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Biomedical subjects

D M Wallace

Publications and source records attributed to D M Wallace.

At least 19 recordsLinked to original sources
PubMed1992

Organization of amygdaloid projections to brainstem dopaminergic, noradrenergic, and adrenergic cell groups in the rat.

The distribution of amygdaloid axons in the various brainstem dopaminergic, noradrenergic, and adrenergic cell groups was examined. This was accomplished by means of the 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 in the medial part of the central amygdaloid nucleus resulted in axonal and terminal labeling in most catecholamine cell groups in the brainstem. Amygdaloid terminals appeared to contract catecholaminergic cells in several brainstem regions. The most heavily innervated catecholaminergic cells were the A9 (lateral) and A8 dopaminergic cell groups and the C2/A2 adrenergic/noradrenergic cell groups in the nucleus of the solitary tract. The medial part of the A9 and adjacent A10 dopaminergic cell groups was moderately innervated. A moderate innervation by amygdaloid terminals was observed on rostral locus coeruleus noradrenergic cells (A6 rostral) and adrenergic cells of the rostral ventrolateral medulla (C1). Noradrenergic cells of the A5, main body of the locus coeruleus (A6), A7, and subcoeruleus were sparsely innervated. Amygdaloid axons were not observed on noradrenergic neurons of the A4 cell group, area postrema, and A1 cells of the ventrolateral medulla. The results demonstrate that the amygdala primarily innervates the dopaminergic cells of midbrain (i.e., A8 and lateral A9 cells) and the adrenergic cells (C2) and noradrenergic (A2) cells in the nucleus of the solitary tract. The possible functional significance of amygdaloid innervation of catecholaminergic cells is discussed.

Amygdala↗
PubMed1992

Paravesical suture granuloma: a problem following herniorrhaphy.

We discuss the diagnosis and management of a paravesical suture granuloma and review 11 such cases reported in the literature. Granulomas are an unusual complication of surgery, which have been noted to occur from several months to 11 years postoperatively. Of the 11 patients reported on 10 had undergone previous inguinal herniorrhaphy and presented with urinary symptoms and a palpable mass, and 1 had undergone femoral herniorrhaphy. In 7 cases the clinical diagnosis was a malignancy. It is important to consider suture granulomas in the differential diagnosis of a suprapubic mass involving the bladder so that unnecessary major surgery can be avoided.

Adult↗
PubMed1992

Phase III randomised study of zoladex versus stilboestrol in the treatment of advanced prostate cancer.

An open randomised Phase III trial was conducted of the depot GnRH analogue goserelin (Zoladex) versus stilboestrol (3 mg/day) in patients with advanced or metastatic prostate cancer. The study included 250 patients and the median follow-up was 43 months. In the Zoladex arm the time to first response was achieved earlier and more patients reported an improvement in symptoms. There was no statistically significant difference between the Zoladex and the stilboestrol arms with regard to survival and time to treatment failure. A major reason for treatment failure was the preponderance of adverse events in patients receiving stilboestrol. It is suggested that stilboestrol should no longer be used for prostate cancer when equally effective alternative treatments are available.

Aged↗
PubMed1992

Urologists' attitudes to the management of bladder cancer.

All consultant urologists in Great Britain and Ireland were sent 2 questionnaires relating to their management policies in bladder cancer; 82% and 78% respectively of questionnaires were completed and returned. The answers demonstrated a wide variation among urologists about the management of common clinical problems.

Attitude of Health Personnel↗
PubMed1991

A correlation between nuclear supercoiling and the response of patients with bladder cancer to radiotherapy.

Single cell tumour suspensions were prepared from biopsy and urine samples from 28 patients with muscle invasive transitional cell carcinoma of the bladder. Nuclear extracts (nucleoids) containing intact chromatin were isolated from these cells and the condensation of DNA supercoils measured by the light scattered from individual nucleoids within a flow cytometer. Exposure of these nucleoids to 10 micrograms ml-1 ethidium bromide produced 78.9% increase in light scatter compared to those treated with 50 micrograms ml-1. This finding is consistent with the known effect of ethidium bromide on DNA supercoiling and confirms that the light scatter signal is responding to changes at this level of DNA organisation. Cell samples were also exposed to 12 Gy of gamma radiation and the effect on nucleoid light scatter recorded. Of the patients studied prior to radiotherapy, those with persistent disease 3 months after treatment generated an increase in nucleoid light scatter of + 9.35 +/- 4.8% after 12 Gy irradiation, of these, 2/14 produced nucleoids that relaxed by more than 10% compared to controls. Those patients with no evidence of disease after radiotherapy gave an increase in nucleoid light scatter after in vitro irradiation of + 19.3 +/- 4.5% of which 10/14 (71%) relaxed by more than 10%. It is proposed that the increased relaxation within the supercoiled DNA from patients whose tumours were undetectable 3 months after therapy, is related to the inherent radiosensitivity of these tumour cells. Such a difference in nucleoid response within tumour cells from patients that responded to radiation may arise due to a decreased affinity of DNA loops for the nuclear matrix. This structural change, at a site associated with the initiation of DNA synthesis, may affect the ability of cells to continue successful cell division after radiation damage.

Biopsy↗
PubMed1991

Optical urethrotomy under local urethral anaesthesia.

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.

Adult↗
PubMed1991

Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder.

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.

Aged↗
PubMed1990

Therapeutic progress--Review XXXVI. Are we making progress in the drug treatment of disorders of the bladder, prostate, and penis?

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.

Humans↗
PubMed1990

Immunohistochemical staining with monoclonal antibody 32-2B to desmosomal glycoprotein 1. Its role in the histological assessment of urothelial carcinomas.

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.

Antibodies, Monoclonal↗
PubMed1989

The amygdalo-brainstem pathway: selective innervation of dopaminergic, noradrenergic and adrenergic cells in the rat.

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.

Amygdala↗
PubMed1988

Structure-activity relationships of recombinant human interleukin 2.

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.

Amino Acid Sequence↗