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Biomedical subjects

D M Wallace

Publications and source records attributed to D M Wallace.

At least 37 records · Page 2Linked to original sources
PubMed1995

The efficacy and safety of oral anticoagulation in patients with cancer.

OBJECTIVES: To compare the complication rate (bleeding and thrombosis) of oral anticoagulation in a cohort of patients with cancer to a cohort without cancer. DESIGN: Prospective cohort study. SETTING: Outpatient anticoagulation clinic in a community hospital. PATIENTS: Consecutive patients enrolled in an anticoagulation clinic: 44 with cancer, 64 without cancer. INTERVENTIONS: Patients received prophylactic doses of Warfarin (target INR 2-3 in the majority of instances) and complication rates were assessed. MEASUREMENTS: Major bleeding (strictly defined), minor bleeding, recurrent thrombosis, proportion of time with therapeutic INR, frequency of clinic visits. RESULTS: The rates of major bleeding, minor bleeding, and recurrent thrombosis were not statistically significantly different in the two groups of patients. Therapeutic INR's were more difficult to sustain in the cancer patients as compared to the non-cancer patients (43.3% vs 56.9%, p < 0.0001). There was a non significant trend towards more frequent monitoring for the cancer patients compared with the non-cancer patients (4.6 vs 3.5 visits per treatment month, p = 0.14). CONCLUSIONS: Oral anticoagulation is safe and effective in the patient with cancer. It is more difficult to sustain a therapeutic INR in the cancer patients and they may need more frequent monitoring to achieve a low complication rate.

Adolescent↗
PubMed1994

Loss of the retinoblastoma susceptibility gene (RB1) is a frequent and early event in prostatic tumorigenesis.

Loss of the RB1 gene is an important event in the initiation and progression of many tumours. Prostate tissue from 43 patients with prostate cancers and ten with benign prostatic hypertrophy (BPH) were studied for loss of heterozygosity of the RB1 gene. Four intragenic polymorphic loci were studied with two techniques. These were restriction fragment length polymorphism (RFLP). Southern blotting and hybridisation with the p123m1.8 and p68RS2.0 probes (to introns 1 and 17 respectively) and also the polymerase chain reaction (PCR) to amplify loci within introns 17 and 20. Protein product (pRB) expression was determined by immunohistochemistry using the NCL-RB antibody in nine patients with cancer and four patients with BPH. Loss of heterozygosity was found in 24 out of 40 (60%) informative patients with cancer. Loss of RB1 occurred with a similar frequency in early-stage and low-grade cancers as in more advanced cancers. Loss of RB1 was also found in one patient with BPH. Expression of pRB was completely absent from seven cancers and markedly reduced in the other two, while nuclear pRB staining was always present in areas of BPH, whether alongside cancer-containing tissue or with BPH alone. We conclude that loss of RB1 is an early event in prostatic tumorigenesis.

Base Sequence↗
PubMed1994

Repeat testing for haematuria and underlying urological pathology.

OBJECTIVE: To assess the incidence of urological pathology in a group of patients referred for the investigation of haematuria and whose symptoms had resolved at the time of investigation. PATIENTS AND METHODS: The results from examination of 395 patients attending for investigation of haematuria were analysed. The group comprised 198 men and 197 women with a mean age of 51 years (range 19-73). RESULTS: In 220 patients (56%) no evidence of haematuria was detected despite its diagnosis in all patients at the time of referral. One-hundred and thirteen patients (51%) without detectable haematuria had urological pathology and 16 of these (14%) had an underlying malignancy in the urinary tract. CONCLUSION: Repeat urine analysis to determine whether haematuria persists has been considered as a way to define a high risk group which requires urgent investigation. Our results clearly indicate that the finding of haematuria, even in one urine specimen, warrants full urological assessment.

Adult↗
PubMed1994

Rapid diagnostic service for patients with haematuria.

OBJECTIVE: To assess the feasibility of a clinic for the investigation of haematuria, with open access to general practitioners. PATIENTS AND METHODS: A total of 395 patients (198 men and 197 women), with mean age 51 years (range 19-73), were referred from 13 general practitioner clinics. All investigations were performed at the patient's first visit at which time either a provisional or a definitive diagnosis was made. RESULTS: Urinary tract infection was the most common diagnosis. Of all the patients, 43 (11%) had a malignancy of whom nine presented with microscopic haematuria. Fifty-nine per cent of patients were discharged after their first visit and 26% were placed on the waiting list for in-patient procedures. CONCLUSION: An open access clinic such as this is efficient and easily run. The high incidence of pathological abnormalities makes it a worthwhile facility.

Adult↗
PubMed1994

Marker tumour response to Evans and Pasteur bacille Calmette-Guérin in multiple recurrent pTa/pT1 bladder tumours: report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party).

OBJECTIVE: To compare the efficacy of Evans bacille Calmette-Guérin (BCG) and Pasteur BCG in eradicating marker bladder tumours and to compare the toxicity of the two strains. PATIENTS AND METHODS: Ninety-nine patients with multiple recurrent pTa or pT1 bladder tumours were allocated at random to six instillations at weekly intervals of either Evans BCG or Pasteur BCG. All tumours were resected except one marker tumour. At cystoscopy 3 months after randomization all tumours including the marker tumour, if still present, were resected. RESULTS: The incidence of adverse events was similar in the two groups but numbers were small and only large differences would have been detected. No statistically significant difference in efficacy regarding the response of the marker tumour or the appearance of other tumours at 3 months was noted in the two groups. There was no evidence of stage progression of the marker tumours. CONCLUSIONS: In multiple recurrent pTa or pT1 bladder tumours clearing the bladder of all except one marker tumour provides a safe and convenient way of measuring the response to intravesical therapy. No significant difference in efficacy or toxicity was detected between Evans BCG and Pasteur BCG.

Administration, Intravesical↗
PubMed1994

Loss of heterozygosity of the retinoblastoma and adenomatous polyposis susceptibility gene loci and in chromosomes 10p, 10q and 16q in human prostate cancer.

OBJECTIVE: To examine prostate tumours for losses of known or suspected tumour suppressor genes to determine some of the important events in the genesis of this common cancer. MATERIALS AND METHODS: Paired tumour and blood samples were obtained from 21 patients who underwent transurethral resection of malignant prostate glands for urinary outflow obstruction. Paired tumour and normal tissue (leucocytes) DNA was extracted and examined for possible losses of several known or suspected tumour suppressor genes, using restriction fragment length polymorphism techniques to detect loss of heterozygosity. RESULTS: Deletions of the retinoblastoma susceptibility gene (RB1) locus were found in six of nine informative cases using two intragenic probes (p68RS2.0 and p123m1.8). The locus related to the familial adenomatous polyposis susceptibility (APC) gene demonstrated loss of heterozygosity in three of seven informative cases using the EF5.44 probe. Losses were also noted in loci on chromosome 10p in four of 19 informative cases (probe cTBQ7), chromosome 10q in eight out of 19 informative cases (probes EFD75 and D10S90) and in 16q in three of 17 informative cases (probe D16S7). CONCLUSION: These findings suggest that losses of the RB1 and APC tumour suppressor genes and suspected tumour suppressor genes on 10p, 10q and 16q may be important events in the genesis of prostatic tumours.

Aged↗
PubMed1994

Characterization of three non-peptide endothelin receptor ligands using human cloned ETA and ETB receptors.

1. A number of putative endothelin (ET) receptor ligands were synthesized with a view to assessing their relative affinity for human recombinant ET receptors. 2. Human (h) and endothelin ETA and ETB receptor open reading frames were cloned by reverse transcription-polymerase chain reaction into the mammalian expression vector pcDNA1 and stable cell lines were created by transfection of Chinese hamster ovary cells. 3. Scatchard analyses of saturation isotherms for the specific binding of [125I]-endothelin-1 ([125I]-ET-1) to membranes, prepared from Chinese hamster ovary cells transfected with hETA or hETB receptors, yielded values for equilibrium dissociation constants (Kd) of 20.5 +/- 1.8 pM and 25.5 +/- 5.5 pM, respectively. Hill coefficients did not differ significantly from unity, suggesting binding to homogeneous, non-interacting receptor populations. 4. Pharmacological characterization of the transfected hETA and hETB receptors was undertaken by measuring the relative abilities of ETA and ETB receptor-selective peptide ligands to inhibit binding of [125I]ET-1. For interaction with hETA receptors, the relative order of potency was ET-1 > ET-3 = FR139317 = BQ123 >[Ala1,3,11,15]-ET-1 = sarafotoxin S6c (S6c). In contrast, the relative order of potency, at hETB receptors, was ET-1 = ET-3 = [Ala1,3,11,15]-ET-1 = S6c >> FR139317 = BQ123. 5. The novel non-peptide ligands, Ro 46-2005, SB 209670 and BMS 182874, were found to inhibit [125I]-ET-1 binding to human recombinant ETA and ETB receptors. At hETA receptors, the calculated pIC50 values were 6.7 (Ro 46-2005), 8.7 (SB 209670) and 5.8 (BMS 182874), while at hETB receptors, the corresponding pIC50 values were 6.8, 7.5 and <5, respectively.6. In conclusion, we have characterized the pharmacology of human cloned ETA and ETB receptors and used these in membrane binding assays to determine the affinity and selectivity of three structurally diverse non-peptide ET receptor ligands. SB 209670 is, to date, the highest affinity non-peptide ligand to be described for ET receptors. As such, it may prove to be a valuable tool in further examination of the physiological and pathophysiological roles of endothelins.

Animals↗
PubMed1993

Local control of T2/3 transitional cell carcinoma of bladder is correlated to differences in DNA supercoiling: evidence for two discrete tumor populations.

Single cell tumor suspensions were prepared from biopsy and urine samples from 48 patients with muscle invasive transitional cell carcinoma of the bladder. Prior to therapy, samples were irradiated in vitro with the condensation of DNA supercoils measured by the light scattered within a flow cytometer. Six months after completing a course of radiotherapy, the in vitro data were correlated with the presence or absence of local disease. After 12-Gy irradiation, nucleoid extraction and staining with 50 micrograms/ml ethidium bromide, 2 predominant forms of supercoiling behavior were seen. Nucleoids scattered either approximately 10% (Type I) or 35% (Type II) more light than unirradiated controls. Those patients with residual disease showed more Type I behavior (21 of 25; 84%) than those patients clear of disease (9 of 23; 39%) (P = 0.02). It is proposed that the ability of these tumor samples to adopt positive supercoiling after irradiation is related to a stronger association between individual DNA loops and their attachment to the nuclear matrix. This difference in nucleoid response within these tumor samples may be related both to intrinsic cellular radiosensitivity and, subsequently, to clinical radiocurability.

Adult↗
PubMed1993

Familial transitional cell carcinoma and the Lynch syndrome II.

A family is presented in which 4 male siblings developed transitional cell carcinoma (TCC). Four upper tract tumours occurred in 3 and in the fourth the tumour was intravesical. Two of these patients also had colorectal adenocarcinoma. There were 2 other relatives in the pedigree with large bowel cancer. It is suggested that this is an example of Lynch Syndrome II, a hereditary non-polyposis colorectal cancer with extracolonic cancer sites. The implications regarding the screening, surveillance and detection of possible carrier status in healthy relatives is discussed.

Adult↗
PubMed1993

Treatment preferences of urologists in Great Britain and Ireland in the management of prostate cancer.

A questionnaire was sent to all full-time British and Irish urologists (n = 278) on the management of prostate cancer and was answered by 229 (82%). The questions included 3 specific clinical situations, namely the management of incidental disease, the timing of treatment for metastatic disease and the mode of hormonal manipulation used for advanced disease. It was found that 79% of urologists preferred a deferred treatment policy for incidental disease in the over-75 age group. Radical prostatectomy was advocated by 10% of those questioned for patients in the under-60 age group. Radiotherapy was the mainstay of treatment for incidental disease in the poorer prognosis groups of incidental disease, namely younger patients with more aggressive tumours. Most urologists treated patients with asymptomatic metastatic disease at the time of diagnosis, with 18% entering patients into the Medical Research Council trial comparing immediate with deferred therapy. Orchiectomy was advocated by 57% of urologists as their first-line treatment for patients where hormonal manipulation was indicated. Consequently orchiectomy should remain the "gold standard" in comparative phase III trials in advanced prostate cancer.

Attitude of Health Personnel↗
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↗