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Biomedical subjects

R David

Publications and source records attributed to R David.

At least 73 records · Page 4Linked to original sources

Sporadic primary hyperparathyroidism in the setting of multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia involving the parathyroid glands, the endocrine pancreas, the duodenum, and the anterior pituitary. The most commonly involved gland is the parathyroid gland, which has been found to be abnormal in 90% to 95% of all patients with MEN 1. The disease process is invariably multiglandular and histologically described as either hyperplasia or multiple adenoma, although the histological distinction between the 2 entities remains difficult and controversial. The prevalence of MEN 1 is approximately 0.002 in 100, whereas the prevalence of sporadic primary hyperparathyroidism due to a solitary adenoma is estimated to be as high as 1 in 100.(2.3) We report herein the first case of sporadic primary hyperparathyroidism in the setting of MEN 1 based on clinical, biochemical, pathological, and genetic studies.

Adenoma, Oxyphilic↗

Effect of low-power He-Ne laser on fracture healing in rats.

BACKGROUND AND OBJECTIVE: Helium-Neon (He-Ne) laser radiation has been found to accelerate fracture healing in laboratory animal models as well as in cultures of cells involved in this process. We investigated the radiological, biomechanical, and histological effects of He-Ne radiation on fracture healing in a rat model. STUDY DESIGN/MATERIALS AND METHODS: Sixty-two rats underwent bilateral open osteotomies of the tibiae followed by internal fixation with intramedullary wires. The right leg received He-Ne laser radiation of 0, 2, or 4 Joules every other day for 2 to 6 weeks while the left leg served as a control. RESULTS: Radiological and histological examinations of the osteotomy sites failed to show any enhancing effect of He-Ne laser radiation on the bone healing process. Biomechanically, the irradiated bones of two of the six test groups were significantly weaker than the controls. CONCLUSION: These results fail to support the previously reported enhancing effect of He-Ne laser radiation on fracture healing.

Animals↗

Neurodevelopment, growth, and viral load in HIV-infected infants.

The relation of HIV-1 infection to infant growth and neurodevelopment was studied prospectively in a cohort of 65 infants born to women at risk for HIV infection. No differences were observed at birth between infected infants (INF) and uninfected infants (SR) of HIV-infected women, and infants of uninfected women (SN) with similar socioeconomic background and exposure to drugs. However, postnatal linear growth and cognitive-motor development of INF infants were impaired when compared to SR and SN infants. Declines in linear growth were observed within the first 6 months of life, whereas delays in neurodevelopment were first appreciated at 12 months. In INF infants, decreased linear growth was positively correlated with developmental delay. Moreover, growth and development were both correlated with HIV viral load. INF infants with high plasma HIV RNA copies (> 5 x 10(5)/ ml) at 6 months of life were more likely to exhibit severe growth and developmental delay than infants with a lower viral burden. The implications of these findings with respect to the mechanism of action of HIV-related growth and neurodevelopmental impairments are discussed.

Body Height↗

Effect of topical anti-inflammatory treatment on the outcome of laser trabeculoplasty. The Fluorometholone-Laser Trabeculoplasty Study Group.

PURPOSE: We investigated the effect of anti-inflammatory treatment on the outcome of argon laser trabeculoplasty. METHODS: In this multicenter, double-masked, randomized, placebo-controlled, parallel comparison study, 140 chronic open-angle glaucoma patients received either 0.25% fluorometholone or vehicle four times a day unilaterally, beginning 24 hours before and continuing one week after argon laser trabeculoplasty. The laser surgeon placed 50 to 60 burns over the inferior 180 degrees of the trabecular meshwork. The patients were followed up frequently for five weeks after the procedure. RESULTS: Following argon laser trabeculoplasty, signs of anterior chamber inflammation were significantly lower in the fluorometholone group. However, there was no significant difference between the fluorometholone and the vehicle groups in the incidence of increased intraocular pressure in the immediate post-argon laser trabeculoplasty period. Intraocular pressure decreased significantly in both groups from day 1 throughout the follow-up period. A significant between-group difference in intraocular pressure decrease was found only at week 5 (7.83 +/- 6.27 [S.D.] mm Hg for the fluorometholone group vs 6.63 +/- 5.79 mm Hg for the vehicle group, P = .046). No drug-related clinically significant adverse events were observed. CONCLUSIONS: Use of fluorometholone is effective in attenuating inflammation and has no clinically significant impact on the outcome of argon laser trabeculoplasty or on the incidence of intraocular pressure spikes during the immediate post-argon laser trabeculoplasty period.

Administration, Topical↗

xGCNF, a nuclear orphan receptor is expressed during neurulation in Xenopus laevis.

Nuclear orphan receptors are DNA binding proteins that share the domain structure of the nuclear hormone receptor superfamily, although ligands are unknown. We have identified an orphan receptor in Xenopus laevis and named it xGCNF based on its high degree of sequence homology to the previously described murine germ cell nuclear factor (mGCNF). In gel-electrophoresis mobility shift analysis experiments in vitro translated xGCNF and mGCNF proteins both bind specifically as homodimers to the same response element, a direct repeat of the half-site consensus AGGTCA with zero spacing (DRO). Transcripts of xGCNF are found in oocytes and in much smaller amounts in the testes. In developmental Northern blots and RNase protection using RNA from different embryonic stages, zygotic expression of xGCNF peaks at midneurula. From late gastrula to midneurula stages, an anterior to posterior concentration gradient of the RNA was observed in whole mount in situ analysis. This antero-posterior gradient of expression was also observed in exogastrulae, both in the ectoderm and mesoderm. In the midneurula embryo, the mRNA was predominantly found in the neural plate and neural crest. Transcription of xGCNF in animal cap explants occurred independent of mesoderm induction.

Amino Acid Sequence↗

Mucinous syringometaplasia. An immunohistochemical and ultrastructural study of a case.

Mucinous syringometaplasia (MS) is an unusual skin lesion of unknown etiology, characterized histologically by epidermal invaginations lined by mucin-laden goblet-like cells and by nonkeratinized squamous cells. The present case study was performed to elucidate further the characteristics of this lesion using immunohistochemistry and electron microscopy. The mucin-laden cells in the MS lesion stained positively for carcinoembryonic antigen, epithelial membrane antigen, and low molecular weight keratins. The ultrastructural examination, which was performed on deparaffined sections, revealed two morphological variants of mucous granules. Electron-dense mucous granules predominated in the mucus-containing cells, which were situated among the keratinocytes adjacent to the epidermal invaginations, mostly in the lower parts of the epidermis. Larger, electron-lucent granules containing flocculent material were found more abundantly in the cells lining the epidermal invaginations. Also, some of the mucus-containing cells showed bundles of tonofilaments; structures that appeared to be isolated short, stubby microvilli; and attachments to adjacent mucus-containing cells and keratinocytes by desmosomes. The ultrastructural and immunohistochemical findings in our case suggest that the mucinous changes occurred as a metaplastic process in the resident epidermal cells and were accompanied by changes in cellular antigen expression resembling those of simple secretory epithelium.

Adult↗

Actions of magnesium, nifedipine and clonidine on the fetal vasculature of the human placenta.

The anticonvulsant magnesium and the antihypertensives clonidine and nifedipine are extensively used for the clinical treatment of preeclampsia and eclampsia. Little, however, is known about the possible effects of these agents on human fetal-placental vascular resistance. We therefore examined the actions of these agents on the human fetal placental vascular bed in vitro relating the concentrations causing any vasoactive effects to the maternal blood levels attained during treatment. Placentas (n = 24) were obtained within 20 minutes of delivery from women (aged 30.2 +/- 0.9 years). In each a placental lobule was bilaterally perfused with Krebs' solution (5 mL/minute, 37 degrees C, 95% O2, 5% CO2) and fetal arterial inflow pressure (FAP) monitored. Submaximal vasoconstriction of the fetal vascular bed was induced by continuous infusion of prostaglandin F2 alpha (4.2 +/- 0.5 microM) which increased FAP from 25.9 +/- 3.9 to 95.1 +/- 6.2 mm Hg. Using a group of placentas for each drug, the effects of MgCl2, nifedipine and clonidine, were examined. Magnesium (0.3-100 mM) (n = 4) dilated the placental fetal circulation with an IC50 of 8.1 mM and a maximal response of 89.7 +/- 3.6% (n = 4). This effect of Mg2+ was not changed during concomitant infusion of the cyclo-oxygenase inhibitor, indomethacin (3 microM). Nifedipine (3-10,000 nM) also produced vasodilatation (maximum response 42 +/- 9%, n = 5). Clonidine (3-1,000 nM) caused no significant change (p < 0.05 n = 5) in vascular resistance (maximum response 11.2-5.7%) relaxation), when compared to controls. Thus in concentrations likely to be therapeutically present in maternal blood, magnesium causes a greater degree of placental fetal vasodilatation than does nifedipine, whereas clonidine is unlikely to have any effect on fetal placental vascular resistance.

Antihypertensive Agents↗

Pigmented lateral periodontal cyst and other pigmented odontogenic lesions.

OBJECTIVE: To report a case of lateral periodontal cyst (LPC) with marked melanin pigmentation in a 38-year-old Black male and to discuss the phenomenon of melanin pigmentation in odontogenic cysts and tumors. RESULTS: Histologically, the epithelial lining of the LPC contained an abundant amount of melanin granules throughout the entire epithelium. Ultrastructurally, epithelial cells contained mature melanosomes (stage IV melanosomes). Melanophages containing aggregates of melanosomes were identified in the connective tissue cyst wall. Perusal of the literature revealed that melanin pigmentation in odontogenic lesions is uncommon. Melanin has been reported in calcifying odontogenic cyst (18 cases), odontogenic keratocyst (8 cases), adenomatoid odontogenic tumor (3 cases), ameloblastic fibroma (3 cases), odontoma (2 cases), and ameloblastic fibro-odontoma, odonto-ameloblastoma, and odontogenic fibroma (1 case each). CONCLUSIONS: Almost all pigmented odontogenic lesions; occurred in Blacks and Asians; they are almost non-existent in Whites. Thus, racial pigmentation probably plays an important role in such lesions.

Adult↗

Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies.

To determine the incidence of transient congenital hypothyroidism due to TSH receptor-blocking antibodies, we screened dried blood specimens obtained from 788 neonates identified as having possible congenital hypothyroidism (from a total population of 1,614,166 babies) and 121 controls. A RRA was used. The potency of blood spot TSH binding inhibitory activity was compared with the severity of congenital hypothyroidism to assess the possible etiological relationship. Maternal serum was studied to confirm the presence of blocking antibodies by both RRA and bioassay. Blood spots obtained from 9 infants contained potent TSH receptor-blocking activity. Samples from 2 additional babies, studied because of clinical suspicion of the disease, were also positive. Long term outcome was known in 8 of the 11 babies, and all had transient disease. Neonates with TSH receptor-blocking activity greater than 132 U/L had a significantly lower T4 level (P < 0.05) and higher TSH (P < 0.005) than those in whom TSH binding-inhibitory activity was less than 132 U/L. All 9 mothers had autoimmune thyroid disease, and 3 had more than 1 affected child. Potent blocking activity was present in 7 maternal serum samples as long as 7 yr after the births of their affected babies. We conclude that measurement of TSH binding-inhibitory activity in dried neonatal blood specimens is a simple and effective method to predict the occurrence of transient congenital hypothyroidism. The incidence of this disorder in North America is 1 in 180,000 normal infants, or approximately 2% of babies with congenital hypothyroidism.

Acute Disease↗

Relationship of growth hormone deficiency and leukemia.

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.

Adolescent↗

Benefits and burdens: researching the consequences of migration in the Sahel.

The consequences of rural out-migration for women and natural resource management are analyzed for four locations in the Sahel region of Africa, located in Burkina Faso, Senegal, Sudan, and Mali. The results show that "the impact of migration on women's management of natural resources varies considerably depending on prevailing gender divisions and relations of labour, of land access and control, and of responsibilities towards family and personal production."

Africa↗

Multiple endocrine neoplasia type 1 (MEN1) in two Asian families.

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.

Adult↗

Abnormalities of water metabolism in children and adolescents following craniotomy for a brain tumor.

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.

Adolescent↗

Intraocular pressure after neodymium:YAG laser treatments in the anterior segment.

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.

Aged↗

Necrotizing enterocolitis and hypothyroidism in a newborn infant: treatment with intravenous L-thyroxine.

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.

Congenital Hypothyroidism↗