Molybdenum supplementation in phenylketonuria diets: adequate in early infancy?

BACKGROUND: Molybdenum concentrations in formulas exceed those in human milk by far. Infants with phenylketonuria require semisynthetic phenylalanine-restricted diets. Because these diets are presently supplemented with molybdenum, a study was conducted to determine whether retention and plasma concentration in the recipients are equivalent to those of healthy breast-fed infants. METHODS: Balance and plasma studies were conducted in healthy breast-fed infants (n = 17) and in patients with phenylketonuria (n = 4) at the age of 4 weeks, and the plasma investigations were repeated at the ages of 4 and 12 months. The samples were analyzed by atomic absorption spectroscopy (balance studies) and high-resolution inductively coupled plasma mass spectrometry (plasma). RESULTS: Molybdenum intake and retention in all infants with phenylketonuria were more than 18 times those of breast-fed infants. The plasma concentrations reflected these differences. A median of 0.04 microg/l was assessed in breast-fed infants at 4 weeks and less than 0.02 microg/l at 4 months of age. Comparative results of infants with phenylketonuria were 2.9 microg/l and 2.5 microg/l, respectively. There were no significant differences between the groups at 12 months of age. CONCLUSIONS: The phenylketonuria diets investigated showed excessive retention and plasma concentrations of the essential trace element molybdenum in early infancy. In view of these findings, the present practice of molybdenum fortification should be revised.     

Auditory sensitivity in the middle-aged population in southwestern Finland

The present study deals with the auditory sensitivity of men and women 40 to 64 years of age living in two municipalities situated in the southwestern part of Finland and the prevalence of defective hearing in this middle-aged population. Hearing acuity was tested in 1043 men (93.2%) and 1221 women (93.1%). It appeared in the investigation that hearing loss increased markedly with age in both sexes. Auditory sensitivity was clearly better in women than in men. Of the entire population 7.1% had evident bilateral hearing loss when an average loss of 25 dB in the speech range was used as the cut-off point. Hearing loss of 35 dB in the speech area was regarded as requiring an otological examination and possible care even when present in only one ear. Of the men 12.1% and 7.9% of the women were in this category; this represents an overall prevalence of 9.9%.     

Candida infection in very low birth-weight infants: outcome and nephrotoxicity of treatment with liposomal amphotericin B (AmBisome®)

Summary Systemic fungal infection occurs in 2 to 4.5% of very low birth-weight (VLBW) infants (<1,500 g) and may be fatal in 25 to 54%.Candida sp. is the major pathogen and amphotericin B the treatment of choice. To reduce side effects and optimize drug action, a formulation of amphotericin B encapsulated in liposomes (AmBisome^?) has been introduced. Data on 21 VLBW infants who received a full course of AmBisome^? was collected and its toxic effects with emphasis on nephrotoxicity and hypokalemia assessed. The median gestational age was 25 weeks (range 23–31) with a median birth-weight of 730 g (range 450–1,370). Antifungal therapy was started at a median age of 13 days (range 1–49). The median dose given was 2.6 mg/kg/day (range 1–5), and the median duration of therapy was 28 days (range 11–79), corresponding to a median cumulative dose of 71 mg/kg (range 12–271). Hypokalemia (<3.0 mmol/l) was observed in 30% before, and 15% during AmBisome^? treatment. Twenty-one days after the termination of therapy, hypokalemia was not present in any patient. Median maximum daily potassium supplementation did not exceed doses usually recommended for VLBW infants. The median of the maximum creatinine levels before treatment was 121 μmol/l (range 71–221) and fell to 68 μmol/l (range 31–171) during treatment and 46 μmol/l (range 26–62) 21 days after the termination of therapy. All patients treated with AmBisome^? eradicated fungi and recovered clinically. AmBisome^? showed no certain nephrotoxicity in VLBW infants in this study.     

Production of MSH-release-inhibiting hormone by a particulate preparation of hypothalami: Mechanisms of oxytocin inactivation

Hypothalami of rabbit and rat contain a membrane-bound exopeptidase which stepwise degrades radioactively-labeled oxytoxin ([9-glycinamide-1-¹⁴C]-oxytocin) to give labeled H-Pro-Leu-Gly-NH₂, which is the release-inhibiting hormone of MSH (MSH-R-IF). Supernatant fractions of rabbit and rat hypothalami contain predominantly an endopeptidase which releases H-Leu-Gly-NH₂ from oxytocin.     

Evaluation of diazepam and pyridoxine as antidotes to isoniazid intoxication in rats and dogs

Because information regarding efficacious treatment of acute isoniazid (INH) toxicity is incomplete and controversial, diazepam and pyridoxine were investigated as iv antidotes in rats and dogs following administration of po lethal doses of INH. There is a marked species variation in the lethality of INH; the lowest consistently lethal dose is 1500 mg/kg for rats and 75 mg/kg for dogs. Of the two species, the dog more closely approximates man's sensitivity to the lethal effect of INH overdose (80–150 mg/kg). Species variation was also observed in the effects of the antidotes. Diazepam exerted dose-related protection against convulsions in rats; paradoxically, survival was increased by the lowest dose (1 mg/kg) but not by higher doses. In dogs, however, diazepam failed to prevent convulsions but provided dose-related protection against death. Pyridoxine, in rats, did not protect against INH toxicity, but in dogs it showed dose-related effectiveness against convulsions, and all doses (75–300 mg/kg) prevented lethality. Significantly, the highest dose of pyridoxine tested in rats (750 mg/kg) was substantially below the optimal pyridoxine-to-INH antidotal ratio recommended for man (a dose that at least equals the amount of INH ingested), but that dose of pyridoxine would be larger than its LD50 for rats. Combined administration of diazepam with pyridoxine protected against convulsions and death in rats and dogs. Used concurrently, the two antidotes are clearly synergistic for controlling the manifestations of experimental INH overdose. These results have important implications for the management of acute INH intoxication in man.