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Biomedical subjects

C Wells

Publications and source records attributed to C Wells.

At least 91 records · Page 5Linked to original sources

Posterior cortical atrophy in Alzheimer's disease: analysis of a new case and re-evaluation of a historical report.

Disturbances of visual function are not uncommon in Alzheimer's disease and several cases with complex impairment of visuospatial abilities have been described. For instance, posterior cortical atrophy has been demonstrated in cases displaying Balint's syndrome as the first symptom of the dementing illness. Such cases showed very high lesion counts in the occipital cortex, as well as in visual association regions in the posterior parietal and posterior cingulate cortex, whereas the prefrontal cortex was consistently less severely involved than usually observed in Alzheimer's disease. This suggests that the distribution of the lesions had been shifted to specific elements of the visual system. In the present study, we report the quantitative analysis of a new case of Alzheimer's disease with possible Balint's syndrome and re-evaluate a case originally described in 1945. The distribution of lesion in these two cases parallels previous observations of Alzheimer's disease cases with early visual impairment. Both cases displayed very high densities of neurofibrillary tangles and senile plaques in the primary visual cortex, secondary visual cortex, visual association areas of the dorsal occipital and posterior parietal lobe and in the posterior cingulate cortex, whereas the prefrontal and inferior temporal regions were comparatively less affected. These cases may define clinical subgroups of Alzheimer's disease and suggest that the breakdown of corticocortical projections that is known to occur in dementia may involve select components of specific functional systems in certain cases. In particular, pathways that subserve motion detection and visuospatial analysis appear to be dramatically affected in these cases presenting with Balint's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Is HIV infection associated with an increase in the prevalence of cervical neoplasia?

OBJECTIVE: To test the hypotheses: (1) that HIV infection predisposes to cervical intraepithelial neoplasia (CIN); (2) that this CIN is a result of HIV related immunosuppression; and (3) that this CIN is a result of immunosuppression causing increased expression of the potentially oncogenic viruses, human papilloma virus (HPV), Epstein Barr virus (EBV) and herpes simplex virus (HSV). DESIGN: A matched cross sectional study. SETTING: The Department of Gynaecological Oncology, The Samaritan Hospital, London; the Department of Genitourinary Medicine, St Mary's Hospital, London; and the Family Planning Clinic, Claremont Terrace, Glasgow. SUBJECTS: Fifty HIV seropositive women enrolled from the Genitourinary Medicine Department and the Drug Dependency Unit at St Mary's Hospital, London, and the Unit of Infectious Diseases at Ruchill Hospital, Glasgow. Forty-three HIV seronegative controls enrolled from the Department of Genitourinary Medicine at St Mary's Hospital, matched against 43 of the seropositive women for age, age at first intercourse, lifetime number of sexual partners, and smoking habit. MAIN OUTCOME MEASURES: Associations between CIN, as detected by cytology and histology, and HIV infection. Association was also sought between CIN and immunosuppression, as measured clinically by T4 cell number, beta-2-microglobulin and p24 antigen. Associations of these with: (1) HPV, as detected by Southern blot testing and the polymerase chain reaction; (2) EBV, as detected by Southern blot testing; and (3) HSV, as detected by tissue culture of endocervical swabs, was also studied. RESULTS: There was no significant difference in the prevalence of CIN or oncogenic viruses between HIV seropositive and seronegative women in the absence of immunosuppression. If the HIV infected women showed signs of immunosuppression, the prevalence of CIN was increased. No association was shown between detection of HPV, EBV and HSV and immunosuppression or CIN. CONCLUSION: HIV infection may only be associated with an increased risk of CIN when immunosuppression is present.

Adult↗

Is endometrial infection with Candida albicans a cause of recurrent vaginal thrush?

OBJECTIVE: It was hypothesised that the endometrium might act as a reservoir for candida, thus infecting the vagina as the endometrium is shed during menstruation. DESIGN: A prospective study of women with recurrent vulvo-vaginal candidiasis. The endometrium was sampled and cultured for candida species. SETTING: Central London STD clinic. SUBJECTS: 26 women were enrolled, of whom 20 completed the study. RESULTS: One patient had a positive endometrial culture for candida species, the isolate being Candida krusei. CONCLUSIONS: The endometrium is not a common resevoir for candida species and therefore, infection at this site is an unlikely cause of recurrent vaginal candidiasis.

Candida albicans↗

Women with HIV presenting at three London clinics between 1985-1992.

OBJECTIVE: To determine the changing patterns of HIV infection in women in three units in London. SUBJECTS: Three hundred and fifty seven HIV seropositive women who have attended outpatient clinics between 1984 and 1992. METHODS: A retrospective review of data obtained from a computerised database and supplemented by direct inspection of the notes. RESULTS: The number of newly identified women with HIV has risen steadily over the period of study with a significant shift towards a heterosexual mode of transmission. This is a reflection of increasing numbers of women from Sub-Saharan Africa rather than a rise in the incidence of HIV in women born in the UK. CONCLUSIONS: The increase in women infected by HIV remains predominantly restricted to women in "high risk" groups. Although encouraging, our data should be interpreted with caution since it suffers from the inherent bias of selective testing. Safer sex education and epidemiological surveillance should continue despite the apparent low risk to women born in the UK.

Africa South of the Sahara↗

Synthesis and antiulcer activity of novel 5-(2-ethenyl substituted)-3(2H)-furanones.

In order to investigate new antiulcer agents, spizofurone 1 (AG-629) was fragmented and reassembled to generate 5-phenyl-2,2-dimethyl-3(2H)-furanone (bullatenone, 2). Because of the antiulcer activity of 2,5-phenyl-substituted 2,2-dimethyl-3(2H)-furanones (3-6) were made and shown to have poor activity. Insertion of an ethenyl link between the furanone and phenyl rings gave 5-(2-phenylethenyl)-2,2-dimethyl-3(2H)- furanone (7). This compound had better activity than 2. Compounds 8-41 were synthesized to evaluate the SAR in 5-(2-ethenyl substituted)-3(2H)-furanones. Electron-withdrawing substituents on the aromatic ring (8, 10, 19, and 20) gave 2-3-fold higher activity. Further increases in the activity were found when the phenyl ring was replaced by heterocyclic nuclei. Compounds that contained a thiophene (29), pyridine (24-26), or quinoline ring (32) had the best activity. Replacement of the methyl group on the furanone ring with a phenyl (34) or p-fluorophenyl (40) substituent in the 2-pyridine series gave compounds with activity that ranked with the best obtained in this study. The best compounds from the above SAR studies were evaluated in the ethanol-necrosis model for duration of cytoprotection action. Compounds 19, 24, and 29, which had the best duration of action, were tested with AG-629 in the acidified aspirin and indomethacin-induced lesion models. Only compound 24 had equivalent activity with AG-629 in both models.

Animals↗

Effects of phosphatidylserine in Alzheimer's disease.

We studied 51 patients meeting clinical criteria for probable Alzheimer's disease (AD). Patients were treated for 12 weeks with a formulation of bovine cortex phosphatidylserine (BC-PS; 100 mg t.i.d.) or placebo, and those treated with the drug improved on several cognitive measures relative to those administered placebo. Differences between treatment groups were most apparent among patients with less severe cognitive impairment. Results suggest that phosphatidylserine may be a promising candidate for study in the early stages of AD.

Aged↗

Rapid induction of early osteoarthritic-like lesions in the rabbit knee by continuous intra-articular infusion of mammalian collagenase or interleukin-1.

Aminophenyl mercuric acetate (APMA)-activated collagenase (C) (60 U/ml) obtained from in vitro cultures of human skin fibroblasts or recombinant interleukin-1 beta (IL-1 beta) (200 U/ml) was infused continuously for 7 days into the rabbit knee synovial space by means of an implanted Alzet osmotic pump. In stability studies in vitro, activated C or IL-1 incubated for 7 days at 37 degrees C, showed no significant loss of biological activity. Alterations in knee cartilage morphology and proteoglycan (PG) content were determined histologically, and the incidence of cartilage damage calculated. C or IL-1 vehicles infused for 7 days, caused no damage. Incidences of damage for C or IL-1 (n = 8-9), respectively, were as follows: loss PG: 88% and 100%; chondrocyte disorganization and loss, 50% and 78%, fissures and or fraying, 25% and 78%; and convergence of inflammatory cells, 25% and 66%. These results confirm the important role of C and IL-1 in cartilage damage.

Animals↗

Pain and allodynia in postherpetic neuralgia: role of somatic and sympathetic nervous systems.

The immediate effects of selective sympathetic and somatic blockades on pain and tactile allodynia in 12 patients with long-standing ophthalmic or high cervical postherpetic neuralgia were compared. For the duration of the somatic blockade, pain was completely abolished in 11 patients and allodynia in 8 patients. In contrast, during the sympathetic blockade only one patient reported total pain relief and three a marginal attenuation of pain while eight remained unchanged; and no patient reported clear alleviation of allodynia. After successful somatic blockade, pain and allodynia reappeared with tactile sensation while thermal sensation was still absent. Pain and allodynia appear to be related to sensory impulses travelling along the large rather than the small diameter fibres; and the sympathetic system may only have a limited role.

Aged↗

Axonemal dynein from Tetrahymena.

Axonemal dynein from Tetrahymena cilia can be separated on a sucrose gradient into two fractions, at least one of which appears to be polymorphic. We have been using immuno-electron microscopy in order to try and locate the different types of dynein molecules within the axonemal structure.

Animals↗

Peroperative monitoring during percutaneous thermocoagulation of the Gasserian ganglion for the treatment of trigeminal neuralgia.

A bipolar electrode has been designed to assess the possibility of locating accurately the electrode tip position within a nerve pathway prior to its thermal coagulation without having recourse to a wake-up procedure. By electrically stimulating each of the peripheral divisions of the trigeminal nerve and recording the evoked activity pre-ganglionically from the electrode, using an averaging computer, a clear triphasic response is recorded. The amplitude of this wave is largest when the electrode is within the stimulated division, thereby confirming electrically the anatomical location. By incorporating a thermocouple in the tip of the electrode a precisely controlled thermocoagulation can then be achieved using a radiofrequency generator. A preliminary series of 12 patients with trigeminal neuralgia requiring operative treatment were assessed in this study. In eight cases a clear response was obtained, in two the signal-to-noise ratio was too small, in one stimulus artefact obscured the response and in one a blood vessel was hit.

Electrocoagulation↗

A comparison of intrauterine insemination, intraperitoneal insemination, and natural intercourse in superovulated women.

In a prospective comparison of IP, IUI, and natural intercourse following superovulation in couples diagnosed as having unexplained infertility, semen factors, or sperm antibodies, pregnancy rates were found to be significantly higher after IP. Pregnancy rates were also higher in the unexplained infertility group when compared with those with semen factors. It was concluded that IP in combination with superovulation offered a simple, inexpensive, safe alternative to GIFT.

Administration, Intravaginal↗

Necator americanus in the mouse: histopathological changes associated with the passage of larvae through the lungs of mice exposed to primary and secondary infection.

The mouse/Necator americanus model was studied to assess the histopathological changes that occur in the lungs following primary and secondary exposure to infective larvae. Groups of BALB/c mice were infected percutaneously and killed on various days post infection. Parasite numbers were counted, the bronchoalveolar leukocyte response was quantified and histological sections of lung material were examined for evidence of host protective inflammatory reactions. An increase in the inflammatory infiltration was observed between days 5 and 9 in both primary and secondary infections but was considerably more intense in re-infected animals. This involved a marked change in the character of the infiltrate, particularly in the number of eosinophils that were recovered in lavage fluid. More worms were trapped in the lungs of challenged mice, as assessed through their inability to escape from lung material incubated in vitro. Overall, the results were found to be compatible with the development of acquired resistance to N. americanus and the expression of host protective immunity during the development of challenge-infection larvae in the lungs.

Animals↗

Self-interaction of dynein from Tetrahymena cilia.

The molecular mass (Mr) and enzymic activity of the larger dynein species from Tetrahymena thermophila has been studied in the high (600 mM) to low (40 mM) ionic strength range. The apparent Mr is found to vary with both ionic strength (by sedimentation velocity and quasi elastic light scattering analysis) and with protein concentration at low ionic strength (by sedimentation equilibrium analysis). These data indicate a strong self-interaction, resulting in dimer formation under low salt conditions. There is no evidence for the formation of species of higher than dimeric mass. A molecular mass for the dynein monomer of 1.64 x 10(6) daltons has been determined, a value rather lower than previous published estimates. The ATPase activity of dynein increases with increasing ionic strength. The possible relationship between this effect and the self-association phenomenon is discussed.

Adenosine Triphosphatases↗