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Biomedical subjects

E Whitehead

Publications and source records attributed to E Whitehead.

At least 19 recordsLinked to original sources

Infection of baboons with simian/human immunodeficiency viruses.

Baboons were evaluated for their utility to serve as a model for testing envelope-based vaccines against human immunodeficiency virus type 1 (HIV-1). The ability of HIV-1 strains IIIB, RF, and SF2 to infect baboons was compared with that of simian/human immunodeficiency virus (SHIV) recombinant viruses comprised of either HXB2 or SF2 env, tat, rev, and vpu genes inserted into the SIVmac239 backbone. Both SHIV recombinants replicated in baboon PBMC in vitro, while no evidence of replication was noted for HIV-1 strains (MN, IIIB, SF2). Infection of baboons in vivo correlated with the restriction of infection in vitro. Virus was recovered by cocultivation methods early after SHIV (HXBc2) infection of two baboons with seroconversion profiles that parallel those observed in simian immunodeficiency virus (SIV)mac-infected rhesus monkeys. One of two baboons inoculated with SHIV(SF2) also seroconverted within 4 weeks; however, the kinetics of infection in a second animal appeared much later, with seroconversion to gp120 not evident until 20 weeks and no virus recovery during 32 weeks following infection. Viral DNA was detected in the lymph nodes of the SHIV-inoculated animals by nested polymerase chain reaction (PCR) amplification. Histopathologic changes were evident in lymph nodes, yet no overt clinical disease was observed. When HIV-1 strains (IIIB, RF, and SF2) were inoculated into baboons, virus was not recovered and no seroconversion to the major HIV-1 antigens was observed. However, viral DNA from the lymph nodes of four animals inoculated with HIV-1 strains could be detected by nested PCR, indicating a persistent but diminutive infection of HIV-1. The baboon thus represents a new animal model for testing HIV-1 envelope-based vaccines including the evaluation of new immunogens, dosages, routes, and adjuvants that act in eliciting protective responses.

Animals

[Bone anchored hearing aids (Audiant): long-term use].

This report concerns the long term utilisation of a bone anchored hearing aid system, Audiant, in a large district general hospital in England serving a population of 500,000. Earlier experience with some of these patients has been previously reported (6). All patients included in this series had been provided with conventional hearing aids but for various reasons, indicated in the text, had found them unsatisfactory. Efforts to overcome some of these difficulties led to the utilisation of the osteointegrated hearing aid. Patients regard it to have significant advantages over their previous hearing aids. Some who had previously used conventional bone conduction hearing aids, are now able to use an ear level processor. Of the eleven patients implanted, eight continue to use their bone-anchored hearing aids, two having had their implant for 6 years, three for 5 years and three for 2 years.

Audiometry

Large maxillary antral mucocele presenting with facial asymmetry.

Maxillary antral mucoceles are extremely rare. We report a case of a large antral mucocele presenting with facial asymmetry. The CT scan was essential for delineating the extent of the lesion and aiding in the pre-operative diagnosis. The pathogenesis, clinical features and radiological aspects of this entity are reviewed.

Facial Asymmetry

Adenosine deaminase from Saccharomyces cerevisiae: kinetics and interaction with transition and ground state inhibitors.

Several adenosine analogs, such as coformycin, 2'-deoxycoformycin and erythro-9-(3-nonyl-p-aminobenzyl)adenine (EHNA), which are strong inhibitors of mammalian adenosine deaminase, are much weaker inhibitors of the Saccharomyces cerevisiae enzyme. The specificity of the yeast enzyme is more restricted than that of mammalian adenosine deaminase, particularly towards the ribose moiety and around position 6 and 1 of the substrate. The sulphydryl group appears to be more masked in the yeast than in the mammalian enzyme. The kinetic effects of pH with adenosine substrate and with the inhibitor purine riboside are reported. The findings on specificity and pH kinetic effects can be interpreted in a model involving proton transfer from the -SH group of the enzyme to the N-1 atom of the substrate.

Adenine

Use of the carbon dioxide laser with the Montgomery T-tube in the management of extensive subglottic stenosis.

Subglottic and tracheal stenosis frequently present difficulties in management. Two cases of subglottic stenosis occurring after prolonged endotracheal intubation are presented where the vertical length of complete obstruction by scar tissue was greater than 2.5 cm. One case was successfully managed by the use of the laser and immediate insertion of a stent. The other case still requires subglottic stenting, although an excellent lumen was established by laser vaporization of the stenosed segment.

Adult

Simian T-cell leukemia virus type I infection in captive baboons.

Human T-cell leukemia virus type (HTLV-I) is a type C retrovirus that has been linked to both adult T-cell leukemia and neurological disorders in humans. Baboons and other Old World non-human primates harbor a related virus termed simian T-cell leukemia virus type 1 (STLV-I), which may also be associated with neoplastic disease. To explore the utility of the baboon as a model for HTLV-I infection and disease, 329 baboons from a colony of 3200 at the Southwest Foundation for Biomedical Research (SFBR) were analyzed for the presence of antibodies against STLV-I. An overall seroprevalence rate of > 40% was found, with higher rates in females versus males. Furthermore, seroprevalence rates increased dramatically with age, reaching greater than 80% in animals over the age of 16. Molecular and antigenic analysis of proviral DNA isolated from both tumor tissue and a cell line isolated from a baboon with non-Hodgkin's lymphoma (NHL) indicates that STLV-I in this colony is closely related to HTLV-I. Furthermore, monoclonally integrated provirus isolated from lymphoma tissue was detected, strongly implicating STLV-I in the etiology of this malignancy. DNA primer pairs homologous to HTLV-I sequences amplified both HTLV-I and STLV-I, but not HTLV-II, providing further evidence for a close genetic relationship between baboon-derived STLV-I and HTLV-I. The detailed study of a large population of naturally infected baboons may therefore shed some light into the complex processes required for the induction of disease associated with HTLV-I infection in humans.

Animals

A reverse-phase HPLC method for cAMP phosphodiesterase activity.

A simple and fast method based on reverse-phase HPLC has been developed for measuring the activity of cAMP phosphodiesterase. It allows quantitation of product and substrate in less than 10 min. The sensitivity (1*10(-11) mol AMP), the accurate evaluation of nucleotides, the unequivocal analysis of product, and the reproducibility of the system, make this method suitable for the evaluation of cAMP phosphodiesterase in biological material, at different levels of purification, and also in kinetic studies.

3',5'-Cyclic-AMP Phosphodiesterases

Experience with a subcutaneous implantable bone conduction hearing aid (Xomed Audiant) in a district general hospital.

Patients with a conductive hearing loss may find conventional hearing aids unsatisfactory for a variety of reasons. Efforts to overcome some of these difficulties have led to the development of the osteointegrated hearing aid. Implantable bone conduction hearing aids are an important advance in the treatment of well selected patients. Only 18 patients, who have been implanted with the Xomed Audiant bone conduction hearing aid, have so far been reported on in the UK. This report concerns a further six patients who have been implanted in one centre. Five of these patients continue to use their Audiant hearing aid 14 to 24 months after being fitted. They regard it to have significant advantages over their previous hearing aids. Four of the five patients use an ear level processor. Two of the patients who had previously used conventional bone conduction hearing aids now use the ear level processor.

Adolescent

A comparison of serum and saliva paracetamol concentrations.

The relationship between serum and saliva paracetamol concentrations was investigated in twenty healthy volunteers. The plasma and saliva drug concentrations showed a significant correlation (r = 0.67). However the agreement between the two methods of measurement was poor with limits of agreement of -15.3 mg l-1 to +15.9 mg l-1 with mean sample values of 19.2 and 19.5 mg l-1 for plasma and saliva, respectively.

Acetaminophen

A comparison of the haemodynamic and hormonal effects of low and conventional dose cyclopenthiazide in normal volunteers.

In this study we compared low (125 micrograms) and conventional (500 micrograms) doses of cyclopenthiazide on the renin angiotensin system, plasma and extracellular fluid volumes and the pressor responsiveness to angiotensin II since we have previously shown that the two doses have the same antihypertensive effect but different effects on plasma renin activity. Following a two week placebo run-in period, 8 healthy male volunteers received 125 micrograms or 500 micrograms of cyclopenthiazide for 2 treatment periods of 4 weeks as part of a double blind, 2-part crossover study with treatment periods separated by a 4-week placebo washout phase. Measurements were made on two study days at the beginning and end of the active treatment periods. On the first day serum potassium, plasma renin activity and plasma angiotensin II levels were measured after a 1 h period of supine rest. Plasma and extracellular fluid volumes were also measured after appropriate equilibration times. The blood pressure responses to angiotensin II were assessed on day 2. The 500 micrograms dose of cyclopenthiazide had a greater effect than the 125 micrograms dose on plasma renin activity, serum potassium, angiotensin II levels and extracellular fluid volumes. Neither drug had any effect on plasma volume or the responsiveness to infused angiotensin II. Low dose cyclopenthiazide failed to increase angiotensin II levels, contract body fluid volumes or attenuate vascular reactivity in normotensive volunteers.

Adult

An open study of ropivacaine in extradural anaesthesia.

Ropivacaine 0.5%, 0.75% and 1.0% was investigated in an open study of extradural anaesthesia in three groups of 15 patients undergoing urological or orthopaedic surgery. Following a test dose of 3 ml of 1.0% lignocaine with 1:200,000 adrenaline, ropivacaine 20 ml was given in incremental doses over 4 min via a lumbar extradural catheter. The onset time for analgesia was short in all groups: T12 was blocked 4-6 min after the end of the injection of ropivacaine. The maximum segmental level was significantly higher in the 0.75% and the 1.0% groups (T2) than in the 0.5% group (T5). Complete motor block was obtained in seven, four and nine patients in the 0.5%, 0.75% and the 1.0% groups, respectively. Duration of analgesia increased with increasing concentration of ropivacaine: mean duration of analgesia was 203 and 266 min at T10 and 253 and 314 min at L5 for the 0.5 and 1% solutions, respectively. Mean duration of complete motor block was 94 and 192 min for the same solutions. Analgesia was satisfactory for surgery in all patients except for one in the 0.75% group. Hypotension was experienced by three, seven and three patients in the 0.5%, 0.75% and 1.0% groups, respectively. Bradycardia occurred in seven patients and was associated with hypotension in five. Backache was experienced after operation by four patients, and three patients complained of a brief mild headache. No late adverse events were seen.

Amides

Malignant melanoma of the larynx.

Malignant melanoma of the larynx is a rare tumour. Only 31 cases of primary laryngeal melanoma have been reported in the literature. Cady et al., (1968) found only four cases in a group of 2,500 cases of laryngeal cancer seen over a 25-year period. A case of primary malignant melanoma of the larynx is presented along with a review of the literature. Problems associated with histological diagnosis are discussed. This patient was regarded as a poor risk for laryngectomy and appears to have control of local disease following application of Carbon dioxide laser.

Aged

Vulnerability of the human Leydig cell to radiation damage is dependent upon age.

Testicular function was studied in three groups of patients previously treated for malignant disease, and a control group of adult males. The adult patients in groups one and two underwent unilateral orchidectomy for a testicular tumour but only in group two was this followed by post-operative high-dose irradiation (30 Gy) to the remaining testis. Four of the five boys in group three had a unilateral orchidectomy between the ages of 1 and 4 years and all five received a similar dose of irradiation (27.5-30 Gy) to the scrotum as in group two. The five subjects in group three were studied between the ages of 12 and 34 years. In group one the median basal testosterone level (16.0 nmol/l) was normal and the basal gonadotrophin levels mildly but significantly increased, reflecting a resetting of the pituitary-testicular axis following unilateral orchidectomy. In group two the median basal testosterone level (12.5 nmol/l) was significantly lower and the median basal FSH and LH levels were significantly higher than the respective values in group one, indicating that irradiation to the testis in adult life may damage both the germinal epithelium and the Leydig cells. All five males in group three showed grossly increased FSH and LH levels, with a median basal testosterone level (less than 2.5 nmol/l) significantly lower than groups one and two. None of the five showed a testosterone response to a stimulation test with human chorionic gonadotrophin or underwent puberty spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The pituitary-Leydig cell axis in men with severe damage to the germinal epithelium.

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease.

Ovarian function has been studied in 44 adult females who previously received quadruple chemotherapy (MVPP) for Hodgkin's disease. The median age at treatment was 23 years, and the length of time between completion of treatment and study ranged from 6 months to 10 years (median, 30 months). Seventeen women maintained regular menses, 10 developed oligomenorrhea, and 17 developed amenorrhea. At treatment, the 17 women who subsequently developed amenorrhea were significantly older (median, 30 years) than those who maintained regular menses (median, 22 years) or developed oligomenorrhea (median, 23 years). All patients older than 36 years at the start of treatment stopped menstruating during chemotherapy. The cause of the menstrual disturbance in these patients was chemotherapy-induced ovarian damage characterized by high serum gonadotrophin and low serum estradiol concentrations. After completion of treatment there were 17 pregnancies, which resulted in 9 normal infants, 3 terminations, and 4 spontaneous abortions. Nine patients took the combination oral contraceptive pill throughout chemotherapy; however, subsequently 4 developed amenorrhea and 3 oligomenorrhea, suggesting that these patients had not been protected from chemotherapy-induced ovarian damage. Estrogen replacement therapy was of definite benefit in the symptomatic patients with premature ovarian failure.

Adolescent