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Biomedical subjects

R Mills

Publications and source records attributed to R Mills.

At least 19 recordsLinked to original sources

Fertility and sexual function following orchiectomy and 2 cycles of chemotherapy for stage I high risk nonseminomatous germ cell cancer.

PURPOSE: We investigate fertility and sexual function in patients following orchiectomy and adjuvant cisplatin based chemotherapy for high risk, stage I nonseminomatous germ cell tumor of the testis. MATERIALS AND METHODS: Between 1985 and 1994, 59 patients with stage I nonseminomatous germ cell tumor and poor prognostic factors were treated with 2 cycles of cisplatin, vinblastine and bleomycin, or bleomycin, etoposide and cisplatin after orchiectomy. At least 32 months following treatment all patients were contacted and asked to complete a questionnaire regarding fertility and sexual activity, and to volunteer for a semen and hormonal analysis. RESULTS: Of the 59 patients 49 (83%) completed the questionnaire. Before chemotherapy 18 (37%) patients had fathered children, 6 (12%) were involuntarily childless and none had a major sexual dysfunction. After treatment 11 (22%) patients fathered children, and 5 (10%) were involuntarily childless, with 4 involuntarily childless before chemotherapy. There were no significant alterations in sexual function. Semen analysis in 27 patients was normal in 23, and revealed mild oligospermia in 2 and azoospermia in 2. In 18 patients with hormone analysis median values for luteinizing hormone and free testosterone were normal but median value for follicle-stimulating hormone was slightly increased. CONCLUSIONS: Two cycles of cisplatin based adjuvant chemotherapy do not seem to affect adversely fertility or sexual activity.

Adult↗

Phase shifting prior to spatial filtering enhances optical recordings of cardiac action potential propagation.

Optical imaging of cardiac electrical activity using a voltage-sensitive dye provides high spatial resolution maps of action potential propagation and repolarization. Charge-coupled-device (CCD) camera-based imaging systems, however, are limited by their low signal-to-noise ratio. We have developed an image processing method to enhance the quality of optical signals recorded using a CCD camera. The method is based on the observation that within a small neighborhood of adjacent pixels, the morphology of the optical action potential varies little except for a phase shift in time resulting from the propagation of the wavefront. The method uses a phase-correlation technique to first correct for this time shift before spatially filtering with a 5 x 5 Gaussian convolution kernel (sigma = 1.179). A length 5 median filter is then applied to further reduce noise by filtering in the temporal domain. The image-processing scheme allows for more accurate extraction of maps of electrical activation, repolarization, and action potential duration.

Action Potentials↗

In vitro evaluation of a malleus head to stapes head 'incus replica' prosthesis.

An ossicular prosthesis produced by making a mould from a cadaveric incus and injecting ionomeric cement into it (incus replica prosthesis, IRP) has been cemented to the malleus head and stapes head and evaluated in fresh human temporal bones using a laser vibrometer. Stapes velocity was recorded under acoustic stimulation and foot plate displacements were derived. Fourteen frequencies between 125 Hz and 8000 Hz have been used. Measurements were made with the ossicular chain intact, following removal of the incus, with the prosthesis cemented to the malleus, but not the stapes, and with the incudo-stapedial joint cemented. In a second series of experiments the performance of the IRP was compared with that of a Causse partial ossicular replacement prosthesis, using the same experimental set-up. The results indicate that the prosthesis performs almost as well as the intact ossicular chain and that cementing the incudo-stapedial joint gives better sound transmission than leaving it uncemented. In addition the IRP outperforms the conventional partial ossicular replacement prosthesis.

Bone Cements↗

Risk factors for chronicity in childhood otitis media with effusion.

One hundred and ninety-one children who presented to the author's clinic with otitis media with effusion (OME) over a 2-year period (1986-1988) have been studied prospectively. Resolution of their OME was considered to have occurred when they had normal findings on pneumatic otoscopy, tympanometry and audiometry on at least two occasions 6 months apart and had subjectively normal hearing in between. The number of operations performed during the course of the disease was used as a surrogate for chronicity. Children with a history of previous aural discharge at presentation were significantly more likely to have chronic OME (P = < 0.02).

Adolescent↗

Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection.

Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.

Adult↗

A longitudinal study of work load and variations in psychological well-being, cortisol, smoking, and alcohol consumption.

The effects of variations in work load (indexed by paid work hours) on psychological well-being, cortisol, smoking, and alcohol consumption were examined in a sample of 71 workers (44 women, 27 men) in the retail industry. Measures were obtained on four occasions over a six-month period, and assessments were ranked individually according to hours of work over the past seven days. Job strain (demand/control) and job social support were evaluated as potential moderators of responses. Paid work hours ranged from a mean of 32.6 to 48.0 hours per week, and ratings of work-home conflict and perceived stress varied across assessments. Salivary cortisol was inversely associated with job strain and did not vary across sessions. Female but not male smokers consumed more cigarettes during periods of long work hours, and self-reported smoking and cotinine concentrations were greater among smokers with higher nicotine dependency scores. Men but not women with poor social supports consumed more alcohol as work hours lengthened. These data indicate that health behaviors are affected only to a limited extent by variations in work load. Results are discussed in the context of adaptation to work and the pathways linking stressful experience with health risk.

Adult↗

Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection.

In lymphoid tissue, where human immunodeficiency virus-type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by >/=3.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared >99.9 percent of virus from the secondary lymphoid tissue reservoir.

Adult↗

Reductions in viral load and increases in T lymphocyte numbers in treatment-naive patients with advanced HIV-1 infection treated with ritonavir, zidovudine and zalcitabine triple therapy.

In order to test the hypothesis that a combination of protease inhibitors with nucleoside analogues-agents known to inhibit different steps of the human immunodeficiency virus (HIV) life cycle--is likely to prove more effective in reducing viral loads than either of those modalities alone, we performed a 60 week, open-label trial in 32 HIV-positive patients with depressed CD4 T lymphocyte cell counts but no active AIDS-defining illnesses. For the first 2 weeks, patients received 600 mg twice daily of liquid ritonavir, a protease inhibitor; then zidovudine 200 mg three times daily and zalcitabine 0.75 mg three times daily were added to the treatment regimen. Mononuclear blood cell fractions were analysed for infected cell levels, using a co-culture system. HIV-1 RNA in plasma was measured both by reverse transcriptase-polymerase chain reaction (RT-PCR) and reverse transcriptase quantitative PCR (QcRT-PCR); lymphocyte counts were determined by standard laboratory methods. In the 2 weeks of ritonavir therapy, both the mean count of infectious blood cells and plasma HIV RNA levels decreased dramatically. Mean CD4 cell counts increased from 173 cells/mm3 at baseline to 286 cells/mm3; CD8 cell counts rose from 951 cells/mm3 to 1,141 cells/mm3. With the introduction of the nucleoside analogues, infectious cell counts and plasma virus dropped another log unit to a nadir at 8 weeks, while CD4 T lymphocyte counts continued to rise slowly. By week 28, 12 patients had withdrawn due to adverse events, none of which were life-threatening. At week 36, infectious material could not be detected in the cells of 10 of the 17 remaining patients; by week 60, four of the seven patients with residual viraemia at week 24 had undergone viral relapse. After the introduction of a more palatable capsule formulation of ritonavir at week 52, infectious cells and plasma virus were undetectable in 50-60% of patients. The combination of protease inhibitors and nucleoside analogues significantly reduces HIV load, and in some patients may suppress viral activity for sustained periods.

Acquired Immunodeficiency Syndrome↗

Long-term follow-up results with the Stamey operation for stress incontinence of urine.

OBJECTIVE: To assess the results of the Stamey operation for genuine stress incontinence in those patients with over 10 years of follow-up. PATIENTS AND METHODS: Of 46 patients who had undergone a Stamey procedure and had a follow-up of over 10 years, 30 were willing to attend for a clinical review and pad testing. RESULTS: Of the 30 patients assessed, 20 were initially cured, a further eight were significantly improved and two were no better. At 10 years, the number totally dry had fallen to 10, but a further 15 were still symptomatically improved. Only three that had shown some initial benefit were subjectively no better than before the operation. CONCLUSION: There appears to be a continuous decline in the cure rate with time from the Stamey procedure. However, most patients maintain some lasting benefit.

Female↗

The management of extensive penile fibrosis: a new technique of 'minimal scar-tissue excision'.

OBJECTIVE: To evaluate the results of excising minimal scar tissue in patients undergoing insertion of a penile prosthesis for extensive corporal fibrosis. PATIENTS AND METHODS: Twelve patients (mean age 58 years, range 44-73) with extensive corporal fibrosis who underwent the insertion of a penile prosthesis were evaluated. Eleven patients had a defect of varying extent after the insertion of the penile prosthesis, and a polytetrafluoroethylene graft was used to cover the area. RESULTS: All 12 patients tolerated the procedure well and currently have a functioning penile implant. CONCLUSIONS: Minimal excision of scar tissue provided better results and fewer complications when compared to other studies which used extensive excision.

Adult↗