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N Fine

Publications and source records attributed to N Fine.

33 records · Page 2Linked to original sources
PubMed1989

Reproducibility studies and effects of bowel preparations on measurements of rectal epithelial proliferation.

Measurements of rectal epithelial proliferation (REP), using tritiated labelled thymidine, correlate with colonic epithelial proliferation, risk for cancer and response to therapies. There have been criticisms regarding its reproducibility and the possible deleterious effects of bowel preparations on this biomarker. We studied paired observations on 7 patients repeated without bowel preparation, 11 repeated after tap-water enema, and 8 repeated after PEG-electrolyte solution or extract of senna purgative and found no significant differences between paired observations. In addition, in a high-risk group for colorectal cancer, 31 persons received PEG or senna preparation and their REP was not significantly different from that of 23 examined without these preparations. Thus, REP is a reproducible biomarker and not affected by several commonly used bowel preparations.

Biopsy↗
PubMed1989

Oral calcium suppresses increased rectal epithelial proliferation of persons at risk of colorectal cancer.

Dietary calcium may inhibit colonic carcinogenesis promoted by high fat, phosphate, and low fibre diets. In persons at risk for colon cancer oral calcium supplements significantly suppress increased rectal epithelial proliferation. This was studied in a cohort of 35 volunteers: 26 first degree relatives of colorectal cancer patients and nine who had had colonic adenomas (mean age 51.6 years, 17 (49%) men, all negative for large bowel neoplasia). 1.25-1.5 g elemental calcium was given in divided daily doses for three months. Rectal pinch biopsies were taken without bowel preparation, before and mean 8.4 weeks during and 7.2 weeks after treatment and incubated with tritiated thymidine. The mean number of labelled cells, as a ratio of the total number of crypt cells (labelling index-LI), and their crypt position, were determined. The mean number of labelled cells decreased during treatment by 29%, especially in the basal three-fifths of crypts. There was also a significant 10% increase in mean number of crypt cells during treatment. [Mean LI decreased by 36% (p less than 0.001) during calcium treatment and almost returned to basal values after cessation.] If a raised LI is a marker of potential malignancy and a randomised clinical trial confirms that calcium suppresses it, dietary intervention studies in high risk persons are indicated.

Administration, Oral↗
PubMed1989

Calvaria derived osteogenic cells: phenotypic expression in culture.

The osteoblast phenotype is characterized by its ability to (a) synthesize a well defined mineralized collagenous matrix, (b) regulate the remodeling process by synthesizing local hormones (PGE2) and specific molecules (osteocalcin) and enzymes (alkaline phosphatase and collagenase), (c) respond to a variety of hormones (PTH, PGs, vitamin-D metabolites, steroids and growth factors), (d) respond to mechanical stimulation. Most of osteoblast culture systems meet many of the above qualifications though most fail to show the PTH effect on DNA synthesis, (c), and mechanical stimulation (d). Here we show that by using trypsin digestion and serum-containing low calcium medium (0.25 mM), all the above listed osteoblast phenotypic characteristics are demonstrated including their responsiveness to mechanical stimulation and the PTH effect on DNA synthesis.

Adaptation, Physiological↗
PubMed1988

Rat epiphyseal cells in culture: responsiveness to bone-seeking hormones.

Cell cultures derived from young rat epiphyseal cartilage were grown for approximately 2 wk in BGJb medium supplemented with 10% fetal bovine serum to reach confluence. These cells were identified as chondrocytes as checked by morphology, the presence of alkaline phosphatase, and a positive type II collagen antibody reaction. The cells also responded to different hormonal treatment. Parathyroid hormone (PTH) increased cyclic AMP production by 50% within 15 min of treatment, whereas prostaglandin E2 (PGE2) caused an increase of 160%. Calcitonin (CT) did not affect cAMP production in these cells. DNA synthesis 24 h after hormonal treatment was increased by PTH (2.5-fold) and PGE2 (2-fold), but not by CT. Among the vitamin D metabolites, 24,25(OH)2D3 increased significantly the [3H]thymidine incorporation into DNA, whereas 1,25(OH)2D3 effect was minimal. These results provide evidence for the use of these cell cultures as a model for cartilage in vitro when studying biological and hormonal responsiveness.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Autoradiographic localization of 24R,25-dihydroxyvitamin D3 in epiphyseal cartilage.

There is emerging evidence for specific binding sites and biologic action for 24,25(OH)2D3 in the epiphyseal cartilage. The present study was undertaken to identify the target cells of 24,25(OH)2D3 in the epiphyses of rat bone using an autoradiographic technique. Pieces of epiphyseal cartilage obtained from 4-day-old vitamin D-deficient rats were incubated for 15 or 60 min with [3H]-24,25(OH)2D3 in the presence or absence of 100-fold excess of 25(OH)D3, 1,25(OH)2D3, or 24R,25(OH)2D3. The pieces were prepared for autoradiographic study by a new modified fixation method. Cytoplasmic and nuclear concentration of radioactivity was observed in all cell layers of the epiphyseal cartilage except for the hypertrophic cartilage zone. The highest concentration of radioactivity was seen in the proliferating chondroblasts of the columnar zone. After 15 min of incubation the radioactivity was seen mainly in the cell membrane and cytoplasm, whereas at 60 min radioactivity was also prominent in the nuclei. The competition with excess of cold metabolites revealed that only 24R,25(OH)2D3 caused a significant decrease in cytoplasmic and nuclear radioactivity. These data support the biochemical studies showing that the epiphyseal cartilage is a target tissue for 24,25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1984

Mechanical and hormonal stimulation of cell cultures derived from young rat mandible condyle.

Collagenase digestion of young rat condyles released cells which were grown in culture during two weeks. Morphologically, two populations of cells were distinguished, one of which reacted to alkaline phosphatase and resembled chondroblast or osteoblast-like cells. Parathyroid hormone stimulated a 2-fold increase in cellular cyclic AMP, whereas calcitonin had no effect. Physical forces activated cellular cyclic AMP to a 2.5-fold of control levels and increased the incorporation of radioactive thymidine into DNA by 50 per cent. In contrast to cultured bone cells, the response to physical forces was not inhibited by indomethacin in cultured condyle cells. It seems, therefore, that condyle cells are specific in their response to bone-seeking hormones and physical forces.

Animals↗
PubMed1984

The influence of bis-dequalinium acetate on bone regeneration induced by grafts of combined inorganic heterologous bone and autologous marrow.

The present study was undertaken in order to determine the influence of BDA on bone regeneration and remodeling. Pieces of Kiel bone soaked with autologous bone marrow were implanted in the axial area of rats. The implantation sites were injected with 0.3 cc of 0.005% BDA 3 to 14 days after grafting; the control group was injected with Hartmann solution. Results indicated that BDA does not interfere with the bone-remodeling process. It does, however, have an inhibitory effect on the early stage of mesenchymal cell proliferation, that is, the development of osteoblasts from bone marrow stromal cells. Extrapolation of these findings to earlier evidence regarding the mode of action of this material is currently being investigated.

Animals↗
PubMed1983

Protracted ambulatory venous infusion of 5-fluorouracil.

5-Fluorouracil (5-Fu) was administered by a constant venous infusion schedule at a dose of 300 mg/m2/d for 30-180 days. The dose schedule was associated with minimal toxicity in 32 patients with gastrointestinal cancer treated by employing a portable infusion pump for ambulatory drug delivery. Cumulative dose of 5-Fu was extended to three to four times that achieved by intermittent bolus therapy or short-term 5-day infusion therapy. Objective tumor regression was observed in six of 22 patients with measurable disease; 10 patients had stable disease, five of whom had a decrease in CEA levels. The responses according to tumor type were as follows: 1/1 gastric cancer; 1/2 hepatoma; and 4/18 colon cancer. The superiority of this new treatment schedule for 5-Fu will need to be established by prospective randomized clinical trials.

Adult↗
PubMed1982

The delivery of cancer chemotherapy by constant venous infusion. Ambulatory management of venous access and portable pump.

Fifty chemotherapy trials with 5-fluorouracil; mitomycin C; vinblastine; Adriamycin; and cis-platinol were initiated employing constant (24-hour) intravenous infusion for protracted periods (14-94 days). The use of the tunneled subclavian line for greater than 2200 patient days was associated with minimal complications and no instances of thrombosis or infection were observed. The use of an ambulatory infusion pump was associated with a pump efficiency of greater than 85% in 38 of 39 evaluable trials. Only four of 50 trials were associated with excess drug infusion and in no instance was a drug complication encountered. Constant infusion cancer chemotherapy is feasible, reliable, and safe. Objective tumor regression is observed but the superiority of this drug schedule over the standard intermittent bolus schedule is yet to be determined. Nonetheless, drug toxicity patterns are altered substantially and, in particular, gastrointestinal side effects of chemotherapeutic drugs may be eliminated without compromising cumulative dose.

Ambulatory Care↗
PubMed1982

Metabolism of cholecalciferol in vitamin D intoxicated chicks.

Vitamin D intoxication was induced in chicks by treatment with large amounts of radioactive cholecalciferol (vitamin D3) either by s.c. injections or by stomach tube. Hypercalcemia and nephrocalcinosis were present, confirming toxicity. The distribution of cholecalciferol and its metabolites in the tissues of the intoxicated birds was compared with that in birds that were treated with physiological amounts of radioactive cholecalciferol. Treatment with pharmacological doses resulted in marked elevation of cholecalciferol and its metabolites in all tissues examined, including elevation of 1 alpha,25-dihydroxycholecalciferol in the intestine. The predominant form of cholecalciferol in these birds was found to be the unchanged vitamin, whereas in birds treated with physiological doses 25-hydroxycholecalciferol was the predominant metabolite. The route of vitamin administration was found to be of importance only when pharmacological doses were given: generally, higher levels were noted when administered via s.c. injections than via stomach tube, except in the arteries. It is suggested that in vitamin D intoxication, the factor responsible for the pathological changes in soft tissues is cholecalciferol itself. High levels of 1 alpha,25-dihydroxycholecalciferol may be responsible for the hypercalcemia.

Animals↗
PubMed1982

Mitomycin C: phase I study of a constant infusion ambulatory treatment schedule.

Thirty patients received mitomycin C by constant infusion for 5 consecutive days (16 patients ) or for extended period by an ambulatory infusion pump (Cor-Med model) for 9 to 30 days (14 patients). The short-term 5-day infusions were delivered at dose rates of 2, 3, 4, 5 and 6 mg/m2/d with a cumulative dose of 15-50 mg. The protracted infusions were delivered at dose rates of 0.75-3 mg/m2/d with a cumulative dose of 21.6-65.2 mg. Marrow suppression was dose-limiting and occurred in 5/6 evaluable patients receiving more than 30 mg in the short-term infusion schedule and 8/10 evaluable patients receiving more than 20 mg in the protracted infusion schedule. The characteristics of the marrow suppression are that: a) thrombocytopenia precedes or is observed without concomitant leukopenia and b) the nadir day is delayed (WBC day 42, platelet day 36). Mitomycin C delivered by constant infusion leads to dose-limiting marrow toxicity at 20 to 30 mg cumulative dose depending upon the dose rate and duration of treatment. For short-term 5-day therapy, 3 mg/m2/d and for protracted therapy (up to 30 d) 0.75 mg/m2/d are the recommended dose rates for the constant infusion schedule.

Adult↗
PubMed1981

Phase I study of protracted venous infusion of 5-fluorouracil.

A Phase I study of protracted continuous infusion 5-fluorouracil was undertaken at a starting dose of 200 mg/m2/day. The drug was delivered via a tunneled subclavian venous access site by a portable infusion pump (Cor-Med) permitting ambulatory monitoring. Seventeen patients were administered 19 courses at incremental dose rates from 200 mg/m2/day to 600 mg/m2/day; treatment was terminated at the onset of stomatitis. At dose rates of 300 mg/m2/day or less, the treatment did not require interruption for up to 60 days or up to 36 g cumulative dose. For dose rates of 350 to 600 mg/m2/day, the treatment always required interruption: mean duration 20 day for 350 mg/m2/day; 9 day for 400 mg/m2/day; and 14 day for 600 mg/m2/day. Mean cumulative dose at the higher dose rates was 10.9 g (350 mg/m2/day); 7.9 g (400 mg/m2/day); and 15.3 g (600 mg/m2/day). Mean cumulative dose at 200 mg/m2/day was 11.5 g and at 300 mg/m2/day, was 22.6 g. Protracted venous infusion allows for a substantial cumulative dose of 5-FU and at dose rate delivery of 300 mg/m2/day may be administered for up to 60 days without adverse effects due to the drug or to the presence of an indwelling venous access line.

Adult↗
PubMed1980

A method for processing paraffin sections of multilayer cultured tissue.

A simple and rapid method is described for processing histological preparations from multilayer cultures growing in plastic Petri dishes, A covering collodion film is utilized to remove the tissue from the plastic dish and transfer it onto a paper block prior to embedding in Paraplast. To avoid any disruption by the collodion of the plasticware, the cultured tissue is first immersed in a solution of collodion and absolute alcohol (1:1) and then covered with pure collodion. All steps are carried out in the cold. This procedure allows morphological, histochemical, immunofluorescent, and autoradiographic studies to be carried out on serial sections of cultured tissue.

Animals↗