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Biomedical subjects

Robert Mayer

Publications and source records attributed to Robert Mayer.

8 recordsLinked to original sources

Interstitial cystitis pathogenesis and treatment.

PURPOSE OF REVIEW: Interstitial cystitis remains an idiopathic illness characterized by urinary frequency, urgency and pelvic pain with substantial morbidity in those affected. There is significant variability in the presentation, severity of symptoms and response to therapy. This review focuses on recent findings on the possible pathogenesis and potential treatments for this disease. RECENT FINDINGS: Interstitial cystitis is manifested by sensory hypersensitivity. A small volume of urine will be associated with an exaggerated sensation of pain or pressure and urinary urgency. There is continued research regarding how this process is initiated and maintained and to what extent systemic dysfunction of the immune or autonomic nervous system may play a role. The urothelial lining has been demonstrated to be capable of secreting a large number of potential signaling molecules that may be significant factors in the disease. SUMMARY: The pathogenesis of interstitial cystitis remains uncertain and the illness has significant diversity. Additional research is needed to establish subtypes that share common processes that can be targeted for treatment as a single effective therapy for the condition remains elusive.

Cystitis, Interstitial↗

Development of glomerulations in younger women with interstitial cystitis.

OBJECTIVES: To evaluate the consistency of cystoscopic findings with hydrodistension in younger women with a clinical diagnosis of interstitial cystitis. METHODS: A retrospective chart review was conducted of patients aged younger than 26 years old at the time of initial cystoscopy and hydrodistension at a single institution. Data included approximate duration of symptoms, development of visible terminal hematuria, presence of ulcers, and semiquantitive evaluation of degree of glomerulations (negligible, moderate, diffuse), and bladder capacity under anesthesia. RESULTS: Eighteen women aged 15 to 25 years old (mean, 17.5 years) were identified. The mean duration of symptoms was 38 months, with an estimated mean age of onset of 16 years. No patient had Hunner's ulcers, and 13 had visible terminal hematuria with moderate-to-diffuse glomerulations. Ten women had repeat cystoscopies, and the mean time to repeat cystoscopy was 17 months. Three women underwent repeat cystoscopy and initially had a relatively normal bladder mucosa, with none or only rare glomerulations, but moderate-to-diffuse glomerulations were seen on the subsequent cystoscopy in addition to the development of terminal hematuria. One patient, conversely on subsequent cystoscopy, showed resolution of glomerulations. CONCLUSIONS: Interstitial cystitis symptoms can develop before an age where adult urologists or primary care physicians familiar with the diagnosis and treatment are usually involved with care. The cystoscopic appearance of the bladder wall after hydrodistension may not be constant over time, and the absence of initial findings of glomerulations or terminal hematuria does not preclude further development of these hallmarks of the disease on subsequent evaluation.

Adolescent↗

Common themes and cell type specific variations of higher order chromatin arrangements in the mouse.

BACKGROUND: Similarities as well as differences in higher order chromatin arrangements of human cell types were previously reported. For an evolutionary comparison, we now studied the arrangements of chromosome territories and centromere regions in six mouse cell types (lymphocytes, embryonic stem cells, macrophages, fibroblasts, myoblasts and myotubes) with fluorescence in situ hybridization and confocal laser scanning microscopy. Both species evolved pronounced differences in karyotypes after their last common ancestors lived about 87 million years ago and thus seem particularly suited to elucidate common and cell type specific themes of higher order chromatin arrangements in mammals. RESULTS: All mouse cell types showed non-random correlations of radial chromosome territory positions with gene density as well as with chromosome size. The distribution of chromosome territories and pericentromeric heterochromatin changed during differentiation, leading to distinct cell type specific distribution patterns. We exclude a strict dependence of these differences on nuclear shape. Positional differences in mouse cell nuclei were less pronounced compared to human cell nuclei in agreement with smaller differences in chromosome size and gene density. Notably, the position of chromosome territories relative to each other was very variable. CONCLUSION: Chromosome territory arrangements according to chromosome size and gene density provide common, evolutionary conserved themes in both, human and mouse cell types. Our findings are incompatible with a previously reported model of parental genome separation.

Animals↗

A randomized controlled trial of intravesical bacillus calmette-guerin for treatment refractory interstitial cystitis.

PURPOSE: We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC). MATERIALS AND METHODS: Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively. RESULTS: A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates. CONCLUSIONS: Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive.

Administration, Intravesical↗

The architecture of chicken chromosome territories changes during differentiation.

BACKGROUND: Between cell divisions the chromatin fiber of each chromosome is restricted to a subvolume of the interphase cell nucleus called chromosome territory. The internal organization of these chromosome territories is still largely unknown. RESULTS: We compared the large-scale chromatin structure of chromosome territories between several hematopoietic chicken cell types at various differentiation stages. Chromosome territories were labeled by fluorescence in situ hybridization in structurally preserved nuclei, recorded by confocal microscopy and evaluated visually and by quantitative image analysis. Chromosome territories in multipotent myeloid precursor cells appeared homogeneously stained and compact. The inactive lysozyme gene as well as the centromere of the lysozyme gene harboring chromosome located to the interior of the chromosome territory. In further differentiated cell types such as myeloblasts, macrophages and erythroblasts chromosome territories appeared increasingly diffuse, disaggregating to separable substructures. The lysozyme gene, which is gradually activated during the differentiation to activated macrophages, as well as the centromere were relocated increasingly to more external positions. CONCLUSIONS: Our results reveal a cell type specific constitution of chromosome territories. The data suggest that a repositioning of chromosomal loci during differentiation may be a consequence of general changes in chromosome territory morphology, not necessarily related to transcriptional changes.

Animals↗

Sentinel node staging of resectable colon cancer: results of a multicenter study.

OBJECTIVE AND SUMMARY BACKGROUND DATA: Sentinel lymph node (LN) sampling, a technique widely used to manage breast cancer and melanoma, seeks to select LNs that accurately predict regional node status and can be extensively examined to identify nodal metastatic disease not detected by standard histopathological staging. For patients with resectable colon cancer, improved identification of LN disease would significantly advance patient care by identifying patients likely to benefit from adjuvant therapy. This study, conducted by 25 surgeons at 13 institutions, examined whether sentinel node (SN) sampling accurately predicted LN status for patients with resectable colon cancer. METHODS: SN sampling involved peritumor injection of 1% isosulfan blue, followed by identification of all LN visualized within 10 minutes. SN sampling was performed on 79 of 91 patients enrolled, followed by multilevel sectioning (MLS) of the nodes and examination by a single study pathologist. RESULTS: By standard histopathology, 7 patients had primary disease that was either benign or not colon cancer and were therefore excluded from further studies. Of 72 colon cancer cases studied, 48 (66%) were node-negative and 24 (33%) contained nodal metastases. SNs were successfully located in 66 cases (92%), with an average of 2.1 nodes per patient. SNs were negative in 14 of 24 node-positive cases (58%). MLS revealed tumor in a SN in 1 of these cases, bringing the false-negative rate of SN examination to 54%. CONCLUSION: This multi-institutional study found that for patients with node-positive colon cancer, SN examination with MLS failed to predict nodal status in 54% of cases. We conclude that SN sampling with MLS, used alone, is unlikely to improve risk stratification for resectable colon cancer.

Aged↗

Incontinence in women: effect of expectancy to regain control and severity of symptoms on treatment outcomes.

Urinary incontinence (UI) is a common problem for women of all ages. Associated with poor self-reported health, UI may have a negative effect on women's lifestyle and quality of life. Because UI is not commonly discussed between women or between women and their care providers, the extent of its impact on their lives is not fully understood. This study provides insight into how a woman's perceived or subjective opinion of the severity of UI and her belief in the ability to regain control of UI influence the effectiveness of treatment.

Attitude to Health↗