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Biomedical subjects

R Lala

Publications and source records attributed to R Lala.

At least 19 recordsLinked to original sources
PubMed2003

Pubertal development in patients with McCune-Albright syndrome or pseudohypoparathyroidism.

Gain or loss of function mutations of the GNAS1 gene lead to McCune-Albright syndrome (MAS) or pseudohypoparathyroidism Ia (PHP-Ia), respectively. Patients with MAS, caused by a post-zygotic missense mutation leading to constitutive activation of Gs alpha, suffer from gonadotropin-independent precocious puberty, and delayed or incomplete sexual development and reproductive dysfunction is found in women with PHP-Ia, an inherited disorder caused by deficient expression or function of the Gs alpha protein. In females with MAS, 50% developed precocious puberty by the age of 4 years, the remaining between 4 and 8 years. Peripheral precocious puberty is often atypical and characterized by alternate periods of rapid progression and regression of pubertal development; menstrual bleeding may occur before breast development. Ovarian cyst growth and regression is often described as a sign of ovarian follicle hyperactivation. Notwithstanding this clinical heterogeneity, a subset of patients with MAS develop relentlessly progressive precocious puberty ultimately resulting in premature epiphyseal fusion and reduced adult stature. Long-term information on reproductive function has been obtained in females: some patients had regular menses without ovarian cysts on pelvic US scan, whereas others were oligomenorrheic and showed recurrent ovarian cysts. In males with MAS, precocious puberty occurred in three patients between 4 and 9 years of age. In one patient, long-term follow-up demonstrated normal plasma testosterone and gonadotropin values at the age of 17 years. On testicular sonography, multiple hyperechogeneic spots were found in both testicles (snow-storm appearance). Female patients with PHP-Ia were oligomenorrheic or amenorrheic; more than half had delayed or incomplete sexual development, They were mildly hypoestrogenic with normal to slightly elevated serum gonadotropin levels. These clinical and biochemical findings indicate partial resistance of the theca and granulosa cells of the ovary to gonadotropins due to deficient Gs alpha activity. Responsiveness might be sufficient to promote some degree of follicular development and steroid secretion, but insufficient to induce ovulation

Amenorrhea↗
PubMed2002

Bone turnover in children and adolescents with McCune-Albright syndrome treated with pamidronate for bone fibrous dysplasia.

Bone fibrous dysplasia is one of the main features of McCune-Albright syndrome, a rare genetic condition caused by constitutive activating mutations of Gs-protein and defined by skin dysplasia, bone fibrous dysplasia, and autonomous multiple endocrinopathies. Raised serum alkaline phosphatase (ALP) and urinary hydroxyproline levels indicating bone metabolic hyperactivity have been reported in these patients. Encouraging therapeutic results have been achieved, mainly in adults, with pamidronate, an aminobisphosphonate. In this study we investigate newer bone metabolic indices in a cohort of 11 children and adolescents treated with pamidronate. Tenfold increases of bone ALP and urinary pyridinoline cross-links were found and osteocalcin levels were twofold higher compared with reference values. After treatment, significant decreases in bone ALP and cross-links (Wilcoxon test P < 0.06) were found. Bone mineral density (BMD) significantly increased during treatment. There were signs of radiological healing as thickening of the cortical bone was found in some cases.

Adolescent↗
PubMed2002

An R201H activating mutation of the GNAS1 (Gsalpha) gene in a corticotroph pituitary adenoma.

In the pituitary gland, activating mutations of the GNAS1 (Gsalpha) gene at Gln227 have been identified in adrenocorticotrophin secreting, growth hormone secreting, and prolactin secreting adenomas. To date, mutations at the codon encoding R201, typically underlying the McCune-Albright syndrome and isolated fibrous dysplasia of bone, have been demonstrated only in growth hormone secreting pituitary adenomas. In this study, a polymerase chain reaction amplified target sequence in exon 8 of the GNAS1 gene was sequenced, identifying the first R201 mutation seen in an isolated basophilic adenoma which generated Cushing's disease in a child. This case adds Cushing's disease to the range of human diseases caused by R201 mutations of the GNAS1 gene.

Adenoma, Basophil↗
PubMed2002

Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.

Acromegaly↗
PubMed2002

Pamidronate treatment in bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.

Thirteen patients with McCune-Albright syndrome (MAS) and bone fibrous dysplasia (BFD) have been treated for 2-6 years with pamidronate, an aminobisphosphonate which inhibits osteoclastic function. MAS is a rare genetic condition caused by constitutive activating mutations of the Gs protein and manifests with skin dysplasia, bone fibrous dysplasia, and multiple endocrinopathies. Raised serum alkaline phosphatase and urinary hydroxyproline have been reported in these patients, indicating bone metabolic hyperactivity. Encouraging therapeutic results have been achieved with pamidronate, mainly in adults. In our study, treatment reduced bone pain, fracture rate and metabolic indices of bone turnover, in particular significantly decreased bone alkaline phosphatase and cross-links (Wilcoxon test; p <0.06), and increased bone mineral density (DEXA). Signs of healing, such as thickening of the cortical bone, were found in some patients. Three patterns of MRI were found: homogeneous hypointense fibrous tissue, 'dotted' hypointense fibrous tissue, and hyperintense cystic images. Pamidronate treatment can be considered a favorable therapeutic option for patients with MAS.

Adolescent↗
PubMed2001

Low birth-weight, microcephalic malformation syndrome in a 46,XX girl and her 46,XY sister with agonadism: third report of the Kennerknecht syndrome or autosomal recessive Seckel-like syndrome with previously undescribed genital anomalies.

We report on two sisters, one 46,XX with normal female phenotype, the other 46,XY with ambiguous external genitalia and agonadism. Both have a low birth weight and microcephalic malformation syndrome leading to early death. The 46,XX patient also had a diaphragmatic defect. The XY sister, in addition to absence of gonads and Mùllerian and Wolffian derivatives, had severe hypoplasia of the pulmonary artery and its branches, multicystic kidneys, and pachygyria. This combination of malformations, in part, fits in the autosomal recessive condition described by Kennerknecht et al. [1993] in a 46,XX and 46,XY pair of sibs with agonadism. The craniofacial appearance of our patients is similar to that observed in the 46,XY sister with agonadism reported by Kennerknecht et al. [1995]. On the other hand, intrauterine growth retardation, microcephaly, and pachygyria are not part of the phenotype of the Kennerknecht "syndrome" and agonadism was not present in our 46,XX patient. We suggest two hypotheses to explain the abnormal phenotype in our cases. The first is that they might represent the third sibship affected by the Kennerknecht syndrome with additional anomalies. Alternatively, our two sibs might have a Seckel or a Seckel-like syndrome. The 46,XY patient would then be the first case of Seckel syndrome with sex reversal and agonadism.

Family Health↗
PubMed2001

Testicular function in men treated in childhood for undescended testes.

PURPOSE: The aim of the study was to evaluate testicular hormones and sperm counts of young men treated in childhood for cryptorchidism METHODS: Testicular volume, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone as well as semen specimens were evaluated in 57 men (mean age, 19 years; range, 18 to 27 years) treated in childhood for unilateral (n = 47) and bilateral (n = 10) cryptorchidism. In 3 unilateral cases monorchidism was found. Thirty-seven patients underwent orchiopexy after hormonal treatment (luteinizing hormone releasing factor, 1.2 mg/d for 28 days followed by human chorionic gonadotropin, 500 IU intramuscularly 3 times a week for 3 weeks). The remainder underwent surgery. Mean age at surgical treatment was 5.4 years (range, 2 to 12 years). These patients were examinated again after a mean period of 13.3 years (range, 10 to 19 years). RESULTS: Reduced testicular volume (<12 mL) was found in 6 of 64 testes (9.3%). LH, FSH, and testosterone levels were found within the normal range in all patients. With linear regression, inverse relations were found between FSH and, respectively, testicular volume (P =.002), sperm concentration (P =.013), sperm motility (P =.023), and normally shaped sperms (P =.019). There were direct relations between testicular volume and sperm concentration (P =.02), sperm motility (P =.000), and normally shaped sperms (P =.001). We did not find any statistical correlation between age at surgery and semen quality. Significantly better results in terms of sperm counts were found in patients directly operated on in comparison to those treated with hormones before orchiopexy. CONCLUSIONS: Presented data indicate tubular impairment in young men operated on in childhood for cryptorchidism; FSH values increase and testicular volume decrease are related to sperm deterioration. Studies on children treated in the first 2 years of life are required to clarify the usefulness of early treatment of cryptorchidism.

Adolescent↗
PubMed2000

Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome.

McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.

Adolescent↗
PubMed2000

Expedited human immunodeficiency virus testing of mothers and newborns with unknown HIV status at time of labor and delivery.

New York State introduced the first statewide program in the U.S. of expedited HIV testing (48-hour turn-around results) of mothers with unknown HIV status at the time of labor or delivery and their newborns on August 1, 1999. We evaluated the results of this program during its first 5 months at Lincoln Medical and Mental Health Center (Lincoln Hospital) in the Bronx, New York. There were 1,274 total live birth deliveries between August 1 and December 31, 1999. The HIV infection status of 539 mothers (42.3%) was unknown to medical providers in the labor-delivery suite, either due to lack of testing during the current pregnancy or unavailability of HIV documentation at the time of delivery. During labor and delivery, a total of 462 (85.7%) mothers with unknown HIV status consented to expedited HIV testing (Single Use Diagnostic System for HIV-1 antibody or SUDS). The newborns of 77 mothers (14.3%) who did not consent were tested immediately after birth. Seventeen tested positive for HIV-1 antibody by the SUDS test. The results of 10 of these infants (58.8%) were subsequently confirmed positive for HIV-1 antibody by Western Blot analysis. This new rapid HIV testing program facilitated early diagnosis of these previously unknown HIV-exposed infants, although the low positive predictive value of the test in our community calls for careful communication of these results pending confirmation.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[Neonatal pseudohypoaldosteronism: when a denied truth can delay a diagnosis].

A child with neonatal pseudohypoaldosteronism is referred. The diagnosis was delayed and complicated as her parents didn't tell us that her sister had been affected by the same illness. The child was born after premature rupture of membranes at 34 weeks. At birth, her conditions were satisfactory. The general conditions of the child gradually worsened and, though she regularly ate human pastorized bank milk, she didn't gain any weight. After 13 days she appeared dehydrated with marbled dry skin and haloed eyes, hypotonic and hyporeflexic. Her suction became more and more weaker, with frequent regurgitations and vomiting. Laboratory tests pointed out hyponatremia (110 mEq/l) and hyperkalemia (6.8 mEq/l). We were able to establish diagnosis of primary pseudohypoaldosteronism measuring plasma concentrations of aldosterone (> 5000 pg/ml), 17 hydroxyprogesterone (normal) and corticosteroids (normal). The child was then supplemented with sodium chlorure. A gradual improvement of general conditions took place. We assumed that both childrens and mother were affected by a milder form of primary pseudohypoaldosteronism, characterized by an autosomal dominant way of transmission. We found high levels of aldosterone with normal levels of blood salts also in the sister and mother patient's. After the neonatal period, pseudohypoaldosteronism can be only suspected in case of positive family history.

Female↗
PubMed1999

Bronchogenic cyst and its progress in a premature infant.

The progressive course of a congenital bronchogenic cyst in a very low birth weight infant with respiratory distress is presented. A bronchogenic cyst, while uncommon, should be in the differential diagnosis of pneumomediastinum or medial pneumothorax even in premature infants who are on ventilators.

Adult↗
PubMed1998

Cryptorchidism: medical and surgical treatment in the 1st year of life.

Since cryptorchidism can cause infertility and early orchiopexy can improve fertility, we tried to determine whether medical and surgical treatment in the 1st year of life can improve testicular fertility. We concluded that this is the best time to treat cryptorchid tests.

Administration, Intranasal↗
PubMed1998

Altered bone mineral density in patients with complete androgen insensitivity syndrome.

Androgens have major influences on the regulation of bone mineralization. Because of their unique peripheral metabolism androgens may act on bone via activation of the androgen and/or estrogen receptor. Patients with complete androgen insensitivity syndrome (cAIS) are natural models to assess androgen actions on bone. We studied bone mineral density (BMD) in 10 patients with cAIS (mean age 13.70, range 4.7-19.8 years); 3 patients were studied before gonadectomy; the others were castrated and 6 were on hormonal replacement therapy. The BMD area (aBMD) was measured by dual energy X-ray; lumbar 'apparent' volumetric density (vBMD) was calculated using the formula vBMD = aBMD x [4/(pi x width)]. In the patients, aBMD (0.72 +/- 0.16 g/cm2) and vBMD (0.23 +/- 0.04 g/cm3) were significantly (p < 0.001) reduced in comparison with those of a control group (n = 15, age 5.0-20.5 years: aBMD 1.028 +/- 0.20 g/cm2; vBMD 0.35 +/- 0.04 g/cm3). Both aBMD and vBMD were also reduced in comparison with normal values for males (aBMD -2.66 +/- 0. 99 SDS, p < 0.001; vBMD -3.08 +/- 1.53 SDS, p < 0.0005) and females (aBMD -2.88 +/- 1.05 SDS, p < 0.001; vBMD -2.84 +/- 1.18 SDS, p < 0. 0007). Real lumbar bone density, assessed by computed tomography in 1 patient, was also reduced (-6.2 SDS and -3.5 SDS for male and female normal values, respectively). Biochemical markers of bone metabolism were normal and not significantly different in patients and controls. Girls with cAIS did not have more fractures than controls. In conclusion, both aBMD and vBMD are reduced in cAIS patients, while bone turnover and the fracture risk seem not to be increased. Our data indicate that both androgens and estrogens may be required for acquisition of bone density during childhood.

Absorptiometry, Photon↗