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NEONATAL MENINGITIS due to bacteria of the genus Proteus is extremely rare.1 At the present time, only 17 proven cases have been reported in the literature,1 and of these, six have been caused by Proteus mirabilis.2-6 Paralleling the experience with neonatal meningitis in general, almost all of these cases either ended in death or developed severe neurological sequelae. It is the purpose of this paper to report two additional cases of P mirabilis meningitis in the neonatal period and to review the special features of, and the literature in, this disease. REPORT OF CASES Case 1.—A boy was born to an 18-year-old Puerto Rican primigravida. The Hinton blood test was negative. Pregnancy was uncomplicated with a gestation period of 40 weeks. Labor began spontaneously and lasted six hours. The fetal membranes were ruptured on the delivery table. The amniotic fluid was clear and the presentation was vertex.

Amniotic fluid was collected at inductive amniotomy or just prior to delivery following full-term uncomplicated pregnancies. Table I lists the means, ranges, and standard deviations for the concentrations of amino acids obtained by ion-exchange chromatography of 16 specimens of amniotic fluid. Each specimen contained the following 22 amino acids: taurine, aspartic acid, threonine, serine, glutamine, proline, glutamic acid, citrulline, glycine, alanine, α-aminobutyric acid, valine, cystine, methionine, isoleucine, tyrosine, phenylalanine, ornithine, lysine, histidine, and arginine. In addition, tryptophan, which could not be detected by the ion-exchange chromatographic method employed, was found in each specimen by paper chromatography. The amino acids present in amniotic fluid were the same as those found in samples of maternal vein, umbilical artery, and umbilical vein serum (table II). Comparisons were made in the concentrations of several amino acids among amniotic fluid, maternal serum, umbilical artery and vein serum, and perinatal urine (table II). Taurine was present in considerably greater concentration in amniotic fluid than in maternal serum. This amino acid is also present in large quantities in umbilical artery and vein serum (table II) and is by far the greatest single contributor to the total free amino acid pool in perinatal urine [1]. In contrast, amino acids such as leucine, valine, and threonine, which are present in much smaller amounts in amniotic fluid than in either maternal or umbilical serum, are found in even lower concentrations in perinatal urine [1]. These comparisons suggest that amniotic fluid is derived from at least three sources, maternal blood, fetal blood, and fetal urine, a finding compatible with existing evidence [3, 24, 27, 30].

Neonatal vitamin B6deficiency was established in the rat. Coenzyme levels in brain of suckling rats from dams fed a B6-deficient diet after parturition were determined by the (1-14C)tyrosine-tyrosine apodecarboxylase method and found to be approximately one-third normal in deficient animals 18 days old. Cerebral sphingolipids were reduced 30 to 50% in animals 18 to 20 days old. Minor alterations were observed in glycerophosphatides and plasmalogens. Cystathionine accumulated to 16 times normal levels. Glycine, citrulline, taurine and the branched-chain amino acid levels were also elevated while gamma aminobutyric acid and serine were reduced. The role of vitamin B6in sphingolipid metabolism has been the subject of much interest. The amino acid changes are largely explicable by reduced activity of known B6-requiring apoenzymes.

HYPERMETHIONINEMIA in infancy occurs regularly with homocystinuria due to cystathionine synthase deficiency.1,2 It has also been seen in association with hereditary tyrosinemia3 and with neonatal hepatitis.4 Interest in the early detection of hypermethioninemia has been stimulated by the fact that homocystinuria due to cystathionine synthase deficiency is one of the more common inborn errors of amino acid metabolism and by the possibility that brain damage in this condition may be prevented by a special low-methionine diet.1In 1966 the Massachusetts Metabolic Screening Program conducted by the State Laboratory Institute, Massachusetts Department of Public Health, incorporated blood filter paper chromatography for the detection of hypermethioninemia and other hyperaminoacidemias in newborn and 4- to 10-week-old infants.5,6 In January 1968, the Guthrie bacterial inhibition assay for methionine (R. Guthrie, unpublished data) was included as a standard test for all blood specimens received in the Massachusetts screening program. These

We have found a genetic trait of arginase deficiency in erythrocytes (RBC) of Macaca fascicularis(crabeater macaque). Measurements of arginase activities and arginine concentrations in RBC, and information derived from breeding experiments indicated that arginase activities in RBC are 12.59 mmoles/g hemoglobin (Hb)/hr (range: 8.36–15.24) in normal monkeys, 4.40 mmoles/g Hb/hr (sd ± 2.37) in hetero-zygotes for this trait, and less than 0.05 mmoles/g Hb/hr in homozygotes for this trait. Concentrations of arginine in erythrocytes are less than 0.01 $mUmoles/ml packed cells in both normal and heterozygous monkeys, and 0.975 $mUmoles/ml packed cells (sd ± 0.556) in homozygous monkeys.

Extract: We have found a genetic trait of arginase deficiency in erythrocytes (RBC) of Macaca fascicularis (crabeater macaque). Measurements of arginase activities and arginine concentrations in RBC, and information derived from breeding experiments indicated that arginase activities in RBC are 12.59 mmoles/g hemoglobin (Hb)/hr (range: 8.36–15.24) in normal monkeys, 4.40 mmoles/g Hb/hr (sd ± 2.37) in hetero-zygotes for this trait, and less than 0.05 mmoles/g Hb/hr in homozygotes for this trait. Concentrations of arginine in erythrocytes are less than 0.01 $mUmoles/ml packed cells in both normal and heterozygous monkeys, and 0.975 $mUmoles/ml packed cells (sd ± 0.556) in homozygous monkeys.There are no significant differences in plasma amino acids and hepatic arginase activity in any animal.Speculation: Study of arginase activity in RBC will be expanded to include a large number of monkeys in order to determine the incidence of arginase deficiency in RBC in this species. The possibility of using these monkeys as an animal model for study of human disease arginase deficiency (e.g., genetic engineering) will be explored.

Proteus mirabilis osteomyelitis occurred in two neonates. The clinical symptoms and roentgenographic findings did not differ significantly from those seen in other forms of bacterial osteomyelitis in the newborn. Nursery contamination with the offending organism was not found, although the circumstances of multiple P mirabilis infections in a single nursery suggested this possibility. Antibiotic therapy consisted of potassium penicillin (G) and kanamycin sulfate in one case, and kanamycin and chloramphenicol sodium succinate in the other case. Both patients made uneventful recoveries.

Mentally retarded non-phenylketonuric offspring from untreated phenylketonuric mothers have been reported upon by a number of groups. To this list we add some additional cases. These offspring commonly have lower I.Q's than their mothers. It is reasonable to postulate that the high concentrations of phenylalanine or its metabolites in the blood of the untreated mother, which is actively transported across the placenta into the blood of the infant, is the cause of the frequently severe damage to the vulnerable infant brain in utero. The fact that artificially produced high concentrations of phenylalanine in the blood of pregnant monkeys and of pregnant rats seems to have culminated in offspring with impaired learning abilities is consistent with this supposition. The results indicating apparently normal mental development, so far, in the nonphenylketonuric offspring of at least 2 phenylketonuric mothers treated with low phenylalanine diets during pregnancy, are encouraging. Because of the advent of routine screening tests for PKU in the newborn, there are an increasing number of phenylketonuric girls, treated in their early years but now on a normal diet, who are approaching the childbearing period and who are mentally normal. Consequently, there is a growing opportunity and responsibility for preventing mental retardation in their future nonphenylketonuric children. It is suggested that dietary treatment during the pregnancies of phenylketonuric mothers be seriously considered, with caution exercised so that the blood concentrations of phenylalanine in the mother under treatment be maintained above 3 but below 8 mg. per 100 ml. Routine urine testing for PKU is, therefore, recommended for all women at the first prenatal visit and at the premarital examination.

The response to ultraviolet light and the histologic appearance of the epidermis was studied in two brothers with histidinemia. One of the siblings demonstrated a decreased minimal erythema dose while the other more pigmented brother showed a normal response. The epidermis appeared to be normal by light and electron microscopy.

The various contractile and control sites of natural actomyosin gel were studied by comparing the kinetics of ATP hydrolysis with those of gel contraction, measured as an increase in turbidity. Contraction of actomyosin gel seems to require the cooperative reaction of ATP (with Mg) at two different sites. One of these sites catalyzes the hydrolysis of ATP and most probably contributes the driving force for contraction; the binding of ATP to the other site appears to break certain links that retard movement of the gel components. At limiting concentrations of ATP, the rate of contraction seems to depend on the rate of breaking these links as well as on the rate of ATP hydrolysis. But when both sites are saturated, the rate of contraction appears to be limited only by the rate of ATP hydrolysis. In addition to these two contractile sites, there are also two different control sites. At one, the relaxing site, the binding of ATP with Mg inhibits ATP hydrolysis and gel contraction. At the other, the binding of calcium activates contraction by overcoming the inhibitory action of Mg and ATP at the relaxing site. This control system—inhibition by substrate and disinhibition by calcium—can be selectively inactivated by heat and reactivated by dithiothreitol, a disulfide-reducing agent. These observations on the isolated contractile system are discussed in relation to the contraction and relaxation of muscle.