Titration of duration discrimination in behavioral pharmacology and toxicology

This study investigated a discrete-trial, titration duration discrimination procedure in behavioral pharmacology. Pentobarbital and d-amphetamine, measured with this procedure, selectively affected discrimination more than response tendencies. Pentobarbital also tended to affect selectively discrimination of longer durations, whereas d-amphetamine did not. Further experiments showed that (1) other algorithms for modulating stimulus duration are useful in behavioral pharmacology and toxicology, (2) threshold estimates are similar with the method of constant stimuli and the method of titration, and (3) this titration procedure permits the separate examination of drug effects upon discrimination and upon response tendencies; the fixed-interval procedure does not. Baseline variability was an important correlate of drug effects in that the endpoints with more variable baselines were also more sensitive to drugs.     

Clastogenicity of diepoxybutane in bone marrow cells and male germ cells of mice

The bifunctional metabolite of 1,3-butadiene, 1,2:3,4-diepoxybutane(DEB), was tested in the mouse bone marrow micronucleus assayand in male mouse germ cell tests, namely the analysis of firstcleavage divisions and the dominant lethal assay. All experimentswere performed with single intraperitoneal treatment of theanimals. In the micronucleus test, DEB doses of 4.5, 9.0, 18.0and 36.0 mg/ kg body weight were tested at a sampling intervalof 24 h for bone marrow. The dose response for the inductionof micronuclei in polychromatic erythrocytes was linear withthe lowest effective dose of 9.0 mg/kg body weight No sensitivitydifference was observed between male and female mice. The cytogeneticanalysis of first cleavage division chromosomes was performedafter treatment of male mice with 17, 26, 34, 43 and 52 mg/kgbody weight of DEB and mating the males to hormonally stimulatedfemales on days 7, 14, 21 and 28 after treatment The two higherdoses caused general toxicity evidenced by the poor mating behaviorof the males. Only 13 and 20% of the mated females were fertilizedon day 7 after treatment of the males with 43 and 52 mg/kg bodyweight of DEB, respectively. An increased number of unfertilizedoocytes was obtained from fertilized females on day 7 aftertreatment of the males with 34 mg/kg body weight of DEB. Witha dose of 26 mg/kg body weight, it was demonstrated that chromosomalaberrations were only induced in spermatozoa (mating on day7 after treatment) while spermatids (mating on days 14 and 21)and spermatocytes (mating on day 28) were not susceptible tothe clastogenic effect of DEB. The response in spermatozoa inthe dose range 17–34 mg/kg body weight was linear up to26 mg/kg body weight and reached a plateau thereafter. The resultsof the dominant lethal experiments performed in the dose range18–54 mg/kg body weight gave results similar to the cytogeneticstudy. With the highest dose tested, the toxicity and cytotoxicityduring the first 8 mating days after treatment dramaticallyreduced the number of pregnant females and, consequently, thetotal implantations, so that no significant dominant lethaleffect could be assessed. During mating days 9–12 (treatedlate spermatids), a significant dominant lethal effect was observed.With the two lower doses (18 and 36 mg/kg body weight), thedominant lethal effect was restricted to spermatozoa. The goodcorrelation of the chromosomal aberrations with dominant lethalmutations confirms the chromosomal origin of dominant lethaleffects. The clastogenic effect of DEB in somatic cells andin germ cells of mice was of the same order of magnitude. ³To whom correspondence should be addressed     

The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF. There by demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (K_D 451-709 pM; receptors/cell 2306-413645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.     

Disturbed behaviour in dementia sufferers: A comparison of three nursing home settings

In order to determine whether a specialist psychogeriatric nursing home was fulfilling its intended role of caring for the most behaviourally disturbed dementia sufferers, 24 of its demented residents were compared with 28 demented individuals discharged from a psychiatric unit to ordinary nursing homes and 30 mobile dementia sufferers in nursing home wards of a geriatric centre. Those in the psychogeriatric nursing home showed more disturbed behaviours than those in the other two settings. Scores on the Rating Scale for Aggressive Behaviour in the Elderly were compared with degree of cognitive impairment for the first time in the literature and showed no correlation with degree of cognitive impairment for the first time in the literature and showed no correlation with congnitive performance.     

BUERGER'S DISEASE IN HONG KONG: A REVIEW OF 89 CASES

Background : A retrospective analysis of 103 case records from 1978 to 1996 with a provisional diagnosis of Buerger's disease was undertaken at the Department of Surgery, University of Hong Kong, Queen Mary Hospital. The aim of the study was to elucidate the clinical course and evaluate the results of surgical intervention of Buerger's disease in Hong Kong Chinese people. Methods : Fourteen patients were subsequently excluded from the study because of inability to fulfil our diagnostic criteria. Data on clinical presentation, investigations, indications and results of surgical intervention were reviewed. Sympathectomies and arterial reconstructions were performed on 42 and four patients, respectively, for critical ischaemia or rest pain. Outcome was analysed with respect to the rate of ulcer healing, pattern of recurrence and limb loss. Results : The patients were all young male heavy smokers with a mean age of 36.5 years. The majority of patients (80%) presented with ischaemic ulceration or gangrene. Vascular reconstruction was undertaken in four patients and satisfactory long-term results were obtained in three patients. Sympathectomy was able to relieve symptoms in 87% of operated patients and ischaemic ulceration healed in 2.6 (mean) ± 1.7 (SD) months after the operation. If the patient continued to smoke, surgical intervention did not exempt the patient from a relapse or amputation. Conclusion : Sympathectomy provides short-term pain relief and promotes ulcer healing in patients with Buerger's disease but carries no long-term benefit. Complete abstinence from smoking is the only means of arresting the progression of the disease.