Sperm morphology in stallions: ultrastructure as a functional and diagnostic tool.

Conventional light microscopic evaluation of a seminal ejaculate does not fully avail potential indicators of functional impairment in spermatozoal organelles. The technique of critical quantitative evaluation of morphologic features of individual structural components of spermatozoa at a light microscopic level in conjunction with critical qualitative evaluation of spermatozoal organelles at an ultrastructural level, as described in this article, is a valuable clinical tool. Compared with a battery of sperm function assays used in human andrology clinics, this relatively less expensive and simple technique is an efficient functional and diagnostic tool.

Simultaneous cochlear implantation and labyrinthectomy for advanced Ménière's disease.

BACKGROUND: Patients with Ménière's disease can develop unaidable sensorineural hearing loss. Cochlear implantation has recently been utilised in this group with favourable results. A more challenging group are those with intractable vertigo, and they have traditionally posed a significant management dilemma. CASE REPORT: Two female patients with unaidable hearing and recurrent incapacitating vertigo attacks despite conservative management underwent simultaneous labyrinthectomy and cochlear implantation. There was complete resolution of vertigo in both patients. Speech perception in quiet conditions and the ability to hear in background noise improved considerably. CONCLUSION: Surgical labyrinthectomy is effective for the elimination of vertigo in Ménière's disease patients. The major disadvantage in the past was loss of residual hearing. Cochlear implantation is now an option in these patients. The benefits of simultaneous labyrinthectomy with cochlear implantation include the prevention of implantation of a fibrosed or ossified cochlea, a decrease in the duration of deafness, and a single operative procedure.

Effect of intratympanic steroid administration on sensorineural hearing loss associated with acute otitis media.

OBJECTIVE: To evaluate a small cohort of patients who presented with symptoms and signs consistent with acute infective sensorineural hearing loss who were treated with intratympanic steroids. METHOD: Seven patients received a 7-day course of oral antibiotics and oral prednisolone followed by 3 intratympanic injections of methylprednisolone and 1 week of topical dexamethasone drops. RESULTS: Hearing improved in 57 per cent of patients (four out of seven). The mean improvement in this group was 24 dB (range, 10-52 dB). The magnitude of the sensorineural hearing loss at presentation was less in those who responded to intratympanic steroid therapy than in non-responders (mean pure tone average of 30 dB versus 65 dB pre-intratympanic steroids, and 14 dB versus 83 dB post-intratympanic steroids, respectively). CONCLUSION: The results of our study suggest that intratympanic steroids provide a valuable contribution to the treatment of acute infective sensorineural hearing loss and may provide additional benefit by virtue of a concentrated local steroid effect in patients who do not respond to antibiotics.

Development of an improved analytical method for the determination of carcinogenic polycyclic aromatic hydrocarbons in transformer oil.

Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer oils and are essential in prolonging transformer in-service lifetime. Issues concerning PAH carcinogenicity demand methods that provide qualitative and quantitative information on the PAH composition of new and in-service oils to allow informed operational decisions to be made. However, current analytical methods focus on PAH fingerprinting, as opposed to quantitative analysis and are also cumbersome, relying on the use of large (>100 ml) volumes of organic solvents, some of which are hazardous. This paper reports a method for the improved quantification of carcinogenic PAHs in transformer oils that is both simple and repeatable. The method uses commercially available solid-phase extraction columns and millilitre volumes of relatively non-hazardous solvents. Extraction efficiencies of > or =74% were obtained for the Environmental Protection Agency priority PAHs. The method has potential for automation and high-throughput analysis and thus is of interest to industries that use transformer oils.

An unusual case of segmental clavicle fracture.

Fracture of the clavicle is a common traumatic injury and comprises 4% of all fractures in adults. Amongst these, midshaft injuries account for the majority and medial fractures are uncommon. Whilst segmental fractures have been reported in the literature, concurrent lateral and medial injuries are very rare. These injuries are, therefore, susceptible to being missed, due to failure to look for a second injury after the initial diagnosis, and difficult X-ray interpretation around the area of the medial clavicle. The nature of segmental fractures can pose a difficult management problem for numerous reasons, and initial operative fixation is usually indicated. Early diagnosis is therefore imperative, and as such, clinical examination is essential even if an obvious mid or lateral shaft fracture is seen on X-ray. This unusual case of combined lateral and medial fractures was initially missed and the presentation and management is discussed.

Histopathological and laboratory assessment of visual dysfunction.

The currently available methods of assessing ocular toxicity are discussed. Manifestations of ocular toxicity are best described clinically; histopathological examination of the eye is beset with problems of preparing the eye for morphological examinations. Electron microscopy is essential to look for chemically induced side effects at the cellular level. Mechanisms of ocular toxicity are poorly understood, and the limitation of animal studies in predicting side effects in man must be appreciated.

Assessment of testicular toxicity in laboratory animals.

The currently available methods of assessing testicular toxicity and fertility are discussed. Compounds inducing testicular atrophy mainly affect the seminiferous epithelium, with progressive loss of spermatozoa, spermatids, spermatocytes, and spermatogonia. Quantitative histometric analysis of spermatogenesis, together with hormone assays, could be used to advantage in defining the underlying mechanisms of toxicity.

Origins of follicular cells and ontogeny of steroidogenesis in ovine fetal ovaries.

Using fetal sheep as the experimental model, we have elucidated some of the key events that culminate in the formation of primordial follicles. A special effort was made to determine the source of the somatic cells that ultimately become granulosa cells of primordial follicles. Between gestational days 38-100: (1) light and electron microscopy was used to characterize changes in ovarian histoarchitecture; (2) incorporation of BrdU was used to identify populations of proliferating cells within fetal ovaries before, during and after, follicular formation; and (3) in situ hybridisation was used to determine the cell-specific and temporal patterns of expression of mRNAs encoding for selected steroidogenic enzymes. At day 38 somatic (pregranulosa) cells were in contact with oogonia and easily distinguished from endothelial and mesenchymal cells. Between days 38 and 45, pregranulosa cell-oogonia complexes progressively coalesced to form 'tube-like' structures referred to as ovigerous cords. These cords consisted of pregranulosa cells and oogonia arranged such that pregranulosa cells formed the outer wall of the cords. Ovigerous cords were avascular, enveloped in a prominent basal lamina, open-ended where they interfaced with the ovarian surface epithelium, and formed a separate compartment whereby oogonia/oocytes were segregated from the surrounding stroma and vasculature until the time of follicular formation. The structural integrity of ovigerous cords was maintained through day 75, at which time primordial follicles (type 1 and type 1a) first emerged from the cords at the interface of the cortex and medulla. On the basis of the sequential structural changes that occurred during the differentiation and development of fetal ovaries and location of proliferating cells identified by the incorporation of BrdU, we conclude that the majority of the granulosa cells in primordial follicles are derived from mesothelial cells originating from the ovarian surface epithelium. In addition, from the cell-specific distribution and temporal pattern of expression of mRNAs for key steroidogenic enzymes we hypothesize that steroid hormones may play a pivotal paracrine/autocrine role in the formation and/or function of ovigerous cords as well as the development of the ovarian vascular network.

Age-related variations in the testes and prostate of beagle dogs.

Variations in the weight and histology of the testes and prostate of Beagle dogs are described. Data were abstracted from records of toxicity studies performed at the Huntingdon Research Centre during the years 1967--77. A sample of 198 dogs aged between 37 weeks and 7.75 years was analysed. When juvenile dogs are studied, a significant proportion show low testicular weight, incomplete spermatogenesis and immature prostate development after 13-week observation periods. The occurrence of these normal variations may complicate the assessment of gonadal toxicity. In other respects, relatively few spontaneous variations from normal are likely to be encountered in these organs after observation periods lasting up to 2 years. 10% of dogs maintained for a 7-year observation period developed testicular neoplasms and a further 8% showed interstitial cell hyperplasia. Epithelial hyperplasia of the ductus epididymis and benign prostate enlargement were also normal features of the aged male Beagle.

Reversible suppression of spermiogenesis in beagle dogs following overdosage with the narcotic analgesic cogazocine lactate.

Acute single overdosage (1.0 mg/kg, i.m.) with the novel benzmorphan narcotic analgesic agent Cogazocine lactate lowered serum LH and testosterone concentrations of Beagle dogs. The effect was rapidly reversible and persisted for less than 24 h after drug administration. Repeated administration (1.0 mg/kg, i.m.) induced reversible suppression of spermatid maturation with subsequent effects on semen characteristics. Examination of circulating LH and testosterone concentrations, together with pituitary and prostate morphology, suggested that the changes were due to inhibition of LH release. It is probable that the underlying mechanism is an exaggerated pharmacological response to repeated overdosage, common to many potent narcotic analgesic agents.

Toxicology studies of linear alkylbenzene sulphonate (LAS) in rhesus monkeys. I. Simultaneous oral and subcutaneous administration for 28 days.

A toxicological investigation was performed with the linear alkylbenzene sulphonate (LAS) using 4 groups of 3 male and 3 female monkeys. Dosages were 0, 30, 150, 300 and 0, 0.1, 0.5, 1.0 mg/kg/day by simultaneous oral (p.o.) and subcutaneous (s.c.) administration respectively, for 28 days. At 300 p.o. and 1.0 s.c. mg/kg/day, the monkeys vomited frequently and usually within 3 hours of administration. An increased frequency of loose or liquid faeces was recorded for animals receiving 150 p.o. and 0.5 s.c. and 300 p.o. and 1.0 s.c. mg/kg/day. Fibrosis of the injection sites was found among all the test groups, the incidence and severity being dose related. Ophthalmoscopy, laboratory examination of blood and urine, organ-weight analysis and histopathological investigation did not detect any further treatment related responses. Previous reports concerning oral administration of tetrapropylene benzene sulphonates (ABS) to dogs record prompt emesis ascribed to local gastro-intestinal effects. Vomiting observed during this investigation was considered to be of possible central origin.

The toxicity of 1-amino-3-chloro-2-propanol hydrochloride (CL88,236) in the rhesus monkey.

The toxicity of 1-amino-3-chloro-2-propanol is associated with acute histopathological change in the medulla oblongata, characterised lesions of focal oedema. Continued administration results in neurological scars. Lesions can be induced at dose levels of 50 mg . kg-1 day-1. Clinical manifestations of neurological involvement are periods of slight incoordination and loss of balance in a few animals only.

Canine pituitary-testicular function in relation to toxicity testing.

The physiological onset and establishment of adult pituitary-testicular function has been characterised for Beagle dogs. Testicular measurements, circulating prolactin, luteinising hormone and testosterone concentrations, semen analyses and the histological appearance of testicular biopsies, suggest that male Beagles attain sexual maturity between 35 and 41 weeks of age. The assessment of testicular toxicity is discussed and attention drawn to possible approaches for investigating primary mechanisms of toxic action on the canine testis. Expected values for testicular size, hormone levels and semen characteristics are reported.

The oral toxicity of clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) in beagle dogs.

When clioquinol was administered to Beagle dogs, disturbances in gait which were associated with abnormal reflexes and reactions, were seen in animals receiving 250 and 400 mg/kg body weight per day. Histopathological examination of the central nervous system (CNS) showed pathological change in the posterior columns of the spinal cord.

The toxicity of gossypol to the male rat.

When (+/-) gossypol acetic acid was administered to male Sprague-Dawley rats for 26 weeks, the most significant toxicological finding was marked suppression of body weight gain in rats receiving 25 mg/kg per day. Minor biochemical changes were noted at this dosage level. Terminal studies showed 6 out of 20 rats receiving 25 mg/kg per day to have varying degrees of testicular pathology. Five mg/kg per day was shown to be a "no effect" level.

The oral toxicity of 1-amino-3-chloro-propanol hydrochloride (CL 88236) in rats.

1-amino-3-chloro-2-propanol (CL 88236) was administered by oral gavage for 12 consecutive weeks to rats at dose levels of 50, 250 and 500 mg/kg/day. All levels gave rise to toxicological effects. Epididymal necrosis and/or atrophy of the seminiferous epithelium was found for some males with each dose of CL 88236. The kidney and liver weights of male and female rats given CL 88236 were higher than control values but no histological changes were found in these organs.

Toxicity of methyl testosterone in the beagle dog.

When methyl testosterone was administered orally to beagle dogs at dosage levels of 2, 4 and 6 mg/kg per day for 27 weeks, hepatotoxicity was induced. The change induced was characterized by enlargement of periportal hepatocytes and the presence of haemosiderin within macrophages. There was some evidence of recovery over a 13-week period.

Toxicity studies with quinine hydrochloride.

Three-month studies in the rat, a rat embryo-toxicity study and a specific study to investigate ototoxicity were carried out with quinine hydrochloride. The results of these studies suggest an acceptable daily intake of 40 mg quinine hydrochloride for an adult. There were no indications of teratogenic effects and no indications of interference with auditory function in rats receiving up to 200 mg/kg.

The toxicity of beta-carotene.

The safety of beta-carotene, a widely distributed food colorant was assessed in tests with cells and in sub-chronic and chronic experiments with animals. Mutagenicity evaluations which included the standard Ames test and the micro-nucleus test of bone marrow cells from mice showed that beta-carotene exerted no mutagenic properties. Embryotoxicity studies in rats and rabbits showed that there was no evidence of embryotoxicity and a multiple generation study in rats showed that there was no interference with the reproductive function in rats given oral doses of up to 1000 mg/kg/day. Chronic toxicity was studied in a 2-year study with dogs in a toxicity/tumorigenicity study in rats and in a mouse carcinogenicity study. Histological findings in the livers of treated dogs and mice, but not in rats, included vacuolated cells with eccentric nuclei which were distributed in periportal areas and which were frequently associated with minimal lipid deposition. There was no evidence that the vacuolisation was dose-related. It was considered that the vacuolated cells were fat storage cells. There was no effect on the tumor profiles in the rat and the mouse studies.