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Biomedical subjects

P Pitt

Publications and source records attributed to P Pitt.

At least 19 recordsLinked to original sources
PubMed1995

Aromatase inhibition with 4-OHAndrostenedione after prior aromatase inhibition with aminoglutethimide in women with advanced breast cancer.

One hundred and twelve post menopausal or post oophorectomy women with advanced breast cancer (BC) who had all previously had aminoglutethimide (AG) were treated with the potent aromatase inhibitor 4-hydroxy androstenedione (4-OHA). Twenty three women (21%) had a partial response to 4-OHA while another twenty five patients (22%) had stabilization of previously progressing disease. Patients responded to 4-OHA both after previously responding to then relapsing on, and after failing to respond to aminoglutethimide. Toxicity was minimal. This study shows that potent aromatase inhibition with 4-OHA is effective in women with advanced BC who have already been treated with a less potent aromatase inhibitor, and suggests that relative changes in oestrogen levels may be more important than absolute levels.

Adult↗
PubMed1994

A collaborative trial of a semi-automatic system for slide preparation and screening in cervical cytopathology.

We report a test of an experimental system for machine-aided screening in cervical cytology, comprising the 'CYTOPRESS' semi-automatic slide preparation system (Nijmegen) and the 'CERVIFIP' interactive scanner (Edinburgh). Material from women attending clinics in Edinburgh and Nijmegen was stratified according to the severity of the conventional laboratory diagnosis and selected randomly within strata for inclusion in the test. Monolayered slides were prepared by CYTOPRESS from cervical scrape material remaining after preparation of conventional smears and scanned by CERVIFIP to determine the positions of the most 'suspicious' objects. The test was based on a set of 701 monolayers, divided equally between 'negatives' and 'abnormals' of various grades, of which 585 (83.4%) were passed automatically as adequate for machine-aided analysis. Approximately 15% of adequate slides were passed as 'negative' without operator interaction. In the remaining 85%, the suspicious objects were inspected by a human operator and a decision was then made either to refer each monolayer for conventional microscopic analysis, or to pass it as 'negative'. Where discrepancies occurred between the conventional laboratory and the system results, a consensus diagnosis was reached by taking into account all relevant information including clinical data. Of those with a consensus diagnosis of CIN 3 or worse an estimated 9.3 +/- 4.1% were passed by the system as 'negative'. Closer investigation of these false-negatives revealed that most, and perhaps all, were preventable by system improvements either planned or in progress. Corresponding false-negative rates for those graded 'CIN 1 or 2' and 'negative-early recall' were estimated, respectively as 18.9 +/- 5.3% and 22.9 +/- 3.1%. Of those with a 'negative-routine recall' consensus, 19.4 +/- 2.5% were referred for conventional microscopic analysis, a level well within acceptable limits for cost-effectiveness. Women whose initial laboratory smears were negative, but whose consensus diagnosis was 'negative-early recall' or CIN, are being investigated further to determine whether cervical abnormalities were in fact present. Over two-thirds of this group were referred by the machine-aided system for conventional microscopic analysis.

Diagnosis, Computer-Assisted↗
PubMed1994

Treatment of advanced breast cancer with formestane.

A total of 147 postmenopausal or postoophorectomy patients with advanced breast cancer resistant to standard endocrine therapies were treated with the potent aromatase inhibitor formestane (Lentaron). Among those available for assessment (n = 143), 32 (22%) had a partial response, while another 28 (20%) had stabilization of previously progressive disease. Patients responded to formestane irrespective of whether they had responded to, or failed to respond to, tamoxifen, medroxyprogesterone acetate, aminoglutethimide and trilostane. Toxicity was minimal. We conclude that formestane is an effective and non-toxic therapeutic agent for the treatment of women with advanced breast cancer.

Adult↗
PubMed1992

Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer.

Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene. Cohorts of patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and another developed reversible disorientation and hallucinations. Mild sweating, peripheral edema, vaginal discharge, and hot flushes were encountered at all doses. Reversible corneal pigmentation was identified in seven cases but was not of clinical importance. The pharmacokinetics of toremifene was studied weekly and in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay that identified the parent compound and three active metabolites, N-desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady state was achieved at 1-3 weeks. The toremifene area under the curve and the maximal concentration were dose-dependent at high doses. The recommended phase II dose is 300 mg/m2 p.o. daily.

Adult↗
PubMed1992

Articular manifestations of Scheie's syndrome.

A patient with the clinical and biochemical features of Scheie's syndrome is reported. Radiological investigation has shown severe progressive juxta-articular cystic lesions, which have not, to our knowledge, previously been described in Scheie's syndrome.

Finger Joint↗
PubMed1992

Circulating PTH and PTHrP levels before and after treatment of tumor induced hypercalcemia with Pamidronate Disodium (APD).

The effect of lowering ionized calcium on circulating parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) was assessed in twenty patients with hypercalcemia of malignancy following treatment with Pamidronate Disodium. Ionized calcium levels fell rapidly in all treated patients. PTH concentrations were initially suppressed below normal in 18 patients, but rose from 0.48 +/- 0.42 pmol/L to 3.63 +/- 3.13 pmol/L (p less than 0.01) after treatment, reaching higher than normal values in some patients even in the presence of persistent hypercalcemia. PTHrP concentrations did not change significantly after treatment. These findings are consistent with an increased sensitivity of parathyroid tissue to changes in ionized calcium following prolonged exposure to hypercalcemia. Regulation of tumor secretion of PTHrP by calcium was not apparent within the range of calcium concentrations in this study.

Calcium↗
PubMed1989

Pain avoidance in rheumatoid arthritis.

Forty-eight patients with rheumatoid arthritis were compared to 52 pain-free controls in terms of tolerance/avoidance and rated intensity of cold pressor pain. The patients had lower thresholds and tolerated the cold pressor pain for a shorter period, although not significantly so. However, the patients rated the novel nociceptive cold stimulus as significantly more painful. The results demonstrate that arthritis patients report novel pain experiences as being more painful, which necessitates special attention to their post-operative analgesic demands needs. Tolerance/avoidance of the cold pressor pain had different correlates in the more and less chronic patient groups, and was respectively related to the affective and sensory qualities of the pain stimulus. The results confirmed qualitative similarities between different chronic pain populations, suggesting that chronicity of the pain problem may be a more important factor in determining pain experience and pain-related behaviours than the specific locus of the pain.

Adult↗
PubMed1988

Survey of the long term incidence of osteonecrosis of the hip and adverse medical events in rheumatoid arthritis after high dose intravenous methylprednisolone.

A prospective, randomised, double blind, matched cohort survey using retrospective data was undertaken to assess the long term incidence of osteonecrosis of the hip and adverse medical effects occurring after intravenous pulsed methylprednisolone used in the treatment of rheumatoid arthritis over the period 1977-86. One hundred and forty three patients were matched for age, sex, duration and severity of the disease, erosive and serological status. Information was obtained by direct questioning and from hip x rays, the latter being read independently by two 'blind' radiologists. Two definite cases of osteonecrosis were identified, one in both the treated and control groups and three possible cases (radiological disagreement) in the treated group. Adverse medical events, when analysed by systems, were similar in both groups. This study did not provide evidence of increased osteonecrosis of the hip or adverse medical events in the treated group compared with the control group.

Adult↗
PubMed1986

Metabolic activity of erosions in rheumatoid arthritis.

The hands of 10 patients with rheumatoid arthritis were investigated with diphosphonate scanning and radiology. Increased uptake of isotope can be associated with some erosions but not all and also reflects other processes more linked to acute inflammatory areas unassociated with the development of erosions. If the latter are the hallmark of active rheumatoid arthritis then bone scans are not.

Adult↗
PubMed1986

Biochemical basis for the antagonism between aminoglutethimide and danazol in the endocrine treatment of breast cancer.

Only 13% of postmenopausal advanced breast cancer patients responded to endocrine treatment with aminoglutethimide plus danazol whilst 33% responded to aminoglutethimide alone, despite a similar suppression of serum oestradiol levels in the two groups. The patients on aminoglutethimide and danazol showed a marked suppression of sex hormone binding-globulin binding capacity and a consequent rise in percent-free oestradiol. This led to the concentration of free oestradiol being less well suppressed than that of total oestradiol and in some patients free oestradiol concentrations were higher on treatment than before. Patients on aminoglutethimide alone showed no change in the binding of oestradiol and the percentage suppression of the free oestradiol concentration was similar to that of total oestradiol. The opposing effects of danazol and aminoglutethimide on the concentration of the free, biologically active fraction of oestradiol in the circulation may explain the poor therapeutic efficacy of this combination in breast cancer patients.

Aminoglutethimide↗
PubMed1986

Remedial surgery for the adolescent with cerebral palsy: a 10-year survey of the numbers, types and results of operations on pupils at the Thomas De La Rue School, Tonbridge, Kent.

The Thomas De La Rue School caters for adolescents with cerebral palsy, many being severely disabled. Over the 10-year period (1967-77) out of a total of 355 pupils, 97 underwent surgery, a total of 147 operations, 145 orthopaedic, being performed, the majority on the lower limbs. The pupils involved, their parents, teachers and house-parents were invited to complete a questionnaire concerning the effectiveness of the operations, the anxieties and psychological problems resulting from surgery, and the effect on schooling. The results are discussed.

Adolescent↗
PubMed1985

Treatment of advanced prostatic cancer, resistant to conventional therapy, with aminoglutethimide.

Fifty-eight patients with advanced, progressing prostatic cancer resistant to conventional therapy have been assessed for their response to treatment with aminoglutethimide (A/G). Eleven men (19%) had objective regression of their disease while in a further eight (14%) progression of the disease was arrested. Median survival in the objective remitters (15 months) and in the group in whom stabilization of disease occurred (9.3 months) was significantly longer than in the non-remitting patients (4.7 months). The drug was well tolerated and no serious side-effects occurred. A/G appears to be a useful treatment in patients with advanced prostatic cancer resistant to conventional therapy.

Aged↗
PubMed1985

Low-dose aminoglutethimide without steroid replacement in the treatment of postmenopausal women with advanced breast cancer.

Fifty-seven patients with actively progressing advanced breast cancer have been assessed for their response to low-dose aminoglutethimide (125 mg bd) without steroid replacement. Eleven women (19%) had an objective response while a further eight had stabilization of disease. However, one patient died with apparent adrenal insufficiency and another developed low plasma cortisol and serum sodium. Furthermore, 4/17 patients who had failed to respond to low-dose A/G subsequently responded when changed to conventional-dose A/G + steroid replacement, while three patients had stabilization of previously progressing disease. These results indicate that low-dose A/G without steroid replacement is potentially hazardous and that low-dose and conventional-dose A/G + steroids do not produce identical results.

Adult↗