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Biomedical subjects

M Cohn

Publications and source records attributed to M Cohn.

At least 37 records · Page 2Linked to original sources

Pretreatment of the primigravid uterine cervix with mifepristone 30 h prior to termination of pregnancy: a double blind study.

OBJECTIVE: To determine the effect of the antiprogestogen mifepristone (RU 486) on cervical resistance before first trimester termination of pregnancy. DESIGN: Prospective double blind randomized placebo controlled study. SETTING: Department of gynaecology in a university teaching hospital, Sheffield. SUBJECTS: 80 Primigravid women greater than 18 years of age, undergoing termination of pregnancy at between 7 and 13 weeks gestation. INTERVENTIONS: A single dose of 600 mg of mifepristone or placebo given orally 30 h before termination of pregnancy under general anaesthesia. MAIN OUTCOME MEASURES: Cervical resistance to dilatation. RESULTS: Pretreatment with mifepristone significantly reduced the amount of force required to dilate the cervix to 10 mm. In comparison with placebo, the mean sum of the peak forces obtained with dilators 4 to 10 mm was reduced from 84.3 N (SD 29.7) to 46.0 N (SD 26.7). Two women in the treated group had a cervical resistance of greater than 100 N compared with nine women in the placebo group (RR 0.18, 95% CI 0.04-0.89). The 8 mm dilator could be passed with less than 5 N force in 16 women (43%) in the treated group compared with none in the placebo group. Women in the active treatment group had more preoperative pelvic pain and vaginal bleeding but less postoperative pain. CONCLUSION: Mifepristone significantly reduces cervical resistance in the first trimester of pregnancy and produces minimal side effects.

Abortion, Therapeutic

Effect of diuretics on captopril-induced urinary zinc excretion.

The urinary zinc/creatinine ratio has been measured in five groups of patients with essential hypertension and in a group of healthy controls. The first four groups of patients consisted of subjects being treated for at least three months with captopril alone, hydrochlorothiazide alone, captopril plus hydrochlorothiazide, or captopril and furosemide. The fifth group comprised hypertensive patients not on any medication. The first four patient groups exhibited significantly increased urinary zinc/creatinine ratios when compared to the control and untreated hypertensive groups, but in the two combination regimens there was little zincuria. It is suggested that both diuretics inactivate the zincuric effect of captopril by binding to its sulphydryl group within the tubular lumen.

Adult

Interleukin-2 receptor is similarly expressed by activated lymphocytes from patients on chronic hemodialysis and healthy subjects.

We studied peripheral blood mononuclear cells (PBMC) from 10 patients on chronic hemodialysis vs 10 healthy controls. T cells were counted by E rosette formation. Interleukin (IL)-2 receptor (IL-2R) carrier cells were identified by Dako-IL-2R, which was chosen as a monoclonal antibody that binds to the alpha chain of IL-2R without interrupting the cell machinery of mitogen-induced IL production. Fluorescein-tagged goat anti-rabbit IgG1* was used for subsequent cell staining, and cells were counted by FACS. Net numbers of PHA-activated IL-2R carrier cells were derived by subtracting appropriate background controls. The average number of these cells relative to numbers of total T cell population in uremic PBMC was statistically not different from healthy controls. Several defects in cellular activation associated with IL-2 mechanisms could be envisaged to account for the impaired proliferative response to PHA, manifested by uremic T cells.

Adult

Enhancement and compression of digital chest radiographs.

The application of digital technologies to chest radiography holds the promise of routine application of image processing techniques to effect image enhancement. Because of their inherent spatial resolution, however, digital chest images impose severe constraints on data storage devices. Compression of these images will relax such constraints and facilitate image transmission on a digital network. We evaluated an algorithm for enhancing digital chest images that has allowed significant data compression while improving the diagnostic quality of the image. This algorithm is based on the photographic technique of unsharp masking. Image quality was measured with respect to the task of tumor detection and compression ratios as high as 2:1 were achieved. This compression can be supplemented by irreversible methods.

Algorithms

Thyroid function in choriocarcinoma: demonstration of a thyroid stimulating activity in serum using FRTL-5 and human thyroid cells.

Hyperthyroidism is a well recognized complication of gestational trophoblastic tumours (GTT) and may be due to high circulating concentrations of human chorionic gonadotrophin (hCG) or its variants. We have studied 24 clinically euthyroid women with GTT. Eight were biochemically hyperthyroid with low or undetectable serum thyrotrophin (TSH) and had a mean serum hCG of 361.2 x 10(3) IU/l compared to 76.2 x 10(3) IU/l in the other patients (P less than 0.01). Purified hCG stimulated iodide uptake into FRTL-5 cells with 25 x 10(3) IU/l being equivalent in potency to 1 mU/l of thyrotrophin (TSH). Sixteen out of the 24 sera (67%) stimulated iodide uptake when applied to the cells at a 1:10 dilution. Sera from all eight hyperthyroid patients contained thyroid stimulating activity. The mean hCG concentration in the 16 stimulatory sera was 238.2 x 10(3) IU/l compared to 37.1 x 10(3) IU/l in the other eight sera (P less than 0.01). Six men with hCG-secreting testicular tumours were biochemically euthyroid although three of their sera stimulated iodide uptake into FRTL-5 cells. In human thyroid cells the mean cAMP production over 4 h with sera from five healthy controls was 54.2 +/- 1.81 pmol/mg cell protein compared to 67.0 +/- 3.8 pmol/mg protein with sera from five choriocarcinoma patients (P less than 0.02). Serum from patients with gestational trophoblastic tumours contains a thyroid stimulating activity which may be hCG and whose presence correlates with hyperthyroidism.

Adolescent

Thyroid-stimulatory effects of human chorionic gonadotrophin in early pregnancy. In vivo and in vitro studies.

Human chorionic gonadotrophin (hCG) shares structural similarity with pituitary thyrotrophin (TSH) and may act as a thyroid stimulator. We have studied serum hCG levels, thyroid function tests and the ability of serum to stimulate cultured thyroid cells in 40 subjects between 6 and 12 weeks of pregnancy. Serum free tri-iodothyronine was increased and serum TSH reduced in pregnancy samples (both p less than 0.05). hCG was detectable in all pregnancy sera with a mean level of 105.6 X 10(3) U/l. Serum from 24 of the 40 (60%) patients stimulated iodide uptake into cultured FRTL-5 thyroid cells. The potency of sera in stimulating cells correlated with the hCG level (r = 0.710, p less than 0.01). The stimulatory activity in some, but not all, sera could be specifically neutralized with antiserum to hCG. Partially purified hCG stimulated iodide uptake and growth of thyroid cells at concentrations of 50 X 10(3) U/l and above. In these experiments, 25 X 10(3) U/l of hCG produced equivalent stimulation to 1 mU/l of TSH. In 8 patients tested before and after termination of pregnancy, the thyroid-cell-stimulatory activity of serum declined rapidly in parallel with serum hCG. hCG may stimulate the thyroid gland at concentrations which prevail in normal pregnancy. Its potential as a physiological regulator of the thyroid gland is not widely appreciated and requires further study.

Adolescent

Induction of suppressor cell activity by cyclosporin A and/or uremic serum in normal versus uremic peripheral blood mononuclear cells.

We investigated induction of suppressor cell activity in peripheral blood mononuclear cells (PBMC) from normal or uremic subjects. The cells were primed with cyclosporin A (CS-A), uremic serum, or both and subsequently cocultured with fresh phytohemagglutinin-stimulated normal allogeneic responders. CS-A-primed normal as well as uremic PBMC significantly suppressed responder cell thymidine incorporation. Uremic serum primed normal, but not the uremic, PBMC exerted a significant suppression on responder cell proliferation. No significant additive suppressive effect was detected following coculture of responders with PBMC primed by CS-A and uremic serum together. Exclusion of a distinct suppressor cell subset by panning, using anti-Leu-2b monoclonal antibody, did not result in blunting suppressive activity of the CS-A or uremic serum pretreated cells. On the other hand, adherent cell depletion of primed PBMC completely abolished their subsequent suppressive effect on responder cell proliferation.

Adult

Induction of suppressor cell activity in normal peripheral blood mononuclear cells by sera from predialytic uremic patients.

Normal peripheral blood mononuclear cells (PBMC) were primed with sera from 22 predialytic uremic patients, normal sera, concanavalin A, or both. Their suppressive activity was subsequently tested on fresh phytohemagglutinin-stimulated allogeneic responders (i.e., genetically unrelated to either primed cell or sera donors). Uremic serum induced suppressor cell activity in the normal PBMC. No correlation was found between serum urea/creatinine levels and their effects on suppressor cell activity. The induced activity, expressed as percent suppression, was similar to that induced by concanavalin A. In PBMC primed with both concanavalin A and uremic serum, an additive suppressive effect was evident. The suppressor subset(s) induced by uremic serum proved to belong to adherent cell population. Addition of indomethacin or catalase to responder systems did not abolish the suppressive effects, thus suggesting a mechanism of action other than prostaglandin or hydrogen peroxide release.

Adult

Dual challenge for glomerular damage in mice: uninephrectomy and repetitive pregnancies.

We examined the effects of unilateral nephrectomy (UNx) and repetitive pregnancies (RP) on glomerular damage and blood pressure in mice. Four groups of 10 female mice, 7 weeks old, underwent sham nephrectomy (SV) alone, sham nephrectomy and six pregnancies (SP), right nephrectomy alone (NV) and right nephrectomy followed by six repetitive pregnancies (NP). UNx resulted in a significant elevation of serum creatinine up to 11 weeks. In all animals pregnancy was associated with a temporary decrease in serum creatinine except at termination of the 6th pregnancy in group NP. UNx and RP did not result in an increase in protein excretion. UNx in both virgin and pregnant mice resulted in blood pressure elevation without any renal histological abnormalities by the end of the 6th pregnancy. We conclude that at least up to the end of the 3rd pregnancy, gestation was associated with augmentation in function of a single kidney. This effect was lost by the end of the 6th pregnancy. Multiple repetitive pregnancies in uninephrectomized animals entailed renal functional deterioration and a rise in blood pressure without renal histological abnormalities on light microscopy.

Animals

Direct determination of creatine kinase equilibrium constants with creatine or cyclocreatine substrate.

The equilibrium constants of two reactions catalyzed by rabbit muscle creatine kinase with creatine or cyclocreatine as substrate were determined by 31P-NMR. The value of the equilibrium constant with creatine as substrate was 172.10(7) M(-1) in agreement with previous work (Veech, R.L., Lawson, J.W.R., Cornell, W. and Krebs, H.A. (1979) J. Biol. Chem 254, 6538-6547). The value with cyclocreatine was 5.62.10(7) M(-1) and the ratio of the two constants is 30.6. It was possible to determine the ratio of the two equilibrium constants in a reaction mixture containing both substrates since it was found that the 31P resonances of P-creatine and P-cyclocreatine were well resolved. The ratio of K1/K2 determined in such experiments was 34.6, of the same order as previously reported by Annesley and Walker (Annesley, T.M. and Walker, J.B. (1977) Biochem. Biophys. Res. Commun. 74, 185-190).

Adenosine Diphosphate

Uninephrectomy and repetitive pregnancies in mice: a combined stimulus for renal hypertrophy.

Three hundred 7-week-old Beit Dagan female mice underwent right nephrectomy or sham operation, and either remained virgin or were exposed to six repetitive pregnancies. Fractional kidney weight, dry weight and protein content were determined at ages 9, 10, 11, 17 and 26 weeks corresponding to the ends of the first, second and third trimester of the first pregnancy and completion of the third and sixth pregnancies respectively. In addition histological sections were evaluated morphologically and morphometrically. Renal dry weight and protein content per kidney increased abruptly to maximal values a week after nephrectomy and remained stable thereafter. Repetitive pregnancies were associated with progressive increments in both parameters. The effects of unilateral nephrectomy and repetitive pregnancy were additive. Following unilateral nephrectomy or pregnancy the number of glomeruli per field, as well as fractional glomerular area, increased more rapidly than in sham-operated virgin controls. However, the maximal glomerular number or fractional area attained did not differ from control values. We conclude that (a) in 8-week-old mice pregnancy is associated with renal cell hypertrophy; (b) repetitive pregnancies in these animals produce progressive augmentation in both renal dry weight and protein content; (c) the effects of repetitive pregnancy and unilateral nephrectomy on renal cell hypertrophy are additive; (d) this would indicate that neither manoeuvre exhausts maximal renal capacity for cell hypertrophy, and would suggest some possibilities for the underlying mechanisms.

Animals

A multicentre randomized trial comparing delivery with a silicone rubber cup and rigid metal vacuum extractor cups.

A total of 258 women requiring assisted delivery where vacuum extraction was thought to be suitable were randomly allocated to delivery with a new silicone rubber cup or metal vacuum extractor cups. There was a tendency for the silicone rubber cup to effect delivery more quickly and to cause less scalp trauma, but to fail to effect delivery on more occasions than metal cups. However, none of these differences was statistically significant. There were no statistically significant differences in the rates of birth canal trauma, maternal blood loss, or neonatal jaundice. The silicone rubber cup produced a cosmetically more acceptable chignon than the metal cups. The introduction of vacuum extractors with silicone rubber cups into obstetric units should be encouraged.

Double-Blind Method