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Biomedical subjects

D C Anderson

Publications and source records attributed to D C Anderson.

At least 505 records · Page 28Linked to original sources

Leptospirosis: a common-source outbreak due to leptospires of the grippotyphosa serogroup.

In the period August 1-10, 1975, seven cases of leptospirosis occurred in residents of Stewart County, Tennessee. Based on serologic evidence, the infection was caused by leptospires of the Grippotyphosa serogroup. Epidemiologic study showed that the patients apparently acquired their infection while swimming in Cub Creek, a small local stream. Stagnation of the stream resulting from subnormal rainfall may have contributed to the timing of the outbreak. The source of leptospiral contamination for the stream could not be determined.

Adolescent↗

Cushing's syndrome, nodular adrenal hyperplasia and virilizing carcinoma.

A 48-year-old hypertensive diabetic woman rapidly became virilized. Urine 17-oxo-and oxogenic steroids and plasma testosterone, androstenedione, DHEA, DHEA-sulphate and androstenediol were greatly elevated. Plasma cortisol was constantly high and was not suppressed by dexamethasone. Circulating immunoreactive ACTH was consistently detectable at 18-24 ng/l. A 450 g carcinoma arising from a nodular hyperplastic right adrenal gland was resected. Production by the tumour of 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and five C-19 steroids, but very little prenenolone, progesterone or cortisol, was shown by blood sampling, tumour culture and dramatic falls after operation. The plasma cortisol fell to half, with no diurnal variation, consistent with persistent Cushing's syndrome, and the plasma ACTH rose to 55 ng/l. She died 3 months later from a myocardial infarction. Autopsy revealed a pituitary basophil adenoma at a site where radiologically there had been an indentation in the fossa floor for at least 7 years. The left adrenal gland showed nodular hyperplasia. Therefore we conclude that mild pituitary-dependent Cushing's syndrome may have been present for many years before development of a virilizing carcinoma. This case demonstrates that adrenal carcinoma in man can sometimes develop as a consequence of nodular adrenal hyperplasia which may in turn be due to long-standing trophic hyper-stimulation.

Adenocarcinoma↗

Leptospirosis in zoo workers associated with bears.

Leptospirosis due to Leptospira interrogans serovar icterohaemorrhagiae was diagnosed in two zoo animal keepers. The implicated source of infection was bear cubs that had microscopic agglutination antibody titers to leptospires of the Icterohaemorrhagiae serogroup.

Adult↗

Thyrotoxicosis: relations between clinical state and biochemical changes during carbimazole treatment.

The relation between clinical and biochemical changes in thyrotoxicosis were studied in 12 patients with Graves's disease who were being treated with carbimazole. Clinical assessment (using the Crooks-Wayne index) was combined with the measurement of free thyroxine and triiodothyronine indices (FT4I and FT3I) and the assessment of two tissue markers of thyroid hormone action--sex-hormone-binding globulin (SHBG) levels and the thyrotrophin responses to TRH. In general the FT4I and FT3I fell rapidly once treatment was started, and returned to normal in one to four weeks, followed shortly by SHBG levels. The thyrotrophin response returned at this time in two patients, who still had borderline high levels of FT3I and SHBG. The clinical score fell more slowly and variably and was less closely related to any of the biochemical indices than these were to each other. During the early phase of treatment with antithyroid drug the clinical evaluation may be an unreliable indicator of persisting thyroid hormone excess, and when the patient seems clinically but not biochemically thyrotoxic the symptoms should be treated on their own merits with beta-blocking drugs and not with increased doses of antithyroid drugs.

Adult↗

A simple method for the assay of eight steroids in small volumes of plasma.

A simple method is described for the simultaneous radioligand assay of four delta5-3beta-hydroxysteroids adjacent to one another on the biosynthetic pathway (pregnenolone [1], 17alpha-hydroxypregnenolone, dehydroepiandrosterone and 5-androsterone-3beta, 17beta-diol), and their four delta4-3keto products (progesterone, 17alpha-hydroxyprogesterone, 4-androstene-3, 17-dione and testosterone). Two plasma aliquots are extracted and fractionated each for four steroids and individual corrections are made for losses. For fractionation, maximum use is made of the high resolution and reproducibility of celite minicolumns, using propylene glycol as stationary phase, and a discontinuous gradient of ethyl acetate in iso-octane as mobile phase. The fractions are then assayed in the appropriate radioligand end-assay system. Each assay was finally validated by demonstrating coincidence of peaks of immuno- and radioactive steroid in extracts of female plasma. Results in pre-pubertal girls and women in the follicular phase of the menstrual cycle suggest that the major change in adrenal steroid production at puberty may be an increase in 17, 20-desmolase activity. There appears to be little reversal of this change in adrenal function after ovariectomy.

Adult↗

Transplacental gradients of sex-hormone-binding globulin in human and simian pregnancy.

An attempt has been made to clarify the degree and control of production of the concentration gradient of sex-hormone-binding globulin (SHBG) between human mother and fetus. SHBG was measured by an improved ammonium sulphate precipitation method using 5 alpha-dihydrotestosterone as ligand. Maternal and fetal (cord blood) plasma SHBG was measured at delivery in twenty-three normal, four twin and one anencephalic pregnancies and in non-pregnant subjects. Comparison was also made with two macaque species, the rhesus monkey (M. mulatta) and the bonnet monkey (M. radiata), sampled shortly after delivery. In the human, a highly consistent gradient (mean 21-fold) was found between mother and fetus, which was independent of fetal sex and weight. Fetal but not maternal SHBG was significantly higher in the twin pregnancies. Maternal SHBG was 5-fold higher than in forty non-pregnant women, and fell with a half-life of 7-1 days immediately post-partium. In the two monkey species, SHBG with similar binding-characteristics exists but levels were 2-5-fold higher in the non-pregnant adult females than in women. In pregnancy, maternal SHBG levels were unchanged in the bonnet (nine observations) and fell markedly in the rhesus monkey (twenty-three observations) ; levels in the infants were comparably low in all three species, though more variable in the monkeys. In seven bonnet moneky mother-infant paris sampled again 2 or 2 weeks later, SHBG had risen mardedly (mean 6-1-fold) in the infants as has been shown previously in the human. The species differences in the non-pregnant females and the mothers may in part be related to species differences in oestrogen production. The macaque moneky appears suitable for studying further the mechanism of the neonatal SHBG rise, in which oestrogens cannot be implicated but thyroid hormones may be involved.

Animals↗

Plasma oestrogens in men with chronic liver disease.

A highly specific radioimmunoassay was used to measure the total plasma concentrations of the three principal unconjugated oestrogens: oestrone E1, oestradiol E2, and oestriol E3 in normal males and in 21 males with various forms of chronic liver disease. In addition, the unbound concentration of plasma E2 was established in the same group. About half of the patients with liver disease had overt feminising changes. Total and unbound plasma E2 concentrations were within the normal range in all patients. Total plasma E1 was significantly elevated only in those patients with liver disease and gynaecomastia, and a similar trend was seen for total plasma E3.

Adult↗

The effects of ovarian wedge resection on circulating gonadotropin and ovarian steroid levels in patients with polycystic ovary syndrome.

Serum gonadotropin, estrogen, and androgen levels were measured daily before and up to 35 days after surgery in 8 patients with polycystic ovary syndrome (PCO) undergoing ovarian wedge resection (WR). To serve as controls, similar assessments were made in 5 women having hysterectomies for non-ovarian disease during the early follicular phases of their cycles. Preoperatively, LH but not FHS, estrone (E1) but not estradiol 17 beta (E2), and both androstenedione (delta) and testosterone (T) levels were higher in the PCO patients than in the normal women. In the PCO patients, surgery had no discernible effect on FSH levels. In the 5 PCO patients who apparently ovulated after WR, LH levels did not fluctuate significantly until the midcycle LH peaks occurred 13-25 days after surgery. In the 3 patients who did not ovulate, there was a transient fall of LH, which reached a nadir on the sixteenth postoperative day and then returned to preoperative levels. In the total PCO group there was a significant fall of E1 (P less than 0.05) and a decrease of E2, which reached nadirs on the third postoperative day. Preovulatory rises of both E1 and E2 were seen only in patients who ovulated following WR. For the androgens, significant decreases (P less than 0.05) of both T and delta were seen during the first 3 days after WR. These were followed by steady increases of both androgens back to preoperative levels. Delta levels remained elevated while T concentrations fell again and were significantly lower (P less than 0.005) at the end of the sampling period than preoperatively. This pattern was seen whether the patients did or did not ovulate. Except for a small transitory fall of androgens, surgery had no discernible effect on the circulating levels of any of the hormones in the control subjects. These results show that in PCO patients, ovarian WR is followed by a profound, temporary reduction of ovarian delta secretion and a persistent reduction of T secretion. Smaller, but significant, decreases of estrogen production were also observed. The mechanism responsible for ovulation following WR appears to be local (intra-ovarian) rather than central since the alterations in ovarian hormone secretion had no discernible effect on circulating gonadotropin levels prior to the onset of midcycle surges.

Adult↗

Effects of estrogens on adrenal 3 beta-hydroxysteroid dehydrogenase in ovariectomized women.

The acute and chronic effects of estradiol (E2) on the serum levels of four delta5,3-beta hydroxysteroids and their four delta4, 3-keto products were studied in four ovariectomized women with and without adrenal stimulation by ACTH. Six hour infusions of saline and of synthetic 1-24 ACTH were administered and later repeated with a two hour infusion of E2 50 mug/h. The patients were then given 50 mug of ethinyl estradiol (EE2) p.o. for 4 to 6 weeks and the control and ACTH infusions were again repeated. Levels of pregnenolone3 (Pe), 17alpha-hydroxypregnenolone (17 Pe), progesterone (Po), 17alpha-hydroxyprogesterone (17 Po), dehydroepiandrosterone (DHEA), androstenedione (Adione), androstenediol (Adiol), and testosterone (T), as well as cortisol and DHEA-sulfate were measured by radioimmunoassay on serum samples taken at 1200 and 1300 h. There was no significant effect of E2 or EE2 in the doses administered with or without exogenous ACTH on 3 betaOHSD activity as reflected in absolute steroid levels or in the ratio of concentrations of each delta5:delta4 steroid pair. During the 4th and 5th hour of ACTH infusion, the plasma level of 17 Pe (mean 22.5-fold stimulation) was most elevated, followed by 17 Po (12.5-fold), Pe (10-fold), cortisol (5.9-fold) and Po (4.5-fold), with smaller increases for the other steroids. These results, as well as the pattern of change in plasma levels in one of the subjects in whom fifteen minute samples were measured, provide further evidence suggesting that the major pathway for cortisol biosynthesis in vivo proceeds from Pe via 17 Pe, and not via Po.

17-alpha-Hydroxypregnenolone↗

Leukocyte function in children with malignancies.

Blood was obtained on 414 occasions from 106 children with acute lymphocytic leukemia (ALL) or solid tumors. Resting and stimulated hexose monophosphate shunt (HMPS) activity and unstimulated and stimulated nitroblue tetrazolium (NBT) dye reduction were assessed on each sample. The values obtained were compared to similar determinations made on blood obtained from 178 healthy children. Resting HMPS activity of all patients with malignant diseases was significantly (p smaller than 0.01) greater, and ability to stimulate HMPSP activity significantly (p smaller than 0.01) less than that noted in healthy control patients. Unstimulated NBT dye reduction of leukocytes obtained from patients with malignant disorders was significantly (p smaller than 0.01) less than that observed in healthy control children. No significant differences were noted in HMPS activity or NBT dye reduction in patients with ALL, rhabdomyosarcoma, or other solid tumors who had bacterial infection when compared to uninfected patients, or when patients were categorized according to the type of chemotherapy provided. HMPS activity and NBT dye reduction of patients with ALL prior to treatment, in remission, and during episodes of relapse did not differ from each other. Thus, a functional impairment in leukocyte function was noted in patients with ALL even when their peripheral blood and bone marrow cells exhibited normal morphology.

Bacterial Infections↗