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Biomedical subjects

S Freeman

Publications and source records attributed to S Freeman.

At least 55 records · Page 3Linked to original sources

Perinatal hypoxia and auditory brainstem response thresholds: no evidence of permanent hearing loss.

It has been suggested that pre-natal and or peri-natal hypoxia can cause permanent hearing loss as a result of interference with the generation of the endocochlear potential, especially if this interference occurs during the critical period of endocochlear potential development. This hypothesis was tested in 4 series of experiments: in neonatal rats exposed to pure nitrogen for several minutes; in neonatal and adult cats respirated with hypoxic gas mixture for an hour; in neonatal rats and cats breathing hypoxic gas mixture for several hours; and in neonatal rats in hypobaric chamber for several days. In each experiment, the auditory nerve-brainstem evoked response threshold was elevated during hypoxia in those animals in which it could be measured but was normal when determined several hours to days later. This is evidence for a remarkable ability of the auditory system to recover from periods of hypoxia even during the critical period of endocochlear potential development.

Animals

Study of irritant contact dermatitis produced by repeat patch test with sodium lauryl sulfate and assessed by visual methods, transepidermal water loss, and laser Doppler velocimetry.

Eleven subjects received patch tests with 2% sodium lauryl sulfate on a total of 34 anatomic sites. The irritant effect was monitored by visual means, laser Doppler velocimetry, and measurement of transepidermal water loss. After 1 week, repeat patch tests with 2% sodium lauryl sulfate were performed on the same site, and the effect was monitored as before. Although the skin had returned to normal or near normal before the repeat patch test, an augmented response to irritation was generally seen after the repeat patch test, particularly in transepidermal water loss, which showed an augmented response in 29 of the 34 anatomic sites. The clinical implications regarding the healing of contact irritant dermatitis are discussed.

Adolescent

Experimental closed head injury in rats: mechanical, pathophysiologic, and neurologic properties.

A model of closed head injury in rats was developed using a calibrated weight-drop device. The development of edema was studied in various brain regions (cerebral hemispheres, brain stem, cerebellum) using a linear specific gravity gradient column. Regional brain tissue density was measured within 1 min, at 15 and 60 min, 18 h, 4 and 10 days after injury to the left cerebral hemisphere, and was compared with values in sham-operated and control rats. Significant edema (i.e., reduced specific gravity) occurred only in the traumatized hemisphere and was maximal at 18 h. A neurologic severity score (NSS) was developed to evaluate the status of the rat after injury. Specific gravity was significantly correlated with NSS at 18 h after injury. The affected hemisphere displayed hemorrhagic lesions as early as one hour post head trauma (HT), which evolved into hemorrhagic necrosis at 18 h. A pathologic score, evaluated 18 h post HT based on size and severity of the lesion, was correlated with the NSS and evaluated for each rat at one hour and 18 h postimpact. This correlation was found to be highly significant. This model of brain injury may be useful in future studies on the effects of therapeutic agents.

Animals

Melbourne trial of adjuvant immunotherapy in operable large bowel cancer.

A controlled randomized clinical trial was undertaken to assess the ability of combined non-specific and specific immunotherapy to alter the disease-free interval and overall survival of patients with Stage B or C large bowel cancer. The immunotherapy consisted of a 2 year programme of vaccinations with BCG and neuraminidase-treated autologous tumour cells. Three hundred and one patients entered the trial. At 5 years of follow-up there is no evidence that this form of immunotherapy can alter either the disease-free interval or survival in this group of patients.

Antigens, Neoplasm

Disposition of unchanged cisplatin in patients with ovarian cancer.

The disposition of cisplatin (cis-diamminedichloroplatinum II) was studied in the first course of treatment in seven patients (56 +/- 12 years) with ovarian carcinoma by analytic methodology specific for the unchanged drug. Particular attention was paid to rapid blood and urine sample processing to avoid drug losses. Patients were catheterized for urine collections. During and after infusion, plasma levels of unbound cisplatin were simultaneously fitted to a one-compartment model. Creatinine clearance was determined at the same time as cisplatin renal clearance and was 38 +/- 16 ml/min/m2. Total clearance of unbound cisplatin was 253 +/- 48 ml/min/m2 and volume of distribution was 11.5 +/- 2.7 L/m2. Cisplatin half-life was similar when determined from plasma (31.6 +/- 6.0 minutes) or urinary excretion rate data (24.4 +/- 4.0 minutes). Urinary excretion of unchanged drug was 23.3% +/- 8.6% of the dose and renal clearance 56.9 +/- 18.0 ml/min/m2. Renal clearance exceeded creatinine clearance in all patients ratio = 1.9 +/- 1.2), confirming previous suggestions of active renal tubular secretion of cisplatin. Renal clearance was nonlinear with time in two of the patients who received the 2-hour infusion, possibly reflecting changing renal tubular reabsorption. Pharmacokinetic studies of unchanged cisplatin rather than total platinum are therefore practical and could be pursued in further studies defining cisplatin disposition in patients.

Adult

Respiratory questionnaires in occupational studies: their use in multilingual workforces on the Witwatersrand.

The mother tongue of the majority of black workers in the industrial workforces of the Witwatersrand is either Zulu or S Sotho/Tswana, and these are also the main languages spoken in the area. However a substantial minority cite one of several other languages as their mother tongue. In consequence, in occupational surveys using a respiratory questionnaire, the accepted practice has been to use multilingual interviewers who administer the questionnaire in whichever of the two main languages the interviewee requests, but work from an English language version. To test the reproducibility of the information so gathered, a standardized questionnaire was administered to 56 subjects on two occasions approximately three weeks apart by each of two interviewers, one of whose mother tongue was Zulu and the other S Sotho. Reproducibility was little affected by whether the interviewer used her mother tongue or not, pointing to the multilingual competence of both interviewers. Reproducibility was, however, less in subjects not interviewed in their mother tongue compared to those who were. In general, reproducibility was also less for symptom than for history questions, though the phlegm question performed comparably to that reported for more homogeneous language/ethnic groups. Thus, even if internally valid, respiratory symptom information obtained by this method may have limited generalizability. However respiratory history information appears more reliable and may prove of value in the investigation of the natural history of chronic lung disease in this and similar communities.

Adult

Immunological, histological and biochemical assessment of brown adipose tissue activity in neonatal, control and beta-stimulant-treated adult dogs.

Significant levels of mitochondrial uncoupling protein were demonstrated on neonatal dog mitochondria prepared from perirenal, bladder and subcutaneous adipose tissue sites. The protein was not detected in homogenates of adipose tissue samples from the same sites in adult, control dogs. However, chronic treatment of adult dogs with a beta-stimulant (LY 79730) led to the appearance of detectable amounts of uncoupling protein in perirenal and bladder but not subcutaneous adipose tissue depots. Decreases in mean cell diameter, increases in the frequency of multilocular cells and of cytochrome oxidase and creatine kinase were also associated with the effects of treatment on dog adipose tissue. The results demonstrate the age-related decline in dog brown adipose tissue and its reversal by chronic treatment with beta-stimulant.

2-Hydroxyphenethylamine

Multi-modality evoked potentials in hypoxaemia.

The auditory nerve-brain-stem evoked response (ABR) has been shown to be insensitive to hypoxic inspiratory gas mixtures which severely depress the EEG. In order to determine the relative sensitivities of additional brain regions and pathways to hypoxaemia, anaesthetized paralysed cats were ventilated with various gas mixtures while recording the evoked responses of the auditory, somatosensory (including peripheral nerve, brain-stem and primary cortical components), visual and vestibular systems. Arterial blood pressure was maintained by dopamine infusion and pH was corrected with bicarbonate. Hypoxic gas mixtures (6-7% O2) presented for 60 min, causing severe hypoxaemia (paO2 20-30 mm Hg; O2 saturation 25-50%), were without effect on the somatosensory, vestibular and visual EPs while the auditory evoked potentials (ABR and cortical components) were depressed. However, if arterial blood pressure was allowed to fall, all of the evoked potentials became severely depressed and isoelectric. These results and others indicate that the cortical components are qualitatively similar to the more peripheral evoked potentials. The resistance of these evoked potentials to controlled hypoxaemia is probably due to their generation by oligosynaptic pathways and to a compensatory switch to anaerobic metabolism and to an elevation of cerebral blood flow.

Animals

The depression of the auditory nerve-brain-stem evoked response in hypoxaemia--mechanism and site of effect.

During severe hypoxaemia in the cat the ABR was depressed in 2 different patterns: if mean arterial blood pressure (MAP) was maintained then all other evoked potentials (EPs--somatosensory and visual) remained. If MAP was not maintained, all of these EPs were depressed. This study sought to document these different patterns of ABR depression and to ascertain their mechanisms. When MAP fell, the ABR loss began with the later waves and progressed to the earlier waves. These are signs of a central brain lesion. The hypoxaemia, detrimental to normal function of the cardiovascular system, leads to depression of MAP, to a fall in cerebral perfusion pressure and blood flow, to cerebral ischaemia and ABR loss. On the other hand, when MAP was maintained, severe hypoxaemia was accompanied by a depression of all of the ABR waves at the same time. The cochlear microphonic potential was also simultaneously depressed. These are signs of a peripheral, cochlear effect similar to the demonstrated depression of the positive endocochlear resting potential of the scala media and of the cochlear microphonic potential during hypoxaemia. This leads to interference with the cochlear transduction mechanism so that all of the auditory evoked potentials, including the ABR, are simultaneously depressed. These results lead to the suggestion that the ABR abnormalities seen in patients who suffered a hypoxic (anoxic) insult or an ischaemic episode (prolonged interpeak latencies, loss of later waves and finally all waves absent or only the first wave remaining) is always due to ischaemia even when the initial insult was hypoxic.

Animals

A computerized approach to the collection and analysis of cardiac action potentials.

A description is given of a microcomputer system for the collection and storage of cardiac action potentials. The equipment required is commercially available and easy to use. Analysis of the data is performed off-line with a mainframe computer. A description of the software used for both data collection and data analysis is given.

Action Potentials