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Biomedical subjects

D Crowther

Publications and source records attributed to D Crowther.

At least 163 records · Page 9Linked to original sources
PubMed1983

The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease.

Ovarian function has been studied in 44 adult females who previously received quadruple chemotherapy (MVPP) for Hodgkin's disease. The median age at treatment was 23 years, and the length of time between completion of treatment and study ranged from 6 months to 10 years (median, 30 months). Seventeen women maintained regular menses, 10 developed oligomenorrhea, and 17 developed amenorrhea. At treatment, the 17 women who subsequently developed amenorrhea were significantly older (median, 30 years) than those who maintained regular menses (median, 22 years) or developed oligomenorrhea (median, 23 years). All patients older than 36 years at the start of treatment stopped menstruating during chemotherapy. The cause of the menstrual disturbance in these patients was chemotherapy-induced ovarian damage characterized by high serum gonadotrophin and low serum estradiol concentrations. After completion of treatment there were 17 pregnancies, which resulted in 9 normal infants, 3 terminations, and 4 spontaneous abortions. Nine patients took the combination oral contraceptive pill throughout chemotherapy; however, subsequently 4 developed amenorrhea and 3 oligomenorrhea, suggesting that these patients had not been protected from chemotherapy-induced ovarian damage. Estrogen replacement therapy was of definite benefit in the symptomatic patients with premature ovarian failure.

Adolescent↗
PubMed1983

Controlled trial of adjuvant chemotherapy with melphalan for breast cancer.

370 patients who had carcinoma of the breast with involved axillary lymph-nodes were randomised after total mastectomy and axillary clearance to receive either no additional treatment or melphalan 6 mg/m2 daily for 5 days every 6 weeks for sixteen cycles. There was a trend towards longer relapse-free survival (RFS) in patients treated with melphalan, but this was not significant either in the whole series or in sub-groups according to menopausal status or extent of nodal involvement. In patients receiving melphalan RFS was not significantly affected by either the occurrence of amenorrhoea or the dosage of melphalan received. Overall survival did not differ significantly between the two groups. The results of this trial suggest that there is no place for the use of melphalan as adjuvant therapy in the management of early breast cancer.

Adult↗
PubMed1983

Gastrointestinal involvement with myeloma.

A patient with IgA-k multiple myeloma is presented. There was initially a good response to chemotherapy but the patient later developed small intestinal obstruction. This was due to multiple polypoid plasmacytomas. The mesenteric nodes were also involved, and were found on immunofluorescence microscopy and flow cytometry with double fluorescent labelling to be composed of two separate populations of cells (IgA-k and IgG-k), one population having a diploid content of DNA and the other tetraploid. These two distinct cell populations differed in both proliferative characteristics and size. The findings are discussed and the literature relating to gastrointestinal involvement in plasma cell dyscrasias reviewed.

Bone Marrow↗
PubMed1983

Blood clearance of radioactively labelled cis-diammine 1,1-cyclobutane dicarboxylate platinum (II) (CBDCA) in cancer patients.

The blood and urinary clearances of cis-diammine 1,1-cyclobutane dicarboxylate platinum(II) (CBDCA, JM8) were determined in four patients with malignancy. A 40 muCi iv injection of 191 Pt/193 Pt (3:1)-labelled CBDCA was followed by serial blood and urine sampling to 72 h. The blood clearance was triphasic, mean values for the fast, intermediate, and slow phases being 10.8 min, 2.5 h, and 125 h, respectively. The fraction of activity excreted in the urine within the first 6 h had a mean value of 66.7%, contrasting with 26.4% for cisplatin. There was only a small fraction of CBDCA excreted by the slow phase (1.5%) as against an average of 20% for CHIP and 27% for cisplatin. The early and rapid renal clearance of CBDCA may account for reduced nephrotoxicity.

Antineoplastic Agents↗
PubMed1983

Serum beta 2-microglobulin in patients with non-Hodgkin's lymphoma.

Eighty-one patients with non-Hodgkin's lymphoma had serum beta 2-microglobulin (beta 2M) estimated at presentation. A significant association was found between beta 2M levels and stage of disease (P less than 0.001), presence of hepatomegaly (P less than 0.001) and bone marrow involvement (P less than 0.05). No association was found between the level of beta 2M and histological group, presence of splenomegaly, lymph-node masses greater than 5 cm in diameter, lymphocyte count or the presence of systemic B symptoms. Pretreatment levels of beta 2M did not help predict response to treatment and achievement of a complete remission, the length of remission obtained or survival.

Adolescent↗
PubMed1983

VAC (vincristine, adriamycin, cyclophosphamide) chemotherapy for metastatic carcinoma from an unknown primary site.

Twenty patients presenting with metastatic carcinoma from an unknown primary site were studied. All patients were treated with a triple chemotherapy regimen of vincristine, adriamycin and cyclophosphamide repeated at three-week intervals. The response rate was 50%, and the four patients achieving complete response are alive and disease-free at 13, 16, 36 and 39 months. Toxicity was minimal and the majority of patients' performance status improved with the chemotherapy. VAC chemotherapy is indicated for patients with metastases, particularly of soft tissues originating from a carcinoma from an unknown primary site.

Adult↗
PubMed1983

Prognostic significance of pretreatment serum beta 2-microglobulin levels in multiple myeloma.

Pretreatment serum beta 2m levels were estimated in 65 patients with multiple myeloma. After correction for changes in renal function, the level of beta 2m attributable to multiple myeloma (beta 2m-m) no longer correlated with the serum creatinine, but showed a strong correlation with the total body myeloma cell mass (P = 0.002). There was an inverse correlation between beta 2m-m and the Karnofsky performance status of patients at presentation (P = 0.001). Patients with a pretreatment beta 2m-m level of less than the median value of 2.94 mg/l survived significantly longer than those with a raised level (P = 0.0008).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Abdomino-pelvic computed tomography in the management of ovarian carcinoma.

121 CT scans were obtained in 75 women with ovarian cancer, including 108 scans of the abdomen and pelvis and 13 of the pelvis alone. 70 patients had epithelial carcinoma. In 48 cases, pelvic CT was performed within 3 weeks after surgery, confirming the operative findings in all but 6. In the abdomen, CT identified intrahepatic deposits and minimal ascites not seen at surgery; however, small peritoneal deposits not usually shown by CT were readily found at surgery. CT was superior to clinical examination, detecting unsuspected disease and delineating areas of known disease more accurately. It was also helpful in assessing suitability for repeat laparotomy. In 7 cases, CT demonstrated an operable lesion which had been thought to be inoperable. In 65 cases (59%), CT contributed additional information which was helpful in management, proving it to be an important noninvasive investigation in patients with ovarian carcinoma.

Abdominal Neoplasms↗
PubMed1983

Lymphocyte migration in malignant disease.

Studies of normal lymphocyte migratory properties in small animals and more recently in man using 111indium oxine labelling techniques are helping the clinician to understand the biology of tumours involving cells of the immune system. However, not enough is known about subset migration to interpret all the various patterns of dissemination observed in lymphoma patients. Such studies are important since they introduce new possibilities for therapy including the use of labelled cells to home a source a radiation preferentially to affected tissue.

Animals↗
PubMed1982

Flow cytometric analysis of lectin binding to human peripheral blood lymphocytes.

The binding of fluorescein-conjugated lentil lectin and concanavalin A to the surface membrane of human peripheral blood lymphocytes was studied by flow cytometry. The lymphocytes bound 3-fold more lentil lectin molecules compared with concanavalin A molecules and lentil lectin binding approached saturation at a much lower concentration than did that of concanavalin A. Lentil lectin identified two groups of lymphocytes: a low-binding T-cell fraction and a high-binding B-cell-enriched fraction. Concanavalin A did not discriminate between these populations in unseparated lymphocytes. Competition studies indicated that lentil lectin and concanavalin A were bound to different sites on the lymphocyte surface, although about 50% of lentil lectin sites were in close proximity to concanavalin A sites.

Adult↗
PubMed1982

Intermittent high-dose cyclophosphamide with and without prednisolone: a study of the relationships between toxicity, response and survival in metastatic lung cancer.

Fifty-seven patients with metastatic lung carcinoma were treated with either high-dose cyclophosphamide (Cy) alone or with a combination of high dose Cy and prednisolone (Pred) 100 mg/m2 orally daily for two days. The Cy was given IV on three occasions, at 1.5 g/m2, 2.5 g/m2 and 3.5 g/m2 with three-week intervals between courses. The overall response rate was 57% (18% CR), a median survival of 24 weeks (range, 6--130) for Cy alone, and 24% (3% CR), a median of 14 weeks (range, 1--94) for Cy + Pred. Patients with small cell carcinoma given Cy alone had a 69% response rate (19% CR), a median survival of seven months, and with non-small cell pathologic conditions 42% (16% CR), a median survival of 16 weeks. Performance scores and survival were better for responding patients. Addition of Pred did not improve the therapeutic efficacy of high dose Cy or ameliorate toxicity. No marked or unexpected toxicity was observed with the high-dose Cy regimen. The blood counts had returned to normal by three weeks in the great majority of patients. A short course of high-dose Cy was not associated with unacceptable side effects and the therapeutic results obtained were superior to those described for Cy at conventional dosage. High-dose Cy is of value to patients with metastatic lung cancer, and the incorporation of the regimen into chemotherapeutic combinations could be advantageous.

Adult↗
PubMed1982

11-week course of sequential methotrexate, thoracic irradiation, and moderate-dose cyclophosphamide for "limited"-stage small-cell bronchogenic carcinoma. A study from the Manchester Lung Tumour Group.

55 patients with inoperable but "limited"-stage small-cell carcinoma were treated sequentially with methotrexate, radiotherapy, and high doses of cyclophosphamide. The treatment was completed over 11 weeks and no maintenance chemotherapy was given. Follow-up lasted 9-29 months. Toxicity was acceptable, despite doses of cyclophosphamide of 1.5-3.5 g/m2. The complete response rate was 53%. Median survival for the total patient group was 12 months, range 2-29+. Patients who attained a complete response had a 17 month median survival; 17 patients remained in complete remission, 9 of whom first underwent treatment 14-29 months previously. Karnofsky performance scores improved after treatment and most patients were able to resume normal activity. The results are similar to those obtained with prolonged combination chemotherapy.

Carcinoma, Small Cell↗
PubMed1982

The effects of Hodgkin's disease and combination chemotherapy on gonadal function in the adult male.

The effects of Hodgkin's disease and quadruple chemotherapy on gonadal function have been investigated in 92 male patients with Hodgkin's disease. Nineteen men were studied before they received chemotherapy. Fifteen of the 19 had a sperm count of 20 million/ml or greater and motility was at least 40% in all 15. In the remaining 74 men, gonadal function was studied after completion of chemotherapy (6 months--8 years). Semen was obtained from 49 men who had received six of more courses of MVPP. Forty-two were azoospermic and five of the remaining seven had a sperm count below 1 million/ml. Decreased libido and sexual activity was common during treatment but in the majority of men these returned to normal after completion of chemotherapy. The median FSH and LH levels and the median increments in serum FSH and LH levels after LHRH administration were significantly elevated compared with an age-matched control group. The mean testosterone level of the patients was significantly lower than in controls suggesting Leydig cell damage but androgen replacement therapy was not indicated in any individual patient. No evidence of hyperprolactinaemia as a result of MVPP therapy was found. These results suggest that sperm storage before chemotherapy represents the main possibility for these patients to have children after completing chemotherapy. Before starting chemotherapy, advice should be given to these patients concerning possible changes in sexual behavior during treatment and the very high incidence of permanent infertility following treatment.

Adult↗
PubMed1982

The "hot spleen" phenomenon in metastatic malignant melanoma: its incidence and relationship with the immune system.

Of patients with Stage II and III malignant melanoma, 34.7% display reversal of the liver-spleen ratio on technetium-99m-sulphur colloid isotope scans. Such an occurrence does not suggest a greater likelihood of relapse or a worse survival. The phenomenom is more common in female patients and there is a significant relationship between the presence of a "hot spleen" and a high IgM level. Patients with Stage II disease and high IgM levels have relapses more quickly than do those with normal IgM levels. Lymphopenia is common in patients with Stage II and III disease and the survival of these patients is worse than that of those with normal lymphocyte counts. In this report, the data are discussed together with results from other investigations, and a unifying hypothesis is presented which explains the phenomenon and relates it to increased activity of macrophages as a result of the presence of the tumor. The usefulness of isotope liver scanning in stage III malignant melanoma is also discussed.

Bacterial Vaccines↗
PubMed1982

Blood clearance of three radioactively labelled platinum complexes: cis-dichlorodiammine platinum II, cis, trans-dichlorodihydroxy-bis-(isopropylamine) platinum IV, and cis-dichloro-bis-cyclopropylamine platinum II, in patients with malignant disease.

The blood clearances of three platinum compounds, cis-dichlorodiammine platinum II (DDP), cis, trans-dichloro-dihydroxy-bis-(isopropylamine) platinum IV (CHIP), and cis-dichloro-bis-cyclopropylamine platinum II (CP), were determined in nine patients with malignant disease. The complexes were prepared using radioactive platinum (191Pt and 193Pt). A 10-mu Ci dose of each complex, containing the equivalent of 1-2 mg elemental platinum, was injected IV into groups of three patients. Serial blood and urine samples were collected over 72 h. No obvious difference was found between the three complexes for blood clearance, median t1/2a being 16.8 (range 11.2-23.5) min and median t1/2 beta 89 (range 63.7-127) h. The urinary excretion was greatest for CHIP, 60% of injected dose as against 42.6% for CP and 38.8% for DDP. Differences in renal excretion of DDP analogues could indicate potentially less nephrotoxic agents. The use of radioactive Pt will allow in vivo dynamic imaging of the distribution of platinum compounds in areas of interest.

Aged↗
PubMed1982

Effects of diphenylhydantoin on killer cell activity and other immunological functions. A sequential study including the interaction of Corynebacterium parvum in melanoma patients.

The effects of a single Phenytoin dose, given to patients with malignant melanoma, upon peripheral blood counts, serum immunoglobulins, lymphocyte subpopulations and lymphocytotoxicity (using Chang target cells) were recorded. Sequential blood samples were taken before and 10, 14, 34, 38 and 58 h after the Phenytoin. Early reductions (P less than 0.05) in lymphocyte count, NK, K and PHA induced cytotoxicity, when compared with initial, pre-Phenytoin values were noted. Immunisation with i.v. C. parvum prevented the reductions occurring after a second dose of Phenytoin. Indeed, significant increases above the values of samples taken immediately before the second dose, were observed in T cells, PHA blastogenesis, NK and K cell Cytotoxicity. The second dose did however cause some immunosuppression; the increase in T cells, NK and PHA induced cytotoxicity above initial values expected from previous investigations were not observed. The immunosuppression, particularly of killer cell function, occurring after phenytoin could have implications for the pathogenesis of malignancy and transplacental carcinogenesis, reported as following Phenytoin exposure.

Bacterial Vaccines↗