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Biomedical subjects

D Fischer

Publications and source records attributed to D Fischer.

At least 199 records · Page 11Linked to original sources
PubMed1991

Mammographically detected breast cancer. Results with conservative surgery and radiation therapy.

At Yale-New Haven Hospital (New Haven, CT) treatment of early stage breast cancer with conservative surgery and radiation therapy (CS & RT) has been utilized with increasing frequency since the 1960s. The authors have reviewed their experience with specific reference to the outcome of those patients whose breast cancer was detected on routine screening mammography. To achieve adequate follow-up, only patients treated before December 1984 are included in this analysis. Of 438 patients treated with CS & RT before December 1984, a total of 41 patients (9%) had nonpalpable lesions detected on routine screening mammography and were treated with CS & RT to the intact breast. Only two patients received adjuvant hormonal therapy and no patients received adjuvant systemic therapy. There has been only one breast failure and one death due to cancer in this group of patients resulting in actuarial survival and breast recurrence-free rates of 100% at 5 years and 92% at 10 years. These results stress the importance of routine screening mammography and raise questions regarding the role of adjuvant systemic therapy in this selected group of patients.

Adult↗
PubMed1991

Assigning functions to nucleolar structures.

Nucleoli provide the fascinating possibility of linking morphologically distinct structures such as those seen in the electron microscope with biochemical features of the formation and stepwise maturation of ribosomes. Localization of proteins by immunocytochemistry and of rRNA genes and their transcripts by in situ hybridization has greatly improved our understanding of the structural-functional relationships of the nucleolus. The present review describes some recent results obtained by electron microscopic in situ hybridization and argues that this approach has the potential to correlate each step of the complex pre-rRNA maturation pathway with nucleolar structures. Evidence is accumulating that the nucleolus-specific U3 snRNPs (small nuclear ribonucleoprotein particles) participate in rRNA processing events, similar to the role played by the nucleoplasmic snRNPs in mRNA maturation. The intranucleolar distribution of U3 snRNA is consistent with the view that it is involved in both early and late stages of pre-rRNA processing.

Animals↗
PubMed1991

Pharmacokinetics of recombinant interferon alpha-C.

Recombinant interferon alpha-C (rIFN alpha-C, Interpharm), is a new type of alpha-interferon that has a specific activity of 1-2 x 10(9) units/mg protein. The pharmacokinetics of rIFN alpha-C were studied in 11 patients with metastatic renal-cell carcinoma. A total of 10 million units IFN alpha-C were injected intramuscularly and the serum level of IFN was evaluated up to 72 h post-administration. Measurable IFN concentrations appeared in the serum as early as 0.5 h, and levels peaked at 4-6 h (Cmax = 53.2 +/- 4.6 units/ml). Relatively high levels persisted for 24 h and declined thereafter with an apparent half-life of 3-4 h. The mean area under the serum-concentration curve (AUC) was 1,259 +/- 145 units h ml-1, indicating good bioavailability of the preparation from the intramuscular injection.

Aged↗
PubMed1991

Sulindac causes regression of rectal polyps in familial adenomatous polyposis.

In familial adenomatous polyposis, sulindac-induced polyp regression has been reported by several authors. In this study, the goal was to confirm these results by a randomized, placebo-controlled, double-blind crossover study in 10 patients with rectal polyps that had been previously treated by colectomy and ileorectal anastomosis. Patients received sulindac, 300 mg/day, or placebo during two 4-month periods separated by a 1-month wash-out phase. One patient was not compliant and was excluded. With sulindac, the authors observed a complete (6 patients) or almost complete (3 patients) regression of the polyps. With placebo, the authors observed an increase (5 patients), no change (2 patients), and a relative decrease (2 patients) in the number of polyps. The difference between sulindac and placebo was statistically significant (P less than 0.01). In biopsy specimens of polyps and normal rectal mucosa of 6 patients, the authors conducted an immunohistochemical study of the cellular proliferation index using the Ki 67 monoclonal antibody (Ki 67 index), at the beginning and at the end of each treatment period. They were not able to show a sulindac-induced modification of the Ki 67 index. The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1991

Clinical, psychological and thallium stress studies in patients with chest pain and normal coronary arteries.

The clinical and psychological profiles of 36 consecutive patients with chest pain and normal coronary arteries (study group) were compared to those of 34 patients with chest pain and significant coronary arterial disease (control group). All 70 patients were hospitalized for chest pain at least once prior to coronary angiography. The features of a typical episode of chest pain were similar in the normal coronary arteries and coronary arterial disease groups, but the female patients with normal coronary arteries had a shorter duration of a typical episode of chest pain, and the male patients with normal coronary arteries had a lower frequency of positive effort tests. Psychological testing showed the women with normal coronary arteries to have a tendency to increased somatization, anxiety, and a lower ability to identify origin of difficulties. The patients in the normal coronary and coronary arterial disease groups had psychological profiles typical of patients with chronic somatic disease. A psychiatric interview demonstrated an increased frequency of depressive trait (score 0-2) in the normal women (0.6 +/- 0.8 vs 0, P less than 0.05), and a tendency to increased somatization, anxiety, and sleeping disorders. Increased somatization was found in the normal coronary men (1.1 +/- 0.7 vs 0.5 +/- 0.7, P less than 0.05). Twenty-five patients of the normal coronary group underwent quantitative thallium stress studies, and 13 patients (52%) had evidence of stress-induced myocardial perfusion defect. There were no differences in the clinical and psychological profiles of the patients with normal and those with pathological thallium stress tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Chest Pain↗
PubMed1991

Expression of transforming growth factor-alpha and epidermal growth factor receptor in human fetal kidneys.

Beginning at the fifth week of fetal life, successive generations of individual nephrons are induced by contact between metanephric mesenchyme and ureteric bud. Following phenotypic transformation, cells of each primitive renal vesicle undergo a phase of rapid cell division. In order to identify genes which might regulate nephron development in man, we screened adult and fetal kidney RNA for expression of a panel of growth-related genes. Among the genes which were expressed at higher levels in fetal kidney was the epidermal growth factor (EGF) receptor. There is controversy as to the most likely physiologic EGF receptor ligand in fetal kidney; we were able to identify a transcript for transforming growth factor-alpha (TGF-alpha) but not EGF on Northern blots of fetal kidney RNA. Since the abundance of TGF-alpha mRNA is low, we confirmed its presence by polymerase chain reaction amplification. Using specific radioimmunoassays, we also provide direct evidence for TGF-alpha but not EGF peptide in extracts of fetal kidney and mid-gestational amniotic fluid. We suggest that TGF-alpha/EGF receptor interactions may serve an important function in development of human fetal kidney.

Base Sequence↗
PubMed1991

Prognosis following local recurrence in the conservatively treated breast cancer patient.

At Yale-New Haven Hospital conservative treatment of early stage breast carcinoma with lumpectomy and radiation therapy has been used with increasing frequency since the 1960s. We have reviewed our experience with specific reference to prognosis following local recurrence. Between January 1962 and December 1984 a total of 433 patients were treated with conservative surgery and radiation therapy using standard techniques. As of December 1989, with minimum evaluable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 ipsilateral breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Extent of disease at the time of local recurrence was clinically categorized as localized (less than 3 cm without dermal involvement) or diffuse (greater than 3 cm and/or with dermal involvement). Seventy-two percent of the recurrences were at or near the original tumor site whereas 28% recurred elsewhere in the breast. At a median follow-up post recurrence of 5.0 years (range 0.3-16.9 years), the 5-year actuarial survival for breast recurrences was 59% and the 5-year disease-free survival was 65%. A number of clinical and pathological features at the time of original diagnosis as well as at the time of local recurrence were tested as possible prognostic indicators for survival following local recurrence. By univariate analysis, significant factors associated with survival following local recurrence included extent of local disease at the time of recurrence (p less than .01), time to local recurrence (p less than .03), with later recurrences doing better, and site of local recurrence (p less than .01), with recurrences elsewhere in the breast doing better. We conclude from this large single institutional experience with a median follow-up post-recurrence of over 5 years that patients experiencing a local recurrence in the conservatively treated breast have a relatively favorable prognosis. The prognostic factors correlating with survival and implications regarding adjuvant systemic therapy at the time of local recurrence are discussed.

Adult↗
PubMed1991

Prognostic factors for local recurrence in the conservatively treated breast cancer patient: a cautious interpretation of the data.

Between 1962 and 1984, a total of 433 patients were treated at Yale-New Haven Hospital with conservative surgery and radiation therapy (CS + RT) to the intact breast. As of January 1990, with a minimum assessable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Of all clinical factors tested, young age was the most significant prognostic factor for local recurrence (P less than .03). In addition, patients with pathologically involved lymph nodes were noted to have a lower local recurrence rate than patients with pathologically negative axillae (P less than .05). These findings were especially notable given the fact that the node-positive group had a higher percentage of T2 tumors and a higher percentage of patients in the young age group. These paradoxical findings, however, may be explained by the fact that 88% of the node-positive patients underwent adjuvant systemic therapy in the form of either systemic chemotherapy or hormonal therapy, while only 8% of node-negative patients underwent any adjuvant systemic therapy. When analyzed as a function of adjuvant therapy, those patients receiving adjuvant therapy had a lower local recurrence rate than those patients not receiving adjuvant therapy (P less than .08). We conclude that adjuvant systemic therapy impacts on the ipsilateral breast recurrence rate in patients treated with CS + RT. The implications of this study in light of the widespread use of adjuvant systemic therapy are discussed.

Actuarial Analysis↗
PubMed1991

[Controlled rubella vaccination at the Stuttgart Public Health Center].

Experience has shown that mass vaccination of pre-puberty girls against rubella (German measles), as recommended in accordance with German legislation and performed by the Public Health authorities, is unnecessary in about three-quarters of all the girls. Besides, only relatively few girls report for such vaccination. It became possible to carry out on-target vaccination by conducting first of all a serological preliminary test with capillary blood. This pin-pointed those pupils who were likely to be susceptible to rubella infection. After the vaccination, this method enabled re-checking by means of a further antibody test. All the pupils who had been successfully vaccinated or were already satisfactorily protected, were issued a certificate to that effect. In our opinion, the increased material and personnel expenditure of such on-target vaccination is justified by the fact that the rate of participation on the part of the pupils is markedly higher, so that vaccination becomes more meaningful than before.

Adolescent↗
PubMed1990

Phytoalexin synthesis in soybean: purification and characterization of NADPH:2'-hydroxydaidzein oxidoreductase from elicitor-challenged soybean cell cultures.

An NADPH:2'-hydroxydaidzein oxidoreductase (HDR) from elicitor-challenged soybean cell cultures was purified to apparent homogeneity by a five-step procedure. The purification procedure included affinity adsorption on Blue Sepharose and elution of the enzyme with NADP+. It was shown by gel filtration and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis that HDR consists of only one polypeptide, which has a Mr about 34,700. The pH optimum of the reaction was 7.0. Apparent Michaelis constants determined for 2'-hydroxydaidzein, 2'-hydroxyformononetin, and NADPH were, respectively, 50, 60, and 56 microM. A low conversion of 2'-hydroxygenistein to the corresponding isoflavanone was also observed but isoflavones lacking a 2'-hydroxyl group and various other flavonoids did not serve as substrates. Enzymatically derived 2'-hydroxydihydrodaidzein gave a positive CD spectrum at 328 nm, which shows its 3R stereochemistry. Antibodies against HDR were raised in rats.

Blotting, Western↗
PubMed1990

Regional nodal irradiation in the conservative treatment of breast cancer.

At this institution conservative treatment of breast cancer was begun in the 1960's. The following analysis represents our experience through 1984 with specific reference to the management of the regional lymph nodes. A total of 432 patients with clinical stage I and II breast cancer were treated between 1962 and 1984 with lumpectomy and radiation therapy. The breast was treated with tangential fields to a median dose of 4800 cGy and electron conedown to a total tumor bed dose of 6400 cGy. Axillary dissection was not routinely performed, particularly in the earlier years. More recently, axillary dissection has been used with increasing frequency if it was felt that the results of the dissection would influence systemic treatment. One hundred eighty-seven patients (43%) underwent axillary dissection (30% pathologically positive) and routinely received regional nodal irradiation (median dose 4600 cGy) to the internal mammary and supraclavicular lymph nodes. Two hundred forty-five patients (57%) did not undergo axillary dissection and routinely received regional nodal irradiation to the internal mammary, supraclavicular, and entire axillary regions to a total median dose of 4600 cGy. As of May 1989 with a median follow-up of 7.5 years, there have been a total of 12 nodal failures for an actuarial nodal control rate of 97% at 5 years and 96% at 10 years. The actuarial 5-year regional nodal control rate was the same for both the group of patients receiving regional RT alone without axillary dissection and the group of patients receiving axillary dissection and supraclavicular/internal mammary radiation. There has been minimal morbidity associated with this treatment policy. We conclude that regional nodal irradiation as described above, with or without axillary dissection, results in a high rate of regional nodal control and minimal treatment morbidity in patients undergoing conservative treatment of early stage breast cancer.

Axilla↗
PubMed1990

Perioperative assessment of cardiac energy metabolism by means of arterio-coronary venous difference in lactate concentration (acDL). A parameter for optimizing ventricular function of the postcardioplegic myocardium.

Fourty-three patients undergoing open heart surgery were subjected to extended hemodynamic and metabolic monitoring (arterial and coronary sinus (CS) lactate concentration). In 95% of patients investigated, a significant increase in CS lactate concentration above the arterial lactate concentration was established at the beginning of reperfusion (RPT). In these cases, a decrease in the CS lactate below the arterial concentration occurs within the RPT creating a cross-over point (COP) from negative to positive lactate extraction values. Whereas the initial rise in CS lactate is an expression of the expected ischemia-induced acceleration of anaerobic glycolysis, the onset of a positive lactate extraction can be related to reconsolidation of mitrochondrial oxidative phosphorylation. We found two groups with an early and late COP at 7.2 +/- 0.8 min (ECOP) and 42.5 +/- 5.2 min (LCOP) (P less than 0.005). Whereas a short cross-over time was associated with a normal postoperative outcome, cardiac recovery was delayed in the LCOP group. With the aid of metabolic monitoring it is possible to identify the COP and cardiac overload situations and so to optimize the perioperative outcome, especially in selected patients (NYHA stage III/IV, re-operation, high-risk operation).

Adenosine Triphosphate↗
PubMed1990

[Arterio-coronary venous difference in lactate concentration--a new objective and topical available parameter for the estimation of the energy metabolism status of the heart].

Cardiosurgical operations were tested experimentally by means of a perioperative metabolic-energetic monitoring and by the conventional method of the hemodynamic monitoring (Swan-Ganz-catheter). By that could be shown that a perioperative monitoring by means of the arterio-coronary venous difference of the lactate level is possible. Intraoperative information about the topical metabolic-energetic condition of the myocardium is to receive as the decisive advantage of this method. An improvement of the therapy results is possible in that way by an optimum of the treatment. A metabolic recovery of the heart during the operation was substantial more favourable for the postoperative myocardial restitution than an early application of catecholamins. This method for perioperative observation should be used specially in risk operations (NYHA-stadium III-IV, reoperations, etc.).

Biomarkers↗