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J Adams

Publications and source records attributed to J Adams.

At least 415 records · Page 23Linked to original sources

Spontaneous gonadotrophin pulsatility and ovarian morphology in girls with central precocious puberty treated with cyproterone acetate.

We have studied four girls with central precocious puberty treated with cyproterone acetate for a mean of 3.6 years (range 1.5-6.3 years). Pelvic ultrasound assessment demonstrated suppression of the ovarian morphology of central precocious puberty despite the presence of spontaneous pulsatile gonadotrophin secretion at night. We suggest that the previously reported effects on gonadotrophin secretion induced by cyproterone acetate therapy, administered in recommended doses, are minor and that the predominant effect of cyproterone acetate in the treatment of girls with central precocious puberty is direct inhibition of ovarian steroidogenesis.

Child↗

Gonadotrophin control of follicular development.

In order to investigate the endocrine requirements for induction of follicle maturation, ovulation and luteal function we have measured plasma LH and FSH concentrations in 109 cycles induced by treatment with LHRH in 25 women with amenorrhoea of diverse aetiology. The major clinical and endocrine subgroupings were polycystic ovarian disease (PCO), Kallmann's syndrome, weight related amenorrhoea and hyperprolactinaemia. By analysis of variance of the LH and FSH concentrations obtained three times per week in the follicular phase in 77 ovulatory cycles (including 24 conception cycles), we found that in women with PCO the mean LH concentration was 19.5 IU/l. In hyperprolactinaemia and secondary amenorrhoea of non-specific aetiology the mean LH concentration was 11.6 IU/l and in patients with hypogonadotrophic hypogonadism and weight-related amenorrhoea it was 7.2IU/l. These mean LH concentrations were significantly different from each other (P less than 0.001). We speculate that the high LH concentrations in the follicular phase may impair the final stages of oocyte maturation and so contribute to the infertility of these patients. FSH concentrations in the follicular phase were lower in patients with hypogonadotrophic hypogonadism and weight-related amenorrhoea than in other groups. Although the differences were statistically significant (P less than 0.001) the difference was small (mean FSH in hypogonadotrophic hypogonadism and weight-related amenorrhoea 4.3 IU/l vs 6.3 IU/l in the others) and of uncertain biological significance. During the luteal phase, no differences between any of the groups in LH and FSH concentrations were found.

Adult↗

Ultrasound demonstration of increased frequency of functional ovarian cysts in women using progestogen-only oral contraception.

Asymptomatic volunteer women with a regular pattern of uterine bleeding and using the progestogen-only oral contraceptive pill were compared with control women who were not exposed to hormones. Pelvic ultrasound scanning at the end of the next bleeding episode after recruitment demonstrated functional cysts with maximum diameters ranging between 30 and 58 mm in eight of the 21 pill users, four of whom also had palpable ovaries, three cysts regressed during the next cycle. Of the 13 women with normal ovaries initially, four developed a new functional cyst of which two were associated with pain. Of the 12 women with cysts seven complained of pain at some time during the monitored cycle. Among 21 control women only one symptom-free (42 mm) cyst was shown on the initial postmenstrual ultrasound scan and this resolved painlessly during the scanned cycle with ovulation from the opposite ovary. Ovulation was also demonstrated in 16 of the remainder; but in none of the three control women who developed asymptomatic functional cysts (35-47 mm in size) while under observation. Since 11 of the 14 pill-users who failed to ovulate also had a functional cyst, the contraceptive efficacy may depend in part on this association. Pain symptoms may make the method less acceptable and give rise to diagnostic problems and inappropriate therapies.

Adult↗

Ovarian ultrasound assessment in normal children, idiopathic precocious puberty, and during low dose pulsatile gonadotrophin releasing hormone treatment of hypogonadotrophic hypogonadism.

Ultrasound assessment of ovarian volume, follicular size, and uterine growth was undertaken in 40 normal premenarcheal girls aged 6 months to 14 years. Ovarian follicles were detected from 6 months of age and increased in size and number, so that after the age of 8.5 years there was a progressive increase in the incidence of 'megalocystic' appearance. Eight girls with idiopathic precocious puberty had large megalocystic ovaries which regressed on treatment with gonadotrophin releasing hormone analogue. These findings contrasted with those seen in two prepubertal patients with hypogonadotrophic hypogonadism in whom the natural sequence of ovarian development was greatly accelerated by pulsatile administration of native gonadotrophin releasing hormone.

Adolescent↗

Variable anatomy of the right coronary artery supply to the left ventricle.

The right coronary artery is "dominant" (contributing to the supply of the left ventricular muscle) in 90% of people. Although the most common pattern is for the right coronary artery to bifurcate at the crux giving the posterior descending (posterior interventricular) artery, a branch may arise before the crux, either as an aberrant acute marginal artery or as an early posterior descending artery, crossing the diaphragmatic surface of the right ventricle. Recognition of this possibility may be important if surgical revascularisation is to be complete. To establish the frequency of these different patterns of blood supply, 22 hearts were studied in the dissecting room, and 100 consecutive coronary angiograms and 100 consecutive operative drawings were reviewed. A vessel arising before the crux contributed to the supply of the left ventricle in one third of cases.

Coronary Angiography↗

Problems in the use of pulsatile gonadotrophin-releasing hormone for the induction of puberty.

The induction of puberty by the administration of subcutaneous 15-micrograms pulses of gonadotrophin-releasing hormone (GnRH) every 90 min during day and night is described in two patients. Too rapid an induction of puberty occurred in one patient while initial progress in the other ceased after the development of pituitary desensitisation. We have attributed these results to the use of GnRH pulses in too high amplitude, and we suggest a more appropriate dose regimen.

Adolescent↗

Trace derivatization of cytosine with pentafluorobenzoyl chloride and dimethyl sulfate.

Methods are being developed for derivatizing trace amounts of DNA adducts for ultimate determination by gas chromatographic techniques. High-pressure liquid chromatography is used to optimize appropriate derivatization reactions for the determination of cytosine. A single vial reaction scheme involves acylation with electrophoric pentafluorobenzoylchloride followed by alkylation with dimethyl sulfate. Currently, the overall yield for this reaction starting with 50 nmole of cytosine is 59 +/- 4.6%.

Acylation↗

Immunomodulatory effects in mice of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose.

In this report, we describe the immunomodulatory characteristics of poly(I,C)-LC, a synthetic, double-stranded nucleic acid polymer, polyinosinic-polycytidylic acid, that is complexed with poly-L-lysine and solubilized by the addition of carboxymethylcellulose. We consistently observed, both in vitro and in vivo, stimulation of macrophage cytotoxicity and augmentation of natural killer-cell activity by poly(I,C)-LC. This immunomodulator also increased the allogeneic mixed-lymphocyte response, without any blastogenic effect on responder cells cultured in the absence of allogeneic stimulator cells. Further, the addition of poly(I,C)-LC to an allogeneic mixed-lymphocyte tumor reaction did not stimulate the development of cytotoxic effector T-cells. Poly(I,C)-LC did, however, have adjuvant activity when admixed with irradiated tumor cells in the immunization of syngeneic mice. Unlike classic adjuvants, poly(I,C)-LC also enhanced the development of specific cytotoxic T-lymphocytes when it was injected either i.v. or i.p. in conjunction with a vaccine delivered at an intradermal site. The results indicate that poly(I,C)-LC has considerable potential as an immunotherapeutic agent, with the ability not only to induce macrophage and NK cell activation but also to stimulate specific cytotoxic T-lymphocytes.

Adjuvants, Immunologic↗

Disturbances of puberty.

The initiation and progress of puberty requires progressive pulsatile stimulation of the pituitary by GnRH and of the gonads by LH and FSH. Gonadal maturation continues throughout childhood and is not confined to puberty. We have discussed the events of normal puberty and emphasized the consonance of the acquisition of different components of sexual maturation, including growth acceleration. Departure from this consonance is a sign of abnormality. The method by which constitutional delay of growth and puberty can be distinguished from gonadotrophin deficiency has been discussed as well as the treatment options for both conditions. We have emphasized the significance of pulsatile gonadotrophin secretion and how the development of a multicystic ovarian morphology on ultrasound can be used as a non-invasive assessment of gonadotrophin pulsatility in girls. Pulsatile GnRH therapy mimics normal puberty. The converse of suppressing the clinical signs of central precocious puberty can be achieved by abolishing gonadotrophin pulsatility with GnRH analogue therapy. We now recognize qualitative pulse abnormalities of gonadotrophin secretion which occur in isolated premature thelarche and in some cases of delayed puberty. Although clinical assessment remains the key to the diagnosis of disorders of puberty, studies of gonadotrophin pulsatility have aided our understanding and treatment of these conditions.

Adolescent↗

Ovulatory disorders in women with polycystic ovary syndrome.

With the use of pelvic ultrasound imaging we have found that more than half of the women presenting to our clinic with ovulatory disturbances have polycystic ovaries. As a group hirsutism is common, the serum LH, the LH:FSH ratio and serum androgen levels are higher than in other groups of patients with anovulation, but many of the women we studied were non-hirsute and had normal levels of these hormones. The aetiology of PCOS remains obscure and there is probably more than one cause. Disturbance of hypothalamic/pituitary, ovarian or adrenal function could all result in the development of polycystic ovaries. Our own data, based on pelvic ultrasound and measurement of serum androgen levels, suggest that an ovarian abnormality, other than the obvious morphological one, may be identified in most women although this does not prove (except perhaps in those women with unilateral PCOS) that the ovary is the primary site of the disturbance. Management of ovulatory disturbances includes symptomatic treatment of dysfunctional uterine bleeding and induction of ovulation. Although the ovulation rate following clomiphene is quoted as about 75%, this is probably an overestimate; less than half the 'ovulators' become pregnant and in those who do there is a high risk of early pregnancy loss. Induction of ovulation in clomiphene non-responders remains a difficult problem. The results of ovarian wedge resection are variable and any beneficial effect is short-lived with the risk of long-term infertility due to pelvic adhesions. Laparoscopic electrocautery may be a useful alternative, but it is too early to assess this form of treatment. Of the medical methods of ovulation induction in clomiphene non-responders, two methods have emerged as being highly promising: the first is administration of HMG following suppression of the pituitary by an LH-RH analogue; so far only a very small number of patients have been treated. The second is low-dose FSH. Initial studies, including our own, have shown a high incidence of ovulation and a pregnancy rate of 50%.

Androgens↗

Immunotherapeutic potential in murine tumor models of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose.

The systemic administration of multiple, nontoxic doses of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose [poly(I,C)-LC] eradicated established experimental and spontaneous pulmonary metastases. Optimal immunotherapy was schedule dependent, requiring three to five injections of poly(I,C)-LC per week for a minimum of 4 weeks; in addition, therapeutic efficiency was partially dosage independent. Immunotherapy by poly(I,C)-LC was found to be limited by tumor burden, although when combined with chemotherapy as a debulking regimen it resulted in increased survival with protocols in which poly(I,C)-LC alone was insufficient. These data suggest that the systemic administration of poly(I,C)-LC may provide a successful adjuvant therapeutic modality against cancer metastasis.

Adjuvants, Immunologic↗

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Aged↗

Isolation and characterization of the rabbit prt gene product.

The product of the rabbit prt gene (PRT), a gene linked to the immunoglobulin kappa-light chain gene ab, was purified from rabbit serum by precipitation with ammonium sulfate and by chromatography on DEAE-Sephadex and Sephacryl S300. Analysis of PRT indicated that it was associated rabbit hemopexin; the molecular weight of PRT (i.e., 68,000), as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was similar to the reported molecular weight of rabbit hemopexin; the PRT phenotypes correlated with the phenotypes of a hematin binding protein; PRT itself bound hematin; and the amino acid composition of PRT was similar to the amino acid composition of rabbit hemopexin. The prt gene, however, need not be the structural gene for hemopexin; it may encode a glycosyl transferase responsible in part for the carbohydrate associated with the protein.

Amino Acids↗