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Biomedical subjects

M J Webb

Publications and source records attributed to M J Webb.

At least 19 recordsLinked to original sources
PubMed1992

Phase II trial of intravenous hexamethylmelamine in patients with advanced ovarian cancer.

A Phase II trial of an intravenous preparation of Hexamethylmelamine was performed in ovarian cancer. Patients who had received prior Platinum based chemotherapy and had measurable disease were eligible. Among 15 evaluable patients, there were no objective responses. Two patients did show clinical and laboratory evidence of improvement. Toxicity was predominantly nausea and vomiting with minimal other toxicity. This intravenous form of Hexamethylmelamine has not shown meaningful activity in ovarian cancer patients who have failed prior platinum treatment.

Altretamine↗
PubMed1992

DNA ploidy of ovarian dysgerminomas: correlation with clinical outcome.

Abnormal nuclear DNA content, as determined by flow cytometry, when combined with conventional prognostic variables such as tumor grade or stage at diagnosis, appears to identify patients who are at increased risk for recurrence of disease. The DNA content of ovarian dysgerminoma, a tumor that is homologous to testicular seminoma and is found in young women of childbearing age, was studied to determine if there is a correlation between DNA content and outcome. Such information would be useful in selecting treatment regimens and making possible the preservation of childbearing potential in women who are likely to have a good outcome. The specimens from 23 cases of ovarian dysgerminoma seen at our institution between 1950 and 1985 were analyzed by DNA flow cytometry. Five of the tumors were diploid (21%) and nineteen were nondiploid (79%). Patient outcome was not predicted any better by nuclear DNA content than by conventional prognostic variables.

Adult↗
PubMed1991

Spontaneous renal rupture during pregnancy.

Spontaneous rupture of the renal parenchyma or renal pelvis during pregnancy has been previously reported in 16 cases. In the case we describe in this report, the patient initially had right flank pain and nausea for 48 hours, which progressed to severe abdominal symptoms that necessitated exploratory laparotomy. Cystoscopic placement of a ureteral stent relieved the obstruction and allowed spontaneous healing of the renal pelvis. Dilatation of the urinary collecting system commonly occurs during pregnancy. Spontaneous rupture of the renal parenchyma or renal pelvis, however, is unusual and often associated with diseased kidneys. Our case is the 8th one of spontaneous rupture of the renal collecting system with no identifiable underlying pathologic condition and the 17th case of spontaneous renal rupture overall.

Acute Disease↗
PubMed1989

Clinical value of in vitro drug sensitivity testing based on short-term effects on DNA and RNA metabolism in ovarian cancer.

The hypothesis that in vitro chemosensitivity testing could predict clinical outcome was tested in women with ovarian cancer. Short-term drug effects on DNA and RNA metabolism (by inhibition of 3H-thymidine and 3H-uridine incorporation) were measured in primary cultures of tumor cells. In vitro inhibitory effects were found with the four drugs tested: cisplatin, adriamycin, melphalan, and methotrexate. From data based on impaired RNA and/or DNA metabolism (greater than or equal to 20% inhibition), correct prediction of "sensitivity" was 79% and that of "resistance" was 84%. An analysis of the predictive value of both assays, used singly or together, revealed a high specificity but moderate sensitivity; the best positive predictive value (94%) was obtained when both RNA and DNA metabolisms were impaired. Our results support the idea that two subsets of patients who are being considered for cytotoxic chemotherapy can be selected; those who may benefit from treatment and those who may not, regardless of the drugs tested in vitro or used in vivo.

Antineoplastic Agents↗
PubMed1989

In vitro sensitivity of ovarian cancer as determined by a short-term biochemical assay: comparison between primary and metastatic sites in the same patient.

Tumor sensitivity of ovarian cancer to cytotoxic drugs in vitro was examined between paired samples taken from the primary tumor and its metastases in the same patient. A 3-hour assay of primary cultures of the tumor was used to determine cellular response to the drugs by measurement of the incorporation of [3H]thymidine. Although there was variability, a reasonable correlation was found between the primary tumor and its different metastases, between the different metastases, and between the different tumor sites and cells from the peritoneal fluid. However, there was discordance between some of the pairings; the rate varied between 12 and 42% when the criterion was greater than 20% inhibition. Consistent drug sensitivity for all sites tested was present in only 8 of the 18 patients. Because of the discordance in some pairings, attempts should be made to sample all metastatic tumors, particularly those which cannot be removed completely by surgery. The discordant subgroup may be a source of false-negative and false-positive results of the assay.

Cisplatin↗
PubMed1989

Cytoreduction in ovarian cancer: achievability and results.

A series of 210 consecutive operations for ovarian cancer performed by the author over a five-year period were analysed in order to assess the ability to perform adequate cytoreduction. Over 63% of the patients had Stage III or IV disease. Bowel resection was necessary in 50 cases, and the surgery was generally well tolerated. Debulking was assessed as a percentage of tumour volume reduction and also by the size of residual tumour after operation. Over 90% tumour volume reduction was accomplished in 82.7% of all cases (75% of Stage III cases), and optimal cytoreduction of nodules to less than or equal to 1.5 cm was achieved in 70.8% of cases (60% of Stage III cases). Survival analysis confirmed the importance of cytoreduction in the management of this disease.

Female↗
PubMed1989

Ovarian remnant syndrome.

Twenty-seven patients with ovarian remnant syndrome were operated on by the author in a 7-year period. All patients presented with pelvic pain as their major symptom. A mass was palpable in 20 patients. In 3 patients, no mass was palpable but a lesion was visible on computed tomographic scanning. In 4 patients, there was no palpable mass and scans were negative, yet an ovarian remnant was found at laparotomy. Segmental bowel resection was necessary to obtain clearance in 8 patients, and partial bladder resection was performed in 2. Previous pelvic operations (mean, 4.3) in this group of patients probably contributed to the development of this syndrome. The ovarian remnant syndrome occurs in a patient who has previously had a bilateral salpingo-oophorectomy. A piece of ovarian tissue remains, and this remnant often produces symptoms, usually pelvic pain and associated dyspareunia. Usually the patient has had a hysterectomy as well as bilateral salpingo-oophorectomy, so that the pain is often dismissed as 'not gynaecological' in origin. This syndrome is not synonymous with residual ovary syndrome, in which an ovary that has previously been intentionally conserved either develops an abnormal pathological process or causes symptoms necessitating its surgical removal (6). Unfortunately, awareness of the problems caused by an ovarian remnant is not widespread, and often these patients have been to many gynaecologists, general surgeons, or even psychiatrists in an attempt to get relief from their symptoms. It is not possible to estimate the incidence of symptomatic ovarian remnants, but certainly when an awareness of the syndrome develops, referral of patients with the problem is common.

Abdominal Pain↗
PubMed1989

Invasive carcinoma of the cervix in young women.

One hundred and seventy-six cases of cancer of the cervix in women age 35 years or less from 1959 to 1980 were compared with 65 cases occurring in the 5-year period from 1982 to 1986. The incidence of the disease in this age group changed little over this time, increasing from 9% to 11%. However, the incidence of adenocarcinoma cell types increased from 10% in the first period to 25% in the more recent cases. A change in management resulted in increased surgical emphasis in treatment; only 24% were treated surgically in the earlier group compared to 80% in the recent group. There has not been an increase in advanced cases or mortality in those young patients in recent years.

Adenocarcinoma↗
PubMed1988

Measurement of tumor cell activity in short-term primary culture. Clinical significance in women with ovarian cancer.

In vitro activity was determined by primary culture of tumor samples obtained at surgery from 63 patients with Stage III ovarian cancer. These patients had completed at least 24 months of follow-up. Proliferative activity was measured after 3-hour culture by 3H-thymidine incorporation and metabolic activity by 3H-uridine incorporation. A large range of individual tumor activity was found; no correlation was present between proliferative and metabolic activity in the same tumor, the distribution of tumors with high and low activity was similar between histologic types, and the activity was not higher in undifferentiated tumors. There was a strong association between in vitro activity of the tumor and patient outcome (both clinical status and survival). On the basis of in vitro activity, a subset of patients was identified within subgroups with known amount of residual tumor; proliferative activity was a better predictor of good outcome in patients with no residual disease, whereas metabolic activity was better in those with more extensive disease. In these patients, a tumor showing high proliferative and/or metabolic activity (greater than 5000 cpm) was associated with poor survival.

Cell Division↗
PubMed1988

Serial D-dimer levels in the assessment of tumor mass and clinical outcome in ovarian cancer.

D-dimer (DD)--an end product of fibrinolysis--was measured in serum by enzyme immunoassay using a monoclonal antibody to the gamma gamma crosslink in patients with ovarian cancer, before primary surgery and during chemotherapy for 12 months or more. Serial DD levels were found to have a high sensitivity for the detection of tumor in patients with subclinical disease (91%) as well as for predicting progression of disease (100%). As determined by a careful second-look laparotomy in patients with complete clinical remission the DD marker was highly predictive of tumors less than 1 cm. The negative predictive value (82%) was higher than the positive predictive value (69%). However, there were 31% of the patients who showed a false-positive result; a close examination of the clinical data of these 9 patients failed to reveal an explanation for the positive DD levels. Despite the lack of specificity (50% in the present series), the findings support the use of DD in the assessment of patients with ovarian cancer, especially those with subclinical disease.

Antibodies, Monoclonal↗
PubMed1988

Cisplatin chemotherapy of ovarian cancer: is short-term in vitro chemosensitivity predictive of long-term patient survival?

The in vitro response to cis-diamminodichloroplatinum (cisplatin) in primary culture of tumour samples obtained at surgery was studied in 61 patients with Stage III ovarian cancer who were also treated with cisplatin. The drug-induced inhibitory effect on cell proliferation (measured by 3H-thymidine incorporation) and metabolism (by 3H-uridine incorporation) was assessed over a 3-hour incubation. At greater than or equal to 20% level of inhibition, the true prediction rate of survival by the proliferative assay was 72% among those with 'sensitive' tumours and of mortality was 66% among those with 'resistant' tumours; at greater than or equal to 50% level of inhibition, the prediction rate of survival by the proliferative assay increased to 88% but that of mortality decreased to 58%. The results with the metabolic assay were comparatively lower at all levels. When the amount of residual disease was taken into the determination of mortality rate, significant differences were found between 'sensitive' and 'resistant' tumours as defined by the proliferative assay in patients with no/minimal disease. The pattern of survival differed significantly between 3 subgroups of tumours, as defined by their responses to cisplatin in the proliferative and metabolic assays -- the best survival was obtained in patients whose tumours were 'sensitive' in both assays.

Cisplatin↗
PubMed1987

Isochromosome 12p mosaicism (Pallister mosaic aneuploidy or Pallister-Killian syndrome): report of 11 cases.

We report on 11 cases of isochromosome 12p mosaicism (or Pallister mosaic aneuploidy syndrome) in which the isochromosome is usually absent in cultured lymphocytes but present in fibroblasts. The patients range in age from a 22-week-gestation fetus to a 45-year-old man. They have a distinct pattern of anomalies which enables one to make a diagnosis based on clinical manifestations alone. Craniofacial manifestations include "coarse" face with prominent forehead, sparsity of scalp hair, hypertelorism, epicanthal folds, flat bridge of nose, and highly arched palate. Affected newborn infants are profoundly hypotonic with sparsity of scalp hair especially bitemporally and a prominent forehead. Most have accessory nipples. Birthweight and growth parameters are usually normal; however, some newborn infants are unusually large. In infancy, the facial appearance becomes "coarse," hypotonia persists, and seizures may occur. As adults, growth may be normal, scalp hair is thicker and the mandible becomes prominent. Most have a generalized pigmentary dysplasia which may be evident with a Wood's lamp only. All cases have been sporadic and there is no consistent pattern of advanced parental age.

Abnormalities, Multiple↗
PubMed1987

Predictive value of serial CA 125 antigen levels in ovarian cancer evaluated by second-look laparotomy.

Serial serum CA 125 levels were measured before definitive surgery and during chemotherapy for 12 months or more in 64 patients with ovarian cancer. In the 42 patients who had a complete clinical remission and thus were subjected to a second-look laparotomy, an absence of disease was not predicted by patterns of CA 125 levels. Whilst rising or persistently high levels indicated the presence of tumour in 92% of patients, declining levels to negative predicted the absence of tumour in only 50%. Although the majority of these patients showed microscopic foci or a tumour mass less than 1 cm, 3 patients had a larger amount of disease. In the follow-up of 49 patients, the accuracy of prediction of a good outcome was better than that of a poor outcome on the basis of CA 125 patterns, with rates of 92% and 79%, respectively. Our findings indicate that CA 125 lacks sensitivity in detecting small tumour masses (less than 1 cm dia.) but rising or persistently high levels suggest a strong likelihood of a residual tumour to be found at a second-look laparotomy.

Antigens, Neoplasm↗
PubMed1987

Intestinal surgery in gynaecological oncology.

Over a 4-year-period, 117 patients had 139 intestinal operations performed in a gynaecological oncology unit. Most of the patients had gynaecological malignancy as the indication for their operation, but 18% had a gastrointestinal primary and 10% had benign pelvic conditions which required intestinal surgery. Most of the patients with malignancy had an ovarian primary cancer. The next most common primary site was the gastrointestinal tract and here carcinoma of the sigmoid colon was the most common. There were 102 large bowel and 36 small bowel operations. Sixteen patients had more than one intestinal procedure. The most common complication of the intestinal operations was prolonged ileus which occurred in 9 instances. Three patients required repeat laparotomy for postoperative bowel obstruction. There were 3 postoperative deaths occurring within 30 days. An assessment of the usefulness of preoperative investigations showed that there was a 10.3% false negative result reported from X-rays, scans or endoscopies. This factor makes it imperative that the surgeon operating on gynaecological malignancy should be capable of dealing with intestinal surgical procedures when required as it is not possible to rely on preoperative investigations to point out those that may require intestinal surgery.

Female↗
PubMed1986

A new autosomal dominant acrofacial dysostosis syndrome.

We report on a family in which a previously undescribed acrofacial dysostosis syndrome is segregating as an autosomal dominant trait. Craniofacial manifestations are those of mild mandibulofacial dysostosis and are quite constant among affected relatives. The acral abnormalities are quite variable, affecting predominantly the radial ray. Variability extends from thumb duplication in one patient to mild hypoplasia of the first metacarpal and first proximal phalanx in most affected individuals. Mandibulofacial dysostosis is a causally nonspecific malformation and as such represents an apparently monotopic developmental field defect. Its occurrence with acral anomalies in several conditions of different cause represents a polytopic developmental field defect.

Adult↗