Vitamin D deficiency and insufficiency in Orthodox and non-Orthodox Jewish mothers in Israel.

BACKGROUND: The modest clothing that Orthodox Jewish women wear exposes very little of their skin to sunlight. Under these conditions they may develop vitamin D deficiency, even in sunny Israel. OBJECTIVES: To determine and compare the vitamin D nutritional status in Jewish orthodox mothers to that of non-orthodox mothers who live in the same metropolitan area in Israel. METHODS: 25-Hydroxyvitamin D was measured by competitive protein-binding radioassay in the sera of 341 Jewish Israeli mothers (156 orthodox and 185 non-orthodox). The sera were obtained 48-72 hours after childbirth during the late summer of 1998 and the spring of 1999. RESULTS: The mean (SD) serum concentration of 25-OHD was significantly (P < 0.002) lower (13.5 +/- 7.5 ng/ml) in the orthodox than in the non-orthodox mothers (18.6 +/- 9.6 ng/ml). Vitamin D deficiency (< 5 ng/ml) and insufficiency (< 10 ng/ml) were more common in the orthodox mothers (5.1% and 32.7% respectively) than in the non-orthodox mothers (2.7% and 13%, respectively). In subgroups of mothers supplemented with 400 units of vitamin D daily during pregnancy, vitamin D deficiency and insufficiency were less common (2.2% and 13%, respectively) in orthodox and non-orthodox mothers (0% and 8.1%, respectively). Vitamin D insufficiency was more common in the winter than in the summer only among non-orthodox mothers. CONCLUSIONS: The high prevalence of vitamin D deficiency and insufficiency in Israeli mothers raises the question whether vitamin D supplements should be given to pregnant women in Israel, at least to orthodox mothers.

Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study.

OBJECTIVE: To report results from a long-term prospective study of safety of haloperidol treatment and prevalence of haloperidol-related dyskinesias. METHOD: Subjects were children with autism requiring pharmacotherapy for target symptoms. After baseline assessments, children received haloperidol treatment; responders requiring further treatment were considered for enrollment into the present study. Six-month haloperidol treatment periods were followed by a 4-week placebo period. The procedure was repeated if further haloperidol treatment was required. At specified times children were evaluated by using multiple instruments. RESULTS: Between 1979 and 1994, 118 children aged 2.3 to 8.2 years participated in the study. The mean dose of haloperidol was 1.75 mg/day. Mainly withdrawal dyskinesias (WD) developed in 40 (33.9%) children; 20 had more than one dyskinetic episode. A subgroup that remained significantly longer in the study and had a significantly higher cumulative dose of haloperidol evidenced a significantly higher incidence of WD. Occurrence rates of tardive dyskinesia (TD) and multiple episodes of TD/WD were higher among girls. CONCLUSION: Female gender and pre- and perinatal complications may be involved in susceptibility to dyskinesias; greater cumulative haloperidol dose and/or longer exposure to haloperidol may increase the risk.

Acute maduramicin toxicity in calves.

A herd of 277 beef-breed calves in three age groups was mistakenly given the poultry coccidiostat maduramicin in a total mixed ration. It caused an acute toxicosis in which sudden death was the sole clinical finding in most cases. One group of 212 calves aged five to eight months suffered a mortality of 51 per cent in eight days and a total mortality of 56 per cent during the 40 days in which mortality was recorded. Mortality of only 3 per cent was recorded in two other groups of calves aged nine to 16 months in eight days and a total mortality of 11 per cent over the 40-day period.

The development of syntactic subjects in Portuguese-speaking children.

In order to separate competence and performance factors in acquisition of knowledge of syntactic subjects, we audiotaped and analysed the spontaneous speech of 20 Portuguese-speaking two-year-olds in natural conversation with Portuguese-speaking adults. We separated the children into three groups based on Mean Length of Utterance in Words: 1.5-1.99; 2.0-2.99; 3.0-4.99. Our cross-sectional data demonstrated that Portuguese-speaking children increased their use of subjects from 28% in the lowest-MLUW group to 57% in the highest-MLUW group. The children in the highest-MLUW group almost perfectly matched the adult speakers in the study on every measure. The increase in children's use of subjects was primarily due to an increase in the use of pronominal subjects. A comparison between Portuguese- and English-speaking children suggests that adult competence about the status of subjects is present at the onset of combinatorial speech, as shown by differential production of subjects. Each group also experiences performance limitations, as shown by the increase in subject use as development proceeds.

Haloperidol-related dyskinesias and pre- and perinatal complications in autistic children.

It has been hypothesized that an association exists between pre- and perinatal complications, central nervous system (CNS) dysfunction, and the development of tardive (TD) and withdrawal dyskinesias (WD). We assessed the relationship between pre- and perinatal complications and TD/WD in a sample of 118 children with autism who participated in an ongoing long-term prospective study of the efficacy and safety of haloperidol. The mean total Rochester Research Obstetrical Scale (ROS) score was significantly higher for children who developed TD/WD compared to those who did not (p = .007) as was the mean score of the ROS Delivery Scale (p = .002). Anesthesia during delivery was more frequent in children who developed TD/WD (25 of 40, 62.5%) than in those who did not (30 of 78, 38.5%) (p = .019). The ROS Not Vertex Presentation item and TD/WD were associated only in females (p = .019). Six of 7 males with short labor developed TD/WD (p = .007). ROS scores did not differ significantly as a function of gender or socio-economic status (SES). Pre- and perinatal complications appear to be related to the development of TD/WD in this sample of children.

Bone biopsies and serum vitamin-D levels in patients with hip fracture.

To assess the correlation between osteoid and vitamin D in patients with a proximal femoral fracture, bone biopsies of the fracture site and the iliac crest were studied; and vitamin-D levels were measured in fasting blood taken on the day of admission. No osteomalacia was found at either site in any of the 95 patients investigated. In 65/95 patients, levels of 25-hydroxy-vitamin D (25-OHD) and 24,25-dihydroxy-vitamin D (24, 25-OH2D) were within the normal range, whereas 30/95 patients were deficient. Because there was no correlation between the amount of osteoid and vitamin-D metabolites in our patients, we concluded that osteomalacia was not a contributory factor in the pathogenesis of the hip fracture.

Vitamin D deficiency in elderly patients in a general hospital.

Serum 25-hydroxyvitamin D (25-OHD) levels were measured in 338 elderly patients admitted to the Geriatric Medicine Departments of a general hospital in Israel in the course of one year. The mean (+/- SD) serum 25-OHD levels were significantly lower (P less than .01) in the elderly patients (13.5 +/- 8.9 ng/mL) than in healthy young controls (24.7 +/- 6.1 ng/mL). One hundred ten patients (35.5%) were either vitamin D deficient (25-OHD less than 5 ng/mL) or had borderline serum levels of 25-OHD (5-9 ng/mL). The mean (+/- SD) serum 25-OHD concentration of patients who were completely mobile before hospitalization was 15.5 +/- 8.8 ng/mL (n = 239). In patients mainly immobilized but able to leave the house occasionally, it was 10.2 +/- 6.3 ng/mL (n = 84) and of bed-ridden patients, it was 5.2 +/- 3.2 ng/mL (n = 15). No correlation was found between serum 25-OHD levels and the patients' age or serum calcium, phosphorus, alkaline phosphatase, and albumin values. Thus, in order to detect vitamin D deficiency in the elderly, it is necessary to measure serum 25-OHD concentration. The results demonstrate that vitamin D deficiency is common among elderly patients even in sunny climates and indicate the need for development of effective programs of prevention and treatment.

Seasonal variation in paired maternal-newborn serum 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D concentrations in Israel.

Seasonal changes were observed in the vitamin D status of mothers and their newly born infants in sunny Israel. Maternal and newborn serum levels of 25-hydroxyvitamin D (25-OHD) were lower (less than 0.01) in March-April (n = 45 pairs), than in September-October (n = 33 pairs). Parallel seasonal changes were also found in serum 24,25-dihydroxyvitamin D [24, 25-(OH)2D] concentrations. In the spring, 20% of the mothers and 40% of their infants had vitamin D deficiency or borderline serum 25-OHD levels. In the autumn, in contrast, none of the mothers and only one newborn were vitamin D-deficient, and one mother and two newborns had borderline serum 25-OHD levels. The results demonstrate that even in Mediterranean climates there are seasonal changes in maternal vitamin D status, which have a significant effect on the serum levels of vitamin D metabolites in their newborn infants. This raises the question as to whether vitamin D supplements should be given to pregnant women in Israel, at least during the winter.

Single oral high-dose vitamin D3 prophylaxis in the elderly.

A poor vitamin D status is common in the elderly during the winter months. Because it is possible that hypovitaminosis D may be a cause of senile osteopenia, a simple method of prophylaxis would be useful. The single, oral, high-dose method was tested in two old-age homes, and the efficacy of vitamin D3 was compared with that of 25-hydroxyvitamin D3 (25-OHD3). The trials showed that 25-OHD3 caused a higher peak value in the serum 25-OHD levels in the second week than did vitamin D3. However, follow-up after four to five months showed that in those patients who received a single, oral dose of 25-OHD3, the serum 25-OHD levels had returned to the baseline low values, whereas in those patients who had had oral vitamin D3, the serum 25-OHD levels still remained significantly raised compared with the baseline values and were within normal limits. It is concluded that the single, oral, high-dose method using vitamin D3 is a safe and simple method of prophylaxis and could be used easily in large populations of elderly persons.

Vitamin D metabolites in amniotic fluid.

To provide further data on vitamin D metabolism in pregnancy, the concentrations of 25-hydroxyvitamin D (25OHD; n = 72), 24,25-dihydroxyvitamin D [24,25-(OH)2D; n = 70], and 1,25-(OH)2D (n = 59) were measured in amniotic fluid by competitive protein-binding radioassays. At term, the mean (+/- SE) concentrations of 25OHD and 24,25-(OH)2D in amniotic fluid (810 +/- 76 and 37.5 +/- 5.4 pg/ml, respectively) were significantly lower (P less than 0.01) than those at 16-18 weeks gestation (1707 +/- 2.67 and 149 +/- 3 pg/ml, respectively). Similarly, the concentrations of 25OHD in pooled amniotic fluid samples, as determined by high pressure liquid chromatography and UV absorbance detection at 254 nm, were 664 +/- 188 pg/ml at term and 1240 +/- 294 pg/ml at midgestation. In comparison, no difference could be found between the mean concentrations of 1,25-(OH)2D at term (4.3 +/- 0.8 pg/ml) and those at midgestation (3.3 +/- 0.4 pg/ml). However, in 14 of 39 amniotic fluid samples obtained at term (35.9%), the concentration of 24,25-(OH)2D was undetectable, while the level of 1,25-(OH)2D was increased. The reciprocal relationship between 24,25-(OH)2D and 1,25-(OH)2D found in more than a third of the amniotic fluid samples at term may be due to a regulatory mechanism responding to the increased fetal demand for calcium in the final stages of pregnancy.

Vitamin D metabolites in human milk.

The concentrations of unconjugated 25-OHD, 24, 25(OH)2D, and 1,25(OH)2D were measured in human milk by competitive protein-binding radioassays following successive preparative Sephadex LH-20 chromatography and HPLC. The mean (+/- SE) concentration of 25-OHD was 0.37 +/- 0.03 ng/ml, of 24,25(OH)2D was 24.8 +/- 1.9 pg/ml, and of 1,25(OH)2D was 2.2 +/-0.1 pg/ml. The concentration of 25-OHD3 in milk as determined by HPLC and UV detection at 254 nm was 0.27 +/- 0.08 ng/ml. The milk concentrations of vitamin D metabolites did not correlate with the maternal serum 25-OHD levels. The total amounts of unconjugated vitamin D metabolites correspond to the known low bioassayable vitamin D antirachitic activity in human milk.

Inadequate status and impaired metabolism of vitamin D in the elderly.

The mean serum concentrations of 25-hydroxyvitamin D and of 24,25-dihydroxyvitamin D were significantly lower (P less than 0.01) in 82 elderly people than in 30 young control subjects. The levels in 30 elderly people confined to their rooms were 8.0 +/- 0.7 (SE) and 0.54 +/- 0.04 ng/ml, respectively; in 31 active old-age-home residents who spent part of their time outdoors, they were 11.4 +/- 0.8 and 0.82 +/- 0.08 ng/ml, respectively; and in 21 elderly farm workers, 14.6 +/- 1.4 and 0.98 +/- 0.10 ng/ml, respectively. In the young control subjects, the levels were 21.5 +/- 1.4 and 1.91 +/- 0.12 ng/ml, respectively. In addition, an intestinal absorption test with a standard oral dose of 25-hydroxyvitamin D3 showed that the serum 25-hydroxyvitamin D3 responses at 4 and 6 h were considerably depressed in 10 of the 20 elderly subjects in whom the test was performed.

Decreased 1,25-dihydroxycholecalciferol and increased 25-hydroxy- and 24,25-dihydroxycholecalciferol in tissues of rats treated with thyroxine.

The effect of thyroxine on the metabolism of vitamin D was investigated in rats. Vitamin D depleted rats were repleted by injections of radiolabelled cholecalciferol or 25-hydroxycholecalciferol (25OHD3). After 3 weeks, a state of hyperthyroidism was induced by daily injections of L-thyroxine for 21 days. The lipid extracts of the Plasma and tissues were analyzed by successive Sephadex LH-20 and high pressure liquid chromatography. The concentrations of 25OHD3 and of 24,25-dihydroxycholecalciferol (24,25 (OH)2D3) were significantly higher and those of cholecalciferol and of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were significantly lower in the plasma and tissues of animals treated with thyroxine than in controls. The present study suggests that alterations in the metabolism of vitamin D may be involved in the disturbances of calcium metabolism observed in hyperthyroidism.

Decreased serum 24,25-dihydroxy vitamin D concentrations in children receiving chronic anticonvulsant therapy.

Serum 24,25-dihydroxy vitamin D (24,25(OH)2D) and 25-hydroxy vitamin D (25-OHD) concentrations and the ratio between the two were measured in 31 Israeli children and adolescents receiving long-term treatment with phenobarbitone or phenytoin and in controls. 24,25 (OH)2D concentrations were significantly depressed in the patients, although the 25-OHD concentrations were similar to those in the healthy controls. In four patients with radiological evidence of osteopenia very low serum 24,25(OH)2D concentrations and serum 24,25(OH)2D: 25-OHD ratios were recorded. The findings suggest that 24,25(OH)2D deficiency may play an important part in the pathogenesis of osteomalacia in patients treated with anticonvulsant drugs and provide further indirect evidence that 24,25(OH)2D is important for normal bone structure.