A de novo translocation, 14q21q,with a microchromosome—14p21p

A familial translocation, t(14;21)(14p21p;14q21q), in a mother and her child is described. The translocation was ascertained through the birth of a Down syndrome baby with the chromosome constitution 47,XX,-14, +der 14, +der 21,t(14;21)(q11; p12) mat. A 1:3 segregation in the maternal meiosis is suggested for the evolution of the unbalanced chromosome state. The main translocated chromosome 14q21q mimics the product of a Robertsonian translocation, while the 14p21p chromosome has the morphology of a satellited microchromosome. The cytogenetic nature of this translocation is discussed.     

Overexpression of amyloid precursor protein reduces epsilon protein kinase C levels

Alzheimer’s disease (AD) is characterized by extracellular deposits of amyloid beta peptide (Aβ), a peptide that is generated upon proteolytic cleavage of amyloid precursor protein (APP). The events leading to the development of AD and their sequence are not yet fully understood. Protein kinase C (PKC) has been suggested to have a significant role in controlling neuronal degeneration and in the aberrant signal transduction taking place in AD. Several studies document a deficit in PKC levels and activity in brains of AD patients when compared with those of normal controls. Such a decrease in PKC could have serious implications since certain PKC isozymes were shown to drive the APP proteolytic cleavage into a non-amyloidogenic pathway. Reduced levels of distinct PKC isozymes could thus contribute to driving APP processing toward an amyloidogenic pathway.     

Alveolar bone loss in liver transplantation patients: relationship with prolonged steroid treatment and parathyroid hormone levels

AIM: To evaluate the relationship among alveolar bone loss (ABL), bone status and calcium-regulating hormones in liver transplantees. PATIENTS AND METHODS: Twenty-one liver transplantees underwent a full oral examination. The correlations among bone densitometry, bone metabolic status and drug treatment were examined. RESULTS: Twelve patients had osteopenia, and six were osteoporotic. ABL was 4.33+/-2.32 mm (range 0.67-9.92). Parathyroid hormone (PTH) levels ranged from 14 to 106 (mean 55.2+/-26.4). The mean 25(OH)D(3) was 11.68+/-4.7, range 3.5-21.1 ng/ml. Nine patients were vitamin D deficient (<10 ng/ml); none of the patients had 25(OH)D(3) levels > or =30 ng/ml. No correlation was found between ABL and current or total glucocorticoids dose, although there was an inverse relation with the duration of treatment (r =-0.474, p=0.03). A positive correlation was found between ABL, PTH (r =0.419, p=0.059) and hip bone mineral density (BMD) (r=0.482, p=0.027). ABL correlated closely with age, PTH, glucocorticoid treatment (duration) and hip BMD (r =0.810, p=0.004). CONCLUSIONS: The majority of liver transplant patients had insufficient 25(OH)D(3) serum levels. Changes in calcium-regulating hormones and hip BMD were correlated with ABL. Therefore, therapeutic intervention aimed at treating vitamin D deficiency and secondary hyperparathyroidism should be considered in these patients. The benefits of vitamin D treatment in the management of secondary hyperparathyroidism and possible decrease in ABL deserve further evaluation in controlled trials.     

Addenda

We describe a female infant with manifestations of complete monosomy for chromosome 21 intrauterine growth retardation, failure to thrive, craniofacial anomalies, arthrogryposis-like features, and psychomotor retardation. Chromosome analysis demonstrated mosaicism for three different cell lines in the various tissues examined; 45,XX,–21/46,XX,del(21)(q11) 46,XX. The existence of these three lines suggests a possible explanation for the few cases of “complete monosomy 21” which have been reported.     

Comparison of sucking patterns at introduction of oral feeding and at term in Israeli and American preterm infants

BACKGROUND: It has been hypothesized that early initiation of oral feeding in premature infants may enhance the maturation of sucking patterns. AIM: To compare preterm infant sucking characteristics in urban level III neonatal care units in the USA and Israel. The two hospitals have different practices regarding the introduction of oral feeding. METHODS: Infants were assessed at 34-35 wk postconceptional age (PCA) and at term. Sucking parameters were assessed with the Kron's Nutritive Sucking Apparatus. RESULTS: 70 infants (38 Americans and 32 Israelis) participated in the study. Oral feedings were initiated earlier (32.6 +/- 4.3 vs 34.5 +/- 1.8 wk PCA, p < 0.01) and full oral feedings were reached earlier (35.4 +/- 2.8 vs 36.5 +/- 2.5 wk PCA, p < 0.05) in the USA infants. American preterm infants produced significantly more sucks (p < 0.001), had a higher suck rate (p < 0.001), more sucks per burst (p < 0.05), and a shorter interburst width (p < 0.01) at 34 wk PCA than Israeli infants. At term, American infants produced significant more sucks (p < 0.001), higher suck rate (p < 0.001), shorter intersuck width (p < 0.001), and a shorter interburst width (p < 0.05) than the Israeli infants of the same PCA. CONCLUSION: Different practices in the care of preterm infants, such as postconceptional age at introduction of oral feeding, may play a role in the development of feeding and feeding organization at term.     

The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosa

Usher syndrome is a frequent cause of the combination of deafness and blindness due to retinitis pigmentosa (RP). Five genes are known to underlie different forms of Usher syndrome type I (USH1). In the Ashkenazi Jewish population, the R245X mutation of the PCDH15 gene may be the most common cause of USH1 (Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, Desnick RK, Willner JP, Avraham KB, Ostrer H, Oddoux C, Griffith AJ, Friedman TB N Engl J Med 348: 1664-1670, 2003). To estimate what percentage of Ashkenazi Jewish children born with profound hearing loss will develop RP due to R245X, we examined the prevalence of the R245X PCDH15 mutation and its carrier rate among Ashkenazi Jews in Israel. Among probands diagnosed with nonsyndromic hearing loss not due to mutations of connexin 26 (GJB2) and/or connexin 30 (GJB6), and below the age of 10, 2 of 20 (10%) were homozygous for the R245X mutation. Among older nonsyndromic deaf individuals, no homozygotes were detected, although one individual was heterozygous for R245X. The carrier rate of the R245X mutation among the normal hearing Ashkenazi population in Israel was estimated at 1%. Ashkenazi Jewish children with profound prelingual hearing loss should be evaluated for the R245X PCDH15 mutation and undergo ophthalmologic evaluation to determine whether they will develop RP. Rehabilitation can then begin before loss of vision. Early use of cochlear implants in such cases may rescue these individuals from a dual neurosensory deficit.     

Predominant factors associated with bone loss in liver transplant patients - after prolonged post-transplantation period

INTRODUCTION: Osteoporosis is a major cause of morbidity in liver transplant recipients and is associated with multiple factors. OBJECTIVES: To evaluate bone mineral density (BMD), bone turnover and calcium-regulating hormones in 29 patients (17 men, 12 women) 2-12 yrs following liver transplantation for non-alcoholic liver diseases. RESULTS: Fifteen patients (52%) were on immunosuppressive treatment with tacrolimus and 14 (48%) with cyclosporine. Eleven patients (38%) were currently on prednisone, 18 patients (62%) had stopped glucocorticoid treatment 6 months to 11 yrs prior to the study. Nineteen patients (65.5%) had decreased BMD according to WHO criteria, 17 (58.2%) at the femoral neck, 13 (44.8%) at the lumbar spine. Nineteen patients (65.5%) had a subnormal (<15 ng/mL) serum level of 25 (OH) D3. These patients had significantly lower BMD at the femoral neck (p = 0.02). Femoral neck BMD negatively correlated with serum parathyroid hormone level (p = 0.06, r = -0.35), length of the post-transplantation period (p = 0.025, r = -0.416) and duration of glucocorticoid treatment (p = 0.029, r = -0.406), regardless of its cumulative dose. Symptomatic fractures were less frequent in tacrolimus treated patients than in cyclosporine users (p = 0.03). CONCLUSIONS: Decreased BMD is frequent following liver transplantation and is affected by vitamin D deficiency, cyclosporine use, and the duration of glucocorticoid therapy, but not by its cumulative dose. Achievement and maintenance of optimal vitamin D status and shortening of glucocorticoid treatment period may have a favorable effect on bone preservation.     

Bone density in axial and appendicular skeleton in patients with lactose intolerance: influence of calcium intake and vitamin D status

BACKGROUND: Lactose intolerance (LI) is a common enzymatic insufficiency, manifesting by poor tolerance of dairy products, leading to low calcium intake and poor calcium absorption from dairy products. These changes might lead to an impairment of bone metabolism [1]. OBJECTIVES: To evaluate the impact of LI on quantitative bone parameters in axial and appendicular skeletal sites. To assess the impact of calcium intake from dairy and non-dairy nutritional sources, calcium regulating hormones and bone turnover on quantitative bone parameters in LI patients. METHODS: We evaluated calcium intake and bone status in sixty-six patients with LI, 49 women and 17 men, aged 20 to 78. Bone mass was assessed at the lumbar spine (LS), total hip (TH) and femoral neck (FN) by dual-energy x-ray absorptiometry (DEXA) and at the radius, tibia, phalanx by quantitative ultrasound. Serum calcium, albumin, inorganic phosphate, calcium regulating hormones and markers of bone turnover were evaluated. RESULTS: Total daily calcium intake was below the recommended by the American Dietetic Association [2] in all study participants (mean 692 mg/day +/- 162). Elevated level of urinary deoxypyridinoline crosslinks (DPD) was observed in 63 (96%) patients and was negatively correlated with total daily calcium intake (r = -0.998, p = 0.025) and with nondairy calcium intake (r = -0.34, p = 0.015). Parathyroid hormone (PTH) level in the upper third of normal range (45-65 ng/L) was observed in 11 (17%) patients. Parathyroid hormone (PTH) was inversely correlated with total calcium intake (r = -0.4, p = 0.001), dairy calcium intake (r = -0.83, p = 0.05), non-dairy calcium intake (r = -0.29, p = 0.043), 25OHD(3) serum level (r = -0.3, p = 0.007) and positively correlated with bone turnover markers (deoxypyridinoline crosslinks [DPD], r = 0.36, p = 0.01 and bone specific alkaline phosphatase [BSAP] r = 0.36, p = 0.01). Decrease in quantitative bone parameters compared to age-matched controls was observed in the axial and in the appendicular skeleton in men and in postmenopausal women: mean z-score for LS -0.87 +/- 0.22 and -1.32 +/- 0.65, p = 0.004 and 0.015, tibia -1.15 +/- 0.53 and -0.44 +/- 0.044, p < 0.001 and 0.27, phalanx -0.98 +/- 0.22 and -0.52 +/- 0.98, p < 0.001. We observed decrease in bone mass in patients with serum PTH in the upper tertile of normal range in the FN (z-score -0.57 +/- 0.6 versus -0.03 +/- 0.9, p = 0.025), TH (-0.51 +/- 0.96 versus 0.04 +/- 0.9, p = 0.05) and radius (-1.84 +/- 0.27 versus -0.07 +/- 1.61, p = 0.025, respectively). z-scores in FN and TH positively correlated with serum 25OHD(3) level (r = 0.31, 0.29; p = 0.014, 0.019). In postmenopausal women serum 25OHD(3) level correlated also with LS z-scores (r = 0.52, p = 0.004); FN and TH z-scores negatively correlated with DPD level (r = -0.51, p = 0.02 and r = -0.55, p = 0.04). CONCLUSION: LI state may lead to increased bone turnover and decreased bone mass especially in men and postmenopausal women. Impaired vitamin D status and low calcium intake may be deleterious to bone in this condition.     

Parental Anxiety Following Discharge From Hospital of Their Very Low Birth Weight Infants*

The uncertainty regarding the future well‐being of very low birth weight infants is a source of considerable anxiety for parents, even after discharge from the hospital. We identify factors related to postdischarge anxiety levels of parents of 65 infants. Infant's weight relative to gestational age; the presence of central nervous system complications; informational support; and a warm, caring attitude by hospital staff explained 35% of the variance in mothers' anxiety levels. Father's age, infant's gender, perception of the infant as problematic, and the availability of child care support explained 33% of the variance in fathers' anxiety levels. Practice implications, including both identification of high‐risk groups and interventions aimed at bringing about change in specific factors, are discussed.