[Headache in the pathology of small cerebral blood vessels: study of patients with systemic lupus erythematosus].

Seventy-two records of patients with systemic lupus erythematosus were reviewed retrospectively. Sixty-one fulfilled the criteria for the disease. Forty-six percent had clinical evidence of central nervous system involvement. The incidence of headache was compared in those with and without central nervous system lupus. No difference in the frequency of headache in the two groups was found and the incidence of hypertension, renal disease and steroid therapy was equally distributed among those with and without headache. A significantly higher incidence of hypertension was found in patients with central nervous system lupus erythematosus. We conclude that headache in systemic lupus erythematosus in the absence of neurologic symptoms or signs is no indication of central nervous system involvement by the process and that small vessel disease of the brain is not a cause of headache.


[The use of drugs in migraine].

Drugs may be given either for treatment of the acute attack or as prophylaxis. Those most commonly used for the acute attack are analgesics, anti-emetics and ergotamine tartrate. A recent work (Volans, 1974) has shown that absorption may be impaired during a migraine attack. It is important therefore that not only is the analgesic given in an easily absorbed form but that a drug such as metaclopromide should be given to help restore the normal activity of the gastro-intestinal tract. Patients having one or more attacks of migraine a week may need prophylactic treatment. The drugs now used include: Methysergide, should only be used for severe cases when no other treatment has been found helpful. Dihydroergotamine, the vasoconstrictor activity is less than in ergotamine tartrate and can therefore be used prophylactically. Pizotifen, possesses powerful anti-serotonin properties. It also has marked antihistamine and antitryptamine properties as well as being a central sedative and anti-depressant. Clonidine, in doses of 1 mugm/Kg renders the blood vessels less sensitive to circulating amines and seems to be effective in about one third of patients with classical or common migraine. Sympathetic Blocking Agents: alpha-blockers: indoramine has recently given some good results; beta-blockers: such as propanolol and pindolol have also been used. Full trials of all the substances are now in progress. Tranquilisers and anti-depressants, two of those commonly used are diazepam and amitryptiline. In either cases a small dose only should be used. Anticonvulsants, phenytoin in doses of 50-100 mgs per day is sometimes helpful particularly in children or in those who have abnormal electroencephalograms.


[Reserpine in the prevention of migraine and in the therapy of tension-vascular headache].

The results of many researches on migraine pathogenesis and our knowledge of the pharmacological action of reserpine led us to start using it in migraine prophylaxis ten years ago. For this purpose, standardized cycles of twenty administrations--heach dose being of 0.20 mg--were given intravenously; each cycle lasted a period of six to eight weeks. The positive data obtained on 300 patients suffering from severe migraine resulted statistically significant. Then, a double-blind clinical trial was carried out in Turin in agreement with a double-blind biochemical trial carried out in Copenhagen by Fog-Møller, Dalsgaard-Nielsen, Byrndum and Kemp Genefke. The results obtained have confirmed the efficacy of reserpine administered in appropriate doses and enabled the demonstration of its pharmacological mechanism. The results obtained also in "tension-vascular headache" with reserpine treatment were reviewed retrospectively and were highly significant.


[The action of reserpine on the concentration of 5-hydroxytryptamine, epinephrine and norepinephrine in the venous blood of migraine patients].

Vasoactive amines, particularly 5-hydroxy-tryptamine (5-HT) have been implicated as the cause of migraine. Our study was a biochemical one on the effect of reserpine on the content of 5-HT, NE and E in migraneurs. The effect of one single infection of reserpine. 23 migrainous patients and 7 controls were given one i.m. injection of reserpine (1,5 mg/1.7 m2 surface). The content of 5-HT in blood platelets of 8 migraneurs and 7 controls 6 hours after the injection of reserpine decreased to comparable levels in both groups. The serotonin releasing effect of reserpine, however, is different from that of tyramine. The effect of prolonged reserpine medication. The effect of i.v. injection of reserpine over a period of 6 weeks on 5-HT, NE and E, was investigated. The doses of reserpine corresponded exactly to the doses already used by Nattero et al. (0.2 mg reserpine 3 times a week for 6 weeks). In correspondance with this work a double blind clinical examination was carried out by Nattero et al. (1975). Blood amine levels were measured weekly. The NE decreased to a minimum of 62% of basal mean value after 3-7 weeks of treatment. The decrease is significant from the third to the sixth week. Basal value was not reached until 6 weeks after withdrawal of reserpine. The concentration of 5-HT in blood platelets decreased to 5% of basal mean value and remained low during the reserpine treatment. The decrease is highly significant. A clinical improvement began 1-2 weeks after the introduction of reserpine treatment, continued during treatment and for 2-6 weeks after. In the open trial performed by us, we can confirm the results of Nattero et al. We demonstrated a marked decrease in concentration of blood amines corresponding to clinical improvement.


[Cranial acupuncture in the treatment of spasticity. Clinical results].

Hospitals in communist China perfected a new acupuncture technique about 3 yrs ago, whereby needles are placed in the scalp to stimulate the cortical centres below. This method is particularly indicated in subjects with neurological damage. Results observed in 45 subjects with cerebral vasculopathy at the neurological clinic of Pisa University and the reflexotherapy service of the University of Turin were encouraging and suggest that clinical experimentation should be attempted on a wider scale.


[Cranial acupuncture in the treatment of spasticity. Neurophysiological findings].

On the basis of a study of the innervation of the cutaneous areas stimulated in cranial acupuncture, a neurophysiological classification of the technique is proposed, considering the bulbar level as the first site of integration of the afferent vessels activated by cranial acupuncture.


[Primary results of the reflexotherapy in the syndrome of irritable colon. Preliminary note5].

After stressing the uncertainties of classifying the syndrome exactly and the part played by psychosomatism in its aetiopathogenesis, some forms of acupuncture have been attempted as alternatives to psychodrugs and antispastic substances. 50 cases are examined in which diagnosis of irritable colon was confirmed by thorough clinical and laboratory examinations, use is also being made of appropriate computerizable tables.


[Hyperbaric treatment in the post-bronchitic emphysema].

Following some introductory mention of the physiology of hyperbaric oxygen therapy and some notes on the physiology of postbronchitic emphysema and its cardiac, hepatic, renal and neurological sequelae, a personal method of hyperbaric treatment is described. The results in the first 50 emphysematous patients submitted to this therapy are reported along with those of the examinations carried out to evaluate respiratory function, and changes in haematosis, and cardiac, hepatic, neurological and renal function. It is concluded that hyperbaric treatment of postbronchitic emphysema should be considered of choice for quick, effective resolution of alterations in haematosis and the organic sequelae deriving from respiratory insufficiency. In association with other therapy (antibiotics, anti-inflammatory and balsamic drugs) it is also capable of stopping or usefully delaying the disease's development.


[Indications and limitations of ultrasonic investigation in abdominal pathology].

Investigation of the abdomen by ultrasounds must now be included among routine tools in abdominal diseases. All abdominal organs, with the exception of the intestine with its gas content, are open to investigation with this technique which combines harmlessness and rapidity with its unique possibility of making differential diagnosis possible in structures with different tissue constitution. The limitations are to be sought more in the examiner's interpretational capacities and in the apparatu's limited resolution power rather than in the technique proper.


[Alithiasic cholecystopathies. Clinical, diagnostic and therapeutic aspects].

The frequency of alithiasic cholecystitis is considered and the various forms are subdivided into diffuse and localized dyskinesia. Symptomatology is described and the former are indicated as being electively medical and the latter surgical forms whether the condition is congenital or acquired. The various forms of cholecystosis are also distinguished with full documentation. Symptomatological techniques and diagnostic conclusions are illustrated for all forms and personal experience with their therapy reported.


[Metabolic alkalosis. Relation between bicarbonate load and the behavior of blood lactic acid in the light of the intra-erythrocyte indices of the acid-base balance].

The plasma an intra-erythrocyte acid-base balance in man was studied, along with blood pyruvate and lactate levels, in acute metabolic alkalosis induced by i.v. infusion of bicarbonate. It was found that the red cell offers a satisfactory expression of the phenomena that occur in the intracellular space. The bicarbonate ion has difficulty in crossing the red cell membrane, while the production of lactate is seen as a fundamental compensation mechanism for rapid buffering of the extra base.


[Therapeutic possibilities in idiopathic headaches. Analysis of about 1000 cases].

This work is an attempt to find an answer to the question: once arrived at the diagnostic identification of a certain type of idiopathic headache, which treatment should be followed? On the basis of recent researches and experience acquired during ten years' activity of our Headache Unit, a diagnostic identification can be made for migraine (in all its types and evolution stages), cluster headache, tension headache and pure psycogenic headache. Among the most widely used drugs, positive pharmacological results were obtained with: cyproheptadine, pizotifen, cinnarizine, lysergic acid derivatives, histamine, reserpine, clonidine and a barbituric acid derivative. The therapeutic cycles were standardized, for each drug, in the way of administration, dosage and total duration of the treatment. A comparison between the data obtained and the pre-therapeutic situation was made. When repeated, the most efficacious therapeutic cycle was evaluated. According to Pearson's dispersion index, each group of patients improved respresents 16.68% of the expected total results (frequency of attacks reduced to 50%, 25% and 0%): for cyproheptadine, pizotifen, methysergide, histamine, clonidine and allil-propyl-malonylurea, the "p" is less than 0.001; for cinnarizine, less than 0.02. This "a posteriori" analysis does not take into account the placebo control, the "anticipation effect", and the "carry over effect". It cannot therefore be a comparison of efficacy among the various drugs. An evaluation based on "among patients" and "inside patient" method by means of the cross over system, can instead give some useful suggestion about which treatment is to be recommended to patients suffering from recurrent headaches. With regard to migraine sufferers: cinnarizine, cyproheptadine, clonidine, histamine, pizotifen und reserpine. For cluster headaches: cinnarizine, cyproheptadine, clonidine, histamine and reserpine. For tension headaches: cyproheptadine. For pure psychogenic headache: allyl-propyl-malonylurea. For migraine attacks or parossystic crises in the course of ondulating or continuous headaches, positive therapeutic results, statistically significant, were obtained with an association of indomethacin, caffeine and prochlorperazine.


[Long-term studies of patients with headache and pathological EEG].

In 53 patients, consulting for headache of different types, a pathological EEG had been observed several years ago; at this time, a neurological or medical origin of the bioelectric abnormalities could not be found. These patients (average age: 32.4 y.) were reexamined systematically after an average delay of 3 years. Generally, one observes a clear improvement or a normalization of the EEG and the clinical state. In 1/9 only of the population the EEG-abnormalities persisted. All these patients belonged to a subgroup, where certain complicating factors (cerebral-organic or general) could be specified. No brain tumour had developed meanwhile. The authors conclude: a pathological EEG in the context of headache does not obligatory indicate bad prognosis.


[Meteorotropy of vasomotor cephalea].

During a period of 823 days (from 1st October 1971 to 31st December 1973), attacks of migraine, non-migraine vascular cephalea and cephalea due to other neighbouring disturbances strong enough to affect working capacity were studied in 4 subjects. 2152 pieces of data were collected. 2) Frequency was at a minimum in summer and peaked in spring and autumn. 3) Comparison with meteorological conditions points to a highly significant recrudescence of disturbances in cold, damp weather, and meteorological periodicity independent of biological (circadian) rhythms.


[Cerebral circulation (measured by isotopes) and acid-base equilibrium of the cerebrospinal fluid during migraine].

In migraine patients a considerable metabolic disturbance characterised by a decrease in bicarbonate and an increase in lactate was demonstrated during the migrainous state. Measurements of the cerebral circulation were taken by means of radioactive isotope and showed a distinct decrease in blood supply to the entire brain during the migraine attack. Following forced hyperventilation during the attack-free interval a pathological reactivity with decreased blood flow was found in the hemisphere which had been indicated as the usual site of the migrainous pain.


[Neurosurgical treatment of headaches].

Apart from headaches due to expanding lesions or vascular abnormalities which require a direct neurosurgical approach, some cases of untractable, acute or chronic headaches may need some neurosurgical management. Among these, "low pressure hydrocephalus" is responsible for a number of cases that can be relieved by ventriculo-atrial or ventriculo-peritoneal shunts: "dural headaches" including some atypic migraines and "cluster headaches" can be cured by sectioning of the afferent meningeal rootlet of the trigeminal nerve in its retrogasserian portion. Some occipital types of headache, "venous headache" or "strain headache", may benefit of a cross section of the occipital dura mater. The Authors have also used in selected cases of untractable headache, their technique of intermittent electrical stimulation of the nucleus ventralis posterolateralis by means of an implanted stimulator.


[Statistical approach to psychosomatic headaches].

Three groups of patients were compared statistically: 79 with the diagnosis psychosomatic headache' (in the strict sense of the term), 450 others whose headache was part of another disorder (termed symptomatic headache'), and 850 patients free from headache symptoms. The following characteristics were found for the group with psychosomatic headache: More psychosomatic diseases in the family, usually the eldest in birth rank, usually living in towns, married, two children, intellectual level above average, overweight, ego-strength with compulsive features, tendency towards oral abuse of different kinds, few other psychosomatic complaints (contrary to the group with symptomatic headache). In the discussion the Authors try to demonstrate the defensive function of this selective somatisation.


[Headache as initial symptom of schizophrenic disease].

Initial schizophrenia was observed in 15 out of 93 out-patients being treated for cephalea in a Regional Neuropsychiatrical Department. Certain abnormal phenomena in the field of consciousness and body sensations are typical of coenasthetic schizophrenia, with vital asthenia and vegetative symptoms. Cephaleas and head dysaesthesias are reported. There is no doubt that coenaesthetic schizophrenia has many points in common with latent schizophrenia; on the other hand it is also closely linked to hypochondriac depression, the syndrome of endogenous juvenile failure, certain latent depressions, hypochondriac euphoria, vegetative and endoreactive dysthmia and pseudoneurotic schizophrenia. Personal studies of stress responses in schizophrenia, and pneumoencephalographic examinations and EEG data in the active stage suggest diencephalic alteration. For diagnostic and initially therapeutic purposes, every patient with cephalea should be examined thoroughly by the psychiatrist; in this way the number of schizophrenias identified and treated will be considerably increased.


Endometrial abnormalities occurring in young women on long-term sequential oral contraception.

Recently the occurrence of adenocarcinoma of the endometrium has been reported in young women exposed to sequential oral contraceptive agents for long periods of time. Twelve young women who had been using Oracon for periods of from 13 to 93 months were subjected to office endometrial aspirations. Tissue specimens showed endometrium which varied in diagnosis from proliferative endometrium to severe atypical adenomatous endometrial hyperplasia bordering on endometrial carcinoma in situ. Adenomatous endometrial hyperplasia is though by many investigators to be a precancerous condition. The progression of endometrial changes from benign proliferation to cystic hyperplasia and adenomatous hyperplasia accompanied by varying degrees of anaplasia in young women exposed to Oracon for long periods of time is significant. It is not surprising, therefore, that adenocarcinoma of the endometrium has been reported in these women at an age where this condition had been relatively uncommon prior to the use of sequential oral contraceptives.


Origin of estrogen in a postmenopausal woman with a nonendocrine tumor of the ovary and endometrial hyperplasia.

The origin and quantity of estrogen and androgen were measured in a postmenopausal woman with clinical signs of estrogen excess and a nonendocrine tumor of the ovary. The plasma androstenedione production rate was elevated 5-fold. The estrone production rate was also five times that normally expected for a postmenopausal women and could be accounted for totally by the extraglandular conversion of plasma and androstenedione. Following removal of the tumor, the concentration of plasma androstenedione and the estrone production rate fell dramatically to normal postmenopausal levels. It is concluded that this markedly increased androstenedione production was the result of excessive secretion of androstenedione by the hyperplastic stromal cells of the ovary containing the mucinous cystadenocarcinoma. The excessive prehormone production together with its normal extraglandular conversion to estrone resulted in the massive increase in endogenous estrogen formation.


Uterus unicornis with uterus solidaris.

Five patients are presented who manifested a heretofore unreported uterine anomaly: uterus unicornis with uterus solidaris. The condition is illustrated and described in detail. Patients with this anomaly have a good fertility potential, although they may expect a high fetal wastage, frequent premature labor and delivery, increased complications of pregnancy and delivery, and an increased incidence of infants that are small for the pregnancy duration. The importance of laparoscopy in diagnosing this anomaly is emphasized.


Uterine anomalies associated with unilateral renal agenesis.

Six cases of concomitant uterine anomalies and absent kidney are reported. Five of these were obstructive in type, 2 representing a mother and daughter relationship. The importance of investigation of the genitourinary system in the presence of uterine anomaly is emphasized. Fertility is unimpaired but obstetric complications are common, especially premature delivery and breech presentation. Treatment can be simple--drainage of unilateral hematocolpos--but excision of the septum may be necessary. The abnormal embryonic development is reviewed.


T-tube suction drainage and/or prophylactic antibiotics. A randomized study of 451 hysterectomies.

The technics of T-tube suction drainage of the retroperitoneal space and of prophylactic antibiotics were evaluated each alone and then in combination in a randomized study of 451 private patients undergoing abdominal or vaginal hysterectomy. As compared with results in a control group, suction drainage alone and prophylactic antibiotics alone were equally effective in reducing the incidence of postoperative pelvic infection and febrile morbidity. When the two technics were used in combination, there was further reduction in the incidence of pelvic infection and febrile morbidity. However, these results were not statistically different from those of either technic alone. Date are presented to indicate that hysterectomy is performed in a bacteriologically contaminated operative field and that a contaminated fluid collection routinely accumulates in the retroperitoneal space. It is therefore suggested that hysterectomy be managed as a potentially infected surgical wound.


Selection of patients for clomiphene citrate therapy.

Ninety-three infertile women were treated with clomiphene citrate alone or in combination with human chorionic gonadotropin (hCG) for absent or infrequent ovulation. The patients were divided into eight categories according to the diagnosis obtained: ovarian androgenic hyperplasia, adrenal androgenic hyperplasia, mixed ovarian and adrenal androgenic hyperplasia, hypothalamic anovulation, postpill anovulation, follicular phase defect, luteal phase defect, and amenorrhea-galactorrhea syndrome. Each group was analyzed individually to compare the ovulation and conception rates and the complications involved. A survey of the data presented in this study shows that the best response was noted in patients with ovarian androgenic hyperplasia. Patients with a functional pathologic adrenal component responded favorably when dexamethasone was used as an adjuvant to clomiphene therapy. Those with hypothalamic anovulation responded better when hCG was added to clomiphene therapy. Women with postpill anovulation as well as those with follicular phase defect were found to be good candidates for clomiphene therapy. In properly selected patients with poor luteal phase defect, hCG secured excellent results both in ovulation and conception. Patients with lactation amenorrhea failed to ovulate when treated with clomiphene alone.


Colposcopic evaluation of patients with abnormal cytologic smears during pregnancy.

One-hundred thirty-two patients with abnormal Papanicolaou smears of the cervix uteri during pregnancy underwent colposcopic evaluation. Seventy-five patients had biopsies during pregnancy, and 34 patients had colposcopic evaluation without performing any biopsy. Postpartum colposcopic evaluation was performed on 95 patients. In 93 patients of this group, the postpartum cytologic and histologic information obtained was the same or less than that obtained in antepartum evaluation. In only 1 case, antepartum colposcopically guided biopsy at 38 weeks' gestation revealed moderate dysplasia, and postpartum cold conization showed carcinoma in situ. In another case, colposcopic evaluation and biopsy during pregnancy showed mild dysplasia while colposcopic biopsy as well as examination of a hysterectomy specimen taken at 16 months after delivery revealed severe dysplasia. No case of invasive carcinoma was missed during pregnancy. The results of this study, in support of previous reports, show that colposcopic evaluation is a simple, safe, and accurate method of investigating abnormal Papanicolaou smears during pregnancy.


Obstetric complications after treatment of intrauterine synechiae (Asherman's syndrome).

This review comprises 36 patients who were treated for Asherman's syndrome from 1968 to 1974 at the Sloane Hospital for Women. Of the 18 patients who later conceived only 6 had uncomplicated term deliveries. Four had premature deliveries resulting in neonatal death. Three had placenta accreta and postpartum hemorrhage, necessitating a cesarean hysterectomy in 1. Two patients required cesarean section for complications due to the syndrome, 2 had spontaneous abortion, and 1 had a cervical pregnancy requiring total hysterectomy. Only 10 babies survived. The incidence and severity of complications in conceptions following treatment for Asherman's syndrome is high, and the obstetrician must be prepared to manage them.


Electronic fetal monitoring during labor.

Intrapartum electronic fetal monitoring tracings from 620 women monitored internally over 60 minutes were analyzed. Fetal heart rate patterns were statistically analyzed against four variables of labor: 1) the presence of meconium; 2) fetal acidosis; 3) 1-minute Apgar score; and 4) clinical correlates considered as etiologic factors in FHR decelerations. No significant etiologic correlation was found between these clinical correlates and FHR deceleration patterns. Statistically significant correlations were established between poor neonatal outcome and fetal acidosis (P less than 0.01) and the presence of meconium (P less than 0.05). No correlation was found between FHR patterns and fetal acidosis. Variable deceleration showed no significant relation to low Apgar score (less than or equal to 6). Late deceleration showed a significant correlation with depressed infants. FHR patterns are best used as an alarm system of fetal difficulty than as an absolute measure of fetal distress.


The choice of long-term anticoagulants for the pregnant patient.

The use of long-term anticoagulants in a pregnant patient poses many problems. In order to minimize the hazards for the patient and fetus the therapy must be individualized. A therapeutic regimen which calls for the use of both heparin and sodium warfarin at various intervals during gestation is discussed.


Pregnancy and lupus nephritis. A detailed report of six cases with a review of the literature.

The maternal and fetal courses of six pregnancies in 5 patients with histories of systemic lupus erythematosus and lupus nephritis were studied. The immediate and remote effects of these pregnancies on specific parameters of renal function are discussed, and a review of the literature is presented.


Studies of human pregnancy. I. Immunoglobulins attached to the trophoblast.

The human placenta was studied for the binding of immunoglobulins IgG, IgM, IgE, and C3 complement to the cell membrane of the trophoblast by use of fluorescein-conjugated and unlabelled antihuman immunoglobulins. Gestations of 8 to 40 weeks were evaluated for placental tissues taken from women undergoing therapeutic abortion, elective induction of labor, cesarean section, spontaneous labor, and toxemia of pregnancy. IgA was increased on the syncytial cytotrophoblast membranes at 8 to 10 weeks' gestation; IgE was present on the surface of the trophoblast only during spontaneous labor; and IgG was observed on the syncytial cytotrophoblastic cell membrane and basement membrane, and in the cytoplasm and the nucleus in all stages of gestation.


Effect of aspirin on bleeding time during elective abortion.

The template bleeding time, indicative of a predictable measure of potential blood loss due to altered platelet function, is unaffected by pregnancy or by the first stage of labor. Two tablets of aspirin (650 mg), but not sodium salicylate or acetaminophen, significantly prolongs the template bleeding time for at least 26 hours after consumption in patients undergoing first or second trimester induced abortion. Patients anticipating induced pregnancy interruption should refrain from any aspirin consumption for at least 26 hours prior to abortion.


Endometrial cytoloty. Using the Milan-Markley Technic.

Increased attention has been given to cytologic and histopathologic technic in the detection of endometrial lesions because of an increasing incidence of endometrial malignancy. The cervical-vaginal smear as performed by most clinicians is inadequate for the detection of endometrial neoplasia. Existing technics for the detection of endometrial lesions are costly and time consuming. An effective, reliable and economical technic has been developed for rapid smearing and fixation of endometrial cells. The routine endometrial screening of 739 patients (1143 specimens) using the Milan-Markley technic detected 4 cases of endometrial carcinoma, 1 case of carcinoma of the tube, 22 cases of endometrial hyperplasia, and 9 of endometrial polypi. It is hoped that this cytologic method will complement existing histologic detection procedures.


Inappropriate fetal bradycardia.

Intrauterine life demands unique respiratory and nutrient mechanisms, and it seems reasonable that some cardiorespiratory responses developed for later extrauterine life would not necessarily be entirely appropriate for the fetal period. In other words, a human fetus may not always be acting in its own best interest when it responds to intrauterine stress with what are appropriate extrauterine responses, such as gasping or the baroreflex (bradycardia). The detrimental effects of in utero gasping of meconium are well known, but the potentially harmful effects of inappropriate fetal bradycardia are little appreciated. A review of this condition is presented.


Pregnancy in patients with renal disease. A study of 44 cases.

A study of 37 pregnant patients with renal disease is presented in an effort to gauge the effect of gestation on renal function and to establish guidelines for effictively managing pregnancy in these patients. Serum creatinine determinations as indicators of maternal well-being are proposed as the basis for deciding to continue or terminate the pregnancy.


Fetal activity acceleration determination for the evaluation of fetal reserve.

Fetal activity acceleration determination (FAD) was performed 462 times on a total of 410 patients for the evaluation of fetal reserve. Simultaneous oxytocin challenge test (OCT) was performed 324 times to evaluate the correlation between the two tests. In 308 instances, FAD was positive and OCT was either negative or probably negative. In 2 cases with inadequate FAD results the simultaneous OCT was suspicious and positive. In four instances of negative FAD the simultaneous OCT was positive. The correlation between the two tests was excellent. The outcome of all cases with positive FAD was also excellent. The result of the present study strongly suggests that the positive FAD indeed provides reassurance of fetal well-being. Only the inadequate or negative FAD requires the performance of an OCT for further evaluation of the fetal condition.


Acidosis, local anesthetics, and the newborn.

Four newborn infants were studied following maternal epidural block with lidocaine or mepivacaine. Each of these neonates, born with a pH of 7.23 or below in the umbilical vein blood, showed an elevated fetal-to-maternal concentration ratio, a possible manifestation of ion trapping of a weak base.


Predicting respiratory distress by thin-layer chromatography of the newborn gastric aspirate.

The analysis of gastric fluid from newborns for lecithin/sphingomyelin (L/S) ratio evaluation is useful in determining whether respiratory distress will follow an early delivery. Without exception, the L/S ratios obtained on 14 gastric aspirates paralleled and were slightly higher than intrapartum values obtained from corresponding amniotic fluids (5.6 vs 3.7). Of 46 normal infants, only 1 had a gastric aspirate L/S ratio less than 2:1. No false positive results were found. The obstetrician can easily obtain gastric fluid at delivery, and by ordering an L/S ratio determination, the neonatologist can have an estimation of lung surfactant levels within 2 hours after birth. In cases where true respiratory distress syndrome (RDS) must be differentiated from other problems of respiratory distress, this information can assist in the early management of patients with RDS. Even after the development of RDS, the procedure offers a prognostic tool which the clinician can use in discussing the outcome with the parents.


Contraceptives and the conceptus. I. Chromosome abnormalities of the fetus and neonate related to maternal contraceptive history.

The chromosomes of 3080 products of conception, consisting primarily of newborn infants and medically induced abortions, were examined. These were from 3 major groups of women, those who had used oral contraceptives (primarily the combination types), those who had used nonhormonal contraceptives, and a control group of those who had not used any contraceptives. In the newborn study population, the chromosome abnormality rate was 5.4 per 1000 infants (when cases of proven hereditary involvement are excluded the figure drops to 3.6 per 1000), and in the entire induced-abortion study series it was 7.3 per 1000. These rates are very similar to those obtained in other surveys. The rate of chromosomally abnormal conceptuses increases with increasing maternal age in both the newborn and induced-abortion groups. No statistically significant relationships were found between the observed or age-adjusted rates of chromosome abnormalities and contraceptive history (P greater than .10 in all cases). The findings make it clear that the use of oral contraceptives has no large effect on the risk of having a chromosomally abnormal child although the possibility of a small increase or decrease in this risk, of at most about 10 per 1000, cannot be ruled out because of the small number of abnormalities found.


Experience with 40,000 Papanicolaou smears.

Forty thousand consecutive cytologic smears and subsequent diagnostic procedures resulted in the diagnosis of 41 carcinomas in situ, 35 microinvasive and invasive carcinomas, and 24 severe dysplasias for a yield of significant neoplasia of one lesion per 400 Papanicolaou smears. Twenty-five of the carcinomas in situ and microinvasive and invasive carcinomas were diagnosed in patients with atypical smears indicating that all patients with persistent atypical smears require evaluation by tissue examination. Seventy-eight percent of the 119 patients subjected to conization either had carcinoma in situ, microinvasive and invasive carcinoma, or significant cervical dysplasia. Post-operative complications following conization were negligible. In addition there were no postconization deleterious effects on three concurrent and nine subsequent pregnancies. A history of gonorrhea places a patient at a higher risk of developing cervical carcinoma. Annual performance of cytologic smear evaluation is indicated in all sexually active women and in all virginal women over 20 years of age.


Recurrent carcinoma in situ of the vagina in patients previously treated for in situ carcinoma of the cervix.

Sixty-six patients were seen at the Mayo Clinic from 1950 through 1974 with in situ carcinoma of the vagina following various forms of treatment for a similar lesion of the cervix. Sixty-three patients have remained free of recurrent disease. One patient has been lost to followup, 1 patient required a second local excision, and 1 patient had recurrent carcinoma that progressed to invasive vaginal malignant disease. The recurrent malignant disease was usually asymptomatic; its presence was suggested by an abnormal Papanicolaou smear and confirmed by Schiller stain or colposcopically directed biopsy. Colposcopic examination of the vagina has greatly facilitated delineation of the lesion; this may allow relatively simple definitive therapy in some instances--that is, local excision or partial vaginectomy. Total vaginectomy, with or without skin graft vaginal reconstruction, must be carried out in patients who have multicentric lesions. The use of vaginal radium or external beam therapy should be limited to the elderly patients or those to whom a functional vagina is unimportant.


Lymph node metastasis in microinvasive epidermoid cancer of the cervix.

A retrospective series of 69 patients indicates that  the definition of a diagnosis of microinvasive cancer of the cervix should indicate a lack of blood vessel or lymphatic permeation as well as invasion of not more than 3 mm below the basement membrane. The incidence of lymph node metastases in this group of patients in whom microinvasive cancer of the cervix had been diagnosed was 7.1%. Two of the 4 patients with positive lymph nodes demonstrated lymphatic or blood vessel permeation on preoperative conization and 2 did not, an incidence of 3.6%. One patient had lymphatic invasion on conization with negative lymph nodes on final surgical specimen. Two patients had recurrent epidermoid carcinoma within less than 10 years and died of recurrent carcinoma. Maximum survival can only be achieved by full treatment of Stage IA lesions. Since surgical mortality was absent in our series, surgical extirpation by extensive (radical) hysterectomy and bilateral lymphadenectomy should give optimum results.


The relation of adenomyosis uteri to coexistent endometrial carcinoma and endometrial hyperplasia.

The relation of adenomyosis uteri to endometrial carcinoma and endometrial hyperplasia has been the subject of only a few studies. These investigations have resulted in opposing conclusions on the association between the conditions. In this study of a 10-year period, all cases were retrieved from the surgical pathology laboratory files of adenomyosis uteri with either simultaneous endometrial carcinoma or endometrial hyperplasia. A control population was selected from patients who underwent hysterectomy for mechanical problems related to the uterus. Adenomyosis was found in association with endometrial carcinoma in 19.4% of 175 cases and in association with endometrial hyperplasia in 20.5% of 254 cases. The control series of 203 patients had a 16.7% incidence of adenomyosis. Statistical analysis showed no association between these conditions.


Secondary surgical treatment of the masculinized external genitalia of patients with virilizing adrenal hyperplasia.

Among 84 patients with virilizing adrenal hyperplasia operated on for deformed genitalia and followed for 7 to 22 years (mean 12 9/12 yr), 25 (30%) required secondary operations. For the most part, the secondary procedures were to provide a vaginal orifice adequate for coitus. The difficulties were due either to failure to adequately exteriorize the orifice at the first operation or to contraction of the outlet due to scar formation. Simple operative procedures to correct these difficulties are described.


Sella turcica abnormalities in an anovulatory population.

In a series of 177 anovulatory patients, x-ray studies of sella turcica revealed 4 patients with pituitary adenomas and 1 with an empty sella. Galactorrhea was present in 15 patients (8.5%) of the total series, but 4 of the 5 patients with pituitary abnormalities also showed galactorrhea. As patients were frequently unaware of the presence of milk in their breasts, careful examination by the physician will delineate a population at high risk for pituitary abnormalities. Clinical and endocrinologic characteristics of the 5 patients with pituitary abnormalities are presented and their management is discussed.


Effect of bromo-ergocryptine on serum hPRL, hLH, hFSH, and estradiol 17-beta in women with galactorrhea-amenorrhea.

Fourteen women with amenorrhea-galactorrhea were treated with bromo-ergocryptine. Serum prolactin hPRL, hLH, hFSH, estradiol 17-beta (E2), and progesterone values were determined before and during treatment. No consistent pretreatment hormonal pattern was found. During treatment hPRL levels fell in 13 of 14 patients, and E2 rose in 12 of 14 patients. Levels of hLH became normal, and amounts of hFSH did not change. Galactorrhea lessened in all cases and ceased in 11. Menses resumed in 11 patients and 3 women became pregnant. Cessation of galactorrhea and resumption of menses occurred irrespective of initial hPRL or hLH levels. It is suggested that improvement of galactorrhea and resumption of menses in some patients with normal hPRL values are the result of increased serum E2 levels and may be due to a direct action of bromo-ergocryptine on the ovary. Bromo-ergocryptine may also be effective in treatment of amenorrhea, unassociated with galactorrhea or elevated hPRL levels.


Electrocardiographic monitoring during hysterosalpingography.

Five hundred hysterosalpinogograms were performed over a 2 1/2-year period at Louisville General Hospital for infertility evaluation, followup of tubal sterilization or localization of intrauterine contraceptive devices. The incidence of significant vasomotor reactions to the procedure was 5.0%. Of the 500 procedures performed, 30 were selected for electrocardiographic monitoring. Among these 30 patients, sinus bradycardia was noted in 5 and sinus tachycardia in 6 patients. No other significant electrocardiographic changes were noted, although transient minor alterations of rate occurred frequently. Predisposing factors and preventive measures are discussed.


[Transport RNA in early embryogenesis of fish. 3. Certain problems of regulation of RNA synthesis at the early stages of development of the loach (Misgurnus fossilis (1)].

tRNA synthesis in the early loach embryos of different ploidy and factors of the activation of synthesis and the maturation of tRNA molecules at the mid-blastula stage have been studied. tRNA synthesis is activated at the early- and mid-blastula and in the beginning of gastrulation. The normal activation of synthesis and maturation of tRNA molecules require the embryo to be maintained in the contact with the yolk at the earlier developmental stages. The methionine starvation may be one of the factors limiting the rate of tRNA maturation. The activity of tRNA synthesis during blastulation was shown to depend on gene dosage. At this stage the paternal and maternal tRNA genes are transcribed independently. In the beginning of gastrulation, the type of tRNA synthesis control markedly changes and the effect of gene dose compensation manifests itself, that is typical for the control of rRNA synthesis as well. The data obtained are discussed with respect to the state of protein synthesizing system at the moment of activation of specific protein syntheses with the onset of morphogenesis.


[Role of mitochondria in the process of steroidogenesis induced by gonadotropins].

Specific inhibitors of RNA and protein synthesis in mitochondria, ethidium bromide and chloramphenicol, suppress the increase in the uterine weight of sexually immature mice and the in vitro maturation of oocytes of anuran amphibians induced by gonadotropins. The effect of steroid hormones on the uterus of mice and the oocytes of amphibians is not prevented by the inhibitors of macromolecular syntheses in mitochondria. In in vivo experiments, the doses of ethidium bromide inhibiting RNA synthesis in the liver mitochondria of mice stimulate RNA synthesis in the nuclei. This stimulation is accompanied by the increase in the activity of RNA polymerases. The possible involvement of mitochondrial genome in the gonadotropin-induced steroidogenesis is discussed.


[Genetics of isoenzymes and development].

Possibilities of utilization of isozymes as markers of the activity of genes in ontogenesis are considered. There are cases of both the synchronous and asynchronous activation of paternal and maternal genes controlling the synthesis of appropriate isozymes. The asynchronous activation is peculiar, mainly, of interspecific hybrids. The organospecific pattern of isozymes in ontogenesis is determined not only by the activity of structural genes controlling their syntheses, but also by numerous genes-modificators active at the translation and posttranslation levels.


[Synthesis of ribosomal proteins in early development of the loach].

The synthesis of ribosomal proteins (r-proteins) in the loach embryos was studied by the way of analysis of protein-labeled ribosomes isolated from the cytoplasm and purified from de novo synthesized polypeptide and contaminating proteins. The ribosomes at the mid-blastula and mid-gastrula stages were shown to contain no de novo synthesized proteins. The synthesis of r-proteins at the stage of organogenesis was revealed by sedimentation analysis of ribosomes in the gradient of sucrose concentrations, density analysis in the gradient of cesium chloride and analysis of the distribution of radioactivity in r-proteins separated from the labelled ribosomes by electrophoresis in polyacrilamide gel. At the stage of organogenesis, the exchange of ribosomal proteins with de novo synthesized r-proteins continues under the conditions of complete inhibition of RNA synthesis and incubation of unlabeled ribosomes with the labelled cytosol. The correlation between the absence of rRNA and r-protein syntheses at the early developmental stages and possible causes of the independence of r-protein synthesis and exchange from the simultaneous rRNA synthesis at the stage of organogenesis are discussed.


[Correlation of tetratogenic and antimitotic activity of a number of derivatives of 2,4-diaminopyrimidine].

The effect of 6 substances, analogues of the antimalarial drug chloridine, on the mitotic activity of liver cells in rat embryos and cells of corneal epithelium in adult rats has been studied. A definite correlation was established between the antimitotic activity and the chemical structure of the drugs under study, and namely the length of alkyl radical in the position 6 of pyrimidine ring. The full correlation was noted between the teratogenic and antimitoic activities of these drugs.


[Reutilization of labelled DNA precursors by the iris cells during the regeneration of the lens and retina in newts].

In the adult crested newts, the proliferating cells of the proximal and distal iris zones reutilize the labelled DNA precursors 4 days after triple injections of 3H-thymidine. The density of radioautographs (intensity of labelling per nucleus) under reutilization is 2.5--3 times weaker than under 3H-thymidine incorporation.


[Nuclear apparatus and differentiation of salivary glands of larvae of Drosophila virilis. 1. Change in DNA and RNA content in different cell structures at the stage of secretion formation].

Changes in the content of DNA, RNA and secretion products have been studied in chromosomes, nucleoli and cytoplasm of the salivary gland cells in the III instar larvae D. virilis. The DNA content doubles twice: 20--30 and 30--40 hrs after the second moult. The first doubling is followed by the intensive formation of secretion products. The RNA content increases from 30 hrs in chromosomes and twice in nucleoli: from the beginning of II instar till 20 and from 40 till 50 hrs. The maximum RNA content is registered at 50 hrs in chromosomes and nucleoli and between 50 and 70 hrs in cytoplasm.


[Relationship between mitotic phases at different stages of embryonic development of axolotl].

Indices and durations of mitotic phases and interphase have been determined in the axolotl embryos at the late blastula, early gastrula and mid-neurula stages. The data obtained suggest that the ratio of mitotic phases changes during embryogenesis and differs in different rudiments of the embryo at the same developmental stage.


[Comparative study of biological effect of purified gonadotropins of sturgeon (Acepenser stellatus) and carp (Cyprinus carpio)].

A comparison was made of the biological effect of purified gonadotropins of the sevryuga and the carp on the activation of adenyl cyclase in the homogenate of the goldfish ovary, the reaction of spermiation in two species of frogs, and the in vitro maturation of oocytes of two amphibian species and sevryuga. The ratio of specific activities of the preparations under study was shown to vary markedly with respect to test-subject and test-reaction. The data obtained suggest, thus, qualitative differences in the effect of the gonadotropins under study and the response of organs-targets. It is proposed to use the system of in vitro maturation of amphibian oocytes for studying the phenomenon of species specificity of gonadotropins of lower vertebrates.


[Heat resistance of aldolase of the hybrid embryos of sea urchins Strongylocentrotus droebachiensis and S, intermedius].

The time of expression of the genes controlling aldolase has been studied in the hybrid embryos female Strongylocentrotus droebachiensis X male S. intermedius. The enzyme heat resistance estimated by the temperature of 50% inactivation following the exposition for 30 min (T50) was used as its genetic marker. T50 of aldolase of the psychrophilic maternal species suffered practically no changes from the stage of mesenchyme blastula till the stage of 11 days old pluteus and equated 35.3 degrees. T50 of aldolase of autumn- and spring-spawning populations of the thermophilic paternal species equaled 39.5 degrees at the stage of 11 days old pluteus. The heat resistance of aldolase of the hybrid embryos did not differ reliably from that of maternal enzyme during the first 4 days of development (at 8 degrees) till the late gastrula stage and attained the maximum (T50 =36.9 degrees) on the 8th day (stage of pluteus). The expression of the genes controlling aldolase appears to take place between these developmental stages.


Ultrasonography in foreign body detection and localization.

The relative advantages and disadvantages of radiographic and ultrasonic studies in foreign body detection and localization are discussed. The value of ultrasonography in finding radiolucent orbital foreign bodies and its clear superiority in the localization of foreign bodies with respect to the walls of the eye is demonstrated by several examples. The information concerning the state of the lens, vitreous, and retina in such traumatized eyes which is obtained by ultrasonography represents a very important additional benefit of such study.


Computerized axial tomography of the orbit.

Computerized Axial Tomography is a noninvasive radiologic technique that gives definition to orbital structures that aids the ophthalmologist in his diagnosis and treatment. This outpatient study is painless, takes approximately thirty minutes, but does demand a very still patient. The globe, horizontal extraocular muscles, and optic nerve are well delineated which allows detection of retrobulbar abnormalities. Eleven examples of the sixty patients studied are presented demonstrating its value as the most informative test now available in orbital diagnosis.


The use of the cryoprobe in the removal of posterior orbital tumors.

Experience with a cryoprobe for the surgical removal of encapsulated and circumscribed tumors, cysts, and neoplasms in the posterior orbit indicates that the instrument is a useful and efficient adjunct to the surgical management of orbital tumors.


Emergency management of acute congestive glaucoma using an anterior chamber microsyringe and needle.

A microsyringe-needle assembly is described for use in aspiration and microinfusion procedures in the anterior chamber. Assets of a lancet pointed 30-gauge needle, surface anesthesia, and fine control of ocular pressure and aqueous humor volume are stressed. Use of the assembly for emergency treatment of acute congestive glaucoma, surgical paracentesis, aqueous sampling, and drug infusion are described. Drug volumes and concentrations must be maintained at levels which do not damage corneal endothelium.


An evaluation of 8-0 Polyglactin 910 synthetic absorbable suture in cataract surgery.

This study describes the operative and postoperative performance of 8-0 Polyglactin 910 in cataract surgery. The evaluation represents a clinical comparison of 7-0 Polyglactin 910 to the same suture in 8-0 size in 155 cataract surgical procedures. In 45 cases, 8-0 Polyglactin 910 was the sole wound closure material used. 8-0 Polyglactin 910 provided high tensile strength, good knot security, batch-to-batch uniformity, ease of handling, minimal reaction, and a predictable absorption rate that was virtually completed in 33 days. When compared to 7-0 Polyglactin 910, 8-0 produced less tissue drag, fibrillation, and reaction. Early in our series, three cases of wound dehiscence occurred. One was caused by trauma and the other two by 8-0 Polyglactin 910 cutting through tissue. This study's conclusion stresses avoiding the tendency of tying the knot too tightly to prevent suture pull-out.


Combined cyclodialysis and cataract extraction.

Combined cyclodialysis and cataract extraction was performed on 78 eyes in a consecutive series of 26 years duration. This operation was performed on eyes with severe glaucoma, inadequately controlled on maximum medical therapy, and with a cataract needing extraction. Glaucoma types included open-angle, angle-closure with peripheral anterior synechias, combined open-angle and angle-closure, and secondary to uveitis. Seventy of the 78 eyes had follow-up of six months or more and the results in these 70 eyes were analyzed. In thirteen percent of the eyes in this study the postoperative intraocular pressure was the same or higher than the preoperative level, or reductions of intraocular pressure were not clinically significant. Eighty-seven percent (61 eyes) had a clinically significant lowering of intraocular pressure following the combined procedure. Thirty-nine percent (27 eyes) of the 70 eyes in this study had a tension of 0-14 mm Hg, and 44% (31 eyes) had a tension of 15-20 mm Hg. Intraocular pressure was improved significantly more often in patients over 60 years of age. Resulting intraocular pressures of 14 mm Hg or less were more likely when the cyclodialysis was performed in the lower quadrant. The results of the combined procedure were not significantly influenced by the type of glaucoma involved or by a history of previous glaucoma surgery. Bleeding was a frequent complication, but was not related to resulting intraocular pressure. Other complications were rare. We conclude that combining cyclodialysis with cataract extraction is safe and effective, and is a suitable procedure when there is need for surgery to relieve severe glaucoma, along with a need for cataract extraction.


Fifty consecutive eyes with anterior segment disease treated by the pars plana approach.

Results of a pars plana approach using the Peyman vitrophage to treat various anterior segment diseases are presented in 48 patients (50 eyes). These included cases of ocular trauma, congenital cataracts, complications following unplanned and planned extracapsular cataract extractions and phacoemulsification, and dense secondary membranes. Visual acuity improved in 86%, remained unchanged in 10% and worsened in 4% of all eyes.


The future of our profession: a true-false test.

You are supposed to draw the conclusions and take the actions. My own belief is that we have a continuing obligation to provide a high quality education to as many qualified applicants as we effectively can. At this time we enjoy a unique opportunity that combines large numbers of qualified applicants with a substantial number of excellent training programs, and an unprecedented public demand for more and better health care. We must state clearly the public need for ophthalmologic eye care and must provide the manpower to deliver such care. Most importantly, we must not forget what it's all about: The philosophy of Mount Carmel is service to God through service to man, a service which is based on a belief in, and love for God. This love provides the finest medical and spiritual care for each patient without discrimination. The primary objective is to relieve suffering and to promote and to restore health in a Christian manner, which demands competence, mercy, love, and respect.


Intravitreous air injection and the Custodis procedure.

Occasional failure follows any form of retinal detachment surgery. Most of these persistent detachments are due to inadequate closure of a known retinal tear by scleral buckling. Avoidance of major reconstructive surgery may be accomplished by the judicious application of an intravitreous air injection under local anesthesia at bedside. Although technically precise, this singular maneuver was found safe and reliable. Its use is suggested as an alternative to classical reoperative procedures.


The emergency management of trauma.

For effective care, the severely injured patient may require the cooperative effort of many physicians and paramedical personnel. In the individual with isolated maxillofacial injury, adequate management may be provided by one or several specialists. In any event, there should be a plan for emergency, semiurgent, and delayed treatment. It is also important for each individual caring for the patient to understand and appreciate the problems within and outside his area of expertise. There is a logical progression of evaluation, with particular attention to the more severe and significant area of trauma. Hemmorrhage, shock, and airway problems take priority. Often the definitive treatment, from a cosmetic and functional standpoint, is delayed.


Penetrating wounds of the neck in civilians.

The management of penetrating neck wounds can be approached in a logical manner. The priorities in saving life are to ensure an airway and to maintain cardiocerebral perfusion. The initial evaluation and heroic life saving measure often rest upon the most inexperienced person, the house officer, who may be handicapped by the lack of experienced support personnel and sophisticated diagnostic and therapeutic equipment required for total management of these most challenging problems. It is hoped that this presentation provides the necessary guidelines for meeting this challenge. The pathophysiology, diagnostic approaches, and therapeutic measures are reviewed in the order in which they would be handled when the patient is brought to the emergency room, taken for special radiographic studies, and then subjected to surgical exploration. Special emphasis is placed upon diagnosis and management of traumatic arterial injuries, since these are the most challenging and most difficult to manage, as well as the most common causes of death following cervical penetrating wounds. Late vascular defects and associated injuries to the lymphatic, neural, airway, and foodway systems complete the discussion.


Reduction of mandibular fractures.

The decision to reduce a mandibular fracture by closed or open intraoral or extraoral techniques is not simple and depends upon multiple factors. That decision can be made only by the surgeon who understands the nature of the injury, the forces acting upon the injury site, and the relationship of the injury to other mandibular structures and to surrounding tissue. Other factors to consider include dentition and occlusion and an understanding of the healing processes, including the effects of concurrent disease and associated and distant trauma.


Complicated mandibular fractures.

In many mandibular fractures, proper alignment of the fragments is only a portion of the management program. Consideration must be given to the possibility of numerous other complications, and the patient should be carefully evaluated for injuries of the cervical spine, skull, head, and chest. The medical background, age, and other factors, such as the patient's ability to cooperate and follow the physician's instructions, may determine the method of applied treatment.


External fixation in maxillofacial surgery.

The role of external fixation in the treatment of facial fractures is well defined. If standard open reduction and internal fixation techniques do not yield a satisfactory result, external fixation techniques may be required. Open reduction has the advantage of effecting precise approximation of fragments. However, this type of fixation may be inadequate, either because no stable point is available or because the angle of traction involved in fixation may result in displacement of the reduced fracture and subsequent malunion. When the facial skeleton is fractured, it tends to collapse inward, and if injury is severe, an external traction point anterior, lateral, or superior to the facial skeleton may be required to obtain a satisfactory result. There are occasions when intermaxillary fixation may be inadvisable, and in these instances external fixation techniques may be an appropriate means of immobilization. Finally external fixation techniques may be required in instances in which massive tissue loss precludes the use of standard open reduction and internal fixation techniques. It must be reemphasized that the methods of external fixation described here are not meant to supplant the standard techniques of open reduction and interosseous wiring, but when judicially employed complement them in achieving the desired result of precise reduction and firm fixation of the fractured facial skeleton.


Complications in the treatment of facial fractures.

The evaluation and treatment of the more common and severe complications of facial fractures are reviewed. This analysis includes such conditions as nonunion and malunion of the maxilla, mandible, and zygoma, temporomandibular ankylosis, diplopia, enophthalmos, hypertelorism, dacrocystitis, and cerebrospinal otorhinorrhea. The discussion attempts to stress the importance of diagnosis regarding cosmesis and functional abnormalities. When possible, the pathophysiology is elucidated and evaluated to decide about methods of prevention. Preferred traditional and improved techniques of management are noted and compared to some of the less satisfactory procedures.


[Etiology of psychosomatic diseases in childhood (author's transl)].

The etiology of psychosomatic diseases in childhood is discussed. At first the most frequent causes of psychosomatic diseases are briefly reviewed; then the fact is discussed in detail that psychosomatic diseases in childhood are only to understand if one pays attention to the disturbed interrelationship between parents and child. This context makes it necessary that the parents are included in the therapeutic approach. In regard to therapy it is very important to reinstitute the psychosomatic unity; this means, to distract the patient from his somatic symptom and confront himself with his own-personal problems. The appearance of a somatic disease is considered as an effective defense-mechanism and may be understood as an "escape into the disease".


[Methods and technique of investigations in the course of sport activities of children (author's transl)].

In order to carry out investigations in the course of sport activities of children an efficient telemetering device is essential, which can also be used on children. The Kinderspital Salzburg has developed a telemetry system in cooperation with the Technische Versuchs- und Forschungsanstalt der Technischen Hochschule Wien and the Messerschmitt-Bölkow-Blohm-Werke München. For the first time in this field a Pulse Code Modulation (P.C.M.) System was utilized, implying high accuracy on data transmission and recovery as required for scientific examinations. The children's physical capacity is determined on a bicycle ergometer, and the performance measured in this fashion is then compared with the performance achieved in sport.


[The differential diagnosis of megacolon in childhood (author's transl)].

The diagnosis of Hirschsprung's disease can be established praeoperatively by the histochemical demonstration of an increased acethylcholinesterase activity in rectal mucosal biopsies. Furthermore the intraoperative diagnosis of the extension of the aganglionary or hypoganglionary segment can be improved by histochemical demonstration of dehydrogenases in the intramural parasympathetic plexus. By these means it becomes easy to localize the correct position of the enterostoma as well as to determine the length of the segment, which should be resected. The results of our histochemical investigation on 92 cases of megacolon, especially on 12 cases of Hirschsprung's disease were reported. The histochemical diagnosis was confirmed finally by an extensive examination of the resected bowel segment.


[Cytogenetic and clinical investigations in trisomia 22 (author's transl)].

Since the introduction of new cytogenetic methods, as the "Pancreatin-Giemsa"-stain and similar methods, it is possible for the first time to determine the chromosomes of group G accurately. There are few cases reported in the literature with an additional small chromosome which could be associated with group G. None of those children presented the classical signs of a Down-Syndrome, therefore a trisomy 22 was discussed. This is the report of a female patient, on whom trisomy 22 was confirmed cytogenetically. So far it was only in a small number of cases possible to prove this thesis by cytogenetic studies. We compare our findings with previous reports of suspected or proven cases of trisomy 22.


[Announcement of an Austrian study group for the treatment of leukemia in children (author's transl)].

The formation of an Austrian study group for the treatment of leukemia in children with international cooperation is reported. An essential aim is the centralisation of treatment at the 3 Austrian University clinics, the St. Anna children's hospital in Vienna and other children's hospitals particularly interested in the treatment of leukemia. Secondly the group undertakes randomised therapeutic studies, at present on two new variants of the Pinkel treatment scheme. Within the first 9 months 33 cases were included in this study in cooperation with the Zagreb University children's clinic (Doz. TIEFENBACH).


[Acute increased intracranial pressure--first symptom of renovascular hypertension? (author's transl)].

The authors report the history of a 7 months old male infant who showed acutely increased intracranial pressure associated with hydrocephalus internus. These symptoms appeared probably as the first manifestation of severe renovascular hypertension. The possible etiologic relations are discussed.


[Pathogenesis of osteopathy caused by anticonvulsives (author's transl)].

After a short survey of the recent suggestions of the pathogenesis of osteopathy caused by therapy with anticonvulsives it is demonstrated in the light of 3 case reports that 1. A vitamin D-sensible rickets, which is only due to abnormal living conditions, can develop in severely cerebral-damaged persons if there is no specific vitamin D administration. 2. An "antiepileptic rickets" is spontaneously reversible if the anticonvulsive therapy is stopped. 3. An enzymatic induction due to anticonvulsives is also detectable in the light of morphologic hepatic changes (biopsy, electron microscopy). Hence it follows that there are demands for a specific control of all patients treated with anticonvulsives. It is recommended to carry out a rickets prevention for a selected patient group.


[Treatment of pneumonia in childhood (author's transl)].

It is necessary to start with antibiotic treatment in infections of the lower respiratory system, especially pneumonias. The finding of the infectious agent is difficult and without security. With simple investigations, as sedimentation rate, white blood cell count and cell differentiation there is a possibility of 80% to get a diagnosis of bacterial infection. In 25 patients aged 1 1/2 to 9 years with x-ray diagnosis of pneumonia the results of treatment with cephacetril (100 mg/kg/d) are given. Clinical symptoms disappeared after 5 days, the average time of illness was 12 days. One patient got a severe pleural effusion.


Surgical management of spinal cord cysts.

A new surgical method, myelocyst-peritoneal shunt, has been performed on a small series of patients with congenital and acquired spinal cord cysts. In all cases, the progressive deterioration of neurological function ceased and all patients had slight to significant objective and/or subjective improvement in neurological function. The technical method is described along with individual case reports. Due to the short length of follow-up, the small number of operations, and the tendency for spinal cord cysts to spontaneously improve, the author discussed only potential advantages and disadvantages of this procedure as compared to prior spinal cord cyst operations. The creation of an in vitro human module spinal cord cyst by means of this operation has made it possible for the author to perform more basic ongoing investigation into the pathophysiology of spinal cord cysts and other similar disorders.


Pattern of spinal cord injury in the elderly.

A study was made of the pattern of spinal cord injury in the elderly who are forming an ever-increasing proportion of our population. It was noted that the elderly patients had a higher incidence of cervical injuries than other age-groups with a much lower incidence of dorsal and lumbar injuries. The mortality rate in complete cervical injuries was very high but in incomplete cervical injuries and those at a lower level the majority survived the acute phase. The cause of death in the acute phase was similar to that of other age-groups. The majority of survivors were able to be discharged to their own homes to the care of relatives and they fared better then those who had to be transferred to long term geriatric hospitals. Most of the late deaths occurred within five years of discharge from hospital but a few survived over ten years. The causes of the accidents were mostly falls at home and less frequently road traffic accidents.


Survival periods in traumatic tetraplegia.

The survival periods in 331 cases of quadriplegia are reviewed. Important features are degree of injury, age at time of accident and ability to survive the first three months. A comparison of comparable circumstances is essential if we are to correctly interpret our respective mortality rates.


Uro-check in paraplegics. (A survey of pathological changes of urinary tract in paraplegics).

On the basis of a Uro-check list, drawn up by the rehabilitation centre Tobelbad near Graz, 120 spinal cord injured persons were followed up, identifying changes in the urological tract. The classification and evaluation of the urological complications revealed a high percentage of severe changes which had occurred during the first decade after the accident. As a consequence it must be ensured that spinal cord injured persons receive yearly check-ups in a urological oriented rehabilitation centre where all modern examination methods, including electronic techniques for the measurement of intravesical pressure and urethral resistance, are available.


Deep venous thrombosis in acute spinal cord injury: a comparison of 125I fibrinogen leg scanning, impedance plethysmography and venography.

Twenty acute spinal cord injury patients were surveyed for deep venous thrombosis (DVT) by 125I fibrinogen leg scanning, impedance plethysmography (IPG), and venography. Leg scanning was a more sensitive indicator of thrombotic events than IPG or venography. IPG was a reliable indicator of accumulated thrombosis. The incidence of dvt assessed by leg scanning alone was 100 per cent. Its occurrence as determined by either of the screening techniques was found to be considerably greater than those of previous reports.


Treatment results of spinal cord injuries in the Swiss Parplegic Centre of Basle.

The results concerning the last 117 acute traumatic spinal cord lesions admitted in the Swiss Paraplegic Centre of Basle have been analysed as regards the rate of neurological recovery. The treatment not only concerns the vertebral damage but also the medical aspects of the spinal cord lesion itself. The routine use of combined Dexamethasone, Rheomacrodex and Hydergine in the very early treatment might have accounted for encouraging results which need to be confirmed in the future.


Medical social work in the 'Centro Nacional de Paraplejicos', Toledo, Spain.

The Medical Social Service in the 'Centro Nacional de Rehabilitación de Parapléjicos' of Toledo is briefly explained. Until 30 April 1975, 141 patients were treated in this hospital and the pertinent statistics are shown. The main social problems were housing, pension and job. The Medical Social Service makes use of all its resources to solve these problems.


The United States National Spinal Cord Injury Data Research Centre.

The National Spinal Cord Injury Data Research Center has been established at Godd Samaritan Hospital, Pheonix, Arizona by the Department of Health, Education and Welfare to develop information related to spinal cord injury in the United States. The research questions to be addressed by the project have been designed to define the magnitude and composition of the spinal cord injured population. How well does the spinal cord injured person cope with his disability? How much and what kind of services does he consume? How much does it cost? What does he produce? The project should add to our knowledge of the optimal methodology for delivery of proper services at the proper time at minimal cost to reduce the disability created by this catastrophic injury. Following the presentation of the above paper, 16 international spinal cord injury centers expressed their desire to participate in the United States Data Center Project.


A basic evaluation framework for spinal cord injury care systems.

Regional spinal cord injury care systems have recently been initiated in the United States. A basic strategy for evaluating effectiveness and cost of care in these systems has been developed and preliminary results from one of the regional systems indicates the utility of the evaluation plan and effectiveness/cost savings of the system.


Information in the early stages after spinal cord injury.

The information of the patient in the early stages after his spinal cord injury is often deficient. The opinion of 60 patients regarding some aspects of the information given to them during these early stages is discussed. The actual approach of patients with acute traumatic para- or tetraplegia, providing early detailed information and including a psychological interview, is presented.


Fine structure and origin of Kaposi's sarcoma.

Tumour cells in Kaposi's sarcoma with visceral involvement were studied by fine structural analysis. In the cytoplasm of these cells rod-shaped tubulated bodies resembling Weibel-Palade granules could be demonstrated. This finding and the occurrence of a basement membrane around the tumour cells characterize Kaposi cells as endothelial cells of blood vessels which may originate from undifferentiated vasoformative cells of the adventitia.


Pituitary thyrotropic tumour secondary to long-standing primary hypothyroidism.

Pituitary neoplasms in primary myxoedema are rare and previously reported cases have mostly been described as chromophobe adenomas. None of them were subjected to modern methods of study. A 26 year-old woman with untreated primary hypothyroidism developed a pituitary tumour which produced bitemporal hemianopsia. Histochemical and ultrastructural studies characterized the tumour cells as thyrotrops. The secretory granules present had a mean diameter of 110 mum and were membrane-bound and surrounded by clear halos. Many of the tumour cells were actively secreting. They had reduced numbers of granules, possessed expanded Golgi complexes, abundant rough endoplasmic reticulum and free ribosomes. Cytoplasmic microfilaments were also seen. A possible mechanism of production of this tumour is discussed.


Modern ideas on chromosome structure.

The structural element of an eukaryotic chromosome is the so-called chromatin fibre. It is a DNA-protein complex of about 100-200 A thickness and most probably running through from one end of a chromatid to the other. The fine structure of this DNA-protein fibre suggests a core of globular histone subunits around which the DNA-molecule is wound. The single strandedness of chromatids is suggested by the structure of premature condensed chromosomes. The course G-banding seen in metaphase chromosomes is presumably caused by groups of much finer bands seen in decondensed chromosomes. The number of such fine bands in the human genome is estimated to be 10 000-100 000, figures which are in the range of the number of genes in man.


The angio-architecture of normal, hypertrophic and denervated muscle. A study in the rat, using micro-angiography and the scanning electron microscope.

The angio-architecture of normal, hypertrophic and denervated rat muscles was studied by micro-angiography and by scanning electron microscopy of vascular casts made of methylmethacrylate. In hypertrophy, there was a slightly coarse-meshed irregular capillary network with some loss of normal parallelism, an increased calibre and a slight spiralization of all vessels. Probably all these changes, except the slight spiralization, increase the circulation. In denervation atrophy, the vascular pattern was much more irregular, with much more marked spiralization and loss of parallelism and narrowed capillaries. The changes probably contribute to the impairment of the circulation.


Nuclear inclusions and other ultrastructural aspects in the liver of animals treated with n-2-acetylaminofluorene.

In the course of two chronic experiments including the administration of N-2-acetylaminofluorene (N-A-AF) to male Wistar rats, alterations were observed in the fine structure of the nuclei isolated from the liver. After the first 3 to 4 months of ingestion of the carcinogen, the heterochromatin became uniformly distributed throughout the nucleus, with dissociation of the nucleolus-associated heterochromatin. At longer intervals (7 months) evidence was found in the nucleus of various types of inclusions, chiefly granular virus-like bodies. Subsequently, the frequency of inclusions diminished but the liver cell nucleus remained large, with numerous large nucleoli. This suggested the existence of a stage of metabolic activation of the liver cell nucleus in the course of experimental induction of hepatocarcinoma with N-A-AF, giving rise to an increase in the nuclear and nucleolar volume by accumulation of synthesis products and disorders in nucleo-cytoplasmic exchanges.


Glycogenous hepatonuclear inclusions in the aged mouse--an electron microscopical study of the histogenesis of nuclear inclusions.

Fifty-three and 84 week old mice have been investigated for liver nuclear inclusions. Light microscopical investigations revealed a significantly higher incidence of intranuclear PAS-positive material in the 84 week old mice. Electron microscopical studies showed a continuous development of nuclear inclusions from invagination of the double nuclear membrane containing all cytoplasmic organelles in various conditions via isolation of the invaginated portion to intranuclear free glycogen as a visible final stage. During the whole process alpha-glycogen is degraded to beta- and gamma-particles. These nuclear changes are not accompanied by other pathological changes either in the cells concerned or in the surrounding liver parenchyma. These nuclear findings are attributed to specific metabolic conditions in the ageing mouse.


Centrioles and cilia in non-tumourous anterior lobes and adenomas of the human pituitary.

Electron microscopy revealed the presence of centrioles and cilia in non-tumourous adenohypophysiocytes as well as in various adenomas of the human pituitary gland. Accumulation of centrioles and cilia was evident in sparsely granulated growth hormone cell adenomas. Abundance of centrioles is a valuable sign in establishing the diagnosis of this tumour. The possible functional significance of centrioles and cilia in adenohypophysial cells has been discussed.


'Collagenous colitis' with watery diarrhoea--a new entity?

A case of chronic watery diarrhoea showed in rectal biopsy a thick subepithelial collagenous deposit in the colorectal mucosa. This deposit was of the same type as that described in the jejunal mucosa in collagenous sprue, and seems to have been the cause of the diarrhoea.


A homeostatic adaptive response to alpha-methyl-dopa in conscious dogs.

Repeated daily administration of an oral dose of 1000 mg of alpha-methyl-dopa (methyl dopa) to conscious dogs produced a conditioned adaptive hypertensive systolic and diastolic arterial pressure response along with the direct hypotensive pharmacological effect. The lower dose of 500 mg/day appeared to be devoid of direct or adaptive response effects, while the higher dose of 2000 mg/day only produced a blood pressure lowering response. The abrupt drug withdrawal unmasking the homeostatic state resulted in a marked systolic and diastolic pressor response which endured for about 10-days with peak effect reached at 17-days after termination of drug treatment. Comparable results were obtained whether the dogs were evaluated while in their normal horizontal body position or in a repositional upright condition.


Classical aversive conditioning of heart rate in curarized rats at different blood gas levels.

In an effort to examine whether normal blood gas tensions were essential for conditioning, paralyzed rats received a classical aversive heart rate (HR) conditioning session while respirated at different peak expired CO2 values. After the session, arterial blood was drawn for analysis. That peak expired CO2 was effective in manipulating PCO2 was indicated by a significant correlation (r=0.594, df=17, P less than 0.05). In addition, only rats with blood gas values similar to those of anesthetized controls displayed a discriminated HR CR. These animals also had lower baseline HRs and greater HR variability. Further, 7 of the 9 rats with normal blood gas values were respirated at peak expired CO2 values from 5.0-5.1 per cent, and no animal ventilated within this range displayed abnormal values. These findings suggest that previous difficulties in obtaining calssical and operant conditioning in paralyzed animals may, in part, be attributable to inadequate ventilation.


Trends in the psychophysiology of individual differences.

Pavlov's typology of higher nervous activity was the first systematic approach to the psychophysiology of individual differences. Pavlov's theory has been further developed by Teplov, Nebylitsyn and their pupils in the Institute of Psychology in Moscow. In particular, Nebylitsyn has delineated a new property of the nervous system and has shown that it is different from strength of nervous system. In the Western research context we can compare the relationship between these two parameters to that between arousal and conditioning level. Eysenck's theory of the physiological bases of extraversion/introversion is discussed in relation to Nebylitsyn's theses and Gray's conception of arousability. Finally, it is suggested that future work in the psychophysiology of individual differences should stress the study of the ontogenetic development of the physiological variables.


Electrolyte abnormalities in very low birthweight infants.

In 30 very low birth weight (VLBW) infants, fed a commercial formula at 200 ml/kg/24 hr to provide 160 cal/kg/24 hr, hyponatremia (plasma Na+ less than 130 mEq/liter) occurred in 23 patients (14 appropriate for gestational age (AGA), 9 small for gestational age (SGA)) between the ages of 2 and 6 weeks. In five infants the hyponatremia recurred even after adequate correction of the deficit. Calcium supplementation given to 14 of the infants did not affect the incidence or severity of hyponatremia. In AGA infants, the hyponatremia was more severe than in SGA babies. Hyperkalemia (plasma K+ greater than 5.5 mEq/liter) was more common in AGA than in SGA infants (16/17 AGA, 7/13 SGA). Decrease in mean plasma chloride concentrations was proportionate to the decrease in mean Na+. Urinary Na+ averaged 1.0 mEq/kg/24 hr and was equal between groups during the first balance at a mean age of 18 days. In subsequent balances it appeared to decrease more rapidly in noncalcium-supplemented than in calcium-supplemented infants, but the difference was not significant (P less than 0.1). Fecal excretion of Na+ did not differ between groups. Symptoms were unrelated to the degree of hyponatremia or hyperkalemia and were nonspecific. Hyponatremia in AGA infants occurred in 50% of instances when growth was less than or equal to 0.75 cm/week, whereas it occurred in only 13.5% of infants when growth exceeded 1 cm/week (P less than 0.01). A similar trend in SGA infants was not statistically significant (P less than 0.2).


Cardiovascular responses to avoidance conditioning in the dog: effects of alpha adrenergic blockade.

Laboratory dogs were trained to press a response panel to postpone shocks during daily one-hour avoidance conditioning periods. Each dog was also confined in the experimental environment for 5 hours prior to the avoidance periods. Blood pressure and heart rate were monitored continuously during these experiments from chronically indwelling arterial catheters. Extended training resulted in the emergence of a cardiovascular response pattern during the pre-avoidance interval characterized by gradual increases in blood pressure together with decreases in heart rate. Elevations in both blood pressure and heart rate were sustained during the avoidance periods. During sessions in which alpha adrenergic activity was suppressed by phenoxybenzamine, absolute levels of blood pressure were found to be lower than during control (non-drug) sessions, but a progressive rise in blood pressure continued to be observed during pre-avoidance. These results suggest that sustained cardiovascular responses during avoidance periods are associated with activation of the sympathetic nervous system, but that the gradual rise in blood pressure during pre-avoidance is due to other factors.


Late hyponatremia in very low birthweight infants. (less than 1.3 kilograms).

Late hyponatremia (plasma Na+ less than 130 mEq/liter) occurred frequently (on 54 of 159 occasions) in 46 very low virthweight (VLBW) infants (less than 1.3 kg at birth) between 2 and 6 weeks of age while receiving a sodium intake of less than or equal to 2 mEg/kg/24 hr. To elucidate possible pathogenetic mechanisms five groups of such infants were studied while receiving a commercially available formula reconstituted to give two different volumes and two different Na+ concentrations. Sodium intake in the nonsupplemented (NS) infants (n = 23) was less than 2 mEq/kg/24 hr. Supplemented (S) infants (n = 16) received approximately 3 mEq Na+/kg/24 hr. A further group of seven infants given a high volume (200 ml/kg/24 hr), high caloric (100 cal/dl) formula and Na+ supplementation (to 3 mEq/kg/24 hr) was also included. Infants were studied from age 14 days until they weighed 1.80 +/- 0.05 kg at a mean age of 47 days. At the time of start of the study, 6 of 20 NS and 6 of 19 S infants were hyponatremic. After supplementation only two episodes of hyponatremia occurred in S infants, both during the first study week, whereas the high incidence of hyponatremia in NS infants period. During baseline urine collections all infants excreted between 80 and 100 ml/kg/24 hr urine, but those receiving 150 ml/kg/24 hr formula decreased their urinary output rapidly to 50 ml/kg/24 hr, whereas infants receiving high volume feeds (200 ml/kg/24 hr) did not decrease their urinary output until the third balance at an average age of 45 days. All infants excreted between 1.0 and 1.2 mEq/kg/24 hr of sodium in their urine during the initial collection. Nonsupplemented infants reduced their urinary Na+ excretion more rapidly than supplemented babies (NS: from 1.03 to 0.55 mEq/kg/24 hr, first vs second balance; S: from 1.00 to 0.80 mEq/kg/24 hr, first vs third balance). Mean potassium excretion remained unchanged in NS and S infants during the study period and was not affected by the volume or caloric content of the formula. Extracellular volume (ECV) and total body water (TBW) were measure serially, and there were no differences between S and NS infants in the distribution of body water. The percentage of TBW and ECV decreased in all groups with increasing postnatal age.


Cross modal transfer of a conditional flexion response in dogs.

Two experiments investigated cross modal transfer of a conditional flexion response. In the first experiment, two dogs with extensive experimental past histories transferred a discrimination based on the pattern of presentation of auditory stimuli to a comparable pattern of visual stimuli. A second experiment with a naive dog demonstrated that such stimulus patterning also occurred from visual to auditory modalities. Additional tests showed that transfer was based on the relationship between discriminative stimuli and that the negative stimulus in the second modality was actively inhibitory. The data were discussed with reference to general attentiveness and rudimentary concept learning.


Double responding in classical nictitating membrane conditioning with single-CS dual-ISI training.

Rabbits were classically conditioned under a single-CS dual-ISI paradigm. Contrary to a previous experiment by Frey (1970), a separate CR was conditioned at each interstimulus interval (ISI), producing a double response (DR) on long-ISI trials. Further experiments indicated that DR development is facilitated by (a) circumorbital US-location and (b) relatively high US-intensity. However, subsequent shifts to nonoptimal conditions did not produce substantial decreases in DR frequency. The presence of DRs appears to be readily amenable to interpretation in terms of a Pavlovian stimulus-trace mechanism in which the US becomes associated with a particular temporal portion of the CS. An instrumental-response-shaping hypothesis of classical conditioning can explain these data only if the hypothetical reinforcement mechanism is assumed to be considerably more complex than had previously been supposed.


The effect of spermidine and spermine on proliferation in vitro of fibroblasts from normal and cystic fibrosis patients.

The effects of spermidine and spermine at varying concentrations upon the replicative ability of human fibroblasts in cell culture have been studied. The average concentrations of spermidine causing a 50% inhibition of prolifertion (ID50) after 3 days of growth for three normal cell strains and three strains derived from patients with cystic fibrosis (CF) were 4.4 X 10(-6) +/- 1.2 M and 6.2 X 10(-6) +/- 2.1 M, respectively. The values for spermine were 2.0 X 10(-6) +/- 0.5 M for normal and 2.2 X 10(-6) +/- 0.1 M for fibroblasts from cystic fibrosis patients. No significant difference between the replicative ability of normal and CF cell strains was seen over a wide range of polyamine concentrations employed for a period of up to 3 days.


A multivariate discriminate analysis of behavioral measures in genetically nervous dogs.

For some years we have studied a strain of genetically nervous dogs in the Neuropsychiatric Research Laboratory, Veterans Administration Hospital, North Little Rock, Arkansas. In the manner of Pavlov and Gantt and later Scott and Fuller we have characterized these dogs in such descriptive terms as timid, human aversive, and catatonic-like. Behavioral tests have been administered on nearly all dogs in this longitudinal study, and we are using these data to try to develop statistical procedures to maximize the discriminatory power of the behavioral assay and to more accurately characterize the behavioral deficit. A multivariate discriminate analysis of 13 variables on 91 healthy and 63 nervous dogs assayed at 3 months of age shows: (1) that much of our present behavioral testing procedures is redundant, and (2) that simple "friendliness to humans" in the dog is as effective for discriminating between the two groups as any of the 13 measures, taken either singly or collectively.


Ketonemia and seizures: metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy.

Metabolic effects of a new ketogenic regimen in which ketonemia is induced by feeding of medium chain triglycerides (MCT) are described, and comparisons are made with effects of the standard high fat ketogenic diet. Eighteen children maintained on the MCT diet for 3 months to 4 years failed to show elevations of serum cholesterol and had only a slight rise in serum total fatty acids, in contrast to the marked hyperlipidemia observed in children on the standard high fat diet. Long term use of the MCT diet did not affect pH of venous blood. Blood glucose fell below 50 mg/100 ml in one-third of the children, the lowest levels being reached 2--3 weeks after the start of the diet. Plasma D(--)-beta-hydroxybutyrate (BHB) and acetoacetate rose gradually after institution of diet therapy, maximum levels being reached after about 1 month. Higher levels of BHB and acetoacetate were achieved in children under the age of 10 years (BHB = 4.3 mM +/- 0.6 SEM, acetoacetate = 1.8 mM +/- 0.3 SEM) than in 10--18 year olds (BHB = 1.6 mM +/- 0.2 SEM, acetoacetate = 0.57 mM +/- 0.08 SEM). Plasma BHB and acetoacetate levels in children maintained on a 3:1 high fat diet were similar to those in children on a 60% MCT diet. Plasma levels of BHB showed a significant correlation with anticonvulsant effect (P less than 0.02). Both the ketonemia and the anticonvulsant action were reversed rapidly by intravenous infusion of glucose.


Cholesterol metabolism in cultured fibroblasts in adrenoleukodystrophy.

The basic biochemical defect of X-linked adrenoleukodystrophy (sudanophilic leukodystrophy, Schilder's disease) is unknown. To investigate reported abnormalities in cholesterol metabolism in vitro, we examined cultured skin fibroblasts of four patients and four normal control subjects. The kinetics of retention and accumulation of [14C]cholesterol by these cells was studied. After 3 days of exposure to tracer amounts of [14C]cholesterol, an apparent steady state between the medium and cellular cholesterol was established. The specific radioactivity expressed per mg of protein was similar for both Schilder and control fibroblasts. tafter labeling the pre-existing cellular cholesterol pool, the rate of loss of label was followed up for a 6-day period. About 23% and 14%, respectively, of the cellular radioactivity in both Schilder's disease and control cells were released into the medium after the consecutive change with fresh nonlabeled medium. No significant differences in [14C]cholesterol rates of uptake or release were observed between control and Schilder's disease fibroblasts. About 44% of the labeled cholesterol was present in an esterfied form after incubation in the presence of unheated serum in both Schilder's and control cultures.


Type I hyperprolinemia: a study of the intestinal absorption of proline, hydroxyproline, and glycine.

Intestinal absorption of proline, hydroxyproline, and glycine was interpreted by investigation of a type I hyperprolinemia patient and six control subjects. Intestinal perfusion was performed. When proline (Pro), hydroxyproline (OH-Pro), and glycine (Gly) were infused together, an increase in proline concentration did not alter aminoacid uptake in the control subjects; however, in the hyperprolinemia patient, uptake of aminoacids became negliglible (Pro, 17--6 muM/min; OH-Pro, 15--0.3 muM/min; and Gly, 13.5--0 muM/min). When each aminoacid was infused alone at increasing concentrations aminoacid uptake increased in controls; in the hyperprolinemic patient, intestinal absorption was less for glycine and hydroxyproline but aminoacid uptake increased with substrate concentration; however, for proline, the uptake remained constant (1l.5--17 muM/min/20 cm of intestinal test segment) (Table 1). When hydroxyproline was infused with an increased concentration of proline in the hyperprolinemic patient, hydroxyproline uptake first increased (9.8--14.3 muM/min/20 cm) then decreased to its basal value, whereas, in the control subjects, uptake increased without decreasing subsequently.


Intracellular deoxyribonucleic acid-modifying activity of phototherapy lights.

Little information is available on the intracellular consequences of the high intensity illumination with visible light that is commonly used in the treatment of neonatal hyperbilirubinemia. The present study was undertaken to determine whether DNA isolated from human cells growing in culture had undergone structural alterations as a result of exposure to high intensity visible light in the absence of added photosensitizers. Analysis of such DNA on alkaline sucrose gradients revealed a diminution is size after illumination. This structural lesion was repairable when the treated cells were subsequently incubated in the dark. These changes were observed at wave lengths (450 nm) of light identical with those utilized in phototherapy and with total light doses (70.4 kJ/m2) representing only 5% of that received by a newborn infant undergoing phototherapy in our nursery for a 24-hr period (1.3 X 10(3) KJ/m2.


Transport of L-cystine by cultivated skin fibroblasts of normal subjects and patients with cystinosis.

Uptake of L-cystine at the plasma membrane of fibroblasts derived from normal and cystinotic subjects was studied. L-Cystine accumulation after a 20-min period was increased in cystinotic fibroblasts incubated in 0.08 mM L-cystine. This effect appeared to be concentration-dependent since accumulation after 20 min at 0.004 mM concentration was decreased in cystinotic cells. Kinetic data suggested that at least two nondiffusional saturable processes with widely different substrate affinities mediate initial L-cystine uptake in skin fibroblasts. In addition, the transport process with high affinity for L-cystine may itself be a two-component system, as suggested by (1) additive inhibitory effect of other neutral amino acids, and (2) preincubation studies in which preincubation with cystathionine enhanced subsequent L-cystine uptake, whereas preincubation with other neutral amino acids depressed subsequent uptake. Affinity constants and maximal velocities of initial uptake did not appear to be altered in cells derived from patients with cystinosis. After 60-sec incubation with L-[35S] cystine, cystinotic cells retained more label as cystine than did normal cells at each concentration studied. These data indicate that initial L-cystine uptakein fibroblasts of patients with cystinosis proceeds at a normal rate by means of all transport systems currently shown to be present in normal cells.