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Biomedical subjects

D S Byrne

Publications and source records attributed to D S Byrne.

12 recordsLinked to original sources
PubMed1998

Effect of intravesical capsaicin and vehicle on bladder integrity control and spinal cord injured rats.

PURPOSE: To determine the acute effect of intravesical capsaicin on bladder mucosal integrity in normal and spinal cord injured (SCI) rats. MATERIALS AND METHODS: Intravesical reagents were instilled in 5 groups of age and weight matched female rats: 1) control + normal saline solution (NSS), 2) control + ethanol (EtOH), 3) control + capsaicin/EtOH, 4) SCI + NSS, 5) SCI + capsaicin/EtOH. Intravesical instillations were performed 4 weeks after a standard T10 SCI. Intravesical capsaicin (1 mM.) was dissolved in 30% EtOH/NSS. The animals (n = 3 each group) were sacrificed at 30 minutes, 24 hours, 72 hours, and 7 days after intravesical instillation. Whole bladders were harvested, fixed in 10% buffered formalin, and paraffin embedded. Tissue blocks were blind coded and sectioned (5 microns thickness) for histopathological analysis. All sections were initially stained with hematoxylin and eosin (H & E). Specific staining for mucin carbohydrate moieties included periodic acid-Schiff (PAS) and alcian blue. Also, immunohistochemical staining for GP51 (a urinary glycoprotein) was performed. RESULTS: Control and SCI rats exhibited similar bladder mucosal histology by H & E and mucin specific stains. Instillation of saline demonstrated no effect on bladder histology, whereas instillation of intravesical capsaicin induced a profound acute effect of thinning of the epithelium, submucosal edema, and diminished presence of GP51. EtOH produced similar pathological findings, but to a lesser degree than capsaicin. Intravesical capsaicin demonstrated a similar effect in both control and SCI animals. The peak effect was seen after 30 minutes and continued for 24 hours. Partial recovery was noted after 72 hours and complete recovery was evident by 1 week. CONCLUSIONS: The control and SCI rats demonstrated a histologically similar mucosa and glycosaminoglycan layer. The effect of saline instillation on the mucosa was negligible. Intravesical capsaicin dissolved in 30% ethanol/NSS had a profound effect on the bladder urothelium submucosa that was more pronounced than that seen with the ethanol vehicle alone in normal animals.

Administration, Intravesical↗
PubMed1996

A single centre's 10 year experience with isolated limb perfusion in the treatment of recurrent malignant melanoma of the limb.

The aim of this study was to assess whether isolated limb perfusion can be performed safely and whether it offers improved disease-free survival for patients with limb malignant melanoma. Between August 1983 and July 1993, 103 patients (78 female, 25 male) with recurrent limb melanoma were treated by isolated limb perfusion (ILP) in Glasgow, U.K. The mean age of the patients was 62 years; 95 had leg recurrence, 8 had arm recurrence. The mean time from original diagnosis to ILP was 48 months (range 1-290). 102 iliac, 5 femoral, 7 popliteal and 8 axillary perfusions were performed. All patients had stage II (local recurrence within 3 cm of primary site) or stage III (regional metastases; tissues excluding nodes, nodes or combination) disease according to the MD Anderson Cancer Centre Staging System. At a mean follow-up of 30.7 months, 68 patients had died of recurrent disease (mean time to death 22.5 months). The 2 and 5 year survival of the group was 50 and 26%, respectively and disease-free survival was 23 and 12%, respectively. At first perfusion, 76% of patients showed complete response and 23% showed partial response. With repeat perfusion, 47% showed complete response and 53% had partial response. In conclusion, ILP is safe and has an acceptable morbidity. It achieves highly satisfactory local disease control but long-term survival is the exception.

Adult↗
PubMed1996

A comparison of dosimetric methods in isolated limb perfusion with melphalan for malignant melanoma of the lower extremity.

The three dosimetric schedules currently used in isolated limb perfusion with melphalan for malignant melanoma of the lower limb were compared in a series of 51 patients. The doses prescribed by each of the three methods (based on total body weight (TBW), limb tissue volume (LTV) and total blood volume in the perfusion circuit (TBV)) were calculated for all patients and were then compared using Wilcoxon's signed-rank test. This revealed that the method based on TBV consistently prescribed much lower doses of drug than either of the other two methods. Pharmacokinetic profiles of melphalan obtained by HPLC analysis of blood samples during the procedure also showed that the method did not reliably predict the concentration of melphalan achieved in the perfused limb. The dosimetric schedule based on LTV prescribed slightly higher doses than that based on TBW. However, the technique is more difficult to practise due to the problems of measuring the limb volume by immersion. We conclude that the dosimetric schedule based on TBW is the most appropriate by virtue of its simplicity, the high doses of melphalan which it prescribes, and the well-controlled toxicity which it produces.

Antineoplastic Agents, Alkylating↗
PubMed1994

Decreased expression of a glycoprotein component of bladder surface mucin (GP1) in interstitial cystitis.

Interstitial cystitis is a disease of unknown etiology characterized by unremitting urinary frequency, urgency and suprapubic pain. Recently, a change in urothelial permeability has been identified in interstitial cystitis patients that is presumably mediated by aberrations in bladder surface mucin. For this study we evaluated qualitative changes in a previously defined glycoprotein component of this layer (GP1) as it occurs in interstitial cystitis patients and normal controls. Paraffinized bladder biopsies were obtained from 23 interstitial cystitis patients (all meeting National Institutes of Health inclusion criteria) and 11 normal controls. All biopsy tissue was stained with hematoxylin and eosin, and periodic acid, Schiff reaction. The tissues were examined immunohistochemically for GP1 using an anti-GP1 serum. Periodic acid, Schiff staining clearly identified bladder surface proteoglycans in all specimens. Moderate GP1 reactivity was noted in all normal control specimens. Alternatively, GP1 expression was absent in 35% of the interstitial cystitis patient biopsies and decreased in 61%. These data demonstrate qualitative GP1 changes in a majority of interstitial cystitis patients. It is unknown whether these differences have an impact on the pathogenesis of interstitial cystitis. However, our findings suggest that the absence or decreased expression of GP1 in interstitial cystitis bladder biopsies may serve as a marker to characterize the disease further in conjunction with clinical findings.

Adult↗
PubMed1993

Screening for occult nodal metastasis in localized carcinoma of the prostate.

Metastatic involvement of pelvic lymph nodes in carcinoma of the prostate alters the prognosis and treatment of this disease. Our goal was to determine if additional techniques, such as immunohistochemical staining, could detect occult microscopic metastatic nodal disease not seen with routine hematoxylin and eosin staining. We examined paraffin embedded lymph nodes from 43 patients with clinical stage A or B carcinoma of the prostate who were candidates for radical prostatectomy and who underwent modified pelvic lymph node dissection with frozen section hematoxylin and eosin staining. Immunohistochemical staining for prostate specific antigen and prostate specific acid phosphatase was performed on the lymph nodes. Monoclonal antibodies to cytokeratins were used to confirm the epithelial origin of the prostate cells. An average of 9 lymph nodes and 42 histological sections per patient were stained. Based on routine hematoxylin and eosin staining the pathological staging was stage A in 3, stage B in 20, stage C in 9 and stage D1 in 11 cases. There were 17 well, 16 moderately and 10 poorly differentiated carcinomas. In 31 of 32 patients with negative nodes no occult metastases could be identified. One patient with poorly differentiated stage C cancer demonstrated occult nodal deposits by prostate specific acid phosphatase and not by prostate specific antigen. In the 11 stage D1 cancer patients immunohistochemical staining confirmed all malignant deposits and additional metastatic lesions were detected in only 1 patient. Unlike other carcinomas, such as breast, in which immunohistochemical staining yields a 14 to 37% occult metastasis rate, these data suggest that occult nodal metastases are infrequently seen in carcinoma of the prostate.

Acid Phosphatase↗
PubMed1992

Melphalan concentration and distribution in the tissues of tumour-bearing limbs treated by isolated limb perfusion.

Levels of melphalan (L-phenylalanine mustard) were measured in the tissues of tumour-bearing limbs treated by isolated limb perfusion (ILP). 41 samples of melanoma tissue, normal fat and skin were excised from 15 patients during ILP. A high performance liquid chromatography assay was used to measure melphalan concentrations. Levels of melphalan were higher in tumour than in fat (P < 0.01, Wilcoxon signed-ranks test), and not significantly different from levels in adjacent skin. In 2 cases there was significant regional toxicity in the treated limb, but this was not related to the levels of melphalan measured in the tissues of the limb. It is encouraging that the concentrations of melphalan which were achieved in large necrotic nodules by ILP were similar to those in well-perfused normal skin.

Adipose Tissue↗
PubMed1992

The pharmacokinetic advantages of isolated limb perfusion with melphalan for malignant melanoma.

We describe melphalan pharmacokinetics in 26 patients treated by isolated limb perfusion (ILP). Group A (n = 11) were treated with a bolus of melphalan (1.5 mg kg-1), and in a phase I study the dose was increased to 1.75 mg kg-1. The higher dose was given as a bolus to Group B (n = 9), and by divided dose to Group C (n = 6). Using high performance liquid chromatography (HPLC) the concentrations of melphalan in the arterial and venous perfusate (during ILP) and in the systemic circulation (during and after ILP) were measured. Areas under the concentration time curves for perfusate (AUCa, AUCv) and systemic (AUCs) data were calculated. In all three groups the peak concentrations of melphalan were much higher in the perfusate than in the systemic circulation. The pharmacokinetic advantages of ILP can be quantified by the ratio of AUCa/AUCs, median value 37.8 (2.1-131). AUCa and AUCv were both significantly greater in Group B than in Group A (P values less than 0.01, Mann-Whitney). In Groups B and C acceptable 'toxic' reactions occurred but were not simply related to melphalan levels. Our phase I study has allowed us to increase the dose of melphalan to 1.75 mg kg-1, but we found no pharmacokinetic advantage from divided dose administration.

Arteries↗
PubMed1990

Antisera to a rabbit urinary tract antigen also react with human bladder and kidney tissue.

The mucin layer covering the bladder transitional cell mucosa appears to function as a primary defense mechanism against bacterial infection. We have previously prepared a glycoprotein fraction (GP1) from the urinary bladder mucosa of NZW rabbits and raised murine antisera against it. These antisera react with bladder, ureter and kidney tissue from rabbits, rats, guinea pigs, and hamsters. We now show that a similar substance occurs in human kidneys and bladder. In order to remove antibodies reactive with the Tamm-Horsfall protein (THP), the antisera were initially absorbed with an immunoadsorbent composed of purified human THP covalently bound to Sepharose CL-4B gel. Using an enzyme linked immunosorbent assay (ELISA) it could be shown that the absorbed antisera did not react with THP but retained a high titer in binding to GP1. Immunohistochemical procedures involving avidin-biotin-immunoperoxidase staining demonstrated that the absorbed anti-GP1 reacted well with six human urinary bladder biopsy specimens and two kidney autopsy specimens while normal murine sera showed little or no binding. Although this reactivity was not as strong as that found with homologous tissue (rabbit) these studies suggest that GP1, an antigen common to several animal species, is also related to a human urinary tract component.

Animals↗