kg). There was a significant fall in plasma AVP from 2.0 +/- 0.3 to 1.2 +/- 0.4 pmol/l (P less than 0.05) 5 min after drinking water and from 1.8 +/- 0.3 to 0.9 +/- 0.2 pmol/l (P less than 0.05) after hypertonic saline. Plasma osmolality fell 30-60 min after water and was unchanged after saline. Plasma renin activity, oxytocin, and total protein all remained unchanged. All subjects reported diminished thirst after hypertonic saline. Gargling with water reduced thirst but did not affect plasma AVP. There appears to be a drinking-mediated neuroendocrine reflex that decreases plasma AVP irrespective of the osmolality of the liquid consumed. The sensation of thirst did not correlate with plasma osmolality and was not always related to plasma AVP concentration.
The dose-response relationships and pharmacokinetics of orally administered 1-desamino-8-D-AVP (DDAVP) were investigated. In water-loaded normal subjects marked reductions in urine flow rate and increases in urinary osmolality occurred. The responses were maximal 2 h after ingestion of 50, 100, and 200 micrograms, and lasted at least 6 h. Plasma DDAVP levels increased in a dose-dependent fashion and its disappearance from the plasma followed an exponential time course, with a half-life 86 to 142 min. In water-loaded adults with central diabetes insipidus (CDI), 200 micrograms oral DDAVP caused marked antidiuresis and mean urinary osmolality increased from 107 mosm/kg to 554 mosm/kg after 3 h. In these patients the effect also lasted at least 6 h. Children with CDI were less sensitive than normal subjects to the 50-microgram dosage and required 100 micrograms orally to achieve a duration of action similar to that resulting from 200 micrograms in adults. Oral DDAVP may be useful for treating some patients with CDI.
The regulation of both arginine vasopressin (AVP) and oxytocin secretion was studied during rapid and prolonged osmotic stimuli in normal adult volunteers. In five subjects given an intravenous infusion of 0.85 mol NaCl at 0.05 ml/kg per min over 2 h there was a significant (P less than 0.05) rise only in plasma AVP, with no significant change in plasma levels of oxytocin. In six further subjects 5 days of restriction to 500 ml fluid daily resulted in significant increases of both plasma and 24-h urinary AVP, whereas there was no change in corresponding oxytocin levels. During another 5-day period in which the same subjects were given an additional 200 mmol sodium as well as having their fluid intake restricted to 1000 ml daily, there were again significant rises in plasma and 24 h urinary AVP with no change in corresponding oxytocin levels. We conclude that, in man, AVP is selectively secreted in response to both dehydration and high sodium intake, whilst even after the stimulus of rapidly increasing plasma osmolality during intravenous infusion of hypertonic saline the rise in oxytocin is not statistically significant. It therefore appears unlikely that oxytocin has a significant role in the physiological control of fluid balance in man.
The influence of endogenous opioids on the posterior pituitary response to stress was investigated by measuring plasma hormone levels in immobilized male and female rats following either acute naloxone treatment or prolonged morphine administration. Naloxone significantly potentiated the oxytocin and arginine vasopressin (AVP) response to immobilization, but in female rats only. The responses of morphine-treated male rats showed differences compared with vehicle-treated controls, although chronic morphine treatment did not reliably alter the oxytocin or AVP responses to immobilization in males or females. In a further experiment to investigate the role of gonadal hormones in determining the sex difference in responsiveness to naloxone, it was found that acute naloxone treatment significantly potentiated the posterior pituitary response to stress in castrated male rats. These results extend previous studies showing a sex difference in stress-induced secretion of posterior pituitary hormones, providing evidence of a sexual dimorphism in the endogenous opioid regulation of this response which is partly determined by circulating gonadal hormones.
Pulmonary tuberculosis produces a broad spectrum of radiographic abnormalities. During the primary phase of the disease these include pulmonary consolidation (50%), which often involves the middle or lower lobes or the anterior segment of an upper lobe; cavitation (29%) or pneumatocele formation (12%); segmental or lobar atelectasis (18%); pleural effusion (24%); hilar and mediastinal lymphadenopathy (35%); disseminated miliary disease (6%); and a normal chest radiograph (15%). During the postprimary phase of the disease, common abnormalities include exudative and/or fibroproductive parenchymal densities (100%), predominantly in the apical and posterior segments of the upper lobes (91%); cavitation (45%) with bronchogenic spread of disease (21%); marked fibrotic response in the lungs (29%); and pleural effusion, empyema, and fibrosis (18%, 4%, and 41%, respectively). Upper-lobe masslike lesions are seen occasionally (7%); spontaneous pneumothorax and intrathoracic lymphadenopathy are rare (5% each). Common causes of a missed diagnosis of tuberculosis are (1) failure to recognize hilar and mediastinal lymphadenopathy as a manifestation of primary disease in adults, (2) exclusion of tuberculosis because disease predominates in or is limited to the anterior segment of an upper lobe or the basilar segment of a lower lobe, (3) overlooking of minimal fibroproductive lesions or reporting them as inactive, (4) failure to recognize that an upper-lobe mass surrounded by satellite fibroproductive lesions might be tuberculous, and (5) failure to consider healed sequelae of primary disease or a positive purified protein derivative skin test as contributory to identifying the patient's pulmonary disease.
This case report documents the retinal changes occurring during a period of slightly more than a year following a branch macular vein occlusion in a 43-year-old male. The patient never experienced any visual disturbance throughout this period. The various diagnostic possibilities considered in his case are presented.
Twelve patients with medullated retinal nerve fibers are presented. The paper discusses the possible roles played by formation of the ganglion cell axons and lamina cribrosa in the development of medullated retinal nerve fibers. In addition to myopia and amblyopia, patients with medullated retinal nerve fibers may show unusual lens tilts, anterior chamber anomalies, unexpected field losses, and unusual direction of the optic nerve.
Visual function and ocular structures were evaluated in a family with retinitis pigmentosa (RP) by dark adaptometry, electroretinography (ERG), perimetry, and fundus photography. All members examined showed gross rod dysfunction by dark adaptometry and ERG. The inferior and nasal segments of each patient's retina showed denser accumulations of pigment than the other segments. All patients showed superior field losses, the extent of which was correlated with the age and sex of the individual. The clinical impression formed from the assessment of visual fields in this sample was that males are more severely affected than females.
Intraocular pressures (IOP's) were measured using the Digilab Pneuma-tonometer with the subject in both the sitting and supine positions. The IOP with the Pneuma-tonometer was greater (17.03 mm Hg) in the supine position than in the sitting position (12.90 mm Hg). The IOP measured with the Pneuma-tonometer, with the subject sitting, was similar to the IOP measured with the Goldmann applanation tonometer (13.42 mm Hg). Inasmuch as IOP tends to be lower with the patient in a sitting position, the clinician should be alert to the possibility that some patients with borderline Goldmann IOP's may have pressures well above the normal range when they are lying down. Due to the continuous recording provided by the Pneuma-tonometer, the ocular pulse pressure can be measured. We found a mean ocular pulse pressure amplitude of 1.77 mm Hg. All values are shown plus or minus 1 SD. Comparison of the ocular pulse pressure amplitude for the two eyes could aid in detecting patients with suspected carotid artery stenosis.
Four normally menstruating subjects were studied throughout the menstrual cycle to investigate changes in plasma LH, arginine vasopressin (AVP), oxytocin (OT) and oxytocin associated neurophysin (NPOT). A clear mid-cycle LH peak was observed in each subject. Mean levels of AVP, OT and NPOT were 2.2 pmol/l, 1.1 pmol/l and 39 pmol/l, respectively. There were no significant differences between plasma levels during follicular, mid-cycle and luteal phases for each of these. Two further subjects with anovulatory cycles were studied in a similar way. In the first subject, with polycystic ovarian disease, posterior pituitary peptide levels were in the normal range, whereas the other subject, recovering from anorexia nervosa, had raised plasma levels of all posterior pituitary peptides (AVP 8.1 pmol/l, OT 1.8 pmol/l, NPOT 131 pmol/l, mean values) despite a normal osmolality. Administration of ethinyl oestradiol, 100 micrograms or 500 micrograms, had no effect of either AVP or OT, but 100 micrograms caused a marked rise in NPOT levels in all cases within 12 h (from mean 64 pmol/l to mean 196 pmol/l) and the levels remained elevated for 3 d.
Patients with progressive autonomic failure with multiple system atrophy show a severely blunted response of plasma arginine vasopressin to the stimulus of head-up tilt. Whether this could be due to lesions either at one or more sites within ascending neural pathways from cardiovascular stretch receptors in the thorax or, alternatively, to lesions affecting vasopressin secreting cells within the hypothalamus was investigated. The arginine vasopressin response to an intravenous infusion of hypertonic saline was determined in six patients with progressive autonomic failure. The mean plasma concentration of arginine vasopressin rose from 1.0 to 3.7 pmol/l, a change comparable to that observed in normal controls. This demonstrates normal functioning of the efferent connections from the osmoreceptors within the hypothalamus and suggests that the loss of vasopressin response to head-up tilt is due to lesions in ascending pathways from cardiovascular receptors. There was a significant rise in mean blood pressure during the infusions on patients with progressive autonomic failure, a change which was not observed with the controls. This may have been at least partly caused by the rise in circulating arginine vasopressin concentrations, since these patients have been reported to be extremely sensitive to the pressor effects of arginine vasopressin.
The posterior pituitary response to immobilization was studied in male and female rats. Plasma levels of arginine vasopressin (AVP) and oxytocin (OT) were measured both in control rats and in rats immobilized in an acrylic restrainer for 1 min. In male rats immobilization did not result in any change in AVP (control: 1.3 +/- 0.2 pmol/liter, mean +/- SEM; immobilized: 2.3 +/- 0.6 pmol/liter), although there was a small but significant increase in OT (control; 4.1 +/- 0.5 pmol/liter; immobilized: 10.2 +/- 2.2 pmol/liter; P less than 0.005). In female rats a marked rise was observed in AVP (control: 1.4 +/- 0.3 pmol/liter; immobilized: 5.5 +/- 1.3 pmol/liter; P less than 0.005), and the rise in OT was considerably greater (P less than 0.01) than that found in males (control: 4.7 +/- 0.8 pmol/liter; immobilized: 26.0 +/- 5.6 pmol/liter; P less than 0.001). Further groups of male and female rats were gonadectomized 2 weeks before immobilization. Basal levels of AVP and OT were unchanged. Orchidectomized males had an increased OT response to immobilization compared with sham-operated males (P less than 0.05) whereas the AVP response was not significantly changed. Ovariectomy did not significantly affect either the AVP or OT responses. Although the neural pathways responsible for the neurohypophyseal response to immobilization are not known, this data demonstrate that the response is dependent on the sex of the rat.
Combinations of etorphine hydrochloride and xylazine hydrochloride in different dosages were tested for their efficacy as immobilizing agents on 16 recently captured feral mares in corrals. The results of these trials led to the utilization of a standard combination of 5.5 mg of etorphine hydrochloride, 150 mg of xylazine hydrochloride, and 3 mg of atropine sulfate in a 7-ml dart syringe for field capture. This combination was used, administered by dart gun from helicopters, to capture 87 free-ranging feral horses from about 80 bands. Five mares died at the time of capture and the remains of three other mares were found near the site of capture 4 mo later. Blood samples collected from each animal and analyzed for hematologic variables, concentrations of urea, and glucose yielded values comparable to domestic "hot-blooded horses." Serum cortisol concentrations (4.7 +/- 0.4 microgram/dl) were comparable to values from undisturbed captive animals. Approximately 48 min of helicopter time were required per horse captured. The cost per animal captured was $159 for helicopter time and $66.70 for drugs and darts.
Erythromycin was compared with a combination of ampicillin plus flucloxacillin for treating adults admitted to hospital with community acquired pneumonia. A satisfactory clinical response to a seven day course of antibiotics was observed in 29 of 36 patients (81%) in the erythromycin group and 35 of 39 patients (90%) treated with ampicillin plus flucloxacillin, as judged by a fall in temperature, improvement in the general condition, diminution of respiratory symptoms and radiographic improvement. Streptococcus pneumoniae was the causative organism most commonly detected and a satisfactory outcome of treatment of diagnosed pneumococcal pneumonia cases was observed in 16 of 18 patients (89%) treated with erythromycin compared with 20 of 22 patients (91%) treated with ampicillin plus flucloxacillin. These results indicate that erythromycin has similar clinical efficacy to ampicillin plus flucloxacillin, given as a seven day course, for the treatment of community acquired pneumonia in adults.