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Biomedical subjects

C D Christian

Publications and source records attributed to C D Christian.

At least 19 recordsLinked to original sources
PubMed1991

Human liver cocaine esterases: ethanol-mediated formation of ethylcocaine.

A new, pharmacologically active metabolite of cocaine, ethylcocaine, has been reported in individuals after concurrent use of cocaine and ethanol. Formation of ethylcocaine may contribute to the common coabuse of these two drugs and the apparent danger of this practice. We have identified a nonspecific carboxyl-esterase that catalyzes the ethyl transesterification of cocaine to ethylcocaine in the presence of ethanol. In the absence of ethanol, this human liver esterase catalyzes the hydrolysis of cocaine to benzoylecgonine, a metabolite that is inactive as a psychomotor stimulant. A second human liver esterase is also described. This enzyme catalyzes hydrolysis of cocaine to ecgonine methyl ester, also inactive as a stimulant. These two liver esterases may play important roles in regulating the metabolic inactivation of cocaine.

Carboxylic Ester Hydrolases↗
PubMed1985

Effects of influenza virus vaccine on hepatic drug metabolism.

Experimental and more limited clinical studies have suggested that influenza vaccination may depress the oxidative hepatic metabolism of various drugs and lead to drug toxicity. The alleged mechanism is the formation of interferon and the resulting decrease in cytochrome P-450 available for drug oxidation. Because of the clinical and basic science implications of these reports, we undertook to study the effects of influenza vaccine on the metabolism of three commonly used drugs: chlordiazepoxide, theophylline, and lorazepam. Our healthy male subjects were studied just before and 1 and 7 days after vaccination. As expected, lorazepam metabolism, which proceeds by glucuronidation and not oxidation, was not altered by vaccination. Surprisingly, however, the oxidation of chlordiazepoxide was also not depressed by the vaccine. Theophylline oxidation, which proceeds primarily by microsomal oxidation (demethylation), was significantly decreased 1 day, but not 7 days, after vaccination. Serum alpha-interferon levels rose after vaccination for only about 8 hours, and levels of gamma-interferon rose to about 500 IU/ml at 24 hours, peaked at 72 hours, and returned to normal by 100 hours after dosing. It appeared that the higher the theophylline clearance before vaccination, the greater the degree of clearance depression after vaccination. Thus the inhibition of drug oxidation after influenza vaccination is selective and each drug should be studied individually. The degree of depression of theophylline clearance is small and transient and appears to be greater in subjects with higher prevaccination clearance.

Adult↗
PubMed1984

Sex ratio in ectopic gestations.

Sex assignment was determined in 80 cases of ectopic pregnancy. Tissue sections of chorionic villi were stained with quinacrine for demonstration of either X or Y chromatin. Forty-one (51.2%) were X-chromatin (Barr body)-positive; 38 (47.5%) were Y-chromatin-positive, and 1 (1.3%) was Barr- and Y-positive in the same nuclei. The sex ratio of ectopic gestations in this study was 0.92 male to 1 female. Based on these data, there appears to be no predilection for ectopic implantation by either sex.

Chorionic Villi↗
PubMed1984

Cimetidine inhibits renal procainamide clearance.

Procainamide and cimetidine are eliminated in large part by the kidneys. Both are secreted by an active transport mechanism in the proximal tubule and each inhibits secretion of the other in the isolated, perfused rabbit tubule. In this study in man, cimetidine inhibited renal clearance of oral procainamide by 36%. This was associated with a 28% decrease in the ratio of systemic clearance of procainamide to bioavailability, an 18% decrease in the elimination rate constant, and a 24% prolongation of elimination t1/2. These results suggest that cimetidine increases plasma t1/2 and decreases systemic clearance of procainamide in part by inhibiting its active secretion by the kidneys.

Acecainide↗
PubMed1984

Diphenhydramine disposition in chronic liver disease.

Diphenhydramine (DPHM) disposition was examined in nine patients with chronic alcohol-related liver disease and in eight normal subjects. Sleep of 1 to 2 hr duration was induced in all subjects by a 0.8 mg/kg iv dose without an apparent increase in cerebral sensitivity in the patients with cirrhosis. Protein binding as determined by equilibrium dialysis (3H-DPHM) revealed a 15% decrease in the cirrhotic patients, while recovery of unchanged DPHM in urine (2%) was of the same order in the two groups. Computerized biexponential curve analysis was used to compare the plasma profiles for five of the patients and six of the normal subjects. Monoexponential curve analysis of the terminal beta-phase, including all subjects, was also used to compare the two groups. The means of plasma clearance and apparent volume of distribution in cirrhotic patients were respectively less and greater than in normal subjects, but these differences were not significant. The t1/2 for the beta-phase (t1/2 beta), which reflects this reciprocal trend, was increased in the patients (15.2 +/- 1.5 and 9.3 +/- 0.9 hr). This correlated in part with severity of disease, with r = 0.723 between t1/2 beta and the serum bilirubin levels. In conclusion, a single intravenous dose of DPHM provided safe and effective sedation in patients with cirrhosis.

Adult↗
PubMed1984

Follicular fluid treatment during the follicular versus luteal phase of the menstrual cycle: effects on corpus luteum function.

Administration of charcoal-extracted porcine follicular fluid (pFF) to rhesus monkeys at the time of menses impairs the subsequent function of the corpus luteum of the menstrual cycle. The following studies were performed: 1) to characterize the luteal phase defect induced by pFF treatment at menses, and 2) to determine whether pFF treatment in the luteal phase alters corpus luteum function. Adult, female rhesus monkeys were injected sc for 3 days with pFF (10, 5, and 5 ml) beginning on day 1 (n = 5) or day 18 (n = 4) of the menstrual cycle. Femoral venous blood was collected daily throughout the treatment cycle and during the posttreatment cycle of day 18 to 20-treated monkeys. Serum LH, FSH, 17 beta-estradiol (E2), and progesterone (P) were measured by RIA. After pFF treatment on days 1-3, FSH and E2 levels in the early follicular phase were less (P less than 0.05) than those of control cycles (n = 7). Serum LH was not suppressed by pFF treatment. Moreover, the preovulatory rise in circulating E2 and the amplitude of the LH/FSH surge were similar in control and pFF-treated monkeys. Although timely midcycle gonadotropin surges occurred in four of five pFF-treated monkeys, serum P was markedly reduced (P less than 0.05) during the first half of the luteal phase. Circulating P increased to control levels during the late luteal phase before normal onset of menses 16.3 +/- 1.0 (SE) days after the LH surge. Treatment with pFF on days 18-20 of the cycle reduced the levels of circulating FSH, but serum LH, E2, P, and the length of the luteal phase remained comparable to control cycles. Moreover, the hormonal patterns and the length of the follicular and luteal phases in the posttreatment cycle indicated normal ovarian function. Thus, pFF treatment at menses results in an aberrant ovarian cycle characterized by an insufficient, rather than short, luteal phase. Whereas pFF treatment in the early follicular phase vitiates development of the dominant follicle and the related corpus luteum, similar treatment at midluteal phase does not suppress concurrent luteal function or subsequent folliculogenesis.

Animals↗
PubMed1984

Poor-prognosis gestational trophoblastic disease: an update.

Ten patients with poor-prognosis gestational trophoblastic neoplasia were treated from 1979 to 1983 primarily with the modified Bagshawe chemotherapy regimen. Four patients were noted to have brain metastases, and one patient had liver metastases. In addition, etoposide (VP-16) was used in seven patients, bleomycin in six, cisplatin in five, 5-fluorouracil in two, and cis-retinoic acid in four patients. Thoracotomy, hysterectomy, and splenectomy were performed after chemotherapy was initiated for isolated resistant disease. At present, nine of the ten patients (90%) are in complete remission for four to 44 months. Significant myelosuppression was encountered in seven patients and life-threatening toxicity was noted in two patients. Currently, poor-prognosis patients are treated with the modified Bagshawe regimen, alternating every other week with etoposide, bleomycin, and cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Gastrointestinal involvement in lymphomatoid granulomatosis. Report of a case review of the literature.

Lymphomatoid granulomatosis is a lymphoproliferative process affecting multiple organ systems usually including the lungs. Significant gastrointestinal involvement, however, has rarely been reported. Pathologic examination reveals a vasocentric polymorphous lymphoid infiltrate. A case of lymphomatoid granulomatosis with gastrointestinal manifestations necessitating aggressive surgical intervention is reported. The clinical presentation, pathologic features, and various aspects of therapy of lymphomatoid granulomatosis involving the gastrointestinal tract are discussed.

Adult↗
PubMed1983

Characterization of a new human endometrial carcinoma (RL95-2) established in tissue culture.

A new human endometrial cell line, RL95-2, derived from a Grade 2 moderately differentiated adenosquamous carcinoma of the endometrium has been passaged successfully in cell culture for more than 2 yr. The cells are characteristically epithelioid with well-defined junctional complexes, tonofilaments, filopodialike extensions, and surface microvilli. Nuclei are large, irregular, and invaginated frequently with multiple, prominent, lamellar nucleoli. The cells have a log phase doubling time of 22 to 34 h followed by continued growth at a reduced rate with no apparent plateau phase. They exhibit a strong tendency for piling up as well as for the formation of glandlike dome structures. Karyotypically the line is trisomic 8 (47,XX,+8) and has an 8% frequency of polyploidization. Both cytoplasmic and nuclear estrogen receptors are present. Antihuman alpha-keratin characterizes the cell line as epithelial, nonstromal. The RL95-2 cell line may provide a useful in vitro system for the investigation of the endocrine regulation of endometrial neoplasia.

Adenocarcinoma↗
PubMed1983

Ectopic pregnancy--a new surgical epidemic.

Between March 1972 and September 1981, 154 patients with the diagnosis of ectopic pregnancy were treated at the University of Arizona. A retrospective review of these cases was performed to determine etiologic and demographic factors. Fertility follow-up was obtained in 58 women. Findings are discussed along with the presentation of various thoughts in an attempt to explain this proliferation of a surgical disease.

Adolescent↗
PubMed1980

Relationship of newborn serum prolactin levels to the respiratory distress syndrome and maternal hypertension.

Prolactin concentrations were measured in mixed cord blood of 782 newborn infants and related to the occurrence of the respiratory distress syndrome (RDS) and maternal cardiovascular condition. Infants of 30 to 33 weeks' gestational age who developed RDS had significantly lower serum concentrations of prolactin than non-RDS infants within this same age range. No difference was observed between RDS and non-RDS infants at 34 to 36 weeks. Prolactin levels in infants delivered by preeclamptic women were greater than the levels in infants of normotensive women from 30 to 39 weeks' gestation. The levels were higher in the 40 to 42 weeks age group as well; however, the difference was not statistically significant. Infants of mothers with gestational hypertension also tended to have elevated serum prolactin concentrations. No differences were observed in infants of women presenting with a history of chronic hypertension. Within the RDS subgroups, serum prolactin levels were significantly greater in infants of preeclamptic women than in infants of normotensive women, being approximately equal to the levels in the non-RDS normotensive group.

Adolescent↗
PubMed1980

Liver function tests and low-dose estrogen oral contraceptives.

Twenty healthy female volunteers were treated with 35 microgram ethinyl estradiol and 0.4 mg norethindrone for a two-month period of time. Liver function tests (serum SGOT, SGPT, LDH, alkaline phosphatase, total bilirubin, total protein, albumin and prothrombin times) were measured at baseline and control prior to treatment, and at one and two months of therapy. There was a 1.25% incidence of abnormalities in the 320 tests conducted during therapy. During the first month of therapy, there was a 1.9% incidence of abnormal tests. 0.625% incidence of abnormal tests was seen in the second month of treatment. A 5% incidence of abnormalities (single episodes in each parameter) was seen in SGPT, LDH, total bilirubin and prothrombin time levels during the two-month period. This was well below the 10-30% incidence of abnormalities reported with 50-100 microgram of estrogen-containing birth control pills in previous studies. There seems to be little effect on liver function tests with use of estrogen preparations containing 35 microgram ethinyl estradiol.

Adult↗
PubMed1979

Efficacy of estradiol vaginal cream in postmenopausal women.

In a double-blind parallel study daily intravaginal administration of conjugated estrogen cream and estradiol cream for 14 days relieved vasomotor and vaginal postmenopausal symptoms in 29 postmenopausal women. By day 14, therapy with the estradiol vaginal cream resulted in plasma estrone and estradiol levels closer to those in premenopausal women than therapy with the conjugated estrogen cream. The extent of improvement and final estradiol plasma levels in the estradiol vaginal-cream group correlated. There was no correlation with severity of symptoms or estradiol plasma level at baseline. The metabolism of the conjugated estrogen cream might account for absence of correlation between improvement and final estradiol plasma levels in the conjugated vaginal-cream group.

Administration, Topical↗