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Biomedical subjects

T M King

Publications and source records attributed to T M King.

At least 19 recordsLinked to original sources

Cystic fibrosis patients bearing both the common missense mutation Gly----Asp at codon 551 and the delta F508 mutation are clinically indistinguishable from delta F508 homozygotes, except for decreased risk of meconium ileus.

The glycine-to-aspartic acid missense mutation at codon 551 (G551D), which is within the first nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator (CFTR), is the third most common cystic fibrosis (CF) mutation, with a worldwide frequency of 3.1% among CF chromosomes. Regions with a high frequency correspond to areas with large populations of Celtic descent. To determine whether G551D confers a different phenotype than does delta F508, the most common CF mutation, we studied 79 compound heterozygotes for G551D/delta F508, from nine centers in Europe and North America. Each subject was matched, by age and sex, with a delta F508 homozygote from the same center. A retrospective cohort analysis was performed on the following outcome parameters: age at diagnosis, sweat chloride, meconium ileus at birth, height, weight, weight for height, FVC, FEV1, chest X-ray score, pseudomonas colonization, pancreatic sufficiency, and Shwachman clinical score. There was less meconium ileus among the G551D/delta F508 compound heterozygotes (relative risk 0.33; 95% confidence interval .13-.86), as well as a trend toward later age at diagnosis of pancreatic insufficiency. No statistically significant difference was found between the groups for any other parameter. These results suggest that the CF genotype can be a predictor of pancreatic and intestinal phenotype. Prenatal counseling for the two genotype groups should differ only with respect to probability of meconium ileus. Clinical outcome (after survival of meconium ileus) for G551D/delta F508 compound heterozygotes and delta F508 homozygotes is indistinguishable; therefore, prognostic counseling should not differ.

Adolescent

[Two-phase test of fecal occult blood screening for colorectal cancer].

The detection of colorectal cancer in an early curable stage has become the focus of considerable interest recently. A two-phase test using both guaiac test and Hemolex latex immuno-agglutination test was applied for fecal occult blood screening of colorectal cancer. A total of 4,725 veterans aging 60 to 69 years were registered, and 2,176 persons (average age 66 years) completed the test giving a compliance rate of 46%. The positive rates of both tests were accounted 20.5% and 6.7% respectively. Five hundred and forty five persons had positive reaction for at least one of the tests. Of these, 90 had a follow up diagnosis with colonoscopy or combined with barium enema. Three rectal adenocarcinomas were detected, of which only one was positive by guaiac test, but two by Hemolex test. A rectal carcinoid was found by rectodigital examination. It was negative by both tests. Nineteen cases were detected to have one or more polyps in colon or rectum, of which only 6 were positive by guaiac test, but 18 by Hemolex test. Hemolex test using antibody against human hemoglobin is based on latex agglutination reaction. It is more sensitive and specific than guaiac test. Moreover, no dietary restriction is required. In the view point of cost-effectiveness, mass screening for colorectal cancer in general public is not recommended, but hospital-based screening for high risk group is still worthwhile to study.

Age Factors

Gestational trophoblastic disease within an elective abortion population.

Gestational trophoblastic disease, most commonly hydatidiform mole, is an unusual condition within the United States. The incidence of hydatidiform mole has been reported to vary from 1 in 1,200 to 1 in 2,000 pregnancies. This report described eight cases of hydatidiform mole among 4,829 patients presenting for elective first-trimester abortion. Factors which might account for the frequency of hydatidiform mole of 1 in 600 are discussed. Although the clinical course of patients with hydatidiform mole appears benign- gross examination of tissue obtained at suction curettage and the liberal use of histologic evaluation in questionable cases is required to make the diagnosis.

Abortion, Induced

The relative significance of human placental lactogen in the diagnosis of retarded fetal growth.

The purpose of this prospective study was to determine whether serial maternal venous hPL determinations could identify pregnancies resulting in growth-retarded infants from a selected population at presumed high risk for IUGR. Our results demonstrated that mean hPL levels in IUGR outcome pregnancies were significantly lower than normal after 33 weeks' gestation. Mean hPL was also lower in some pregnancies resulting in normal-weight neonates with abnormally low PI or short CHL, suggesting that these neonates, despite normal birth weight achievement, may represent previously unsuspected.

Birth Weight

The effect of chlorotrianisene as postpartum lactation suppression on blood coagulation factors.

Coagulation changes and increased risk of thromboembolic disease may occur in association with estrogen administration. The puerperium is also a high-risk period for thromboembolism, and estrogen administration at this time may increase this risk. Patients with congenital deficiency of antithrombin III have recurrent venous thromboembolic disease, suggesting that low levels of this factor may be associated with "hypercoagulability" states. We studied 50 postpartum patients who received chlorotrianisene (Tace) or placebo for lactation suppression in a prospective, double-blind, randomized fashion. Antithrombin III values were significantly lower on the third day post partum in the treated group compared to the placebo group (p less than 0.05). In addition, our clinical data from a total of 99 patients support the previous evidence that estrogens delay rather than prevent breast engorgement. Thus, with questionable benefit and a possible increased thromboembolic risk, it would appear prudent to discontinue the practice of estrogen administration for lactation suppression.

Adult

13, 14-dihydro-15-keto-prostaglandin F2alpha concentrations in human plasma and amniotic fluid.

An antiserum to 13,14-dihydro-15-keto-prostaglandin F2alpha (PGF2alphaM) was prepared and a radioimmunoassay evaluated in various reproductive states. PGF2alphaM plasma concentration was 63.6 +/- 10.3 pg/ml (mean +/- SEM) in cycling women. The concentration fluctuated throughout the menstrual cycle and pregnancy, but no discernible patterns were noted. PGF2alphaM concentrations were elevated at the time of urea + oxytocin induced abortion (238 +/- 54 pg/ml) and during late stages of normal labor (352 +/- 107 pg/ml) but were not elevated during labor prior to 7 cm dilatation. Following intra-amniotic instillation of 5 mg of PGF2alpha tromethamine into the amniotic sac, PGF2alphaM concentration increased in the amniotic fluid. In the plasma of these patients there was an eighteenfold rise in plasma PGF2alphaM concentration compared to a 3.5-fold rise in PGF2alpha at 1 hour, suggesting changes in PGF2alphaM may be more easily detected than the parent compound. While PGF2alphaM may be a useful index of PGF2alpha production, it appears that PGF2alphaM is of little value in predicting the occurrence of uterine contraction.

Abortion, Induced

Placental histopathology of midtrimester termination.

Placentas spontaneously passed after second-trimester terminations of pregnancy using either hypertonic sodium chloride or hyperosmolar urea plus prostaglandin F2alpha (PGF2alpha) were examined to determine histologic characteristics. The placentas of hypertonic sodium chloride terminations demonstrated a type of "coagulation necrosis" that has been described previously, while placentas of pregnancies terminated by hyperosmolar urea plus PGF2alpha showed a similar pattern in about one half the cases but a histologic pattern of less severe damage in the remaining cases. The 2 groups showed no significant differences when characteristics such as injection-abortion interval or estimated hypertonicity of the fluid were examined.

Abortion, Induced

Patterns of intrauterine growth retardation.

A prospective study of 70 singleton pregnancies at high risk for intrauterine growth retardation (IUGR) was undertaken to determine 1) the differences in intrauterine growth patterns; 2) the diagnostic accuracy of obstetric techniques; and 3) the frequencies of perinatal complications. Thirty infants displayed signs of IUGR. Although only 14 infants had low birth weights, these 14, as well as the remaining 16 infants under study, displayed many other features of growth abnormalities, including a low ponderal index, short stature, and small head circumference. These data demonstrate various patterns of IUGR. Although the perinatal complications occurred primarily in the low-birth-weight group, the major growth abnormalities observed in the non-low-birth-weight group demonstrate the need for additional short- and long-term follow-up studies in both groups.

Adult

Intravascular spill of hyperosmolar urea during induced midtrimester abortion.

Intravascular spill of hypertonic sodium chloride and the resultant serious and occasionally fatal consquences have been reported in association with induced midtrimester abortion. This report details 3 cases of intravascular spill of hyperosmolar urea. Although urea may pose less concern, because of its ability to readily cross cell membranes and its action as an osmotic diuretic, inadvertent intravascular spill can produce symptoms that include nausea, headache, sensations of warmth, and intense uterine cramping. In addition, abnormal blood pigments may occasionally be noted in the urine. Treatment includes intravenous hydration, careful monitoring of fluid/electrolyte balance and renal function, and avoiding the use of oxytocic agents.

Abortion, Induced

Intrauterine ethanol-induced termination of pregnancy in cynomolgus monkeys (Macaca fascicularis).

The effectiveness of locally applied ethanol in terminating early pregnancy in cynomolgus monkeys was studied. In a randomized trial ethanol (70 per cent, 1 ml.) or saline (0.9 per cent, 1 ml.) was injected extra-amniotically through a sterile blunt-end needdle inserted through the cervix into the uterine cavity. Six of seven monkeys receiving ethanol showed vaginal bleeding beginning one or two days after treatment. With the one failure, alcohol leakage occurred from the Luer-lock needle joint at the time of injection and the amount entering the uterus was unknown. No animal receiving saline showed any vaginal bleeding. The six monkeys showing vaginal bleeding were found to have nonenlarged or subnormally enlarged uteri one month after treatment. All monkeys subsequently resumed menstrual cycles within one year. Three monkeys became pregnant and were delivered at term of healthy offspring. Histologic evaluation of uteri from ethanol-treated monkeys revealed necrosis of decidua and, to a lesser degree, of the placenta one day after injection. The high efficacy of 70 per cent ethanol in inducing endometrial sloughing and the documentation of normal subsequent pregnancies in 50 per cent of treated monkeys make this technique worthy of consideration as a menstrual induction agent in women.

Abortion, Induced

Cytologic detection and clinical significance of Actinomyces israelii in women using intrauterine contraceptive devices.

Pancervicovaginal (Papanicolaou) smears exhibiting pseudomycilial-like clumps of organisms obtained from 35 women employing IUD's were studied by direct immunofluorescent technique for identification of A. israelii and A. naeslundi. In every case the specific fluorescence was achieved with species-specific antiserum against A. israelii. The clinical profile of these 35 women was retrospectively analyzed.

Actinomyces

Hyperosmolar urea for elective midtrimester abortion. Experience in 1,913 cases.

Intra-amniotic hyperosmolar urea (59.7 per cent) augmented by intravenous oxytocin (332 millimicron per minute), prostaglandin F2alpha (20 mg.), prostaglandin F2alpha (10 mg.), or prostaglandin F2alpha (5 mg.) was utilized for 1,913 patients requesting elective midtrimester abortion. Injection-abortion intervals ranging from 13.70 to 21.49 hours were achieved with failure rates of 0.7 to 6.7 per cent. Despite frequent pre-existing medical conditions, the complication rate compared favorably with those of other methods for terminating midtrimester pregnancy such as saline amnioinfusion or dilatation and evacuation.

Abortifacient Agents

The cold sterilization of abortion cannulae.

The purpose of this study was to determine if cold sterilization is a feasible method for sterilizing abortion cannulae and, if so, to find the appropriate solutions and time intervals for this sterilization process. Study findings show that abortion cannulae can be cold sterilized by soaking them for a minimum of 10 minutes in a solution of Cidex or 95% ethanol. Soaking the cannulae for 20 minutes in a 2% tincture of iodine solution also appears to be useful for decontamination purposes.

Abortion, Induced

Bacteriologic culture results obtained before and after elective midtrimester urea abortion.

Twenty patients undergoing elective midtrimester abortion by urea amnioinfusion had bacteriologic culture data obtained before and after the procedure. Despite the presence of pathogens in the vagina and cervix prior to the procedure, only 20% of patients exhibited endometrial growth following abortion. Factors that seem to favor such endometrial growth include increased injection-abortion intervals and the requirement for curettage to manage incomplete abortion.

Abortion, Induced

The pharmacologic inhibition of premature labor.

Oxytocin, elevated estrogen-progesterone ratio, fetal corticosteroids, prostaglandins, catecholamines, and changes in uterine blood flow have all been implicated as triggers of labor. In approximately one-third of cases of threatened premature labor contractions stop spontaneously. Thus placebo-controlled randomized trials of any new drug for inhibition of premature labor are necessary, as the spontaneous cessation of contractions always favors the claimed therapeutic efficacy. Alcohol inhibits the release of endogenous oxytocin and has an additional direct effect on the myometrium. In one study alcohol was more effective than placebo in the postponement of delivery. Isoxsuprine, ritodrine, and terbutaline have also been shown to be better than placebo in the inhibition of premature labor, and the beta adrenergic agents appear to be more effective than alcohol. Prostaglandin inhibitors such as indomethacin are currently under investigation. Success is correlated with early administration of the therapy, which requires treating some patients whose contractions might have stopped spontaneoulsy. As different factors may be involved in triggering premature labor, if one therapeutic approach fails another should be initiated promptly.

Adrenal Cortex Hormones