Biomedical subjects
Publications and source records attributed to R David.
The use of growth hormone (GH) has been implicated as a possible risk factor for leukemia. We present data from six patients that support a working hypothesis that an increased risk of leukemia may exist in patients with GH deficiency not related to exogenous use of GH.
Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disease characterized by neoplasia of the parathyroid glands, anterior pituitary and endocrine pancreas, is rarely reported in Asian populations. The MEN1 gene, mapped to chromosome 11q13 but yet to be cloned, has been found to be homogeneous in Caucasian populations through linkage analysis. Here, two previously unreported Asian kindreds with MEN1 are described; linkage analysis using microsatellite polymorphic markers in the MEN1 region was carried out. The first kindred, of Mongolian-Chinese origin, is a multigeneration family with over 150 living members, eight of whom are affected to date. The second kindred is of Chinese origin consisting of four affected members. Linkage to chromosome 11q13 was confirmed in both kindreds, supporting evidence for genetic homogeneity. A recombination in the larger kindred localizes the gene distal to marker D11S956, consistent with its placement from previous studies. We also show that it is feasible to use these markers for predictive testing, as four gene carriers were detected in 13 family members with unknown disease status in the first kindred.
We conducted a retrospective analysis of the cases of 122 children operated on for various brain tumors, to determine the incidence and natural history of postoperative diabetes insipidus (DI), and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Abnormalities of water homeostasis were observed in 15 patients (12%). DI, with or without SIADH, was observed in 10 patients (8%), while SIADH alone was seen in five (4%). DI was permanent in five subjects (50%), whereas SIADH resolved completely in all affected individuals. Parenteral desmopressin (dDAVP) was an effective mode of therapy in the postoperative period. The effect did not correlate with a dosage strictly based on body weight.
Intraocular pressure (IOP) increase soon after neodymium:YAG (Nd:YAG) treatments in the anterior segment has been reported. To evaluate this complication in a large sample of patients, we conducted a retrospective study of all Nd:YAG treatments during three years. Three hundred forty capsulotomies and 212 iridotomies were performed with the Q-switched Nd:YAG laser. An IOP elevation of 10 mm Hg or more within two hours of laser surgery was seen in 15 eyes (4.4%) that had a capsulotomy but in 45 eyes (21.2%) that had an iridotomy. In 13 of the 15 eyes in which the IOP increased after capsulotomy, additional risk factors (glaucoma, high myopia, aphakia) were found. Our results indicate that posterior capsulotomy with the Nd:YAG laser in otherwise healthy, pseudophakic eyes is usually not accompanied by immediate IOP elevation. Elevation can be predicted by risk factors and therefore anticipated in a small group of vulnerable patients.
Gastrointestinal complications of hypothyroidism are well documented and include constipation, obstipation, and abdominal distention, as well as ileus, pseudo-obstruction, tumor-like mass of the intestine, and megacolon. We report herein on a 2-week-old, full-term female infant, who had both necrotizing enterocolitis (NEC) and congenital hypothyroidism. We further describe the response to therapy with intravenous L-thyroxine. To our knowledge, the patient's course is the first report of intravenous L-thyroxine in the management of congenital hypothyroidism when oral replacement is not an option. The possible causal relationship between NEC and hypothyroidism is discussed.
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During adrenarche, levels of adrenal androgens increase. Although the regulatory mechanisms of adrenarche and premature adrenarche (PA) are not fully understood, it has been suggested that, unlike the cortisol (F) response to glucocorticoid suppression, which is not age dependent, before adrenarche the major adrenal androgen, dehydroepiandrosterone sulfate, is not suppressible by glucocorticoid. As these studies were performed using long term, high dose glucocorticoids, we sought to evaluate the F and adrenal androgen or androgen precursor suppression in response to low dose glucocorticoids [a single evening dose of dexamethasone (DEX), 0.3 mg/m2]. Twenty-four children (aged 1.3-8.75 yr; 4 males and 20 females) known to have PA, as determined by their response to ACTH-(1-24) (Cortrosyn; 0.25 mg, given by iv bolus), were studied. The children with PA could be divided into two groups, as defined by their morning F level after DEX administration: group I (n = 12), F levels below 5 micrograms/dL; and group II (n = 12), F levels of 5 micrograms/dL or more. Although the mean baseline values of F, testosterone, dehydroepiandrosterone, delta 4-androstenedione, 17-hydroxyprogesterone, and delta 5-17-hydroxypregnenolone did not differ between groups I and II, the mean levels in group I vs. group II of dehydroepiandrosterone, delta 4-androstenedione, and delta 5-17-hydroxypregnenolone were significantly greater in response to ACTH and lower in response to DEX (P < 0.05). Although no clinical difference was noted between the 2 groups, the mean SD for bone age adjusted for chronological age was greater and approached significance in group I, suggesting a greater degree of biological maturity in this group. These results suggest an increased sensitivity of the hypothalamic-pituitary-adrenal axis to changes in ACTH secretion in this subgroup of patients with PA.
We evaluated the use of sonography in monitoring the efficacy of suppressive therapy with a gonadotropin releasing hormone analogue in girls being treated for isosexual precocious puberty. Ten girls 5 to 9 years of age underwent serial sonography and hormonal stimulation tests on the same day. Sonographic trends of decreasing ovarian volume and uterine length indicated early suppression even when absolute values were above threshold. Changes in ovarian volume were the most sensitive predictor of pituitary-gonadal suppression. Sonography is a sensitive and accurate method of monitoring medical therapy; ovarian volume and analysis of interval change are the most sensitive barometers of change.
The hippocampus is a major center for the regulation of the hypothalamic-pituitary-adrenal axis. There is experimental evidence that chronic exposure to high levels of glucocorticoids may be toxic to the hippocampus. We observed elevated mean basal and 60-min cortisol (F) levels in response to adrenocorticotropin stimulation (0.25 mg cortrosyn, i.v. bolus infusion) in 15 children with HIV infection. Furthermore, in eight of the children for whom data was available, in addition to high peripheral cortisol levels, neurologic dysfunction and hippocampal atrophy were noted on CT scan. These preliminary data suggest that in HIV-infected children an altered cortisol secretion may be associated with specific central nervous system damage.
OBJECTIVE: To evaluate the efficacy of 0.5% brimonidine tartrate, an alpha 2-adrenergic agonist, in preventing intraocular pressure (IOP) elevation following argon laser trabeculoplasty. DESIGN: In a multicenter, double-masked, randomized study, 248 patients (248 eyes) who underwent argon laser trabeculoplasty were allocated to four treatment groups: (1) brimonidine administered before and after the procedure; (2) brimonidine administered before the procedure; (3) brimonidine administered after the procedure; and (4) a vehicle administered before and after the procedure. RESULTS: In the first 3 hours after argon laser trabeculoplasty, only one (0.54%) of the 183 brimonidine-treated patients had a postlaser IOP increase of 10 mm Hg or more, while increases of this magnitude occurred in 13 (23%) of the 56 patients who received only the vehicle (P < .001). The three brimonidine-treatment groups demonstrated significant mean reductions in IOP from the pretrabeculoplasty level (-4 to -8 mm Hg), whereas the vehicle-treated group showed an increase in mean IOP (4 mm Hg). Side effects associated with brimonidine treatment included conjunctival blanching (40.9%), lid retraction (7.6%), and a slight lowering of the systolic blood pressure. CONCLUSIONS: One drop of 0.5% brimonidine administered either before or after surgery was found to be efficacious and safe in preventing posttrabeculoplasty elevations in IOP.
OBJECTIVE: To report five cases of prolactin (PRL)-secreting macroadenomas in adolescents, including their presentations and responses to bromocriptine mesylate treatment. PATIENTS: Five adolescents (three females and two males) aged between 12.5 and 17 years were diagnosed as having PRL-secreting macroadenomas at the pediatric endocrine service at New York University Medical Center between 1987 and 1989. Presenting complaints included visual field deficits, gynecomastia, and amenorrhea, both primary and secondary. All patients demonstrated some feature of hypogonadism or pubertal arrest. Diagnostic criteria included an elevated serum PRL level (mean, 1670 micrograms/L; range, 610 to 3700 micrograms/L) and visualization of a pituitary tumor that measured greater than 1 cm by either a computed tomographic scan or magnetic resonance imaging (mean size, 2.7 cm; range, 1.4 to 4 cm). INTERVENTIONS: Each patient was treated with bromocriptine mesylate at an oral dose of 7.5 mg/d. The patients continued with that treatment for the duration of the study period. MEASUREMENTS AND RESULTS: Anterior pituitary function was evaluated in four of five patients before treatment. All four were growth hormone deficient. Three patients were also gonadotropin deficient. Thyrotropin (thyroid-stimulating hormone) and corticotropin (adrenocorticotropic hormone) deficiencies were demonstrated in three patients who had multiple pituitary deficits. Follow-up testing included serial PRL measurements and radiographic imaging of tumor size. All patients demonstrated a marked decrease in PRL levels, as well as in tumor size (mean shrinkage, 70%). The three patients who initially had visual field deficits showed significant improvement of vision with bromocriptine therapy. Follow-up study of anterior pituitary function showed significant improvement with bromocriptine treatment in three patients. CONCLUSIONS: Bromocriptine was quite effective in the shrinkage of PRL-secreting macroadenomas in all our patients. It is a noninvasive treatment that can preserve and restore vision, as well as pituitary function, which is integral to continued growth and sexual maturation of the adolescent. Bromocriptine is preferable to surgery or radiation in the treatment of PRL-secreting macroadenomas in the adolescent.
An increased incidence of mitral valve prolapse (MVP) has been reported in adult patients with autoimmune thyroid disease. The aim of this study was to assess the incidence of MVP in children and adolescents with juvenile autoimmune thyroiditis (JAT). Cardiac echo studies using M-mode, 2D, and Doppler examinations were performed on 23 patients (21 females, 2 males). The patients were studied at a median age of 12 years (range 5-20 years). Only one patient was found to have evidence suggestive of MVP, an incidence (4.3%) similar to that seen in the normal pediatric population. We, therefore, conclude that the incidence of MVP in children and adolescence with JAT is not increased.
This is an immunohistochemical and ultrastructural study of two small cell carcinomas of the ovary with a review of the literature. These cases showed a dimorphic population of small and large cells sharply demarcated from each other. Cytokeratin 18 and vimentin were mainly expressed in the large tumour cells, some of which also stained for alpha-smooth muscle actin. Periodic-acid-Schiff-positive, alpha-1-antitrypsin-positive hyaline globules were present in one case. Ultrastructural findings included filamentous nucleolonema as well as evidence of smooth muscle differentiation. Some of these observations have not been previously reported. Certain of the above features seem to support a germ cell origin of small cell carcinoma, but they cannot be considered specific for germ cell neoplasms. Thus, small cell carcinoma of the ovary cannot be classified into one of the known categories of ovarian tumours at the present time.
We describe a 29-year-old patient who developed acute colitis limited to the sigmoid and left colon with features mimicking ischemic injury after a prolonged administration of trifluoroperazine and levomepromazine, two phenothiazines in association with haloperidol, another neuroleptic, and biperidene, an anticholinergic compound. The discontinuation of these drugs was followed by a prompt and complete recovery, and no other cause of acute colitis was found. The subsequent administration of sultopride, a neuroleptic from the benzamide family and then the readministration of haloperidol were well tolerated. No colonic disorder occurred for the following months. This case strongly supports the view that neuroleptic agents, in particular phenothiazines, may induce acute colitis and that haloperidol, a butyrophenone derivative, or sultopride, a benzamide-related neuroleptic, can be administered thereafter without recurrence of the disease.
Out of a total of 2272 diurnal curves (DC) of intraocular pressure (IOP) obtained from 1178 patients 690 first curves of the right eye of all patients were analysed. For each DC there were 4-6 IOP readings taken between 8 am and 6.30 pm of the same day. The patients' diagnosis, age, sex, type of IOP lowering medication, diabetes, and the calendar month of the year were recorded. In 40% of cases the highest IOP was found at the earliest morning measurement with some 65% of peaks occurring before noon. The lowest IOP measurement showed no specific predilection for any particular time of the day. These findings were true for all diagnosis groups. The mean range of IOP fluctuation during the DC was 5.0 mm Hg in normals, 5.8 mm Hg in patients with open angle glaucoma (OAG), and 6.8 mm Hg in patients with ocular hypertension (OHT). Patients treated with timolol had a lower mean IOP fluctuation range than those on other types of IOP lowering treatment. No association was found between all other parameters examined and the diurnal IOP distribution.
In the largest reported family of patients with multiple endocrine neoplasia type 1 (MEN 1), hyperparathyroidism was expressed at first screening in 33 patients by elevation of ionized calcium (IC) (30 cases) or parathyroid hormone (three cases) without elevation of albumin-corrected total calcium (ACTC). Three of these 33 patients have shown a progressive rise in IC and later an elevation of ACTC. However, the age distribution suggests that in others the level of IC may remain stable at a minimally elevated level throughout life with ACTC remaining normal except for transient rises at the times of intercurrent illness or surgical operation. Even when ACTC is normal preoperatively, patients with an elevation of IC require radical subtotal parathyroidectomy or total parathyroidectomy and forearm implantation to restore IC to a normal level. Institutions that rely on ACTC as a screening test for hyperparathyroidism in MEN 1 will miss the diagnosis in nearly half of patients under the age of 30. The greatest deficiency in using ACTC occurs in the follow-up of patients who have undergone parathyroidectomy for MEN 1. Only three of 11 recurrences were evidenced by this measurement.
Two patients with ankylosing spondylitis (AS) and recurrent uveitis had rubeosis iridis each with an episode of spontaneous hyphema. Rubeosis iridis has been reported to occur in some cases of uveitis, but it has not been seen in those associated with AS. We suggest that AS be included among the conditions that can lead to the development of rubeosis iridis, with consequent silent hyphema.
Delineation of major T helper cell recognition sites of human immunodeficiency virus (HIV-1) proteins represents one important step in the design of an efficient acquired immune deficiency syndrome (AIDS) vaccine. Towards this end, we have explored the immunogenicity of HIV-1BRU proteins in the mouse model. Preliminary experiments revealed that inbred mice primed with whole inactivated HIV-1 developed strong CD4+ T cell proliferative responses to a variety of recombinant viral proteins including reverse transcriptase (RT). To characterize further the mouse T cell responses to this protein, several Ad- or Ed-restricted T hybridoma cells (THC) were established from BALB/c or DBA/2 mice. These THC were tested for their capacity to recognize a series of 15-mer synthetic overlapping peptides spanning three segments of HIV-1 RT that had been preselected on the basis of either alpha-helicity, amphipaticity, and/or for containing rare amino acid sequence patterns. Peptides corresponding to a C-terminal region (residues 528-560) of RT were recognized by several of the THC established from RT-primed mice. Furthermore, a non-alpha-helical peptide from this region (A3, 528-543) was capable of priming mice with different H-2 haplotypes for both peptide A3 and native RT CD4+ T cell recognition. In addition to the recently identified RT determinant 203-219 capable of triggering both mouse and human CD8+ CTL, the present results identify a good candidate for an immunodominant RT epitope capable of eliciting RT-specific T helper cell responses.