Social cognition in pediatric-onset multiple sclerosis (MS).

BACKGROUND: Pediatric-onset multiple sclerosis (MS) patients represent a subpopulation who are diagnosed during the course of development. Social cognitive deficits have recently been recognized in adults with MS. It is critical to identify whether these youngest patients with the disorder are also at risk. OBJECTIVE: To determine whether pediatric-onset MS is associated with social cognitive deficits. METHODS: Consecutively-recruited participants with pediatric-onset MS were compared to a group of age- and gender-matched healthy controls on Theory of Mind (ToM) task performance. Tasks measured facial affect recognition (Reading the Mind in the Eyes Test), detecting social faux pas (Faux Pas Test), and understanding the perspective of another (False Beliefs Task). RESULTS: Twenty-eight (28) pediatric-onset MS participants (median age 17 years) and 32 healthy controls (median age 16 years) completed the study. The MS participants performed worse than controls on all three ToM tasks: Reading the Mind in the Eyes Test (p = 0.008), the Faux Pas Test (p = 0.009), and the False Beliefs Task (p = 0.06). While more MS than control participants were impaired on a measure of information processing speed (the Symbol Digit Modalities Test; 38% versus 6%), it did not account for the differences in ToM performance. CONCLUSIONS: Social cognition may represent an area of cognitive functioning affected by MS in the pediatric-onset population. These processes are especially important to study in younger patients as they may have long range implications for social adjustment, employment, and well-being.

Serologic responses of infertile women to the 60-kd chlamydial heat shock protein (hsp60).

OBJECTIVE: To determine whether women with Chlamydia trachomatis-associated tubal infertility are more likely than other infertile women to have antibodies to a particular region of the 60-kd chlamydial heat shock protein, hsp60. DESIGN: Serologic responses to the chlamydial hsp60 were examined in 43 infertile women seropositive for Chlamydia trachomatis, including 21 women with tubal infertility, 13 women with endometriosis, and 9 women with other causes of infertility. Antibody responses were localized to regions of hsp60 using five nonoverlapping recombinant polypeptides. RESULTS: Sixteen women with tubal infertility had anti-hsp60 antibodies compared with seven women with endometriosis and two women with other causes of infertility. Antibodies of 11 women with tubal infertility reacted predominantly with a region of hsp60 containing amino acids (201 to 300) compared with 1 women without tubal infertility. In contrast, antibodies that localized to the carboxyl terminus, amino acids (401 to 544), were seen equally in all groups. CONCLUSIONS: Among seropositive infertile women, antibodies that localized to amino acids (201 to 300) were immunodominant in those with tubal infertility but not in those with infertility due to other causes.

Subfascial dextran 70 collection after intraperitoneal instillation of Hyskon.

Our patient developed a subfascial collection of dextran 70 after intraabdominal instillation of Hyskon. Seroma and wound dehiscence should be ruled out. A nonleaking peritoneal closure may decrease the incidence of this complication. A nonleaking fascial closure will decrease the extension of the dextran 70 collection and prevent separation of the skin.

Recovery of Chlamydia trachomatis from the endometrium in infertile women with serum antichlamydial antibodies.

Upper genital tract infection with Chlamydia trachomatis appears to be a frequent cause of salpingitis and tubal infertility. However, the prevalence of active infection in women with infertility has not been well-defined. To examine this question, endocervical and endometrial cultures for C. trachomatis were obtained from infertile women with serum antibodies to C. trachomatis. The first 19 consecutive patients with titers greater than or equal to 1/32 were cultured. C. trachomatis was recovered from the endometrium or endocervix in six (32%) of the women examined and from the endometrium in five (26%). These findings indicate that a significant portion of infertile women with serum antichlamydial antibodies may have active upper genital tract infection with C. trachomatis at the time of presentation.

Plasma dextran levels after abdominal instillation of 32% dextran 70: evidence for prolonged intraperitoneal retention.

Postoperative ascites in patients receiving intraperitoneal dextran 70 may result from slow absorption. We tested this by instilling 250 ml of dextran 70 into the peritoneal cavity of patients undergoing tuboplasty. Serum dextran levels were undetectable until 24 hours after operation and rose during the next 4 days. Ascites in patients with intraperitoneal dextran 70 results from third spacing in response to the persistent osmotic load.

Correlation between serum antichlamydial antibodies and tubal factor as a cause of infertility.

Although salpingitis frequently produces tubal damage and infertility, many women with tubal factor as a cause of their infertility do not have a clinical history of salpingitis. In order to investigate whether or not some such cases might be due to subclinical chlamydial infections, we measured antichlamydial antibodies in the serum of 172 women consecutively undergoing evaluation for infertility. Only 16 (9.3%) had a prior history of salpingitis. Sixty-one (35%) had antichlamydial antibodies (S+), and of these 75% had tubal factor as a sole or contributing cause of their infertility, versus 28% of the seronegative (S-) women (x2 - 34, P less than 0.001). There was no association between chlamydial seropositivity and any infertility factor other than tubal factor in multivariant analyses. Subclinical infections with Chlamydia trachomatitis may be a major cause of tubal infertility in the United States, and chlamydial serologic studies may be useful in identifying the subset of infertile women likely to have tubal factor.

PIP: Although salpingitis frequently produces tubal damage and infertility, many women with tubal factor as a cause of their infertility do not have a clinical history of salpingitis. In order to investigate whether or not some such cases might be due to subclinical chlamydial infections, we measured antichlamydial antibodies in the serum of 172 women consecutively undergoing infertility evaluation. Only 16 (9.3%) had a prior history of salpingitis. 61 (35%) had antichlamydial antibodies (S+) and of these, 75% had tubal factor as a sole or contributing cause of their infertility, vs 28% of the seronegative (S-) women (chi square=34, P0.001). There was no association between chlamydial seropositivity and any infertility factor other than tubal factor in multivariant analyses. Subclinical infections with Chlamydia trachomatis may be a major cause of tubal infertility in the US, and chlamydia serologic studies may be useful in identifying that subset of infertile women likely to have tubal factor.

Cytoplasmic progesterone and estradiol receptors in normal, hyperplastic, and carcinomatous endometria: therapeutic implications.

This study was designed to determine whether the presence of progesterone receptors (PR) and/or estradiol receptors (ER) could be used to predict progestin responsiveness of recurrent or advanced endometrial cancers. We have demonstrated the presence of physicochemically similar cytoplasmic progesterone and estradiol receptors in normal, hyperplastic, and carcinomatous endometria. All normal endometria contained both PR and ER. Seventy-three percent of endometrial hyperplasias were PR(+) and 93% were ER(+). A decreasing concentration of progesterone receptor activity was observed with increasing tumor anaplasia [grade 1, 84% PR(+); grade 2, 55% PR(+); grade 3, 22% PR(+)] and in irradiated tumors. A statistically significant (p less than 0.001) relationship has been demonstrated between the presence of specific cytoplasmic PR and response to progestin therapy in recurrent or advanced endometrial adenocarcinomas. Thus, we conclude that a PR assay may be used to help select the most appropriate therapy for patients with recurrent or advanced endometrial adenocarcinoma.

Estrogen replacement therapy.

The use of estrogen replacement therapy in postmenopausal women is under close scrutiny. The indications and side effects of replacement therapy are reviewed, and recommendations regarding its use are made. Hot flashes, atrophy of the vaginal epithelium, and prevention of osteoporosis have been established as indications for estrogen replacement therapy. Prevention of cardiovascular disease, aging changes of skin, and the occurrence of mental illness have also been suggested as indications, but beneficial effects of estrogen replacement therapy for these problems have not been clearly established. Studies have shown that side effects of estrogen replacement therapy include endometrial cancer, hypertension, gallbladder disease, and angina pectoris. Breast cancer may also be a risk factor, but a consensus of opinion has not been established. Pulmonary embolism, cerebral vascular accident, or myocardial infarction has not been associated with estrogen replacement therapy. The use of progesterone with estrogen replacement therapy has been shown to reduce the occurrence rate of endometrial carcinoma, but it does not prevent all the actions of estrogen. Oral administration of estrogen is the preferred route despite misgivings about portal absorption and liver metabolism. Further studies must examine this question. Various agents have been shown to be effective in treating some climacteric symptoms. These include progesterone for hot flashes and calcium for the prevention of osteoporosis. Other agents may also be effective but have not been tested critically.

Normal glucocorticoid receptor numbers in a child with glucocorticoid-resistant relapsed acute lymphocytic leukemia.

Glucocorticoid receptors were quantified in circulating lymphoblasts from a child with relapsed acute lymphocytic leukemia refractory to multiple glucocorticoid containing drug regimens. The number of receptor sites in this patient's lymphoblasts was found to be similar to the number of receptor sites in lymphoblasts from a group of newly diagnosed children with acute lymphocytic leukemia. This patient differs from previous reported cases of relapsed acute lymphocytic leukemia in that all previous relapsed patients with normal receptor numbers obtained complete remissions when glucocorticoid containing treatment regimens were employed.

Glucocorticoid receptors in the lymphoblasts of patients with glucocorticoid-resistant childhood acute lymphocytic leukemia.

Glucocorticoid receptor sites were measured in lymphoblasts of six patients with childhood acute lymphocytic leukemia in relapse who were resistant to glucocorticoid therapy and compared to the number of receptor sites found in the lymphoblasts of 12 patients with acute lymphocytic leukemia who achieved initial complete remissions on glucocorticoid-containing chemotherapy regimens. Resistant patients as a group were found to have lower receptor site levels. This data supports the hypothesis that reduction in the number of receptor sites per cell is one mechanism by which cells become resistant to glucocorticoids. However, the clinical usefulness of these measurements to prospectively select glucocorticoid-resistant patients appears limited because four of the six resistant patients had measurements within one standard deviation of the mean for the 12 patients who achieved remission.

Binding of medroxyprogesterone acetate in human breast cancer.

Human mammary tumor cytosol containing macromolecules which bound 3H-MPA (3H-medroxyprogesterone acetate or 1,2-3H-6 Alpha-methyl-17 alpha-acetoxy-pregn-4-ene-3,20-dione) and 3H-R5020 (6,7-3H-17,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione) similarly with high affinity (Ka approximately equal to 2 nM-1) and specificity. The progestin-binding components had sedimentation coefficients of about 4S and 7S in sucrose gradients and had approximately the same number of binding sites for Ma and R5020 as revealed by gradient centrifugation and saturation analysis. Among the steroids tested, these components had the highest affinities for progestins and were probably progesterone receptors of human breast cancer. A 4S component of human serum bound 3H-R5020 but not 3H-MPA. With 3H-MPA and 3H-estradiol used as the tracers, the concentrations of progesterone and estrogen receptors have been determined in 236 human breast cancers by saturation analysis. Our results on the receptor content and response of 31 of these tumors to endocrine therapy suggest that progesterone receptor may be a better marker of a hormonally responsive breast cancer.

The effect of copper in vivo on specific progesterone binding by human endometrial cytosol.

Copper has been shown to interfere with specific progesterone binding by human endometrial and myometrial cytosol in vitro. These results suggested that one possible mode of action of the copper-bearing intrauterine devices (IUDs) is through interference with the action of progesterone at its target sites. A prospective study was carried out to determine whether the proposed mode of action of copper-bearing IUDs could be demonstrated in vivo. The results of this study revealed a significant difference in specific progesterone-binding capacity between proliferative and secretory endometria (P less than 0.001). However, when secretory endometria of the controlled subjects were compared with those of the copper-bearing IUD wearers, no significant difference was observed in the specific progesterone-binding capacity (P greater than 0.2). These data suggested that copper released from copper-bearing IUDs in vivo may not interfere with the binding of progesterone to its receptors in vitro. It is doubtful that the contraceptive effectiveness of copper-bearing IUDs could be due to the ability of copper to prevent progesterone from exerting its full effects on the endometrium.

The Sertoli cell in mixed gonadal dysgenesis.

Since 1937, over 100 cases of mixed gonadal dysgenesis have been described. Thus far, no correlation has been made between the light and electron microscopic morphology of the gonad and the appearance of the ipsilateral internal genitalia. In the case presented in this paper the presence or absence of the Sertoli cell in the ipsilateral gonad correlates with the morphology of the internal genitalia on that side.

Preoperative localization of virilizing tumors by selective venous sampling.

Two postmenopausal patients with virilization had preoperative localization of ovarian tumors by selective blood sampling from both ovarian and adrenal veins and assay of hormone levels. In the first patient, the peripheral concentrations of testosterone (T), androstenedione, and estrone were 936, 1,508 and 73 pg. per milliliter, respectively, levels which are above the ranges found in normal postmenopausal women. The catheterization study showed an increase in the left ovarian vein of all hormones except cortisol. It was predicted that a tumor was present in the left ovary. At operation a 7 by 4 mm. lipid cell tumour was found. In the peripheral blood of the second patient, the T level (4,518 pg. per milliliter) was markedly elevated and the estradiol concentration (73 pg. per milliliter) was increased. At retrograde catheterization the concentration of T in the right ovarian vein was markedly elevated at 120,400 pg. per milliliter. At operation a hilus cell tumor of the right ovary was found. These two cases represent the third and fourth consecutive androgen-secreting tumors from this institution that have been localized by selective ovarian and adrenal vein catheterization and sampling.

Androgen, estrogen, and progesterone by a lipid cell tumor of theovary.

In a 64-year-old woman with a virilizing lipid-cell tumor of the left ovary, serum progesterons, androgens, estrogens, and cortisol levels in the peripheral and ovarian veins were measured. Although virilization was the only symptom of hormone production by the tumor in this patient, endocrine studies showed that several steroids were secreted by this neoplasm. Of the steroids measured, androstenedione was the principal secretory product. Pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, and testosterone were also secreted, but in quantities which were one third to one sixth the amount of androstenedione. The tumor's pattern of hormone secretion was similar to patterns of steroid production by ovarian stromal cells found in previously reported in vitro studies. This case and a review of the literature demonstrate that androstenedione appears to be the predominant secretory product of lipid cell tumors, whereas testosterone is the predominant secretory product of hilus cell tumors.

Effect of metal ions on the binding of 17beta-estradiol to human endometrial cytosol.

The influence of zinc and other metal ions on the binding of 3H-17beta-estradiol to human endometrial cytosol was studied. Zn2+ began to interfere with estrogen binding when its concentration in the cytosol exceeded 50 micronM. At a concentration of 5 mM, all of the specific binding of 17beta-estradiol, including more than 50% of the nonspecific binding of the hormone, was destroyed. Analysis of the binding data revealed that one possible site of action of the cations on the binding protein might be the sulfhydryl group(s) of the 17beta-estradiol binding site. The inhibition of 17beta-estradiol binding brought about by Zn2+ was partially abolished by dithiothreitol. Among the metal ions tested, Cu2+ was found to be the most potent inhibitor, followed by Cd2+, Zn2+, and Pb2+. At 1 mM, Mn2+, Ba2+, Ca2+, and Mg2+ had little effect, but at 5 mM, their inhibitory action became more appreciable. K+ and Na+ had no effect on 17beta-estradiol binding. The stimulatory effect of 5 mM Zn2+, Ca2+, Mg2+, and K+ on the binding of 3H-17beta-estradiol to a macromolecular fraction from bovine endometrium was not observed in human endometrial cytosol.