Michael Jaffe

Long-term intracaval calcium infusion therapy in end-organ resistance to 1,25-dihydroxyvitamin D

Two boys aged six and four with the syndrome of hereditary resistance to 1,25-dihydroxyvitamin D3 with rickets alopecia and growth retardation are presented. After unsuccessful therapeutic trials with pharmacologic doses of vitamin D or its active metabolites, the patients were treated by long-term intracaval infusions of calcium through an implantable catheter. A total of 0.5 to 0.9 g of elemental calcium was infused daily for 18 months and the serum calcium concentration was maintained at 9 to 10 mg/dl. Bone pain subsided within one week of treatment. Serum phosphorus, immunoreactive parathyroid hormone, and 1,25-dihydroxyvitamin D concentrations and alkaline phosphatase activity were normalized within four to nine months. Radiographs of the knees and hands revealed progressive healing of rickets with complete resolution after one year of treatment. The patients gained 12 cm and 8 cm per year in height as compared with 3 cm and 2 cm, respectively, in the previous year. A transilial bone biopsy obtained from one patient prior to treatment revealed severe osteomalacia associated with osteitis fibrosa. A follow-up biopsy examined after 12 months of therapy showed almost complete healing of osteomalacia and normal mineralization. These observations indicate the following: (1) Long-term intracaval calcium infusions are an effective mode of therapy for these patients, and (2) When adequate serum calcium and phosphorus concentrations are maintained, healing of rickets and normal growth rate could be achieved even in the absence of a normal 1,25-dihydroxyvitamin D3 receptor-effector system.

Water, Electrolyte, and Endocrine Homeostasis in Infants with Bronchiolitis

ABSTRACT: Twenty-two of 23 consecutive infants with bronchiolitis, 5.5 ± 3.5 mo of age, showed a 1.9 ± 1.4% increase in body weight, increased urinary osmolality of 737 ±193 mmoI/L with low plasma osmolality of 275 ± 4 mmol/L, and markedly elevated plasma antidiuretic hormone (ADH) levels of 114 ± 225 pg/mL. Increased ADH, which usually suppresses plasma renin activity, was associated with increased plasma renin activity of 11-55 ng angiotensin 1/mL/h (normal for age <10 ng angiotensin 1/mL/h). Hyperaldosteronism was evident from the low fractional excretion of sodium of 0.27 ± 0.2% and high fractional excretion of potassium of 21 ± 15%. Serum sodium concentrations were normal. All of the pathologic findings returned to normal when the bronchiolitis subsided. A control group of 10 infants with nonrespiratory febrile illness did not show any of the above abnormalities. Thus, bronchiolitis of infancy is characterized by both increased ADH secretion and hyperreninemia with secondary hyperaldosteronism, which induce water retention but counterbalance each other with respect to serum sodium. Increased ADH secretion as well as increased plasma renin activity are not “inappropriate,” but rather suggest a response to the perception of hypovolemia by intrathoracic receptors. We therefore conclude that the clinical management of bronchiolitis requires close monitoring of body wt and plasma osmolality-urinary osmolality relationship; serum sodium levels may be misleading.

Structural changes in PVDF fibers due to electrospinning and its effect on biological function.

Polyvinylidine fluoride (PVDF) is being investigated as a potential scaffold for bone tissue engineering because of its proven biocompatibility and piezoelectric property, wherein it can generate electrical activity when mechanically deformed. In this study, PVDF scaffolds were prepared by electrospinning using different voltages (12-30 kV), evaluated for the presence of the piezoelectric β-crystal phase and its effect on biological function. Electrospun PVDF was compared with unprocessed/raw PVDF, films and melt-spun fibers for the presence of the piezoelectric β-phase using differential scanning calorimetry, Fourier transform infrared spectroscopy and x-ray diffraction. The osteogenic differentiation of human mesenchymal stem cells (MSCs) was evaluated on scaffolds electrospun at 12 and 25 kV (PVDF-12 kV and PVDF-25 kV, respectively) and compared to tissue culture polystyrene (TCP). Electrospinning PVDF resulted in the formation of the piezoelectric β-phase with the highest β-phase fraction of 72% for electrospun PVDF at 25 kV. MSCs cultured on both the scaffolds were well attached as indicated by a spread morphology. Cells on PVDF-25 kV scaffolds had the greatest alkaline phosphatase activity and early mineralization by day 10 as compared to TCP and PVDF-12 kV. The results demonstrate the potential for the use of PVDF scaffolds for bone tissue engineering applications.

Sleep patterns of infants and young children in Israel

The sleep habits of 661 Israeli children between the ages of 4 months and 4 years were described by their mothers. Twenty-eight per cent reported that their children woke up at least once a week. In the group of regular wakers, the mean number of interrupted nights per week was 4.7, and the mean number of awakenings per night was 2.0. Significant age-related changes in sleep patterns were indicated. The results of this study suggest that sleep and settling patterns in different sociocultural groups are quite similar. These data indicate the existence of an inherent pattern in the maturation of sleep behaviour in the developing child.

CPAP treatment of obstructive sleep apnoea and neurodevelopmental deficits.

Four boys aged 6‐16 years with neurodevelopmental deficits were treated with CPAP for obstructive sleep apnoea. Their diagnoses were: Obesity with mild mental retardation, (2) attention deficit hyperactivity disorder, (3) epilepsy associated with left hemiparesis and (4) mild mental retardation due to fragile X syndrome. Previous therapeutic attempts, including adenotonsillectomy, amitriptyline and methylphenidate in our patients prior to CPAP treatment were unsuccessful. A follow‐up period of 12‐48 months demonstrated a number of clinical benefits such as improvement in sleep quality and daily arousal, and a decrease in the frequency of seizures and episodes of pneumonia. Polysomno‐graphic studies indicated a significant improvement in sleep parameters such as apnoea frequency, awakenings, sleep efficiency and arterial oxygen saturation. Side effects were mild and readily alleviated. CPAP is a feasible therapeutic intervention in intractable obstructive sleep apnoea of childhood, even when associated with neurodevelopmental deficits. CPAP, neurological deficit

Prognosis of motor development and joint hypermobility.

In a study of 59 infants aged 18 months there were 20 with joint hypermobility and delayed motor development, 19 with joint hypermobility and normal motor development, and 20 normal controls. They were reassessed for motor function 3.5 years later at the age of 5 years. Both gross and fine motor performance were significantly delayed in the group of children who exhibited joint hypermobility and motor delay in infancy. No significant delay was evident in those with joint hypermobility only. Joint hypermobility resolved more frequently in children who presented normal motor development at age 18 months. Infants with joint hypermobility and motor delay are a subgroup associated with a less favourable motor outcome and careful follow up is indicated.

Apnea of Infancy, Seizures, and Gastroesophageal Reflux: An Important but Infrequent Association

Seventeen infants between 3 and 37 weeks of age were sequentially admitted for investigation of apnea of infancy or apparent life-threatening events associated with suspected regurgitation. They all underwent an overnight polygraphic study, including esophageal pH monitoring. In nine infants, gastroesophageal reflux was diagnosed. In five of them, the reflux was associated with apnea. However, unassociated episodes of apnea and gastroesophageal reflux occurred (7.1 times and four times, respectively) more frequently than associated episodes. In two of the five infants, a seizure preceded both reflux and apnea and might have acted as a trigger for the apparent life-threatening events. Infants with apparent life-threatening events or apnea of infancy frequently demonstrate gastroesophageal reflux that cannot be consistently related to their events. However, when the association is demonstrated, a common epileptic convulsive etiology should be considered. (J Child Neurol 1996;11:98-100).

The Motor Development of Fat Babies

The motor development of a group of fat babies was compared with that of a group of normal weight babies. A significant correlation was found between excessive weight and gross motor delay. Over the ensuing year, both weight and development reverted to normal in the majority of infants. The possible relationship between observations is discussed, and a plea is made that a comprehensive evaluation of the motor-delayed overweight infant be performed before con cluding that the delay is due solely to the excessive weight.

Sleep characteristics of asthmatics in the first four years of life: a comparative study.

The association between asthma and sleep disturbances was assessed as part of a community survey of sleep patterns in children aged 4-48 months. A questionnaire covering the area of past and present sleep and settling behaviour, as well as health history and demographic data, was administered to 752 mothers of children visiting 14 well baby clinics. Fifty one (6.8%) of the children who were diagnosed as having asthma by their paediatricians were compared with the remaining healthy controls (children with perinatal problems, other chronic illnesses, developmental problems, or repeat admissions to hospital were excluded). Thirty nine per cent of the children with asthma and 38% of the normal controls were identified as regular wakers. The number of interrupted nights each week, settling time, and sleep duration were comparable. In the children with asthma an uninterrupted nights sleep was acquired later than in the control group. Parental perception of the severity of the sleep problem was similar in the two groups, as were the calming techniques. It is concluded that this study does not support a significantly increased prevalence of sleep disturbances among young children with asthma compared with their healthy peers.

High dose intravenous gamma-globulin in intractable epilepsy of childhood

Eight children aged between 1.3 and 13 years suffering from epilepsy refractory to conventional anticonvulsive therapy were treated with high dose intravenous gamma globulin (200 mg/kg, 3 times per week, repeated after 3 weeks). Immunological studies after therapy showed normal results. In four children, clinical and EEG findings markedly improved. In one other case a partial response was noted. No improvement was observed in the remaining three cases. We confirm that although the mechanism is still obscure, high doses of i.v. gammaglobulin may have a beneficial effect in a significant number of children with intractable epilepsy.