Biomedical subjects
Publications and source records attributed to D M Wallace.
Recommended definitions to be used in the reporting of results of lithotripsy treatment are presented. It is suggested that these are the minimum requirements for reporting such treatment.
A series of 46 patients underwent 76 optical urethrotomies under local urethral anaesthesia in the out-patient clinic; in 70% of patients the strictures were controlled by local anaesthetic urethrotomy alone; 61% felt either no pain or mild pain during the procedure; 72% expressed a preference for local anaesthesia should the procedure have to be repeated and 82% were happy with the result of their treatment. Optical urethrotomy under local urethral anaesthesia produces results comparable to those reported by others using general anaesthesia. If large numbers of patients are to be treated, possibly repeatedly, then out-patient urethrotomy may result in more efficient use of resources.
Following 2 pilot studies which showed 57 and 61% response rates to intravenous cisplatin for transitional cell carcinoma of the bladder prior to definitive treatment, the West Midlands Urological Research Group (WMURG) and the Australian Bladder Cancer Study Group (ABCSG) independently began randomised trials to test the survival benefit of neo-adjuvant intravenous cisplatin prior to radiotherapy in T2-T4 M0 transitional cell carcinoma of the bladder. Both trials failed to recruit their target numbers of 250 patients in the West Midlands and 320 in Australia. Since they had similar treatment protocols and eligibility criteria, they were combined in an overview analysis, achieving a total number of 255 patients. Each treatment group was compared with its own control group and the differences were pooled to give an overall result. There was no difference in survival between treated and control patients. The odds ratio was 1.13 with the control groups faring marginally better than the chemotherapy groups. Even with 255 patients the 95% confidence interval of the odds ratio was wide (0.80-1.57). Although there is no clear evidence of a clinically worthwhile benefit from neo-adjuvant cisplatin, this approach must be tested in a larger study using combination treatments with greater activity in metastatic disease.
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This paper discusses the novel application of drugs, many of which were first developed for, or have an established role in other indications, in the treatment of disorders of the bladder, prostate and penis. These novel applications have often followed on from an increase in the understanding of the pathophysiological processes involved in the urological condition. Urology also lends itself to novel routes of administration, such as intravesical and intracorporeal routes as well as the more conventional oral, parenteral, and intra-nasal routes.
A series of transitional cell carcinomas of bladder were stained immunohistochemically with the monoclonal antibody, 32-2B, to desmosomal glycoprotein 1. All of the sections showed positive staining with the antibody. Assessment of staining intensity, by 3 independent examiners, revealed a strong negative correlation between density of desmosomal staining and degree of invasion (P = 0.012). Nests of strongly staining cells were identified in several invasive tumours, possibly indicating early squamous differentiation. Invasive tumour cells in the subepithelial stroma also stained strongly with the antibody. Correlation with clinical course, however, revealed no significant association between desmosomal staining and the incidence of recurrence or progression. It is suggested that staining with this antibody may be of value in detecting both stromal invasion and early squamous differentiation of transitional cell carcinomas. Both this and previous studies emphasise the value of this antibody as an epithelial marker in neoplasia.
The present study investigated the organization and distribution of amygdaloid axons within the various brainstem dopaminergic, noradrenergic and adrenergic cell groups. This was accomplished via Phaseolus vulgaris leucoagglutinin lectin (PHA-L) anterograde tracing technique combined with glucose-oxidase immunocytochemistry to catecholamine markers (i.e. tyrosine hydroxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase). Injections of PHA-L within the medial part of the central amygdaloid nucleus resulted in axonal labeling within most catecholamine containing cell groups within the brainstem. The most heavily innervated catecholaminergic groups were the A9 (lateral) cells of the substantia nigra, the A8 dopaminergic cells of the retrorubral field and the C2 adrenergic cells of nucleus of the solitary tract. Amygdaloid terminals frequently contacted cells within these regions. A moderate amount of amygdaloid terminals were located within the rostral A6 (locus coeruleus) and A2 (nucleus of the solitary tract) groups. Amygdaloid terminal contacts were apparent on the majority of the rostral A6 and A2 neurons. Light or no amygdaloid terminal labeling was observed within the other brainstem catecholaminergic cell groups. Thus, the amygdala mainly innervates the A8 and lateral A9 dopaminergic cells of midbrain, rostral locus coeruleus (A6) noradrenergic neurons and the adrenergic (C2) and noradrenergic (A2) cells within the nucleus of the solitary tract. Selective innervation of these brainstem catecholaminergic systems may be important for integration of amygdaloid-mediated defensive and stress-induced behaviors.
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Structure-activity relationships of recombinant human interleukin 2 were investigated by preparation, purification, and characterization of 21 missense mutants. A key role for residue Phe42 in the high-affinity interaction with receptor was indicated by (a) the reduction of 5-10-fold in binding affinity and bioactivity upon mutation of this residue to Ala and (b) the lack of evidence for conformational perturbation in Phe42----Ala in comparison with the wild-type protein as investigated by intrinsic fluorescence, second-derivative UV spectroscopy, electrophoresis, and reversed-phase HPLC, suggesting that the drop in binding is a direct effect of removal of the aromatic ring. In contrast, the conservative mutations Phe42----Tyr and Phe42----Trp did not cause significant reductions in bioactivity. UV and fluorescence spectra indicated approximately 60% overall exposure to solvent of tyrosines in the wild-type molecule, the tryptophan (residue 121) being buried; fluorescence data also showed that Trp42 in Phe42----Trp is likely to be within 1 nm of Trp121 and about 50% exposed to solvent. Phe44----Ala, Cys105----Ala, and Trp121----Tyr also exhibited reduced bioactivity, but these mutants are conformationally perturbed relative to wild type. None of the remaining mutants had detectably reduced bioactivity, even though several showed signs of altered conformation. Four mutants were recovered in very low yield, probably because of defective refolding.
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A series of transitional cell carcinomas and mucosal biopsy specimens of bladder were stained immunohistochemically with the monoclonal antibody HMFG-2. Staining characteristics ranged from luminal staining in well differentiated, superficial lesions to staining of all cells in invasive carcinomas. Invasive tumour nests also stained strongly with the antibody. There was good correlation between the staining pattern and histological assessment of both tumours and mucosal biopsy specimens. Correlation with clinical course showed that it was also a good predictor of subsequent disease progression of superficial tumours. It is suggested that HMFG-2 staining is a sensitive indictor of malignant transformation and that it may have a role as an adjunct to conventional histological examination in the assessment of urothelial carcinomas.
Portacaval anastomoses were performed in the rat to study urothelial carcinogenesis in this model and the promoting effect of dietary tryptophan. We were unable to produce any urothelial cancers or premalignant changes; some animals formed uric acid stones and developed papillary hyperplasia in the bladder. We conclude that the initiating carcinogen is likely to be exogenous and may be dietary in those experiments that have produced urothelial cancers.
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Zoladex is a potent decapeptide analogue of luteinising hormone releasing hormone (LHRH). The drug is formulated as a 3.6 mg depot dispersed in a matrix of d,l-lactide-glycolide copolymer, which is totally biodegradable. This formula releases drug continuously for at least 28 days and reliably suppresses serum testosterone into the castrate range. The effect of the depot was studied in 29 patients with locally advanced or metastatic carcinoma of the prostate. Average age at entry was 71 years (range 52-87) and follow-up was from 13.5 to 34.5 months (median 23). Endocrine studies showed that medical castration was maintained in all cases. Three patients experienced bone pain in the first month of treatment and two others had temporary nephrostomies for worsening ureteric obstruction. Subjective improvement was seen in 23/28 cases (82%). There were no complete responses, but partial response was seen in 24/28 (85.7%) using our own criteria, 24/28 (85.7%) using the criteria recommended by the British Prostate Group (BPG) and 15/28 (53.6%) using NPCP criteria. Stable disease was seen in 3/28 patients (10.7%) by our own or BPG criteria, and in 12/28 patients (42.9%) according to NPCP criteria. Progression of disease was measurable in 21 patients (72.4%) whatever criteria were applied; 11/29 (37.9%) have died, giving a median survival of 10 months (range 2.4-26). Following these encouraging results, a multicentre randomised comparative study with stilboestrol 3 mg daily is being undertaken.
Invasion of a bladder tumour involves the degradation and penetration of the subepithelial basement membrane. A retrospective study of 69 superficial and 15 invasive transitional cell carcinomas of bladder and a prospective study of 43 mucosal biopsies were performed in order to assess the usefulness of immunohistochemical staining of the basement membrane components, type IV collagen and laminin as prognostic indicators in superficial bladder cancer. There was a significant association between pT category and basement membrane staining. The incidence of progression of superficial tumours with patchy or absent basement membranes was significantly greater than those with complete basement membranes but there was no association with superficial recurrence. Biopsies of dysplastic epithelium had thickened and reduplicated basement membranes, possibly as a result of increased cell turnover. The results suggest that a balance exists between basement membrane production and degradation in early malignancy. This technique may be of value in the early identification of microinvasion and in the prediction of subsequent progression.