Comparison of equine and rabbit antilymphocyte preparations in renal transplantation.
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Adult↗
Biomedical subjects
M Harding
Publications and source records attributed to M Harding.
'Invisible disability'.
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Dental Care for Persons with Disabilities↗
Estrogen and progesterone receptors in ovarian cancer.
To determine whether steroid hormone receptor expression is clinically relevant in ovarian cancer, cytoplasmic and nuclear estrogen (ER) and progesterone (PR) receptor levels have been measured and their concentration calculated by Scatchard analysis. Of 89 samples from patients with non-pretreated epithelial ovarian cancer, 33% were ER-positive, PR-positive (ER+PR+) and 40% ER-negative, PR-negative (ER-PR-); 20% were ER+PR-, and 7% ER-PR+. There was no correlation between receptor status and patient age, menopausal status, or tumor grade, although serous tumors were more likely to be ER+. The incidence of PR+ tumors was highest in early disease and decreased with increasing International Federation of Gynecology and Obstetrics (FIGO) stage. Survival of patients with advanced disease (FIGO Stages IIC, III, or IV) was significantly prolonged by optimal initial cytoreductive surgery (P = 0.002), platinum therapy (P = 0.003), and tumor expression of PR (P = 0.009). On multivariate analysis, PR positivity was still associated with improved survival, although this did not retain statistical significance (P = 0.09).
Adult↗
Does lymphangiography have any role in the management of early non-seminomatous germ cell tumours?
Since 1980, 51 patients with non-seminomatous testicular germ cell tumours (NSGCT) and normal or equivocal initial computed tomography (CT) imaging have also had lymphography performed. Radiological records of these patients were reviewed to determine the extent to which lymphography (LAG) contributed to patient management. Forty-nine patients were retrospectively confirmed to have normal CT but of these 14 (29%) were considered to have nodal metastatic disease on lymphography. These patients and seven others with marker only evidence of tumour received chemotherapy and all remain disease-free. Six of thirty-six patients relapsed, but the incidence was not significantly higher in patients who did not undergo LAG (2 of 8:25%) than among those whose initial LAG was normal (4 of 28: 14%). All relapsing tumours achieved a complete remission with chemotherapy. We conclude that although LAG may have resulted in earlier treatment for some patients, several may have been overtreated on the basis of radiological abnormalities which did not represent metastatic disease. We believe that the success of salvage chemotherapy means that LAG may be safely abandoned as a staging procedure for NSGCT.
Humans↗
Oestrogen and progesterone receptors in carcinoma of the cervix.
Oestrogen (ER) and progesterone (PR) receptors have been measured in 102 cervical carcinomas. With positive levels defined as concentrations exceeding 20 fmol/mg protein for cytoplasmic receptor and/or 200 fmol/mg DNA for nuclear receptor, 24% of tumours were dual receptor positive and 51% were dual receptor negative. The majority of adenocarcinomas (81%: 13/16) expressed ER (P less than 0.001) though only 54% (7/13) of these tumours co-expressed PR. There was a significant correlation between tumours positive for ER and those arising in premenopausal women (P = 0.011), with good or moderate differentiation (P = 0.027) and of smaller size (P = 0.025). Median follow-up is 19 months. Apart from advanced stage, tumour bulk (greater than 5 cm) was the only parameter associated with inferior progression-free survival, and most larger tumours were of advanced stage. No prognostic significance could be detected for receptor status.
Adenocarcinoma↗
Neurone specific enolase (NSE) in small cell lung cancer: a tumour marker of prognostic significance?
Pretreatment serum levels of neurone specific enolase (NSE) were measured in patients with small cell lung cancer (SCLC). Median values were significantly higher in patients with extensive compared with limited stage disease (48 ng ml-1 v. 17 ng ml-1: P less than 0.001). Serial NSE levels paralleled the clinical response to treatment. In 37 patients with limited SCLC, receiving identical chemotherapy, the pretreatment NSE level was of prognostic significance: with an approximate reduction in median survival of 10% for each 5 ng ml-1 incremental rise in NSE (P = 0.004).
Biomarkers, Tumor↗
Excretion of porcine parvovirus through the genital tract of boars.
The putative binding of porcine parvovirus (PPV) to semen components in vitro was examined along with the shedding pattern of PPV in oronasally infected boars. Porcine parvovirus DNA was determined to be bound to spermatozoa that had been incubated in vitro with PPV and washed to remove loosely adherent virus. To determine whether PPV was shed in the semen, four 8-month-old boars, seronegative for PPV, were inoculated oronasally with a virulent strain of PPV. Prior to virus inoculation, a catheter was surgically implanted in the vas deferens for the purpose of collecting cauda epididymal semen free of extrinsic contamination. Epididymal semen specimens were collected prior to inoculation and daily thereafter for 21 days. A fifth boar was inoculated oronasally with PPV, but semen was collected by electroejaculation twice weekly for an equal period of time. Reproductive glands and semen specimens from all boars were examined by nucleic acid hybridization for the presence of viral DNA. All boars seroconverted to PPV, as evidenced by serum antibody titers ranging from 512 to 8,192 hemagglutinating inhibition units/50 microliters. Porcine parvovirus DNA was detected in epididymal semen of 3 of 4 catheterized boars on postinoculation days 5 through 9, but not in semen obtained by electroejaculation. Viral DNA was consistently detected in tissue samples collected on postinoculation days 8 and 21 from the scrotal lymph nodes (4 of 5 boars) and epididymides (3 of 5 boars).
Animals↗
Phase II studies of mitozolomide in melanoma, lung and ovarian cancer.
Seventy-seven patients were treated with oral mitozolomide to assess the activity of this drug in melanoma, lung and ovarian cancer. Partial responses were seen in five of 18 evaluable patients with small cell lung cancer (SCLC) and three of 20 with melanoma. No activity was apparent in non small cell lung or epithelial ovarian cancer. The major toxicity was myelosuppression which necessitated reduction in the initial dosage from 115 to 90 mg/m2. However, even at this dose level, unpredictable WHO grade 4 toxicity occurred in non-pretreated patients. Thrombocytopenia was more common than leucopenia and eight patients required platelet transfusion for spontaneous or tumour-related haemorrhage. Myelotoxicity was considered responsible for two deaths and was a significant contributory factor in a further three. Non-haematological toxicity was minor. Thus, despite demonstrable activity in SCLC and melanoma, unpredictable myelosuppression is likely to preclude further assessment in combination chemotherapy regimes in these tumours.
Adult↗
'A third study of caries in preschool aged children in Camden'.
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Child, Preschool↗
Structure of chick chromosomal genes for calbindin and calretinin.
The chick chromosomal gene for calbindin (the 28,000 Mr intestinal calcium-binding protein) was cloned, and all the exons and flanking regions were sequenced. The promoter region contains typical ATAAA and GGGCGG boxes, the latter being unusual in "non-housekeeping" genes. Three polyadenylation signals are found in the calbindin gene that correspond to the three known mRNAs. Transcription termination is not efficient because homology with consensus sequences found downstream from the polyadenylation signal is weak. There are ten introns, most of which do not fall at homologous positions, neither with respect to the sixfold repeating structure of the calbindin protein, nor with respect to previously sequenced genes for calmodulin and other calcium-binding proteins. The gene for the related protein calretinin was cloned and partially sequenced. The introns are in the same positions in the calretinin and calbindin genes. The introns have apparently been inserted during the divergence of the calcium-binding protein superfamily.
Animals↗
Adriamycin, vincristine and mitomycin C as first and second line therapy for advanced breast carcinoma.
Forty-three patients with advanced breast cancer were treated with adriamycin, vincristine and mitomycin C at 6 week intervals. Adriamycin 40 mg m-2 and vincristine 1 mg m-2 were given on days 1 and 22: patients treated early in the study received 10 mg m-2 mitomycin C, but in view of repeated treatment delays the dose was reduced to 6 mg m-2. Thirty-two women had received prior hormone therapy and 24 previous chemotherapy. Responses were seen in 15 of 38 evaluable patients (40%) with a further 9 (24%) achieving disease stabilization. Median duration of response was 10 months and of disease stabilization was 5 months. Overall median survival for the whole group was 8 months, but 16 months for the 15 responding patients, five of whom survived beyond 2 yr. Responses were seen more frequently in patients who had received no prior chemotherapy. Myelosuppression may have contributed to three of the five early deaths in the non-pretreated group. Other significant side effects were alopecia, gastrointestinal toxicity and malaise.
Adult↗
Pharmacokinetics of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (iproplatinum, CHIP) in patients with normal and impaired renal function and following intraperitoneal administration.
CHIP is a quadrivalent platinum (Pt) complex, introduced clinically as a less toxic alternative to cis-platinum. The drug's major route of excretion is via the kidneys, and in this study the pharmacokinetics of unchanged CHIP, filterable Pt and total Pt have been determined following intravenous administration to patients with a range of renal function. Total Pt and filterable Pt in plasma decayed biexponentially and was fitted to a two-compartment model, whereas unchanged CHIP declined monoexponentially and was best fitted to a one-compartment model, according to Akaike's information criteria. There is a correlation between the unchanged CHIP clearance and 51Cr-EDTA clearance. The pharmacokinetics of CHIP was determined following intraperitoneal (i.p.) administration (dose, 150-300 mg m-2 4 h dwell time) and a regional advantage (peritoneal peak concentration/plasma peak concentration) of approximately 30 fold was seen. It is likely that the dose of CHIP will need to be reduced in patients with impaired renal function, and the use of i.p. CHIP in ovarian carcinoma warrants further study.
Female↗
A randomized trial of oral nabilone and prochlorperazine compared to intravenous metoclopramide and dexamethasone in the treatment of nausea and vomiting induced by chemotherapy regimens containing cisplatin or cisplatin analogues.
Eighty patients receiving their first course of chemotherapy with regimens containing cisplatin or cisplatin analogues entered this open crossover study comparing nabilone 2 mg and prochlorperazine 5 mg given orally every 12 h for four doses against metoclopramide 2 mg/kg loading dose intravenously (i.v.), then 3 mg/kg as an (i.v.) infusion over 8 h and dexamethasone 20 mg (i.v.) over 3-5 min at the time of chemotherapy. There was complete control of nausea and vomiting in 24 patients (32%) given metoclopramide and dexamethasone compared to 14 patients (19%) given nabilone and prochlorperazine. For the 70 patients who completed the crossover assessment of emesis on a linear analogue scale significantly favoured metoclopramide and dexamethasone (P = 0.02). However, there was no overall patient preference for the metoclopramide and dexamethasone combination (nabilone and prochlorperazine 31 vs. metoclopramide and dexamethasone 26; 13 no preference), because a significant proportion of the patients receiving the cisplatin analogue carboplatin preferred nabilone and prochlorperazine (16 vs. 5; 1 no preference; P = 0.013). For patients receiving cisplatin chemotherapy metoclopramide and dexamethasone remains the antiemetic of choice but for regimens containing carboplatin, nabilone and prochlorperazine is better tolerated and preferred by the patients.
Adolescent↗
Phase II evaluation of mitozolomide in ovarian cancer.
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Adult↗
A pilot study of carboplatin (JM8, CBDCA) and chlorambucil in combination for advanced ovarian cancer.
Forty-six patients with previously untreated, advanced ovarian cancer received carboplatin (JM8, CBDCA) and chlorambucil (CLB) to assess the efficacy and toxicity of this combination. Carboplatin 300 mg m-2 was given on day 1 with CLB 10 mg daily for 7, 10 or 14 days; 6 treatment courses were given at 4-6 weekly intervals in the absence of disease progression. Tumour response was assessed, where possible, by restaging laparotomy after 6 treatment cycles. Five complete and 16 partial remission were seen in 37 evaluable patients giving an overall response rate of 57%. The median survival of all patients was 15 months. The major toxicity was myelosuppression. Nausea and vomiting were generally minor (WHO, grades I or II) and most courses were given on an outpatient basis. Leucopenia was the major factor causing treatment delays, particularly with the 10 and 14 day CLB regimens. Thrombocytopenia was minimal in the early chemotherapy cycles but the data suggest that cumulative toxicity may occur. This combination may provide a satisfactory degree of efficacy with less toxicity than cisplatin-based regimens.
Adult↗
Results of treatment of non seminomatous germ cell tumours; 122 consecutive cases in the West of Scotland, 1981-1985.
Between January 1981 and December 1985, 122 patients with non-seminomatous germ cell tumours (NSGT) were seen at a regional referral centre. Of these, a total of 98 patients received chemotherapy for metastatic disease. Treatment was given within collaborative EORTC Urology group studies, all of which involved cis-platin-containing schedules. Ninety patients had tumours of testicular origin, and their 2 year actuarial survival rate is 91%; 8 had tumours of extragonadal origin and their 2 year actuarial survival is 25%. Patients with testicular tumours were subdivided by volume of metastatic disease using the recommendations of the Testicular Cancer Subgroup of the MRC Urological Cancer Working Party and survival was significantly worse in the group with very large volume metastatic disease (VLVM, 57%) compared with the groups with large volume metastases (LVM, 100%) and small volume metastases (SVM, 98%). There were 31 patients with Stage I disease at presentation; of these 6 were treated by prophylactic abdominal radiotherapy and 25 were managed by a policy of surveillance only. Seven of these Stage I patients (23%) relapsed with metastatic disease (median 8 months); all have been successfully treated with chemotherapy. These data confirm that the majority of patients now presenting with metastatic NSGCT are curable with chemotherapy, but that a small proportion with very large volume metastases or extragonadal tumours require alternative chemotherapy schedules.
Antineoplastic Combined Chemotherapy Protocols↗
The sensitized patient. A single center study.
1. In a 20-year period from 1966 to 1986, 650 renal transplants have been performed at the Toronto Western Hospital (University of Toronto). The 10-year actuarial patient survival is 62% and the actuarial graft survival is 35%. 2. A multivariant analysis using the Cox proportional hazard model indicated recipient age, donor source, graft number and time period were factors which independently influenced patient survival and that age and time period were variables which independently effected graft outcome. 3. Sensitization alone, using either peak or current PRA, did not significantly influence graft survival. Sensitization interacting with gender did affect graft survival, which was significantly lower in female patients with a high current PRA. Sensitization interacting with age produced different effects in the younger and older patients. The highly sensitized older patient has a better survival than the highly sensitized younger patient. However, for less sensitized patients the reverse was found; younger patients had a better survival than older patients. Also increasing levels of sensitization correlated with decreased survival in younger patients. 4. Predictive models based on the survivorship analysis of Kalbfleisch and Prentice were constructed to illustrate the impact of these variables on outcome.
Actuarial Analysis↗