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Ethanol was found to exhibit anticonvulsant activity in nontoxic doses as measured by four of six well-standardized methods. The effective dose of ethanol, as determined by the various tests, was found to be linearly related to its plasma concentration. The initial increase in low-frequency electroshock seizure threshold, induced by a single large dose of ethanol, was followed by a significant decrease. The central nervous system tends rapidly to accommodate to the ethanol milieu so that the electroshock seizure threshold does not exactly parallel the plasma ethanol concentration. The significance of these observations is discussed.

Zinc and cadmium concentrations were determined in 36 first trimester intact human embryos and in liver, brain, and kidney of 14 second and 1 third trimester fetuses. Zinc was found in all first trimester specimens. It increased sevenfold between the 31st and 35th day of gestation. Cadmium was present in 57% of specimens in concentrations from 0.032μg/gm to 0.07μg/ gm of wet tissue. In second trimester specimens, mean zinc concentration in brain was 5.6μg, in kidney 15.7μg, and in liver 167.7μg. Cadmium was present in 80% of livers (mean, 0.113μg/gm), 28% of kidneys (mean, 0.05μg/gm), and 17% of brain specimens (mean, 0 140μg/gm). Mothers of these abortuses did not live in areas of Japan where endemic cadmium poisoning exists; however, higher cadmium content of the average Japanese diet may be reflected by cadmium concentration in these specimens.

This study was designed to test in experimental animals the hypothesis (Renwick, 1972) that human spina bifida and anencephalus are causally related to maternal consumption of blighted potatoes. Gavaging of pregnant rats with blighted potatoes on days 5–11 or daily ip injections of solanine or glycoalkaloids (5–10 mg/kg) extracted from B5141-6 potatoes, given on days 5–12 or 7–17 of gestation, resuited in minor skeletal and renal tract abnormalities, but failed to produce neural-tube defects. Daily injections (days 5–12) of 20 and 40 mg/kg of the glycoalkaloid caused 100% fetal and maternal mortality, respectively. Daily ip injections of 5 mg/kg of solanine into New Zealand White rabbits on days 0–8 of gestation produced abortion in one-third of the treated animals, 23% resorptions, but no teratogenesis. Single yolk-sac injections of 5–20 mg/kg of solanine into 20–22 h incubated white Leghorn eggs produced 63–90% mortality within 72 h without significant teratogenesis. Diced B5141-6 potatoes containing an average of 260 mg of solanine per kg of tuber fed ad libitum to time-mated rhesus monkeys for a period of 25 days postcopulation produced no maternal toxicity; on the other hand single injections of 40 mg/kg of the glycoalkaloid extract and two injections of 20 mg/kg of solanine killed adults within 48 h of treatment. At autopsy nasal, oral, and periorbital hemorrhage was present; there was accumulation of serosanguinous pleural and peritoneal fluids and mild hepatic and splenic congestion. Examples of human toxicity and mortality from consuming potatoes with a high solanine content are reviewed.

Epidermolysis bullosa is a rare hereditary skin disease, in which slight trauma disrupts the cohesion between the epidermis and the dermis, resulting in the formation of vesicles, bullae, and ulcers. Sorsby (4) described three principal types of this disease. The cases presented in this report are of his third or hypoplastic dystrophic type (25 per cent of all cases), which is transmitted by an autosomal recessive gene. Onset occurs at or shortly after birth. Widespread bullae follow very minor trauma, affecting both skin and mucosa, and heal with excessive scarring. The skin is thin, xerodermatic, and presenile in appearance. The nails are deformed or absent. The teeth are hypoplastic, and extensive caries develop early in life. Death may occur in early life. Case Reports Case I: M. C., a boy, was born on Feb. 2, 1952. On the first postnatal day, widespread skin bullae developed following minor trauma. Bullae in the oral cavity caused feeding problems. With growth, he continued to have numerous blisters ...

The teratologic and toxicologic effects of alkaloidal (alpha-chaconine alpha-solanine total glycoalkaloidal extract (TGA-extract)) and phenolic compounds (chlorogenic and caffeic acid) derived from Solanum Tuberosum L. were studied in pregnant and nonpregnant female rats. At the 95% confidence limit there was no marked difference in the potencies of alpha-chaconine alpha-solanine and the TGA-extract. The chronic administration of alpha-chaconine alpha-solanine and the TGA-extract to nonpregnant animals in a dose of 40 mg/kg/day for 2 days and in a dose of 20 mg/kg/day for 8 days had fatal effects in 40 and 42% of the animals respectively. 8 injections of alpha-chaconine (5-20 mg/kg/day) on Days 5-12 of pregnancy or 2 injections (40 mg/kg/day) on Days 5 and 6 of pregnancy resulted in a maternal mortality rate of 40-66% and a fetal mortality rate of 15-100%. However a similar schedule of treatment with alpha-solanine and the TGA-extract was lethal only to the fetus. Maternal or fetal death did not occur as the result of 8 daily injections of chlorogenic (5-500 mg/kg) and caffeic acid (40-187.5 mg/kg) on Days 5-12 of pregnancy. Neural tube defects did not occur as a result of any of the treatments though some 21-day-old fetuses had rib abnormalities.

This study was designed to quantitate the effects of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DIC) and 5-(3,3-bis(2-chlorethyl)-1-triazeno)-imidazole-4-carboxamide (BIC) on growth and selected components of rat fetal organs. Twelve-day pregnant rats were given single intraperitoneal injections of 600 mg/kg of DIC and 900 mg/kg of BIC and autopsied on day 21 of gestation. Fetal liver, brain, kidney, and placenta were removed, weighed, and assayed for total DNA, RNA, and protein. DIC significantly reduced weight, total DNA, RNA, and protein of all four fetal organs as compared to age-matched controls. The brain was most severely affected by this compound. BIC also significantly reduced weight, DNA, RNA, and protein of fetal brain, kidney, and placenta, but in fetal liver only weight and total protein were significantly depressed, while DNA and RNA remained essentially unchanged. The effect of BIC was maximal on the placenta.

This is a concept of multiple congenital contractures, based upon clinical experience with the malformation and available literature, leading to a conception of the multiple categories of etiology, which cause neuropathic or myopathic muscle weakness or limb immobilization. The muscle weakness and imbalance of muscle power around the joints elicits a physiological compensatory collagenic response, which replaces atrophied muscle fibers with connective tissue and thickens the joint capsule sufficiently to result in prenatal fixation of limb segments at the joint.

Single ip injections of 600 mg/kg 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DIC) and 900 mg/kg 5- [3,3-bis(2-chlorethyl)-1-tria-zeno] -imidazole-4-carboxamide (BIC) were given to pregnant Wistar rats at day 12 and the animals were killed 4 hafter injection and at days 13–17 of gestation. Fetal tissues were used to determine total DNA, RNA, and protein and the data used to derive cell number and cell weight, RNA, and protein/ cell, Both compounds reduced total fetal body weight, DNA, RNA, and protein But reduction of RNA by BIC was not statistically significant These effects were observed 4 h after injection, increased with age (days 13-17X and were 3-4 times greater for DIC than BIC. By using the value of 6.2 μμg DNA/ cell, cell number and percell values for weight, RNA, and protein, and weight: DNA, RNA: DNA, and protein: DNA ratios were coinputed. The percell values and ratios in the DIC-exposed animals were 8–44% greater and in BIC-treated animals 0–11% greater than control animals of the same gestational age. Percentage of body water was the same in the experimental and control animals. The differences in DNA, RNA, and protein are believed to be related to drug-induced growth retardation incident to total fetal DNA reduction resulting in diminished cell number.

In experimentally induced myelocele in rats, efforts to find neural cells in amniotic fluid (AF) were unsuccessful. Creatine phosphokinase (CPK) and aldolase concentrations studied in serum of 118 and cerebrospinal fluid (CSF) in 9 patients with myelomeningocele showed serum CPK to be significantly elevated and more responsive to additional muscle injury than aldolase, but both enzymes appeared in lower concentrations in patients with myelomeningocele than those with infantile atrophy or cerebral palsy. In CSF, CPK, and aldolase concentrations averaged 4.2 I.U. and 2.7 S.L.U. per milliliter, respectively. Significant CPK elevation (p less than 0.001) was also found in AF from myeloschitic fetuses and maternal rat serum. Although these findings suggest that increased CPK concentration is an indicator of myelocele in rats, the technique is impractical for prenatal detection of human fetus occurs too late in gestation. This does not, however, preclude the value of CPK for detecting onset of paraparesis. In all myeloschitic human fetuses, the CSF communicates directly with AF for at least 3 to 4 weeks. This implies that CSF is probably the principal source of increased alpha-fetoprotein concentration encountered in AF of all pregnancies with NTD. When biological variables are recognized, it is evident that increased concentration of amniotic fluid alpha fetoprotein is a reliable indicator of fetuses with open myelocele and/or anenciphalus.

Seventy cases of multiple congenital contractures (arthrogryposis) were evaluated. Associated anomalies not previously described with this condition were found. The authors conclude that the condition is a syndrome of multiple congenital contractures and joint disturbances (eg, dislocations) which are the end result of many etiologies. The value of utilizing health department data derived from school placement changes, applications for state and city financial aid, and required reporting of orthopedic disabilities was demonstrated. The abnormality was limited to the upper extremities in 11% and to the lower in 43%. Both upper and lower extremities were involved in 46%. Treatment is prolonged, even though started very early, and requires a wide variety of orthopedic procedures.

UMMARY Out of 1,283 cases of cerebral palsy diagnosed at the Children's Division of the Institute of Physical Medicine and Rehabilitation, 143 (11 per cent) acquired their neurological disability after the neonatal period. In 46 per cent of these the cerebral palsy was acquired from infection, in 17 per cent from trauma and in 11 per cent from cerebrovascular lesions. Nearly three-quarters of the total had the spastic type of neuromotor deficit. Nearly half had a quadriparesis. All the cerebrovascular lesion cases had a hemiparesis. In 41 per cent of the total the children could not walk; 35 per cent were deficient in one or more areas of the activities of daily living; 41 per cent were mentally retarded. About a third had sensory, perceptual and/or visual deficits, and over half had speech deficits. There are many opportunities for preventing acquired cerebral palsy. Prevention is more likely to be effective in infective, traumatic or postsurgical cases than in those secondary to cerebrovascular accident, tumor or seizures. The chances of prevention are highest in the area of central nervous system infection, through immunization techniques, early diagnosis and vigorous treatment, and greater respect for the potential damaging powers of all infections. The prevention of traumatic neurological defects depends on home and school educational programmes, vehicle safety engineering, and greater respect for and compliance with existing safety regulations. Reasumea Enquete effectuee dans une institution sur 143 cas de paralysie cerebrale acquise Parmi les 1.283 cas de paralysie cerebrale diagnostiques dans la Division des Enfants du ‘Institute of Physical Medicine and Rehabilitation’, 143 (11 pour cent) ont acquis leur infirmite neurologique apres la periode neonatale. Dans 46 pour cent des cas la paralysie cerebrale provenait d'une infection, dans 17 pour cent d'un traumatisme et dans 11 pour cent d'un accident cerebrovasculaire. Presque trois quarts du total avait le type spastique de deficience neuromotrice. Presque la moitie avait une quadriparesie. Tous les cas dus a des accidents avaient une hemiparesie. Dans 41 pour cent du total les enfants etaient incapables de marcher; 35 pour cent etaient deficients dans un ou plusieurs domaines de la vie de tous les jours; 41 pour cent etaient retardes mentalement. Un tiers environ avait un defaut sensoriel, perceptuel et/ou visuel, et plus de la moitie avait des difficultes de langage. Il existe de nombreuses opportunites pour prevenir la paralysie cerebrale acquise. La prevention semble devoir etre plus efficace dans les cas d'infection, de traumatisme, et les cas post-chirurgicaux que dans les cas dus a un accident cerebrovasculaire, une tumeur ou des crises. Les chances de prevention sont les plus elevees dans le domaine des infections du systeme nerveux central grâce aux techniques d'immunisation, a un diagnostic precoce suivi d'un traitement vigoureux et un plus grand respect de la puissance destructive de toutes les infections. La prevention des deficiences neurologiques dues a un traumatisme depend des programmes d'education a la maison et a l'ecole, de la fabrication de vehicules non dangereux, et d'une respect et d'un obeissance plus grands aux regulations de securite en usage. Zusammenfassung Ein Bericht uber 143 stationare Patienten mit erworbener Zerebrallahmung Bei einer Gesamtzahl von 1283 Fallen diagnostizierter Zerebrallahmung in der Kinder-abteilung des Instituts fur Physikalische Medizin und Rehabilitierung wurde festgestellt, dass 143 (11 prozent) der Falle ihre neurologischen Behinderungen nach der Neuge-borenenphase erworben hatten. Bei 46 prozent der Patienten traten die neurologischen Erscheinungen als Folge einer Infektion auf bei 17 prozent als Folge von Trauma, und bei 11 prozent als Folge von Gehirngefassschaden. Beinahe drei viertel der Gesamtgruppe litten an der spastischen Form von neurologischem Defizit. Etwa die Halfte hatten Lahmungen der vier Extremitaten. Alle auf Gehirngefassschaden beruhende Falle litten an Hemiparese. 41 prozent der Gesamtzahl waren gehunfahig; 35 litten an Totalbe-hinderung einer oder mehrer Aktivitaten des Alltagslebens; 41 prozent waren geistig zuruckgeblieben. Etwa ein drittel hatten sensorische oder perzeptuelle Storungen, oder Sehstorungen; mehr als die Halfte hatten Sprachstorungen. Es gibt verschiedene Moglichkeiten, die erworbene Zerebrallahmung zu verhindern. Die Prophylaxe wird viel eher bei Fallen von Infektion oder Trauma, sowie chirurgischen Fallen, als bei solchen mit Gehirngefasschaden, Tumoren oder Krampfanfallen gelingen. Patienten, bei denen es sich um eine Infektion des Zentralnervensystems handelt bieten die gunstigsten Moglichkeiten fur Prophylaxe, die mittels Immunisiermethoden, fruhe Diagnose und grundliche Therapie durchgefuhrt wird. Das potentielle Schadigungs-vermogen aller Infektionen soll stets vor Augen behalten werden. Die Prophylaxe der traumatisch-neurologischen Art der Krankheit wird von dem Erziehungsregime zu Hause sowie auch in der Schule abhangen, von der Verlasslichkeit der Autofahrer und der besseren Beachtung gegebener Verkehrssicherheitsvorschriften.

In laboratory animals, prenatal contractures have been induced by viruses, neuromuscular blocking agents, toxins, insecticides, hyperthermia, and limb immobilization. In agricultural animals, prenatal contractures are related to pregnant animals foraging on plants containing toxic alkaloids. Epizootics of prenatal contractures in cattle have been related to Akabane viral infections, which can now be prevented by vaccination. Human arthrogryposis (multiple congenital contracture) may occur in any synovial joint in a large variety of combinations. Several lethal syndromes commonly associated with prenatal contractures (Pena Shokeir 1 and 11, Potter's) provide supportive evidence for the following concept of prenatal contracture etiology. Evidence is provided that indicates that the following multiple etiologic factors are related to production of human arthrogryposis: mutagenic agents, mitotic abnormalities, toxic chemicals or drugs, hyperthermia, neuromuscular blocking agents, and mechanical immobilization. These multiple factors mediate their effect via the central nervous system (craniospinal motor neuraxis), motor end-plates, or by primary degeneration of muscle. The resultant effect is loss of muscle mass with imbalance of muscle power at the joints, which provokes a collagenic response (Law of the Connective Tissue). The collagenic response consists of partial replacement of muscle volume and collagenous thickening of the joint capsules. The latter process leads to joint fixation.