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Biomedical subjects

H Bruckner

Publications and source records attributed to H Bruckner.

At least 19 recordsLinked to original sources

Self-incompatibility in passionfruit: evidence of gametophytic-sporophytic control.

Self-incompatibility in passionfruit was studied in families originated from crosses among plants that presented differences in reciprocal crosses. The three families, obtained by crossing S(3) plants, exhibited one incompatible group; no reciprocal differences were observed. The phenotype of the families was the same as the parent plants, S(3). These results suggest the presence of a gene ( G), gametophytic in its action, associated to the sporophytic gene S, modifying the incompatibility reaction in passionfruit. The reciprocal difference exhibited in the crosses among the parents could be explained as a matching between plants homozygous for S, but homozygous and heterozygous for G. Actually this would be a partially compatible cross, not detectable when the evaluation is done based on fruit set data. As the family originated from this kind of cross is homozygous for S and heterozygous for G, no reciprocal differences are expected, and the phenotype should be the same as the parental plants, as observed in the present work.

Crosses, Genetic↗

Adjuvant and neoadjuvant therapies of pancreatic cancer: a review.

The survival of patients diagnosed with pancreatic cancer is dismal. Few patients on initial presentation are suitable for surgical resection. This has prompted clinical studies with chemotherapy and/or radiotherapy designed either to increase the number of patients eligible for surgery (neoadjuvant therapy) or to prolong the survival of patients who had undergone surgery (adjuvant therapy). None of these studies may at this time be considered definitive. Wherever possible, patients felt eligible for neoadjuvant or adjuvant therapy should be entered on clinical trials. Where this is not possible, clinicians should exercise their best judgment in offering this type of treatment to pancreatic cancer patients under their care.

Chemotherapy, Adjuvant↗

Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial.

BACKGROUND: Resection of pancreatic carcinoma is resource-intensive with a limited impact on survival. Chemotherapy and/or radiotherapy (RT) have been shown to be effective palliation. To examine whether preoperative chemoradiotherapy as the initial treatment improves survival for patients with a regional pancreatic adenocarcinoma with a minimal chance of being resected successfully, an outcomes trial was conducted. METHODS: Patients with radiologically regional tumors were staged by laparotomy and/or computed tomography followed by endoscopic ultrasonography, angiography, and/or laparoscopy. Those with locally invasive, unresectable, regional pancreatic adenocarcinoma initially were treated with simultaneous split-course RT plus 5-fluorouracil, streptozotocin, and cisplatin (RT-FSP) followed by selective surgery (Group 1). Patients determined to have a resectable tumor initially underwent resection without preoperative chemoradiotherapy, with or without postoperative chemoradiotherapy (Group 2). RESULTS: Over 8 years 159 patients presenting with nonmetastatic pancreatic adenocarcinoma were administered RT-FSP or underwent surgery for resection. Group 1, comprised of 68 patients initially treated with RT-FSP, had a 0% mortality rate within 30 days of entry. In 20 of 30 patients undergoing surgery after RT-FSP, tumors were downstaged and resected. Group 2, comprised of 91 patients who initially underwent successful resection, had a 5% mortality rate within 30 days of entry. Postoperatively, 63 of these patients received chemotherapy with or without RT. The median survival for Group 1 was 23.6 months compared with 14.0 months for Group 2 (P = 0.006) despite more advanced disease cases in Group 1. Survival favored RT-FSP regardless of whether lymph nodes were malignant. The dominant prognostic factor of earlier stage pancreatic carcinoma having an expected survival advantage was reversed by the initial nonoperative treatment. CONCLUSIONS: Based on a reversal of the expected trend that patients with earlier stage resectable carcinoma (T1,2, N0,1, M0) who undergo removal of their tumors survive longer than patients with more advanced regional disease (T3, N0,1, M0), survival was found to improve significantly for patients reliably staged as having locally invasive, unresectable, nonmetastatic pancreatic adenocarcinoma when initially treated with RT-FSP.

Adenocarcinoma↗

Current surgical therapy for carcinoma of the pancreas.

Despite progress in treating many solid tumors, pancreatic cancer continues to be a grave illness. Each year, >29,000 new cases of adenocarcinoma of the pancreas are diagnosed in the United States. Of these patients, only 10-20% have resectable tumors and 25,000 patients (83%) die within 12 months of diagnosis. Until recently, surgery has been the only "effective" therapy available for select patients. Historically, the operative mortality after radical pancreatic resection has been variable, ranging 1-30%, and is both operator- and institution-dependent. Even with a safe and complete surgical resection, the actual 5-year survival after surgery alone is essentially zero, although rates up to 5% have been reported. Despite what would appear to be a dismal outlook, slow progress has occurred in the operative and postoperative care of patients with pancreatic cancer. Advanced imaging techniques and laparoscopy have limited the number of unnecessary laparotomies, and novel adjuvant and neoadjuvant chemotherapy approaches have yielded promising results. This review will summarize the recent literature concerning the surgical therapy and trends in the treatment of carcinoma of the pancreas from 1990 to 1999.

Adenocarcinoma↗

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.

Antineoplastic Agents↗

Hypertensive crises induced by treatment of malignant pheochromocytoma with a combination of cyclophosphamide, vincristine, and dacarbazine.

Combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) is an effective treatment regimen for malignant pheochromocytoma. There have not been any significant acute cardiovascular effects reported following CVD treatment. Among seven patients with malignant pheochromocytoma treated with CVD at our institution, two patients with labile hypertension developed hypertensive crisis following CVD treatment. The marked increase in blood pressure correlated with an increase in urinary excretion of catecholamine metabolites in one patient. Further hypertensive crises following subsequent CVD treatments were avoided by optimizing each patient's antiadrenergic therapy. Similar to the approach used preoperatively for patients with resectable pheochromocytoma, maximal antiadrenergic therapy is essential in preventing hypertensive crises in patients with malignant pheochromocytoma undergoing CVD treatment.

Adrenal Gland Neoplasms↗

Mucin-associated sialosyl-Tn antigen expression in gastric cancer correlates with an adverse outcome.

The expression of sialosyl-Tn (STn) antigen was evaluated by immunohistochemistry in primary gastric cancers. Twenty-one of 31 (68%) gastric cancers expressed STn, regardless of tumour location, stage or histological type. Eighty-one per cent of patients with STn-positive tumours died of their disease or had recurrent cancer, compared with 20% of patients with STn-negative tumours (P < 0.002). STn may be a useful prognostic marker in patients with gastric cancer.

Aged↗

Management of hypocalcemic effects of WR2721 administered on a daily times five schedule with cisplatin and radiation therapy. The New York Gynecologic Oncology Group.

PURPOSE: To determine the effects of the chemoprotective agent, WR2721, administered on a daily x 5 schedule with cisplatin and radiation therapy, on calcium and parathyroid hormone (PTH) levels. PATIENTS AND METHODS: Twenty women with cervical cancer were enrolled in a clinical trial to determine the maximal safe dose of WR2721 plus radiation therapy and cisplatin on a novel daily x 5 schedule. Detailed studies of the effects of WR2721 on calcium and PTH levels were initiated after a patient developed symptomatic hypocalcemia. RESULTS: Treatment with WR2721 resulted in a rapid decline in serum PTH levels within 4 hours, which fell below the lower limits of normal at 24 hours, then returned to within normal limits at 48 hours. In contrast, serum levels of ionized calcium were not affected acutely, and declined by only 7% within 24 hours. However, this small decrease persisted for the 5 days of treatment. Hypocalcemic effects were successfully managed with oral calcium carbonate and calcitriol supplements. In one patient, particularly sensitive to the effects of WR2721, serum levels of ionized calcium decreased to less than 3.0 mg/dL despite oral calcium supplements. CONCLUSION: The effects of WR2721 on serum ionized calcium levels are mediated by direct inhibition of PTH activity; other effects such as inhibition of renal tubular calcium reabsorption cannot be excluded. We recommend that patients treated with WR2721, cisplatin, and radiation therapy receive routine oral calcium and calcitriol supplementation and that serum ionized calcium levels be monitored frequently.

Adult↗

A GC cluster repeat is a hotspot for mit- macro-deletions in yeast mitochondrial DNA.

In a random collection of mit- mutations of the yeast strain 777-3A we find that deletions are exceptionally frequent in the OXI3 gene, a large mosaic gene coding for subunit I of cytochrome oxidase. About 10% of all oxi3-mutants carry the same macro-deletion, del-A, extending from the 5' non-translated leader of OXI3 to intron 5b of this gene. Determination of the respective wild-type sequences and of the del-A junction sequence revealed that the end-points of the deletion are in two GC clusters with 31 bp sequence identity which are located at a distance of 11.3 kb. We speculate that not only the sequence identity of the two GC clusters but also the palindromic structure of these putatively mobile elements of yeast mitochondrial DNA (mtDNA) plays a role in deletion formation.

Base Composition↗

Phase II evaluation of dibromodulcitol and actinomycin D, hydroxyurea, and cyclophosphamide in previously untreated patients with malignant melanoma.

In this Eastern Cooperative Oncology Group (ECOG) phase II study, dibromodulcitol (DBD) and a combination of actinomycin D, hydroxyurea, and cyclophosphamide (AHC) were compared with methyl-CCNU, the current ECOG standard, in patients who had received no prior chemotherapy for disseminated malignant melanoma. The response rates were 6% (3/50) for AHC, 9% (3/34) for DBD, and 14% (7/49) for methyl-CCNU. Median survival times were 4, 5, and 6 months, respectively. Neither regimen appears to offer any advantage over methyl-CCNU as front-line therapy for patients with disseminated melanoma.

Adolescent↗

Treatment of primary undifferentiated sarcoma of the liver with surgery and chemotherapy.

Primary undifferentiated sarcoma of the liver is a rare tumor with survival reliant on total excision of the tumor. The authors report such a tumor, initially nonresectable, in a 7-year-old girl whose tumor was successfully excised following treatment with cisplatin and Adriamycin (doxorubicin). The light and electron microscopic details of this patient's tumor are presented.

Antineoplastic Combined Chemotherapy Protocols↗

Portable infusion pumps in ambulatory cancer chemotherapy.

Fifty-seven adult patients receiving chemotherapy were treated with a total of 133 infusions using portable user-worn infusion pumps, the Autosyringe AS*2F Cormed ML6-4, and two earlier versions of the latter, the Sigmamotor ML6-2 and ML6-3. Ninety-eight infusions were given on an ambulatory basis. Fourteen infusions were given through peripheral venous catheters, 115 through central venous catheters, and four intra-arterially. Of 127 evaluable infusions, 65 were completed within 5% and 87 within 10% of the planned rate; results are similar for both inpatient and outpatient infusions. The Cormed ML6-4 pump was equal to the Autosyringe AS*2F in reliability but superior to the latter in patient preference. There were no instances of dangerously rapid administration of the drug. The only serious catheter complications were a pneumothorax after insertion of a subclavian catheter in one patient and cellulitis in a leukopenic patient with a Broviac catheter. All but three patients preferred outpatient therapy to hospitalization. Outpatient therapy costs about $300 per day less than in-hospital treatment.

Adult↗

CEA monitoring among patients in multi-institutional adjuvant G.I. therapy protocols.

The Gastrointestinal Tumor Study Group (GITSG) has since 1975 included protocols for monitoring carcinoembryonic antigen (CEA) levels in its colorectal cancer adjuvant trials. Among the 563 patients on the colon cancer study (GI 6175) and the 207 patients on the rectal cancer study (GI 7175), one third had preoperative CEA determinations and more than 90% had some postoperative CEA monitoring. Colon cancer patients whose preoperative CEA was greater than 5 ng/ml had a greater probability of recurring than those whose values were lower (33% versus 18% recurrence with 21 months minimum follow-up; p < 0.05). The prognostic value of preoperative CEA was apparent only in patients with Dukes' C1 colon tumors. Preoperative CEA values were not of prognostic significance among the rectal adenocarcinoma patients. Although elevated levels of CEA after resection of either colon or rectum cancers were strongly associated with subsequent tumor recurrence, no single CEA value, arbitrarily defined as "elevated", provided an adequate screening test with both high sensitivity and high specificity. Postoperative CEA elevations were more strongly predictive of recurrence when part of a steadily rising trend. In the colon cancer study, the median monthly increase in CEA for disease-free patients was estimated to be zero, and for the relapsed patients 5.8%. The corresponding estimates for patients on the rectal cancer protocol were zero and 7.8%. Only 36 of the 344 disease-free patients on the colon protocol and 14 of the 94 disease-free patients on the rectal protocol (15%) exhibited a rate of increase of CEA as high as 3% per month over the entire period of observation. Two thirds of the relapsed patients on both studies showed a rate of increase this high or higher. The patterns of CEA rise in individual patients were quite varied, however, and monthly rates of increase as established in our study are not to be used as guidelines in patient management.

Carcinoembryonic Antigen↗

Methyl-GAG in patients with malignant neoplasms: a phase I re-evaluation.

Methyl-GAG was given to 71 patients with advanced malignancies as a weekly brief infusion (30-120 minutes) or as a biweekly 24- or 120-hour infusion. Mucositis (stomatitis, pharyngitis, esophagitis, and, rarely, inflammation of other mucous membranes) was dose-limiting in all three schedules. Generalized fatigue, malaise, myalgia, dysesthesias, nausea, and vomiting were more frequent in the brief-infusion schedule. Myelosuppression was mild and not dose-related. Fever, ventricular arrhythmias, skin rash, tender swelling of the palms, neuropathy, and paralytic ileus were rare. Toxicity was increased in patients with renal insufficiency or "third-space" fluid but was not increased by hepatic dysfunction. Cumulative and overlapping toxicity was evident only in the weekly schedule. Higher doses of methyl-GAG were tolerated when the duration of infusion was increased. The recommended doses for phase II trials are 700 mg/m2 weekly as a 1-2 hour infusion, 850 mg/m2/24 hours biweekly, and 1500 mg/m2/120 hours biweekly. Therapeutic effects were seen in all schedules and included objective responses in colon carcinoma (one of 13 patients), renal cell carcinoma (one of nine), and Hodgkin's lymphoma (one of two) and objective improvements in esophageal carcinoma (one of three), endometrial carcinoma (two of two), and leiomyosarcoma (one of three).

Adult↗