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Biomedical subjects

G Kiefer

Publications and source records attributed to G Kiefer.

At least 19 recordsLinked to original sources

DNA cytophotometric analysis of breast cancer. Follow-up for 10 years.

Forty-four cases of newly diagnosed invasive ductal breast cancer were studied by static cytometry at the time of diagnosis and were followed for 10 years to determine if the survival rate correlated with the nuclear DNA measurements. In 22 cases the stem line was in the 2c range, in 15 cases in the 3c range and in 7 cases in the 4c range. Thirty-four percent (n = 15) of the patients died of metastases during the first five years, 11% (n = 5) died of metastases between 5 and 10 years, and 55% (n = 24) survived for > 10 years without metastases. No correlation between increased tumor cell proliferation and recurrence of tumors could be found. In this study all patients with diploid tumors, tumor size T1 and negative lymph node status survived for > 10 years. In the presence of node metastasis (T1N1M0) all patients (n = 4) having tumors with the stem line in the 2c range survived for 5 years but only 2/4 for > 10 years. The percentage of patients surviving for 10 years showed no significant differences between the groups: in the 2c range, 59% (13/22); in the 3c range, 53% (8/15); and in the 4c range, 43% (3/7). The small number of cases does not allow definitive statistical conclusions, although the logistic regression analyses showed that stem line, pT and pN were the important prognostic factors for five-year survival. However, only pT and especially pN were of prognostic value for 10-year survival.

Breast Neoplasms

Effects of a three-drug antineoplastic protocol of wound healing in rats: a biomechanical and histologic study on gastrointestinal anastomoses and laparotomy wounds.

Using biomechanical and histologic approaches, the effect of perioperative administration of a drug protocol containing 5-fluoruracil, Adriamycin, and mitomycin C (FAM) on the healing of gastrointestinal anastomoses and laparotomy wounds in rats was examined. Application of FAM immediately before operation resulted in significant impairment of wound healing in the early postoperative period. Once the proliferation of fibroblasts and collagen synthesis had led to an increase of mechanical strength, no negative effect on wound healing could be detected applying the same chemotherapeutic agents. These findings indicate the early inflammatory phase of the wound healing process to be most vulnerable to the chemotherapeutic effects. This has significant implications if the theoretical advantages of starting adjuvant chemotherapeutic treatment in the immediate postoperative period are implemented.

Anastomosis, Surgical

Triploidy syndrome in a liveborn female.

We present the autopsy report of a liveborn triploid female, born after 36 weeks of gestation, who died at the age of 20 hours. External features were diagnostic: fetal hypoplasia, hypertelorism, microstomia, micro-and retrognathia, preauricular skin tag, low-set ears, and 3-4 syndactylia. All internal organs were hypoplastic. There were atrial and ventricular septal defects. Adrenals and kidneys were fused, the gallbladder was absent, and ovarian hilum cell were found to be hyperplastic. Triploidy, 69xxx, was confirmed cytogenetically. The placenta was hypoplastic and, microscopically, revealed a peculiar type of immaturity, so-called hydatidiform villous hypoplasia, findings which have not been previously reported. We suggest that the generalized fetal and placental hypoplasia and the severe hypoplasia of all internal organs are caused by a proliferative deficiency of the triploid cells. In addition, the nuclear DNA content was determined by cytophotometrically from placental stromal cells and was found to be about 50% above the normal diploid DNA value; i.e., a triploid DNA value was confirmed.

Abnormalities, Multiple

Failed anterior acromioplasty. A review of 51 cases.

This report is a retrospective review of 51 patients, each of whom had a failed acromioplasty that was performed after presumptive diagnoses of impingement tendinitis. The purpose of the review is to analyze the failures, define their causes, and make recommendations regarding further management. Average age at time of initial surgery was 40 years (range, 20-64 years), and the follow-up period averaged 5.5 years (range, three to nine years). Thirty-four patients were found to have symptoms and signs that corresponded to a recognized clinical diagnosis and were thought to be sufficient to be a major cause of their pain. Twenty-three had a diagnosis other than continuing impingement. Success of a second surgical procedure was significantly greater in nonworker's compensation (WC) patients than in WC patients. Repeat acromioplasties in WC patients have poor results and are not recommended. Seventeen patients had no clear cause for their continuing shoulder tendinitis; however, time and supportive therapy allowed five patients to improve over an average 18-month period. In all categories, WC patients fared poorly, so prognosis must be guarded in this group. Non-WC patients may be helped with repeat surgery following an appropriate diagnosis for the cause of failure.

Acromioclavicular Joint

Macrophage size determinations in the diagnosis of tuberculous effusions.

This study investigated the usefulness of macrophage size determinations in lymphocyte-rich pleural effusions to improve the cytologic diagnosis of tuberculous pleurisy. The size of pleural macrophages was analyzed by quantitative morphometric planimetry in 18 effusions due to tuberculosis, 21 effusions following radiotherapy for malignant disease and 10 effusions due to congestive heart failure. Macrophages were identified and clearly separated from mesothelial cells by latex phagocytosis and immunostaining with the monoclonal antibody My4 (CD14). The mean macrophage area (+/- standard deviation) in tuberculous effusions (92 +/- 14 sq micron) was significantly smaller than in postradiation (141 +/- 28 sq micron) and heart-failure effusions (154 +/- 22 sq micron) (P less than .0001). There was also a smaller ratio of mesothelial cells in tuberculous effusions (0.5 +/- 0.9%) in comparison with effusions following radiotherapy (4 +/- 5%) or congestive heart failure (10 +/- 12%). In summary, this study demonstrated some cytomorphologic parameters that may be helpful in the differential diagnosis of tuberculous effusions.

Adolescent

Antitumor cell and antimetabolic effects of 5-ethyl-2'-deoxyuridine and 5'-substituted 5-ethyl-2'-deoxyuridine derivatives.

A series of forty 5'-ester derivatives of 5-ethyl-2'-deoxyuridine (EDU) have been evaluated for their inhibitory effects on the growth and metabolism of murine leukemia L1210 cells. Several EDU esters proved as potent as EDU in their inhibitory effects on L1210 cell growth (inhibitory dose-50:5-10 micrograms/ml), suggesting that these esters were readily hydrolyzed to release the parent compound EDU. That the EDU esters had to be hydrolyzed first to EDU was further suggested by the dependence of their antiproliferative action on the thymidine kinase activity of the cells. It was further ascertained that EDU and its esters acquired their antiproliferative effects by an interaction with dCTP biosynthesis, possibly at the CDP ribonucleotide reductase step. Under conditions where thymidine was readily incorporated, we were unable to demonstrate any incorporation of EDU into L1210 cell DNA.

Animals

2-14C-1-Allyl-3,5-diethyl-6-chlorouracil I: Synthesis, absorption in human skin, excretion, distribution, and metabolism in rats and rabbits.

With 14C-potassium cyanate as the starting material, 2-14C-1-allyl-3,5-diethyl-6-chlorouracil was synthesized for in vitro and in vivo absorption studies in human skin and for metabolic studies in rats and rabbits. The radioactivity in the horny layer, epidermis, and dermis of the human skin was determined after different intervals of time, and the radioactivity excreted in the urine was measured by collecting samples for 5 days from a patient and also under occlusion conditions. Almost 90% of the radioactivity remained on the surface and approximately 6.28% penetrated and was systemically absorbed. Over a 5-day period, a total of 3.25% was excreted. Almost 3% was systemically absorbed and cumulated in the system. After intraperitoneal application in male and female rats, most of the radioactivity was excreted in the feces and urine, with female rats excreting more in the urine than male rats. The radioactivity rose in the organs in the first 3 hr and then decreased. At the end of 144 hr, no appreciable radioactivity could be found in the organs and tissues, except in the carcass where the cumulation was maximum (1%). After intravenous injection in rabbits, most of the radioactivity (80%) was excreted in the urine and only 4% in the feces. At the end of 96 hr, approximately 3% was cumulated in the body. The drug was quantitatively metabolized in both rats and rabbits: Metabolite 1 (70-85%), Metabolite 2 (10-15%), Metabolite 3 (5-10%), and Metabolite 4 (0.3%).

Administration, Topical

2-14C-1-Allyl-3,5-diethyl-6-chlorouracil II: Isolation and structures of the major sulfur-free and three minor sulfur-containing metabolites and mechanism of biotransformation.

The metabolites of 1-allyl-3,5-diethyl-6-chlorouracil in rabbit urine were isolated by preparative thick-layer, liquid-column, and gas chromatography. With the aid of mass and 1H-NMR spectra, and by comparison with an authentic sample, the major metabolite, 1, was identified as 6,8-diethyl-2-hydroxymethyl-tetrahydrooxazolo-[3,2-c]-pyrimidine-5,7(4H,6H)-dione, Metabolite 2 as 1-allyl-3-ethyl-5-(1-hydroxyethyl)-6-methylthiouracil, Metabolite 3 as 1-allyl-3,5-diethyl-6-methylthiouracil, and Metabolite 4 as 6,8-diethyl-2-hydroxymethyl-tetrahydrothiazolo-[3,2-c]pyrimidine-5,7(4H,6H)-dione. The mechanism of the formation of sulfur-containing metabolites is discussed, and a new metabolic pathway for the formation of methylthio compounds is proposed.

Animals

A simple method for the use of gallocyanin-chrome alum as an electron strain.

A method has been elaborated for the demonstration of DNA in the electron microscope. The method uses glutaraldehyde fixed tissue pieces from which RNA has been removed by incubation with RNase. DNA is stained by gallocyanin-chrome alum in the tissue block. Embedding and cutting is done in the usual manner. The method is based on histochemical observations at the light microscope level which show sufficient specificity and a good stoichiometry of the staining reaction.

Animals

2-14C-1-(2'-deoxy-beta-D-ribofuranosyl)-5-ethyluracil: synthesis and biotransformation in rats.

With 14C-urea as the starting material, 2-14C-1-(2'-deoxy-beta-D-ribofuranosyl)-5-ethyluracil [2-14C-beta-5-ethyl-2'-deoxyuridine] was synthesized for metabolic studies. After intravenous administration in rats, the radioactivity disappeared in the blood within 72 hr, being eliminated primarily in the urine (97%). The major elimination took place in the first 24 hr (92%). Little radioactivity was detected in the organs and tissues after 3 days. Approximately 50% of the urine radioactivity probably was due to an unidentified conjugate, 30% was due to Metabolite II, and 20% was unchanged drug. Metabolite II was identified as 5-ethyluracil by mass and 1H-NMR spectra and by comparison with an authentic sample.

Animals