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Biomedical subjects

W Fowler

Publications and source records attributed to W Fowler.

At least 19 recordsLinked to original sources
PubMed1993

Report of phase II trial of concurrent chemoradiotherapy with radical thoracic irradiation (60 Gy), infusional fluorouracil, bolus cisplatin and etoposide for clinical stage IIIB and bulky IIIA non-small cell lung cancer.

PURPOSE: To assess the response rate, median and long-term survival of patients (pts) with locally advanced, initially inoperable non-small cell lung cancer (NSCLC) treated on a phase II study of radical thoracic radiotherapy (TRT) and concurrent radiosensitizing chemotherapy. METHODS AND MATERIALS: From 3/87 to 7/90, 41 previously untreated patients at Fox Chase Cancer Center with locally advanced non-small cell lung cancer, 24 with bulky clinical Stage IIIA, and 17 with IIIB disease, received concurrent thoracic radiotherapy (60 Gy/2.0 Gy/d in 6 weeks) and 2 cycles of infusional 5FU (640-800 mg/m2/24 hrs x 5 d); cisplatin (20 mg/m2 qd x 5); and etoposide (50 mg/m2 d 1, 2, 5) administered days 1 and 28 of TRT. RESULTS: Forty of 41 were evaluable. Response rate was 90%, with radiographic CR in 20%. Thirteen pts (33%) underwent thoracotomy and complete resection with clinical downstaging in 10, including three pathologic CR's. Overall median survival was 14 months and 2-year survival was 38% with no difference between CS IIIA and IIIB pts (p = 0.2224). At median potential follow-up of 42 months, 8/40 pts. (20%) are alive and progression-free, including 4 of 13 resected pts. The chief toxicity was esophagitis, occurring in 32 pts. (80%), Grade 3-4 in 21 (52%), with 13 (33%) requiring hospitalization and 7 (18%) needing TPN. Grade 3-4 granulocytopenia was noted in 20 pts. (50%) with ten episodes of fever mandating intravenous antibiotics. Cardiac ischemia was documented in 2 (5%). Of 13 thoracotomy pts, six underwent lobectomy without perioperative mortality; 3 of 7 pneumonectomy pts died post-operatively, two from broncopleural fistula, and one from ARDS. CONCLUSION: This aggressive regimen produced a 2-year survival (38%) comparable to the best arm of cancer and leukemia groups B study 8433, which administered radical thoracic radiotherapy after protoadjuvant vinblastine and cisplatin in similar and earlier stage non-small cell lung cancer patients. Toxicity, particularly esophagitis, was severe, but of short duration. An unacceptably high complication rate was seen following pneumonectomy, but not lobectomy.

Adult↗
PubMed1993

Accelerating language acquisition.

How much can the development of language and other skills be accelerated in the general population? High correlations between early verbal and mental competencies and parent and teacher language socialization practices suggest enormous potential for widespread improvement. Here we report follow-up research in progress in studies of late adolescent children from diverse ethnic and educational backgrounds who participated in a language enrichment programme during infancy in the home or day-care. In 39 of 44 home-stimulated children located to date (nearly all from college-educated families) 62-93% were: in gifted or advanced programmes, obtaining high grades, avid readers and skilled in writing (over half read before school and wrote creative material independently) and generally highly skilled in verbal, mathematical and other academic domains. They also excelled socially and in sports, and showed intellectual independence. Additional subjects and data (on competence, later experiences and Scholastic Aptitude Test [SAT] scores) are currently being collected. Preliminary data analyses suggest that although early language enrichment can in the short term easily increase competence in all groups well beyond norms generated by current socialization practices, long-term outcomes are a complex function of developmental dynamics between the early, complex, foundation of high skills and motivation for learning, and the interaction with facilitative parental resources.

Adolescent↗
PubMed1993

32P following negative second-look laparotomy for epithelial ovarian cancer.

PURPOSE: Peritoneal seeding remains a prominent failure pattern in patients with invasive epithelial ovarian cancer, even following a pathologically negative second-look laparotomy (2LL). In an attempt to decrease the risk of peritoneal recurrence, we have treated patients with no clinical or histopathologic evidence of disease at 2LL with 15 mCi of chromic phosphate suspension intraperitoneally (32P). METHODS: Between 1973-1987, 69 patients with stages I-III invasive epithelial ovarian cancer in complete clinical remission were found to have no evidence of disease at 2LL. Fifty-one patients received intraperitoneal 32P. Thirty-five patients, otherwise eligible for 32P, did not receive it primarily due to other treatment protocols, peritoneal adhesions, or the recommendation that no further therapy be given following a negative 2LL. Patients in both groups were comparable with regard to stage, histology, grade, median age, residual disease following initial surgery, and chemotherapeutic regimen. The median follow-up for uncensored patients is 58 months (minimum, 18 months). RESULTS: The 5-year actuarial disease-free survival rate from the date of 2LL was 86% for those receiving 32P and 67% for those not receiving 32P (P = 0.05). The corresponding 5-year overall survival rates were 90 and 78%, again favoring patients treated with 32P. COMPLICATIONS: There were minimal acute side effects from 32P. Late adverse effects were similar in the two groups. Bowel complications were seen in 3 of 51 patients receiving 32P and 1 of 18 patients not receiving 32P. CONCLUSIONS: We have found intraperitoneal 32P administration immediately after 2LL to be a safe and well-tolerated therapy. Our data suggest that 32P confers a survival advantage to patients with a pathologically negative 2LL. These findings suggest a continued role for second-look laparotomy with the use of 32P in selected patients.

Chi-Square Distribution↗
PubMed1992

Absence of malignant hyperthermia contractures in Becker-Duchenne dystrophy at age 2.

Two 2-year-old males underwent muscle biopsy that established the histopathologic diagnosis of Becker dystrophy in one, and Duchenne dystrophy in the other. Concomitant contracture testing with caffeine or halothane was normal for malignant hyperthermia (MH). The results suggest that acute hypermetabolism or acute rhabdomyolysis during anesthesia, in patients with these disorders, is related to the X-linked myopathy and its associated muscle deterioration, rather than to the autosomal dominant MH.

Age Factors↗
PubMed1992

Ha-ras polymorphisms in epithelial ovarian cancer.

Unusual restriction fragment length polymorphisms (RFLPs) of the Ha-ras locus have been found in DNA from leukocytes and tumor tissue of cancer patients. To determine whether rare alleles would be observed frequently in patients with ovarian cancer, Ha-ras RFLPs were studied in DNA from 42 different ovarian epithelial tumors and from the peripheral blood leukocytes of 76 normal individuals. Four common, seven intermediate, and seven rare alleles were detected overall. Similar fractions of rare alleles were found in DNA from ovarian cancers and from the peripheral blood of normal individuals. Thus, the frequency of unusual Ha-ras RFLPs did not distinguish patients with ovarian cancers from apparently healthy individuals.

Alleles↗
PubMed1991

Congenital gallbladder duplication: preoperative diagnosis by ultrasonography.

Congenital gallbladder duplication, an uncommon but potentially complicating malformation, is rarely diagnosed preoperatively. A case in which the diagnosis was achieved by real-time ultrasonography is presented and correlated with hepatobiliary scintigraphy. The efficacy of these diagnostic modalities is discussed, and the available literature is reviewed.

Female↗
PubMed1990

Assessing the validity of memory complaints: performance of brain-damaged and normal individuals on Rey's task to detect malingering.

Rey (1964) proposed a brief screening test to assess the validity of memory complaints and hypothesized that the ease of the task would mislead malingerers to perform more poorly even than persons with impaired memory due to brain injury. Lezak (1983) suggested cut-offs, but only one empirical report on Rey's task could be located in the literature. That study by Goldberg and Miller (1986) supported Lezak's cut-offs; however, the criterion groups were psychiatric and mentally retarded inpatients. In the present study, Rey's test, along with other neuropsychological tests designed to determine various types of memory dysfunction, was administered to brain-damaged (n = 18) and comparison (n = 16) groups. The results again generally supported Lezak's cut-offs.

Adult↗
PubMed1988

Intraperitoneal chromic phosphate therapy after second-look laparotomy for ovarian cancer.

Between 1973 and 1985, 118 patients in clinical remission after initial surgery and postoperative chemotherapy for epithelial ovarian carcinoma underwent second-look laparotomy at the University of North Carolina. No evidence of disease (NED) was found in 57 of these patients; 43 patients received 15 mCi of radioactive chromic phosphate (32P) suspension given intraperitoneally in the immediate postoperative period. In 29 other patients, only microscopic or minimal residual disease (nodules less than 2 cm in size) was found, seven received 32P alone, ten received 32P and further chemotherapy, and 12 received chemotherapy alone. The 4-year postsecond-look survival of the patients with NED at second-look was 89% for those receiving 32P and 67% for those who had not. The respective figures for patients with minimal residual disease at second-look are 59% versus 22%. Irrespective of treatment, a group at high risk for failure after negative second-look laparotomy has been identified; those with an initial International Federation of Gynecology and Obstetrics (FIGO) stage greater than I and histologic grade greater than 1. A comparison of our data with 18 previously published series, indicates that use of postsecond-look intraperitoneal 32P can improve the progression-free interval, and possibly overall survival, of patients with NED or minimal residual disease without adding significant complications.

Carcinoma↗
PubMed1987

Primary radiation therapy for medically inoperable patients with endometrial carcinoma--stages I-II.

Surgery with or without adjuvant radiation is the established method of treating patients with Stage I and II adenocarcinoma of the endometrium. However, patients who are poor operative risks must be treated with radiation therapy only. We report on 73 such patients treated at the University of North Carolina between 1969 and 1980. All patients had an adenocarcinoma of the endometrium; 41 were FIGO Stage I, 32 Stage II. The minimum follow-up period was 4 years. Life table analysis shows a disease-free survival of 72% at 3 years and 57% at 5 years for Stage I patients. There was a strong correlation between histologic tumor grade and survival in these patients; the 5-year survival for grade 1 was 72%, for grade 2 59%, and for grade 3 31%. The difference between G1 and G3 is significant at the p = .045 level. Coexisting medical conditions were responsible for 12 deaths; almost as many as the 16 cancer-related deaths. Stage II patients have an actuarial disease-free survival of 36% at 3 years and 26% at 5 years, significantly worse than Stage I patients (p = .029 at 3 years). Failures were seen in 16/41 (39%) Stage I and 19/32 (59%) Stage II patients; 29/35 (83%) of these recurrences had component of local/pelvic failure and 15/35 (43%) of the recurrences were local/pelvic only. Specific suggestions on how to improve local therapy for these patients are presented.

Actuarial Analysis↗
PubMed1982

Mononuclear-cell infiltration in ovarian cancer. I. Inflammatory-cell infiltrates from tumour and ascites material.

Malignant effusions and tumour tissue obtained at surgery provided material for a study of the prognostic value of the various inflammatory cells in the prognosis of human ovarian cancer. Ascitic fluids predominantly contained inflammatory cells; tumour cells, both singly and in clusters, were a minor component. Tumour cells were usually in excess in dispersed solid material. Some patients had significant proportions of lymphocytes and macrophages in their solid tumour, and these patients invariably responded to therapy. Sedimentation-velocity separation at unit gravity provided tow populations of inflammatory cells. One consisted of mononuclear cells similar in size to those in the patients blood: the other consisted of one or more large macrophage populations, distinct in morphology and enzymatic markers from both blood monocytes and each other. T lymphocytes were enriched in ascites fractions (78%) and in the tumour-derived mononuclear fraction (71%) compared to patient blood (60%). The T-cell subset characterized by ANAE reactivity was markedly depleted in the tumour-infiltrating fraction (17%) compared to patient blood (62%) or patient blood (51%). Esterase-positive monocyte-like cells were more frequent in the tumour-infiltrating fraction (17%) than ascites (7%) or blood (12%). B lymphocytes were infrequent in solid tumours and difficult to assess in ascites. Histiocyte-like macrophages were present in the higher-velocity tumour-cell containing fractions of both solid and ascitic material. The variation in infiltrating cells between patients and between tumour and ascites of the same individual was marked.

Ascitic Fluid↗
PubMed1982

Mononuclear-cell infiltration in ovarian cancer. II. Immune function of tumour and ascites-derived inflammatory cells.

Mononuclear cell fractions were isolated from blood, ascites and solid tumours of patients undergoing surgery for Stages III and IV adenocarcinoma of the ovary, and evaluated for their response in NK, ADCC and PHA assays. Control experiments with the same fraction of normal blood indicated that these responses were not influenced by the enzymes used to isolate the tumour and ascites inflammatory cells. The inflammatory cell fractions isolated from both tumour sites which sedimented in the velocity range of blood mononuclear cells were adequate in number and composition for comparison with similar cells from blood. E RFC values in both ascites and tumour fractions exceeded those of patient blood. However, there was a marked difference in distribution of the T subsets between blood, ascites and tumour, which could cause the variable test results between the different cell sources. PHA responses of patient blood and ascites fractions were about half that of normal blood. Tumour-infiltrating lymphocytes (TIL) were less than 10% as responsive as normal blood. The depressed PHA responses of the TIL were not due to the presence of a suppressor cell population. NK activity of patient blood was less than that of normal blood, but not as much as the ascites of TIL cells. The activity of the ascites-derived lymphocytes was enhanced by treatment with interferon. ADCC activity against both CRBC and SB cells was normal or higher than controls in patient blood, and depressed in the ascites-derived fractions. TIL responded to less than 10% of the patient blood values. The results indicate a lack of response by ascitic and TIL cells in assays dependent on FcR-bearing effector cells and a greater loss of PHA-reactive cells from the tumour than from blood and ascites. These data could result from intratumour inactivation, or a failure of the particular subset to localize either in the ascites or the tumour site.

Adenocarcinoma↗
PubMed1982

Mononuclear-cell infiltration in ovarian cancer. III. Suppressor-cell and ADCC activity of macrophages from ascitic and solid ovarian tumours.

Macrophages have been isolated from ascitic and collagenase-dispersed tumours from patients undergoing surgery for ovarian cancer. Macrophages were present in varying proportions in both sites, though the ration of macrophages to tumour cells was higher in ascites. Marked variation in size (as detected by sedimentation velocity) and cytochemical markers in the macrophages was noted. Highly enriched macrophage fractions were isolated from the ascites and collagenase-dispersed solid tumours by a combination of sedimentation velocity and selective EA RFC or adherence techniques. Suppressor activity in the PHA assay was detected in tumour macrophages (4/10 giving less than 50% inhibition), ascitic macrophages (1/15) and blood monocytes (2/7). Lymphocyte fractions from tumours were unresponsive to PHA and failed to suppress the blood response. Suppressor activity was also present in the purified tumour-cell fraction of 6/14 patients. ADCC activity was tested in a few patients. When the activity was determined against the SB target cells, tumour-derived macrophages were inactive, whereas the ascitic fraction showed low but significant activity which averaged much lower than patients blood values. The ADCC assays carried out with the CRC target cell indicated activity within the range of patient blood values in 4/4 ascites and 2/4 tumour macrophage fractions. Cytotoxicity was also assessed against co-purified autologous tumour cells. Although activity was detected in many of the tests, the results seemed to reflect target cell sensitivity. There appeared to be a correlation between cytotoxicity with test macrophages and normal blood mononuclear cells. The results indicate that the cytochemical heterogeneity and the variation in size between macrophage fractions is associated with a spectrum of activities.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1980

Fibrin assembly: a comparison of electron microscopic and light scattering results.

To test the validity of a proposed two step fibrin assembly mechanism and directly visualize the molecular species present at various stages of fibrin formation, we have carried out an electron microscopic investigation. Assembly conditions duplicated those of a recent light scattering study and specimens were prepared at different time points with the use of a negative staining technique recently employed to visualize the trinodular structure of fibrinogen. Under near-physiological buffer conditions, protofibrils structurally similar to those postulated by Ferry have been found at early stages of fibrin assembly. In parallel with the light scattering results, a dramatic increase in fiber diameter was found in specimens prepared during the postulated lateral association stage of gelation. Light scattering and electron microscopic results both showed that high ionic strength reduces the rate and extent of fiber formation. Reptilase cleavage is shown to result in typical cross striated fibrin.

Batroxobin↗