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Biomedical subjects

T J Anderson

Publications and source records attributed to T J Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Trial of Sinemet CR4 in patients with Parkinson's disease.

OBJECTS: to compare the efficacy of Sinemet CR4 (CR4), a slow release levodopa preparation, with that of standard Sinemet in patients with Parkinson's disease and motor fluctuations. METHODS: forty-five patients with Parkinson's disease of mild to moderate severity and motor fluctuations were entered into the 12 month trial. After a four week baseline period of optimal therapy, standard Sinemet was completely substituted by CR4 over 12 weeks, and clinical status monitored regularly over another 36 weeks. Evaluation was based on standard rating scales and patient's and physician's opinion ratings. RESULTS: forty-two patients completed the study. The mean optimum total daily dosage of Sinemet CR4 was 702 mg, significantly greater than the mean optimum daily dose of standard Sinemet--496 mg (p less than 0.01). Median number of doses per day was less, being 3 and 4 respectively (p less than 0.01). There was reduction in tremor (p less than 0.01) and rigidity (p less than 0.05) with Sinemet CR4 therapy compared with standard Sinemet, but no difference in disability scores, bradykinesia, gait, or postural instability. Twenty-five patients rated the change to Sinemet CR4 from standard Sinemet as "more helpful", 15 "about the same", and two "less helpful". There were no serious or unexpected adverse effects. CONCLUSIONS: it was concluded that Sinemet CR4 was at least as effective as standard Sinemet, and it seemed particularly helpful in those patients with wearing-off who require frequent doses of standard Sinemet throughout the day.

Aged↗
PubMed1992

p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters.

The p53 locus on the short arm of chromosome 17 at 17p 13.1 was examined for loss of heterozygosity, mutation, mRNA and protein expression in 60 primary breast cancers. Allele loss around the p53 locus was detected in 19/45 informative tumours (42%). p53 mutations in the evolutionarily conserved exons 5 to 9 were detected in 17/60 (28%) by amplification mismatch and confirmed by direct DNA sequencing. p53 mRNA expression was detected by Northern blot in 36/59 (61%) of tumours, and p53 protein expression using antibody 1801 on frozen-tissue sections in 13/44 of the tumours examined. p53 mutation was significantly associated with oestrogen-receptor-poor tumours (p less than 0.01) and hence with poor prognosis, but not with other clinical or pathological parameters. There was no statistical correlation between loss of heterozygosity around the p53 locus at 17p13.1 and p53 mutation. Furthermore, p53 mutation was not associated with p53 expression detected by immunohistochemical staining with antibody 1801 or as p53 mRNA. In addition, events on 17p (allele losses, p53 mutation, p53 expression) were independent of c-erbB-2 expression. In breast cancer, by contrast with colorectal, lung and ovarian cancer, there appears to be no clear association between p53 DNA abnormalities and p53 expression.

Alleles↗
PubMed1992

Assessment of non-palpable mammographic abnormalities: comparison between screening and symptomatic clinics.

A retrospective study found that a breast screening clinic generated fewer localization biopsies for non-palpable mammographic abnormalities than a symptomatic clinic (3.36 versus 9.89 per 1000 mammograms, respectively) and that a greater proportion of such biopsies were malignant. This study determined the reason for this difference. There were 108 of 304 (35.5 per cent) and 17 of 130 (13.1 per cent) carcinomas in women attending the screening and breast clinics respectively (relative risk 2.72 (95 per cent confidence interval 1.70-4.34)). This difference was regardless of age. The characteristics of the mammographic abnormality, the Wolfe pattern, a family history of breast carcinoma, parity and age at first pregnancy were similar in both groups. Women attending the screening clinic were referred for localization biopsy after assessment by clinicians and radiologists at a joint clinic; there was no joint assessment for patients attending the breast clinic. The same staff attended both clinics, although the proportion of time spent at each varied. This study suggests that all women with a non-palpable mammographic abnormality should be reviewed at a joint assessment clinic before localization biopsy is recommended.

Biopsy↗
PubMed1992

Pathological features predictive of local recurrence after management by conservation of invasive breast cancer: importance of non-invasive carcinoma.

The pathological features of 236 clinical stage I and II invasive breast carcinomas treated by conservation were reviewed. On follow-up (minimum 2 years) 13 patients (6%) have developed breast relapse, 10 (4%) regional lymph node relapse and 26 (11%) distant metastases. Nineteen patients have died from breast carcinoma. On univariate analyses lymph node metastases, increasing amounts of non-invasive carcinoma and multiple foci of invasion were significant risk factors for breast relapse. A Cox's multivariate analysis showed the first two of these to be independently significant. The results are in agreement with other published series and confirm that assessment of non-invasive carcinoma is important. The study compares simple quantitation with the original method reported to define cases with an "extensive intraduct component".

Breast Neoplasms↗
PubMed1992

Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast.

Steroid receptor was assessed immunohistochemically in 158 samples of normal breast for variation through the menstrual cycle. Patterns and intensity of reaction were used in a semi-quantitative scoring system to examine the influence of cycle phase, cycle type, parity and age. The changes in oestrogen receptor for natural cycle and oral contraceptive (OC) cycles indicated down-regulation by progestins. Progesterone receptor did not vary significantly in natural cycles, but increased steadily through OC cycles. This study provides strong evidence that both oestrogen and progesterone influence breast epithelium, but dissimilarities from the endometrium are apparent. The interval since pregnancy had a significant negative effect on frequency and score of oestrogen receptor and score of progesterone receptor. Multivariate analysis established the phase of cycle and OC use as independent significant influences on oestrogen receptor. The interval since pregnancy was an independent significant factor for both oestrogen and progesterone receptor presence.

Age Factors↗
PubMed1992

Ras p21 in breast tissue: associations with pathology and cellular localisation.

Immunocytochemistry with monoclonal antibody Y13-259 demonstrated p21 ras in paraffin sections of breast tissue from 171 women: 85 with invasive breast carcinoma, 14 with non-invasive carcinoma and 72 with benign changes only. Many different tissue elements contributed to ras expression. Semiquantitative assessment showed that intensity of immunostaining in the normal epithelium of large ducts, small extralobular ducts and terminal duct lobular units (TDLU) was usually exceeded by that of myoepithelial cells. Vascular smooth muscle and apocrine epithelium also stained strongly, but the flat epithelial cells lining cysts did not express detectable p21 ras. There was a progressive increase from normal epithelium through epithelial hyperplasia of usual type and atypical hyperplasia to carcinoma in situ, without further increase in invasive carcinoma. Expression in carcinomas was inversely related to oestrogen receptor content but independent of the prognosis-associated variables of size, histological type, vascular invasion or lymph node metastasis.

Antibodies, Monoclonal↗
PubMed1992

The nature of breast dense core granules: chromogranin reactivity.

Ultrastructural immunoreactivity for chromogranin with the LK2H10 antibody was examined in nine cases of breast carcinoma and one example of normal resting breast. These tissues were selected for study on the basis of argyrophilia or LK2H10 immunostaining by light microscopy. In two cases, positive reactivity with the chromogranin antibody was seen in breast neuroendocrine-like dense core granules. In a further six cases chromogranin reactivity was not seen in similar granules that showed the neuroendocrine properties of ultrastructural argyrophilia and uranaffinity. Inability to exhibit the full complement of neuroendocrine characteristics in breast carcinomas contrasts with the facility to demonstrate them in tissues of usual neuroendocrine differentiation. Furthermore, in two mucoid carcinomas and one example of normal resting breast ultrastructural cytoplasmic LK2H10 reactivity was evident, which was not localized to dense core granules, although these were present in two of the cases. Our findings demonstrate the heterogeneity of breast dense core granules and discourage acceptance of such characteristics as evidence of histogenesis of these carcinomas from a neuroendocrine cell type in breast tissue.

Adenocarcinoma, Mucinous↗
PubMed1992

Botulinum toxin treatment of spasmodic torticollis.

We reviewed the efficacy and adverse effects of repeated botulinum toxin injections into hyperactive neck muscles of 107 successive patients with spasmodic torticollis. They received 510 injection treatments over a median period of 15 months (range 3-42 months). One patient failed to benefit at all, but 101 (95%) patients reported considerable (moderate or excellent) benefit from at least one treatment. On a global subjective response rating, 93% of 429 treatments resulted in some improvement and 76% in moderate or excellent improvement. Pain reduction followed 89% of 190 treatments with moderate or excellent reduction after 66%. Median duration of benefit was 9 weeks. All torticollis types responded equally well and injections into two (or more) involved neck muscles were more effective than injection into a single muscle. The most frequent adverse effect was dysphagia, occurring after 44% of all treatments, but this was severe after only 2%. Antibodies to botulinum toxin were detected in the serum of three out of the five patients in whom loss of treatment efficacy occurred. We conclude that botulinum toxin treatment is the most effective available therapy for spasmodic torticollis and practical advice is provided for anyone wishing to set up the technique.

Adult↗
PubMed1991

Primary systemic therapy for operable breast cancer.

Eighty-eight patients presenting with operable breast cancer of 4 cm or greater in diameter (T2, T3, N0, N1, M0) have received primary systemic therapy. Response was assessed following 12 weeks of systemic therapy by linear regression analysis of changes in tumour volume. Definitive locoregional surgery (mastectomy n = 82, wide local excision n = 6) was performed on completion of systemic therapy (3-6 months). Response was observed in 24 (39%) of the 61 patients who received endocrine therapy; all 24 had tumours with an oestrogen receptor (ER) concentration of greater than or equal to 20 fmol mb-1 cytosol protein. Cytotoxic therapy was reserved for patients with tumours of ER concentration less than 20 fmol mg-1 cytosol protein (n = 27) or when endocrine therapy had failed (n = 20). Response was observed in 34 patients (72%). The overall survival rate at 3 years was 86%, with 81% remaining free from local relapse. We propose that the treatment policy outlined in this paper should now be tested against orthodox management by controlled randomised trial.

Adult↗
PubMed1991

Comparative pathology of breast cancer in a randomised trial of screening.

In the Edinburgh Randomised Breast Screening Project (EBSP) to December 1988 there were 500 cancers in the study population invited to screening and 340 cancers identified in the control population. The size and negative lymph node status characteristics of invasive cancers from the two populations were significantly different (P less than 0.05). The cancers detected by screening were predominantly 'early stage', with 16% noninvasive (PTIS) and 42% invasive stage I (pT1 node negative), whereas cancers were frequently 'late stage' (more than pT2) and inoperable in nonattenders (44%) and controls (36%). Grouped according to customary size ranges of invasive cancers, the proportion of cases lymph node positive differed in those screen detected compared with controls, but the benefit in favour of screen detection was not constant. In comparisons of cancers detected at prevalence and incidence screens, as a test of conformity with screening theory, no significant differences were apparent according to size and lymph node status, yet the characteristics of histological type of cancer discriminated significantly (P less than 0.05). When these same histological characteristics were used to compare survival, the capacity to separate invasive cancers into two groups having good and poor survival probabilities was evident, with a significant improvement for the screen detected poor survival group compared with controls (P less than 0.05).

Breast Neoplasms↗
PubMed1991

Genesis and source of breast cancer.

Premalignancy and cancer risk as indices of cancer origin have become less confusing. Firstly, we are now aware of the time scale of events leading up to clinical presentation, and secondly the nature of probability, inherent to a biological system influenced by genetics, the environment and hormones, is more widely appreciated. Improved understanding of the early phases of cancer, especially origins and sources, stems from correlation of epidemiological, endocrine and histological information. Such data specifically address the modulating influences on structure and activity of breast epithelial units by factors that are linked to cancer risk. Morphology of the normal breast remains a corner stone on which to build concepts of the cellular events involved in the genesis of cancer. Another line of evidence derives from well defined histological characteristics of pathological processes that have been reliably associated with increased cancer risk. These two aspects of analysis encourage belief that heterogeneity is a characteristic of this disease, which has more than one mode of origin and follows variable courses of aggression. In consequence, the aims behind programmes of breast cancer detection and prevention can become more realistic.

Breast↗
PubMed1990

Relationship between tumour aromatase activity, tumour characteristics and response to therapy.

Aromatase activity has been measured in human breast cancers by incubating tumour minces with [7 alpha-3H]testosterone and characterizing purified oestradiol (E2) fractions by chemical derivative formation. Of 247 primary tumours, 178 showed evidence of oestrogen biosynthesis, levels varying between 0.5 and 12.5 fmol E2 produced/h/g tissue. These values were quantitatively small but at least comparable with those in other peripheral tissues. There was no correlation between presence or level of aromatase activity and the histopathology of the tumours although oestrogen biosynthesis was more likely to be present in more cellular tumours. Aromatase activity was also unrelated to age, menopausal status, lymph node status and T stage of the patient from which the tumour was derived. In a subgroup of patients presenting without clinical evidence of distant metastatic disease, no significant relation was detected between tumour aromatase and disease-free interval, but tumours without aromatase activity were associated with increased survival at 36 months after primary treatment. A statistically significant correlation was also detected between the presence of tumour aromatase and oestrogen receptors. Furthermore, in small subgroups of patients with "advanced" breast cancer tumour aromatase was related to response to aminoglutethimide but not tamoxifen therapy. Whilst these results do not conclusively define a role for local synthesis of oestrogen in the progression of breast cancer, this possibility still exists and further studies on tumour aromatase are warranted.

Aminoglutethimide↗
PubMed1990

Eaton-Lambert myasthenic syndrome: two cases with typical and atypical features.

Eaton-Lambert myasthenic syndrome is a rare disorder of neuromuscular transmission. We are unaware of previous New Zealand reports and present two patients. Characteristic abnormalities in compound muscle action potential amplitude following repetitive nerve stimulation and on single fibre electromyography were present. Both patients also showed mild patchy abnormalities in peripheral nerve conduction. The clinical picture resembled Guillain-Barre syndrome in one patient who developed severe generalised weakness and respiratory failure. In both patients the neurological presentation lead to the recognition of a previously asymptomatic small cell lung carcinoma.

Aged↗
PubMed1990

Edinburgh trial of screening for breast cancer: mortality at seven years.

Between 1979 and 1981, 45,130 women in Edinburgh aged 45-64 were entered into a randomised trial of breast cancer screening by mammography and clinical examination. The initial attendance rate was 61% but this varied according to age and socioeconomic status and decreased over succeeding years. The cancer detection rate was 6.2 per 1000 women attending at the first visit; the rate fell to around 3 per 1000 in the years when mammography was routinely repeated and to around 1 per 1000 at the intervening visits with clinical examination alone as the screening method. After 7 years of follow-up the mortality reduction achieved was 17% (relative risk = 0.83, 95% CI 0.58-1.18), which was not statistically significant, even when corrected for socioeconomic status. In women aged 50 years and over a mortality reduction of 20% was achieved.

Age Factors↗
PubMed1990

Outcome of surgery for non-palpable mammographic abnormalities.

Four hundred and ninety-three women underwent 515 localization biopsies for non-palpable mammographic abnormalities. The mammographic abnormality was located with a hooked wire in 509 cases. Specimen radiology was performed on all excised tissue. The mammographic abnormality was visualized in the first piece of tissue excised in 402 (78.1 per cent) cases and complete excision was achieved in 476 (92.4 per cent). A palpable nodule was removed in 38 (7.4 per cent) cases and in 17 (44.7 per cent) was shown to contain a carcinoma. The mammographic abnormality was missed in 14 (2.7 per cent) cases or only partly excised in 13 (2.5 per cent). Overall 144 (28.0 per cent) localization biopsies were malignant. The mammographic abnormality was not visualized on the specimen radiograph more frequently in women aged under 55 years, in women with dense breast (Wolfe grade DM or DY) or in those whose mammographic abnormality contained only microcalcification. The 27 women in whom the mammographic abnormality was not visible on the specimen radiograph underwent repeat mammography 2 months later. Only two women required a further localization biopsy and the mammographic abnormality was recovered in the first piece of tissue excised. Women with a carcinoma underwent mastectomy or wide local excision, and residual carcinoma at the localization biopsy site was found in 64 (44.4 per cent) cases. Oestrogen receptor analysis by ligand binding assay was possible in only 71 (49.3 per cent) carcinomas. If the specimen radiograph does not show the mammographic abnormality within pieces of tissue excised and there is no palpable nodule it may be best to conclude the biopsy. In this series these missed lesions were usually benign. Only rarely is a second localization biopsy required and this is performed without difficulty.

Adult↗