[Three case histories of cortical and sub-cortical auditory lesions. Audiological and tomodensimetrical confrontations (author's transl)]. The authors describe three case histories of auditory lesions involving the cortex or subcortex of the temporal lobes. In two of the cases there are minor lesions of the hemisphere producing an amusia without verbal deafness or agnosia of non-verbal sounds. In one of the two patients, the total transitory deafness makes the use of the term cortical deafness debatable. In the third case, a bilateral vascular lesion of the temporal lobes had produced a pure verbal deafness without loss of tone discrimination or loss of the capacity to recognise changes in rhythm or sound frequency. In these three patients in whom there was no anatomical verification, the data given by the scanner and the study of evoked cortical potentials recorded over the two cerebral hemispheres allowed a fairly good study of the correlations between the topography of the lesions and their semiotic consequences.


[Petromastoid clearance using plastic surgery in the surveillance of large cavities. Re-suture of the ear canal (author's transl)]. The lesions met with in chronic otitis media and especially in cholesteatoma, can be extremely widespread and, after petromastoid clearance there is a large resulting cavity which is impossible to survey by the usual route of the ear canal. A plastic surgical technique on the ear canal, is described which allows an easy surveillance without esthetic damage. It consists of a resection of a part of the cartilage of the ear canal with conservation of the skin of the inner and outer ear canal. This skin is used to re-suture the piece of cartilage which has been sectioned.


Evaluation of computerized tomography, cinelaryngoscopy, and laryngography in determining the extent of laryngeal disease. A prospective study of over 100 cases comparing computerized tomography (CT) and correlating these studies with photographic motion picture studies of the larynx, conventional tomography and contrast laryngography has been performed. The authors give illustrative examples of cases in which the CT scan has been documented as providing equal and often times greater information concerning not only tumors, but also cystic lesions and traumatic lesions. With the newer technology, the reduced radiation (which is less than one half that of conventional tomography), and the decreased expense (now comparable to that of laryngography alone), eliminates the need for conventional laryngography and tomography examinations. The incorporation of motion picture documentation of the lesions allowing future comparative studies between the original lesion and the CT are recommended for a more accurate retrospective classification and assessment of therapeutic results.


Leiomyosarcoma of the cervical trachea. Report of a case with reconstruction using a latissimus dorsi island flap. A case of leiomyosarcoma of the cervical trachea is described, detailing clinical presentation, pathologic diagnosis and surgical management. The rarity of this tumor in this location accounted for difficulties in clinical diagnosis and pathologic classification. Surgical treatment involved resection of two thirds of the circumference of the infracricoid trachea, with partial resection of the cricoid cartilage and thyroid gland. The defect was reconstructed using bilateral "butterfly" advancement flaps and a latissimus dorsi myocutaneous island flap. The technique and advantages of the latissimus dorsi flap are briefly described.


Endoscopic Teflon keel for anterior glottic web. Anterior glottic webs are generally repaired with a McNaught keel placed and removed by laryngofissure. Attempts have been made since 1922 to repair these webs endoscopically. An endoscopic technique using a Teflon keel which has been successful in properly selected cases is presented.


Benign tumors and lesions of the larynx in children. Surgical excision by CO2 laser. Benign lesions of the airway in infants and children may endanger the airway and compromise laryngeal function. The CO2 laser provides an elegant method of transoral surgical excision without compromising laryngeal function or airway competence. It avoids the risks of such other treatment modalities as external surgical approaches, prolonged steroid therapy, and radiation. It is applicable to a wide variety of lesions without the necessity of tracheotomy. Hospitalization is minimized. Ten cases are presented to show the wide applicability of this technique. Gross pathology and pre- and postoperative findings are demonstrated and discussed, as is the safety and efficacy of the laser soft-tissue interaction.


Effects of irradiation of cervical lymph nodes. The effects of irradiation upon the functional integrity of lymph nodes were studied in the isolated cervical region of the dog. After 6000 rads were applied in one dose plan, the measure of lymph flow was determined by the migration of radiogold from the larynx to the associated primary lymphatic terminals at intervals of 2, 4, and 12 weeks, and six months post-irradiation. Interference with lymph flow was identified by radionuclide stasis in the injection depot; alteration in the direction of flow was identified by relative concentration of the tracer item in the associated nodal terminals. The lymph flow was minimally distorted by irradiation in the test period unless secondary damage to the associated lymphatic channels intervened. The relative migration was consistent with the normal data in 52%, depressed in 13% and increased in 35% of the cases studied. Major obstruction and rerouting of lymph flow contralaterally was evident in 19% of the subjects due to fibrosis secondary to local infection.


Clinical course of unusual malignant sarcomas of head and neck. The clinical manifestations of 29 recently encountered sarcomas of the head and neck were analyzed in an attempt to define more accurately the diagnostic characteristics and therapeutic responses of these unusual tumors. The host factors of age, sex distribution, race, habits and associated features differ sufficiently to distinguish the sarcoma from the carcinoma population. In addition, the clinical course of sarcoma patients as monitored by mode of presentation, site of involvement, tumor histology, diagnostic features and certain elements of management and outcome, further indicates that these tumors can be defined and managed as a distinct group of lesions. A review of the recent literature supports the major conclusions of this study.


Radiation fibrosis and necrosis of the larynx. The deleterious effects of ionizing radiation upon the normal tissues of the larynx, even when it is not the specific target of the radiation therapist, are always apparent to the observant and experienced laryngologist. On occasions they are so marked as to obscure the diagnosis of concomitant persistent or recurrent cancer. There is a direct relationship between the number of rads delivered and the severity of the subsequent radiation reaction. A system of classifying such reactions is proposed. Grade 0 is normal. Grades I and II are expected. Grades III and IV may be considered complications and require specific and even energetic treatment. In grade IV reactions, which require operative intervention, laryngectomy may be the treatment of choice.


Cholesteatoma of the frontal and ethmoid areas. Cholesteatomas of the frontoethmoid region must always be considered in the differential diagnosis of a mass in the frontoethmoid region. A painless, slow-growing mass, often accompanied by proptosis and diplopia, but without history of trauma or infection, should make one suspect  of this pathologic entity. Although histologically a benign lesion, the keratinizing squamous epithelial lining will continue to desquamate and expand, leading to erosion of surrounding structures which could be life-threatening. In order to prevent recurrence, complete removal of the cyst lining is mandatory. Cosmetic reconstruction, often requiring obliteration of the surgical cavity, should be delayed for one year to insure against recurrence of the covering of active squamous tissue adjacent to dura, cribriform plate or ocular structures.


Recurrent layngeal nerve section for spasmodic dysphonia. Spasmodic dysphonia is a severe disorder of phonation accompanied by extreme tension of the entire phonatory system. The expressive functions of speech such as laughter, singing, and whispering are much less affected if at all. Psychotherapy, speech therapy, stimulant and psychotropic drugs, hypnotism and acupuncture have all been tried as treatment without success. In 1976, Dedo reported 34 patients who were managed with recurrent laryngeal nerve section for spasmodic dysphonia. All of these patients had marked improvement in voice with relief of spasticity. Twenty-two patients with documented spasmodic dysphonia present for at least one year have been managed at the Cleveland Clinic since Dedo's report. None of them had any improvement with conventional voice therapy and were subjected, therefore, to recurrent laryngeal nerve section.


Laryngeal nerve crush for spastic dysphonia. Four patients with spastic dysphonia refractory to speech and phychiatric therapy were treated by crushing the recurrent laryngeal nerve. Vocal cord paralysis was produced in all patients. Vocal spasticity subsided in all patients. Vocal cord motion returned in four to six months. Three of four patients remained free of spasticity for a minimum of 24 months.


The problem of the collapsing upper lateral cartilage. The collapsing upper lateral cartilage is an airway problem that admits to no ready solution, such as the deviated nasal septum or deflected columella. It is my understanding from experienced nasal surgeons that an attack directly on the upper lateral cartilage has not provided a solution, but in general makes the problem worse. A look at the nasal septal base by simultaneous viewing of both nasal chambers may reveal a dimenionsal of 1 cm or more. In that event, a fairly radical narrowing of the septal base in the plane of the pyriform crest by a subperiosteal and subperichondrial approach with well-placed transfixion sutures can increase the air-flow across that plane. It has done so in eight patients. This operation is for the experienced nasal surgeon, or the otolaryngologist who has prepared himself by careful cadaver preexperience.


Intercellular junctions in the differentiating rat otocyst. Intercellular junctions between cells of the rat otocyst on the 12th day of gestation were studied using lanthanum tracer and freeze-fracture techniques. At the luminal surface, the intercellular space is closed by a series of tight junctions. Gap junctions are also present between cells both within and below the luminal junctional complex. The presence of tight and gap junctions at this early stage in the differentiating otocyst is probably essential for the development of a normally functioning adult ear.


Electrical stimulation of the auditory nerve in cats. Long term electrophysiological and histological results. Each of five cats (one congenitally deaf) had Pt-Ir electrodes placed in the modiolus. Some electrodes were stimulated with a 100 micronamp, 0.25 msec balanced biphasic 50/sec pulse for 2 hours for a total of 20 to 40 hours each over periods of several months. Pre- and poststimulation measures of click-evoked N1 responses, averaged brain stem potentials, and impedances showed no long-term effects of damage to the nerves. Light microscopy showed very acceptable tissue tolerance and no evidence of damage caused by electrical stimulation. The deaf cat had about 10% residual nerve fibers which responded to stimulation.


[Cutaneous symptoms of carcinoid tumours of the small bowel (author's transl)]. Cutaneous symptoms of carcinoid tumours are classified in 4 groups: --Acute type: flusch and vasomotor signs (the caracters of which are described). --Chronic type: telangiectasia, hyperpigmentation, sclerodermia-like, cutaneous maetastasis. --Rare type with non-diagnostic sign. --Types in association with other dermatological conditions either unrelated disease or with a likely related disease such as phacomatosis. Dermatological diagnosis is generally easy as cutaneous symptoms is concomitant with metastatic tumours and increased levels of serotonin and 5-H.I.A. The carcinoid syndrom may take place in the concept of the tumours of the A.P.U.D. system on clinical, embryological, histological and biochemical basis.


Brain stem potentials evoked by electrical stimulation of the cochlea in human subjects. Brain stem potentials were recorded from scalp electrode to biphasic square wave electrical stimulation of implanted electrodes in the cochlea of three patients. Reliable potentials could be recorded that appeared 1.5 to 2.0 msec prior to the customary acoustically-evoked brain stem potentials. The effects of variations in electrical stimulus parameters of rate and intensity were measured. Brain stem potentials can provide objective indices of the effectiveness of electrical stimulation of the cochlea in man.


Giant functioning cervicomediastinal parathyroid cyst. A rare case of a large cervicomediastinal parathyroid cyst associated with hypercalcemia and an elevation of serum parathyroid hormone is presented. The pathogenesis of such a large cyst is discussed, hemorrhage into an adenoma being the most likely cause. Clinical investigations which should be carried out for any cystic mass at the root of the neck should include a serum calcium, and if this is found to be elevated, the possibility of the cyst being of parathyroid origin should be considered. In view of the high concentration of parathyroid hormone found within the cyst, aspiration of the cyst contents for parathyroid hormone estimation might well prove a valuable test to confirm the diagnosis.


Micromethod for determination of middle ear gas composition. This is a microchromatographic method for simultaneous determinations of O2, N2, CO2 and N2O in gas samples of 40-100 microliters. A Packard 836 U gas chromatograph with a thermal conductivity detector and helium gas as carrier was used. The combination of Porapak and 5A molecular sieve column system was found adequate and is described in detail. The fidelity of this method was proved by a high constancy of the retention time, the linearity of the response and the reproducibility of results. The present method proved to be reliable for determination of all middle ear gases in man and experimental animals during general anesthesia with N2O.


Osteomas and exostoses of the external auditory canal. A clinical, histopathologic and scanning electron microscopic study. Osteomas of the external auditory canal are considered clinically to be discrete, pedunculated bone lesions arising along the tympanosquamous suture. They are benign lesions but often are slowly progressive in size. Exostoses of the external auditory canal are broad-based elevations of bone usually multiple and bilaterally symmetric, involving the tympanic bone. It appears that both clinical and histopathologic evidence is sufficient to justify the impression that these two lesions should be considered separate entities and clinical diagnostic and histopathologic criteria have been suggested for diagnosis of these lesions.


Accuracy of frozen section diagnosis of parotid lesions. The accuracy of frozen section diagnosis was analyzed in a review of 132 parotid lesions. Of 107 benign lesions, 93% were correctly diagnosed on frozen section analysis, but of 25 malignant lesions, only 9 frozen sections were accurately interpreted. This study points out the difficulty encountered in using the frozen section technique when dealing with malignant parotid lesions and the importance of the surgeon's active participation in the analysis.


Restenosis of the mitral valve.

Restenosis of the mitral valve. It is suggested that restenosis is inevitable after mitral valvotomy and that only the time taken for it to occur is variable. The major factor affecting the lapse of time between operations is the extent of the original valvotomy. Calification of the valve is less important, and coincident mitral incompetence and the age of the patient have almost no influence on the time taken for restenosis to develop. A study has been made of 281 second closed valvotomies and 53 third ones. The operative mortality for second closed valvotomy was 6.7% and for third closed valvotomy 4%. Late emboli were rare. The average follow-up period after second valvotomies was 12.8 years: the condition of 29% of these patients was still satisfactory; 21% had had third valvotomies. At 5 years the condition of 53% was satisfactory. The average length of follow-up after third valvotomy was 6.4 years: the condition of 47% of patients was still satisfactory and the results were similar to those after second valvotomy. It is concluded that closed valvotomy remains the operation of choice when restenosis has occurred.


Urinary schistosomiasis in Saudi Arabia. The distribution, aetiology, pathology, and clinical aspects of urinary schistosomiasis are outlined and it is emphasised that mortality from the disease is not due to the parasitic ova passed in the urine and faeces but to the complications caused by fibrotic immunological reactions to the retained ova. The treatment both of these complications and of the infestation itself is discussed. The special circumstances governing the transmission of the disease in Saudi Arabia are described and it is suggested that in view of these the energetic application of hygienic, educational, and therapeutic measures should make the complete eradication of schistosomiasis possible in that country.


The postural function of the iliotibial tract. A new definition of the iliotibial tract is made. Its anatomical and physical characteristics are summarised and its known functions discussed. The various postures adopted by standing Man are looked at and one resting posture is closely analysed. Hence a new role is proposed for the iliotibial tract. In the hip bone a new bony effect of the iliotibial tract is proposed. The presence of this structure is traced in the fossil record and linked to the anthropological evidence of upright posture.


Duplication of the upper urinary tract.

Duplication of the upper urinary tract. The possibility of ureteric duplication should always be considered in children presenting with urinary infection. A high degree of suspicion should be present during X-ray investigation. Surgery is nearly always required to cure the problem, vesicoureteric reflux requiring reimplantation and a ureterocoele involving both uncapping and reimplantation techniques. Heminephroureterectomy is rarely required except in cases of bizarre ectopic opening in which incontinence is the presenting feature and the associated renal segment is dysplastic. Ureteropyelostomy is required for the rare situation of saddle reflux in the bifid ureter of incomplete duplication. It is occasionally employed for complete duplication, but it must be stressed that the primary defect is always at the lower end of the ureter and such bypass surgery must be combined with a ureterectomy and, when necessary, reimplantation of the remaining ureters.


The isolated circuit diathermy.

The isolated circuit diathermy. When using the conventional diathermy generator in surgery failure to apply the plate electrode can always present a serious risk of a thermoelectrical burn at any point where the patient makes contact with an earthed object on the operating table. The recent introduction of the earth-free (isolated circuit) diathermy should, under most conditions, provide complete protection against such risks. However, there are still certain circumstances under which even the isolated circuit may give rise to a thermoelectrical burn. Two such hypothetical examples are described; the sequences of events for these are fairly frequent occurrence.


Comparison between general and local anaesthesia for repair of groin hernias. A prospective study of 104 cases has been carried out to compare the use of local and general anaesthesia for the elective repair of groin hernias. There were no apparent disadvantages in using a local anaesthetic procedure. Patients having local anaesthetic herniorrhaphy required postoperative analgesics and antiemetics significantly less often and also returned home sooner (3.2 days) than patients having a general anaesthetic (4.1 days). These findings argue strongly in favour of local anaesthesia as a suitable alternative to general anaesthesia for repair of groin hernias.


Axillary hyperhidrosis: surgical cure with aesthetic scars. By using a technique in which the hair-bearing skin of the axilla is undermined through three small incisions the eccrine glands can be methodically removed. The resulting scarring is minimal and is aesthetically acceptable. In a series of 25 patients (50 axillae) 23 were totally cured of their hyperhidrosis. The remaining 2 patients were sufficiently improved not to require any further treatment. The technique may be undertaken under either local or general anaesthesia.


Kutler repair for the amputated fingertip. Fingertip amputation is a common injury. Although the damage may not be extensive, the disability produced can be considerable. Different surgical procedures are available for reconstruction, but none is absolutely satisfactory. Twenty-four cases of fingertip amputation have been treated by primary skin closure using the Kutler bilateral V-Y advancement technique. The procedure was found to be simple and satisfactory, both functionally and cosmetically.


PTFE (Goretex) femoropopliteal reconstruction for limb salvage. We present the results of the use of polytetrafluoroethylene (PTFE, Goretex) grafts for limb salvage in 20 cases of femoropopliteal or more distal arterial reconstruction. There appears to be no relationship between graft survival and 'run-off' or the overall disease state of the vessels. Cumulative graft patency was almost 50% at 6 months, which is in contrast with higher patency rates reported from other countries.


Management of the diabetic foot.

Management of the diabetic foot. If the diabetic foot fails to respond adequately to a short period of basic primary treatment surgery must be considered. The main factor determining its nature and extent is the severity of large-vessel disease. If investigation shows this to be of minor significance local surgery is usually successful. In the presence of definite large-vessel disease, however, major amputation is usually necessary, though arterial reconstruction with local distal amputation may occasionally be feasible. The factors to be taken into consideration in the choice of treatment are discussed.


Sudden postoperative death due to coronary thromboembolus. In the last few years sudden deaths have been an object of active research in cardiology, as a high proportion of deaths from coronary arteriosclerosis are sudden and unexpected. In surgical materials, such sudden fatalities during the early postoperative period are relatively rare, because the patients are in the hospital under observation and intensive care can be started immediately in the event of coronary attacks. In the present rare case the patient died suddenly during the 5th postoperative night without any alarming symptoms of coronary thromboembolus.


Pregnancy and small cell carcinoma of the uterine cervix. A fatal case of a 22-year old pregnant patient with small cell cervical cancer is reported. The fulminant course of the disease was attributable more to the histological type of the tumour than to the pregnancy. Delay in diagnosis as a result of the pregnancy created a problem emphasized, by difficulty of cytological examination due to the very small size of the cancer cells.


Liver hilus dearterialization. A histological and electron microscopical study in the dog. Liver histological and electron microscopical changes were studied in six dogs after liver hilus dearterialization and in two dogs after sham operation. All specimens were taken in vivo. In light microscopy a marked dilatation of the sinusoids was noted 90 minutes after dearterialization. After 24 hours it was even more pronounced. The hepatocytes were shrunken. On the seventh day these alterations persisted in the central area only. None of these changes were found in the sham-operated controls. In electron microscopy rounding and swelling of the mitochondria was observed on the first day after dearterialization. On the seventh day they looked normal. Damage of the endoplasmatic reticulum was found to persist even on the seventh day. The bile canaliculi membrane was damaged after dearterialization but not after sham operation. Dilatation of the sinusoids and widening of the space of Disse was observed on the first and seventh day after dearterialization. In the controls none of these changes were seen. In both dearterialized and sham-operated dogs a transient decrease in liver glycogen was noted. In conclusion, light and electron microscopical studies demonstrated reversible ischemic changes in the liver. These correlated well with our liver pO2 measurements which indicated transient hypoxia and our biochemical studies which indicated reversible damage of the liver.


Liver damage after liver hilus dearterialization in dogs. Twenty-one harrier dogs underwent a standardized liver hilus dearterialization with (7) or without (14) cholecystectomy using six sham-operated dogs as controls. Seven dogs died, only one of which was in the dearterialization and cholecystectomy group. S-OCT and s-GDH were increased at 90 minutes after dearterialization. There was no statistical difference between the groups at 90 minutes. On the first day after dearterialization, the activity of s-OCT, s-GDH, s-ALAT rose significantly (p less than 0.005). The activity of s-ASAT was, however, increased to the same extent both in the dearterialized and the sham-operated animals. A normalization of the serum enzyme activities was usually seen after one week. S-ALP increased on the first day (p less than 0.005) and still higher values were noted on the seventh day after dearterialization. Cholecystectomy did not affect any of these results except mortality. Liver oxygen consumption, in vitro was unchanged throughout the experiment. The oxygen consumption of bile duct mucosal scrapings one week after dearterialization was similar to the corresponding values in the controls. The results indicate that the dearterialization leads to a definite but mild and reversible mitochondrial and cell membrane damage. The results indicate further the need of adequate controls when the effects of dearterialization on the liver are studied.


Vascular access for haemodialysis with autogenous vein graft arteriovenous fistulas. Nine autogenous vein grafts (AVG) have been used in nine patients to create arteriovenous fistulae for haemodialysis. All the patients lacked vessels for construction of a regular arteriovenous fistula. Three of the AVG failed during dialysis treatment 3, 10 and 14 months respectively following construction. Another AVG thrombosed but function was restored by thromboectomy. The same graft was later complicated by a false aneurysm and rupture but was then reconstructed with a vein patch. One AVG with a false aneurysm in the proximal anastomosis was repaired within six weeks.


[Evolution of plasma concentration of gonadotropins and corticosterone during the growth of the male rat (author's transl)]. Plasma LH, FSH and corticosterone were determined between the 15th and 90th day of life, in normal male Rat. Plasma gonadotropins and corticosterone at basal conditions or after psychic aggression increased from the 15th to the 40th or 45th day of life; then all hormones decreased to adult age. The development of plasma gonadotropins and corticosterone are carried out in a parallel manner during the period studied. It was thought that perhaps the elevation of gonadotropins secretion might have stimulated the adrenals.


[Modifications of the accessory glands of male genital tract of intact and castrated rats after sulpiride treatment (author's transl)]. Sulpiride or Dogmatil (Delagrange, Paris) was injected to male rats at the rate of 40 mg/day for either 10 or 20 days. Ponderal fluctuations of the accessory organs followed by a quantitative analysis of fructose and of serum acid phosphatases issued from testis epididymis and prostates (PAP) were studied. The coagulating glands alone reacted strongly and their initial weight doubled in 20 days. On the contrary, the fructose decreased sharply in all accessory glands especially in the coagulating glands. The PAP decreased slightly. The fact the concentration of serum PAP remained relatively high even in the castrated males, can be explained by the increase in the lysosomial activity due to retention and diminution of secretion granules. Fructose and PAP are conditioned by androgens and their quantitative decrease suggests that the testosterone level decreased. Hyperprolactinemia induced by Sulpiride is concomittent to testosterone diminution and the effect of each hormone cannot easily be separated. In the castrated animals the effects of Sulpiride were minimized due to the difficulty in observing significant variations between treated and untreated castrates.


[Thyroid incorporation of radioactive iodine in neotenic tritons (Triturus helveticus Raz.). In vivo studies by high resolution radioautography. Comparison of iodine incorporation in adults and larvae]. In vivo kinetics of radioiodine incorporation have been established for 70 newts, collected from Triturus helveticus Raz. populations where spontaneous neoteny occurs. Fifty of these newts which appeared to present four degrees of neoteny (more or less metamorphosed), have been studied. Main results obtained were: 1) The intensity of the iodine incorporation varies according to the degree of neoteny. The higher is this one, the lower is the intensity. 2) In general, iodine uptake rates are more or less similar to these of adults, but more often the evolution of the 125I uptake approaches a plateau-curve. From thyroid radioautographies on some animals (17 neotenic and 2 adult newts) for which in vivo iodine kinetics have been examined and on 9 normal larvae in premetamorphosis or in metamorphosis, we have noticed in those neotenic thyroids, a very small number of silver grains on apical vesicles and colloidal lumina when the degree of neoteny is the highest. This number of marked apical vesicles and colloid is more important in the neotenics which have lost some larval characters. Silver grains on colloid droplets indicating thyroid hormone excretion are inexistent in the most larval neotenics, more numerous in most metamorphosed neotenics. But they always are less numerous than in metamorphosing larvae. For a few animals, the fixation curve is very high, probably because of a stimulation of thyroid function, induced by the test and not because of a goitrous tendancy, as radioautographic observation of their thyroid shows. Thyroid function and its relation with the origin of this total and accidental neoteny are discussed.


[Renal osteodystrophy in two children : a comparison of the effects of 1 alpha-hydroxycholecalciferol (author's transl)]. Two children suffering from renal osteodystrophy were treated by 1 alpha hydroxycholecalciferol (1 alpha OHD3) 1 microgr. each day, for 18 months. In both the level alkaline phosphatase decreased at the same time as endogenous immunoreactive CT increased, iPTH did not change steadily, whereas plasma creatinine rise. As plasma calcium concentration did not increase, it is suggested that the increase in endogenous CT concentration is a part of the favourable response to the treatment by 1 alpha OHD3.


[Metabolic investigation of a population of institutionalized epileptics (author's transl)]. 77 epileptics receiving a combination of anticonvulsants have been studied. 25(OH)D3 levels were diminished in 38% of the patients, markedly so in 25%. iPTH levels were elevated in 13%. Total, as well as ionized, serum calcium levels were significantly lower in the epileptic patients, as compared with a control population. Serum P, Mg, and plasma total CO2 levels remained unaltered. Alkaline phosphatase levels were increased, as well as gamma-GT levels. A transiliac bone biopsy was performed in 15 patients and histomorphometric studies were achieved on decalcified and undecalcified sections. Osteomalacia was present in 4 out of the 15 cases, hyperosteoidosis in one. Three biological features distinguished the cases with osteomalacia : iPTH levels and alkaline phosphatase values were significantly higher, and serum P levels were significantly lower (all were below 2,4 mg/dl) as compared with the non-osteomalacic patients. In an epileptic population, the serum Ca value is lower than in a control population by 0,5 mg/dl. When in addition the serum P is low (which was a feature of male patients), the danger exists for osteomalacia to develop. The former abnormality is connected with low 25(OH)D3 levels, the primary event, while the latter is probably related to high (secondary) iPTH levels.


[Osteomalacia in hyperphosphoethanolaminuria without hypophosphatasia (author's transl)]. Increased urinary excretion of phosphorylethanolamine (P.E.A.) is one of the salient features of hypophosphatasia. This inherited disorder is generally transmitted as an autosomial recessive trait and is characterized by abnormal mineralization of bone, premature loss of deciduous teeth and reduced tissue and serum alkaline phosphatases (A.P.) levels. The authors report a series of patients presenting with pains of skeletal origin attributed to an osteomalacia syndrome on the ground of a bone biopsy. These patients had no history of rickets during childhood but complained of early severe caries of the permanent dentition before the age of twenty. They had neither malabsorption nor renal tubular abnormalities. Their serum 25 OH vitamin D was normal and their serum A.P. levels were within the normal range with a normal isoenzyme distribution. All these patients had increased excretions of urinary P.E.A. and the latter correlate significantly with the degree of osteomalacia. Control patients with a malabsorption syndrome, showing osteomalacia and serum A.P. of the same degree of magnitude as the patients of the first group, have a normal P.E.A. excretion and no correlation appears between the degree of osteomalacia and the P.E.A. excretion. The cases with increased P.E.A. excretion may correspond to adult pseudohypophosphatasia. The signification of increased P.E.A. excretion is discussed.


[Erythrocyte metabolism in vitamin D deficiency rickets]. In an attempt to explain the hemolysis observed in vitamin D deficiency rickets in the infant, we studied erythrocytic glycolysis, the level of ATP and some of the key enzymes of the glycolytic pathway. This study was performed in one group of vitamin D deficient infants and in one control group. The values obtained in these two groups did not differ significantly. In the absence of a defect in the glycolytic pathway, we suggest that an anomaly exists in the red cell membrane of these patients.


[Metabolism of bone in culture (author's transl)]. A method for studying in vitro bone matrix resorption by the use of 35S injection was investigated. Various hormones were tested and their effects on 35S and 45Ca metabolism were compared.


[Effects of 1,25(OH)2D3 on bone mineralization in vitamin D deficiency (author's transl)]. Two cases with vitamin D-deficient osteomalacia of digestive origin (coeliac disease) have been treated orally with 1,25(OH)2D3 in dosages of respectively 8 and 3 microgram/24 h. Serial transiliac bone biopsies have been performed. Mineralization fronts were normalized after respectively 4 and 1.5 months, whereas mineralization rates, as demonstrated by double tetracycline labeling, were normalized respectively after 2 and 1.5 months. In both cases osteomalacia healed completely despite persistently low 25(OH)D levels in the serum. It is obvious from these studies that 1,25(OH)2D3 per se is able to cure vitamin D-deficient osteomalacia, a finding that has been disputed. Whether 25(OH)D acts more rapidly on bone, as suggested by the studies performed in one case with anticonvulsant osteomalacia, remains to be proven.


[Bone histology and 25-OH vitamin D plasma levels in alcoholics without cirrhosis (author's transl)]. Bone mineralization is impaired in alcoholic non cirrhotics admitted to hospital for withdrawal. The defect is more marked in women than in men. Low 25-OH vitamin D plasma values may be observed in these patients and seem to be related to malnutrition. The degree of bone demineralization is not statistically correlated to 25-OH vitamin D plasma level.


[The effects of 1 alphahydroxycholecalciferol in patients with renal osteodystrophy, Paget's disease of bone and in normal subjects (author's transl)]. The administration of 1 alpha hydroxycholecalciferol (1 alpha OHD3) (2 microgr. per day) increase the plasma immunoreactive calcitonin (i CT) concentration in normal subjects after six days. This effect is also observed in patients suffering from Paget's disease of bone, suggesting that the mechanism responsable for the secretion of CT following the administration of 1 alpha is not disturbed in that disease. By contrast, the absence of increase in plasma iCT in the patients suffering from chronic renal failure suggests an impaired secretion of CT in that disorder.


[Radioimmunoassay of ADH in human urine (author's transl)]. A simple efficient procedure for extracting and concentrating arginine-8-vasopressin (AVP) from urine has been coupled with a specific and sensitive radioimmunoassay in order to measure antidiuretic hormone (ADH) excretion in normal humans under various physiological stimuli. Antisera have been raised in rabbits injected with lysine-vasopressin (LVP) or AVP coupled with bovine serum albumin. The antiserum selected for the assay which inhibits the antidiuresis induced in the rat by AVP is used at a final dilution of 1 : 50,000 and possesses a high association constant of 1 x 10(11) 1.mol-1. The limit of detection of the RIA system is 0.5 micronUI/ml of urine (1.25 pg). Urinary ADH has been extracted from urine by Miller and Moses method. Mean recovery of added vasopressin averaged 90.2% +/- 11 (SD) and assay of serial dilutions of such extracts showed that they behave in the assay system in the same way as synthetic AVP standards. Moreover comparison of the results obtained by the RIA to those given by the biological method using the ethanol anesthetized rat showed excellent correlation (r = 0.9 p less than 0.001). Under ad libitum fluid and food intake, mean daily urinary excretion of AVP (uncorrected for recovery) determined in 22 subjects was found to be 30.58 +/- 11.64 mU/h with no significant difference between men and women. In response to an oral waterload ADH became undetectable at the peak of diuresis. Following a 16 hr fluid deprivation, ADH rose moderately. A significant correlation has been found between urine osmolality and AVP excretion rate.


[Experimental hepatic encephalopathy. The effect of portocaval shunt on the evolution of the anterior hypothalamic neurosecretion in the rat (author's transl)]. The evolution of the anterior hypothalamic neurosecretion is studied in control, sham-operated and portocaval shunt rats. In sham-operated related to control rats, no modification of the anterior hypothalamic neurosecretion is observed. In portocaval shunt rats, the hypothalamic neurosecretion increases. This increase is mainly observed into the median eminence in all the portocaval shunt rats. The hypothesis according to which the modification of neurosecretory acitivity of the hypothalamic structures may be related to a discrepancy between the central monoamines is discussed.


[Digestive hormones and gastric diseases. Facts and hypotheses (author's transl)]. Relationships between hormonal secretions from the GI tract and gastric functional and/or pathological abnormalities could be studied according to 2 main lines : 1) gastric secretory changes could be the main symptom of hormonal secretory tumors, i.e. acid hypersecretion in the Zollinger Ellison syndrome, acid hyposecretion in pancreatic cholera and in somatostatinoma. In these cases, hormonal hypersecretion is directly responsible for the functional disturbances and the related symptoms; 2) gastric pathological conditions are sometimes accompanied by changes in hormonal secretion, but the level of interdependence is variable : high blood gastrin is directly depending upon the atrophic gastritis in pernicious anemia; this mechanism was also suggested in case of gastric carcinoma. Concerning ulcer disease, numerous problems are unsolved in respect to blood gastrin (basal and stimulated) abnormalities, as well as somatostatin and GIP secretions.


Immunoglobulin levels and genetic polymorphisms in the Sukuma of Tanzania. In a sample of 150 Sukuma from north central Tanzania, immunoglobulin G, M, A, and E levels were studied in relation to the phenotypes in 22 polymorphic systems. No strong associations were detected, though there is a suggestion of an association between IgG and haptoglobin type, with elevation of mean levels in heterozygotes.


Changes in plasma inorganic phosphorus and alkaline phosphatase activity during the adolescent growth spurt. Longitudinal data on changes in the concentrations of plasma inorganic phosphorus and plasma alkaline phosphatase activity in 23 girls and 44 boys during the adolescent growth spurt are reported together with the height velocities, ages and sexual maturity ratings. The average age at the peak of the growth spurt was 12.5 years in the girls and 14.1 years in the boys with mean annual height gains of 7.0 and 9.7 cm/year respectively. In both sexes, plasma alkaline phosphatase activity rose and fell with the growth velocity during the growth spurt. Plasma inorganic phosphorus rose to reach a peak in the 4 months before the peak of the growth spurt in height; this rise was statisically significant in the boys but not in the girls. Values subsequently fell rapidly towards the normal adult concentrations. Plasma calcium, total protein, and albumin concentrations were also followed during this time, but were not at any point significantly different from normal adult values. These findings provide a guide for the interpretation of plasma biochemistry in adolescent patients.


Red cell adenosine deaminase (ADA) polymorphism in Southern Africa, with special reference to ADA deficiency among the !Kung. Studies have been carried out on polymorphism of adenosine deaminase in 36 Southern African populations comprising more than 3000 individuals. The common variant allele ADA2 has been found to attain polymorphic frequencies only in those populations descended from non-indigenous (i.e. non-Negro and non-Khoisan) groups. Its presence in certain other populations at low frequencies could be ascribed to small-scale Caucasoid admixture. A deficiency of the enzyme is found in certain members of the !Kung division of the San ('Bushman'). The low levels of enzyme activity are not associated with severe combined immunodeficiency and the gene which determines them appears to be polymorphic in the !Kung and possibly in some other San populations as well as possibly in Negro populations which have received substantial contributions of San genes.


Anthropometric survey of children in rural Khartoum, Sudan. The results of a cross-sectional anthropometric survey of Sudanese children up to the age of thirteen years and six months is reported. Children in whom a quick clinical examination revealed pathology were excluded, as were children who did not have a true birth certificate. Height, weight and mid-arm circumference were measured in all children, head and chest circumference were measured in children up to the age of 5 years and 6 months. Skinfold thickness at biceps, triceps, subscapular and suprailiac sites were measured in children above the age of 30 months. The children were found to be shorter and lighter, and to have less subcutaneous fat than British children. The findings are also compared with those from other African populations. Comparison with a survey performed in the same village seven years earlier reveals that the heights and weights of the children have hardly changed despite a considerable improvement in economic status. The children have a lower weight for height than British and other African populations.


The secondary sex ratio, paternal age, maternal age and birth order in Japan. The simultaneous effects of several variables on the secondary sex ratio have been examined using data from over 3.7 million births which occurred in Japan during 1975--6. A weak and negative association between sex ratio and birth order was observed but it was not significant in the statistical sense. A negative effect of paternal age--birth order interaction was obtained when maternal age was controlled. The quadratic model is much more powerful than the linear model in explaining the sex ratio variability.


Cultural and biological determinants of lipoprotein concentrations. A general linear model is presented here for biological and cultural inheritance involving ten parameters to be estimated from 16 correlations in nuclear families, providing ample degrees of freedom to test goodness of fit. Applied to six lipoprotein traits the model fits acceptably to all, although there is evidence of transient maternal effects for cholesterol and lipemia. Genetic heritability in children ranges from 0.175 for triglyceride to 0.562 for total cholesterol. Cultural heritability in children ranges from 0.012 for VLDL to 0.149 for HDL-cholesterol.


Age at menarche in rural France.

Age at menarche in rural France. Data upon age at menarche have been collected among 254 schoolgirls of a relatively endogamous rural population in central France. The median age at menarche estimated by probits was 13.05+/-0.18, SD1.42. This accords well with results obtained from urban samples in the years 1965-68. Both rural and urban samples give a median age 0.5 year earlier than date from a national survey performed in 1950.


Nutrition and menarche in rural Hyderabad. Mean age at menarche was estimated in 739 rural Hyderabad girls aged 12 to 18 years using the status-quo method. These girls had been previously measured and were divided into four groups according to their height at age five. Those who were short at age five had a significantly later menarche (15.2+/-0.13) than those who were tall at age five (13.7+/-0.19). Since 14% of the short-at-five girls had had signs of severe undernutrition and none of the tall had had these, the shortness and late menarche are both attributed to undernutrition.


Harpenden electronic read-out (HERO) skinfold calipers. The Harpenden skinfold caliper has been modified so as to give a simple digital display or an output which may be fed directly to more sophisticated equipment (e.g. digital computer or X-Y plotter) for further analysis.


Family handedness in three generations predicted by the right shift theory. The hand preferences of Open University (OU) students and their relatives, including children, are described. As in earlier series, estimates of heritability are higher for mothers than fathers. There is no evidence of smaller heritability for paternal than maternal grandparents. The distribution of left-handedness in families is examined in the light of predictions of the right shift theory and on the assumption that the shift depends on a single gene. Good agreement is found between the observed and expected numbers of R x R, L x R and L x L families. Predictions are successful for both strict and generous criteria of sinistrality. Generation differences are found between OU students and their parents and between the students and their children. These are discussed from the viewpoint of a possible heterozygote advantage in intelligence. The higher proportion of sinistral children born to sinistral mothers than fathers can be partly accounted for by supposing that the right shift is more effective in females than males.


Choice of ascertainment model II. Discrimination between multi-proband models by means of birth order data. Probability models have been developed for family data, where each family has been selected or ascertained through a group of m probands, where m is a known parameter, not a random variable. The birth orders of the probands among the affected children are reported for each family. It is demonstrated that this information is sufficient for choice of ascertainment model. The conditional probability that an ascertained family with s children has r affected ones, depends, in addition to the segregation parameter, on the birth order of the youngest proband only. By means of the joint distribution of the birth orders of the other probands, it can be demonstrated if the ascertainment takes place through affected children near to or distant from each other in relative birth orders. Statistical methods have been developed for cases with two and cases with m probands.


The 'singles' method for segregation analysis under incomplete ascertainment. Li & Mantel (1968) proposed a simple new method of segregation analysis under complete ascertainment. This paper shows that, with a slight modification, the method is also valid under incomplete ascertainment. The assumptions concerning ascertainment are discussed and the method compared with the maximum likelihood method and Weinberg's proband method.


Isolation by distance: reply to Lalouel and Morton. Lalouel's assertion that I misinterpreted Malécot's work on isolation by distance may or may not be correct. If so, my assertions of error in Malécot's derivation are wrong, although they do apply to others who have used models involving a spatial continuum. Lalouel's other claims of error in my derivations of the consequences of a spatially continuous model of population reproduction and migration are incorrect, with the exception of one isolated misprint.


[Immunochemical properties of cyanogen bromide fragments of human serum albumin (author's transl)]. Fragments A, B and C obtained by CNBr degradation of human serum albumin (HSA) were studied by specific quantitative precipitation with anti-HSA sera. A co-precipitation has been observed between fragments B and C as well as between C and A which follow each others in the albumin molecule. On the contrary, there was no co-precipitation between fragments B and A which correspond respectively to the N- and C-terminal part of the albumin molecule. Moreover, using inhibition of passive haemagglutination, it has been observed that fragment A does not inhibit anti-B antibodies and fragment B does not inhibit anti-A antibodies. These results indicate that there are common antigenic sites to fragments B and C as well as to C and A but not to B and A. This is in agreement with the data upon the structure of HSA showing that it is made of three domains in linear sequence.


A study of the breakdown of the third component of human complement (C3). This paper reports the description of fragments of human C3, purified from aged sera. Sera were incubated at different temperatures (4 degrees, 20 degrees and 37 degrees C) for 8 days or more. At 4 degrees C, the major isolated fragment was C3b which showed a heterogeneity of structure. Under reducing conditions, it liberated a 40,000 dalton fragment which reacted against an anti-C3d and which we called "C3d-like". At 20 degrees C, C3b was partially destroyed to yield the C3c- and C3d-fragments. At 37 degrees C, C3d and C3c were obtained. C3c presented a structural heterogeneity. It was made either of two chains of 75,000 daltons or of three chains with 75,000, 38,000 and 31,000 dalton MW. The comparison of these fragments with those obtained by tryptic hydrolysis led us to propose a pathway to the degradation of C3 and to bring some informations about the structure of this molecule.


[Influence of the irritant used to provoke the peritoneal exudate used in the macrophage migration inhibition test (author's transl)]. The effect of the irritant chosen to provoke the peritoneal exudate in donors of cells for the in vitro migration inhibition test was studied. Guinea-pigs with delayed hypersensitivity to tubercle bacilli were used. Irritants studied included starch, Bayol and thioglycollate medium. The exudates obtained with thioglycollate were found to show greater inhibition than those obtained with the other irritants in the in vitro response to PPD, Inhibition of migration was seen when 1 microgram/ml of PPD was added to the culture medium; with this dose the inhibition of migration was 53%. The state of activation of macrophages caused by the irritant thus appears to have some importance for their responsiveness to factors liberated by specifically sensitized lymphocytes.


Homozygous expression of a dominant gene for Charcot-Marie-Tooth neuropathy. A kindred of 68 French Acadians who were heterozygous for a dominant gene of Charcot-Marie-Tooth disease associated with peripheral nerve hypertrophy are described. Marriage between 2 heterozygotes resulted in 2 homozygous offspring. Clinical features of the homozygotes were similar to the classic description of Dejerine-Sottas disease. Laboratory studies in this family revealed no chemical, metabolic, or chromosomal abnormalities in either the homozygotes or the heterozygotes.


Degeneration of the cerebellar system in X-chromosome-linked copper malabsorption. Examination of the cerebellar system of 5 autopsied patients with X-chromosome-linked copper malabsorption led to the discovery that among cerebellar afferent systems, only the dorsal spinocerebellar tract showed consistent degenerative changes. Cerebellar cortical lesions comprised granule cell loss and Purkinje cell abnormalities that included nuclear and cytoplasmic degenerative changes with cell loss and deficient dendritic arborization as well as the presence of somatic sprouts. Perisomatic baskets were often absent in the area of sprouting Purkinje cells. Cerebellar cortical topographical analysis revealed relative sparing of the caudal portion of the cerebellum. The nodulus was intact in all patients. The dentate nucleus and the superior cerebellar peduncle were preserved. The red nucleus was consistently degenerated.


Synthesis of antibodies and immunoglobulins bearing recipient allotypic markers and donor idiotypic specificities in irradiated rabbits grafted with allogeneic cells from hyperimmune donors. Irradiated rabbits were grafted with a mixture of bone marrow, lymph node and spleen cells from donors hyperimmunized against TMV. Recipient and donors were characterized by different a allotypic specificities. Antibodies synthesized in the recipients display allotypic markers from the recipients but idiotypic specificities cross-reactive with those of donor antibodies. The results show that the differentiation of new host B cells is influenced by the presence of donor memory cells and are interpreted in the light of network concepts.


Endoneurial fluid pressure in wallerian degeneration. Endoneurial fluid pressure (EFP) was recorded by an active, servo-null pressure system after a glass micropipette was inserted into rat sciatic nerve undergoing wallerian degeneration. The lesions were produced by crushing the left sciatic nerve of the anesthetized animal at its point of entry into the thigh. Eighty-four animals were employed in this experiment, in which EFP was recorded from sham-operated rats and other controls as well as from rats with wallerian degeneration. The experiment was designed so that EFP could be recorded from 2 or more experimental animals at daily intervals starting at day 0 and concluding on day 28. Pressure progressively increased during the first week, reaching a peak elevation four to five times normal. The subsequent decline in EFP was more gradual, with values approaching normal during the third week after injury. Linear regression analysis showed the progressive increase in EFP to be statistically significant (p less than or equal to 0.01). To determine the time at which EFP was maximum, we used the Marquardt computer algorithm for lease-squares estimation of nonlinear variables. By this procedure the peak value for EFP occurred at six days. These biophysical observations were correlated with subsequent microscopic examination of 1 mu thick sections of Araldite-embedded sciatic nerve. Microscopy confirmed the presence of wallerian degeneration associated with edema, which was observed in every instance of elevated EFP.


[Equal sensitivity of normal or tumoral fibroblasts to cytotoxic and cytostatic effects of normal or "Corynebacterium parvum" activated peritoneal exudate cells (author's transl)]. Cytotoxic and cytostatic properties of peritoneal exudate cells from BALB/c mice either normal or pretreated with Corynebacterium parvum normal were studied using as target cells two lines of BALB/c fibroblasts one normal (BALB) and one transformed by Kirsten virus (K.BALB).. C. parvum activated cells displayed higher cytotoxic as measured by 51Cr or 3H-thymidine release and cytostatic, as measured by 3H-thymidine incorporation, activities against these lines of syngeneic cells. Cytotoxic effect of normal peritoneal cells was evident when 51Cr or 3H-thymidine release was used whereas no such effect was found when cytolytic plaque formation test was used. Sensitivity of both BALB and K.BALB target cell lines was found to be equal to cytotoxic and cytostatic activities of C. parvum activated or normal syngeneic peritoneal cells.


Determinants of survival in children with brain tumors. A study was conducted in metropolitan Baltimore to examine time trends in survival and factors which influence survival of children with brain tumors. One hundred eighty-four cases diagnosed from 1960 to 1975 were identified; 76.5% occurred in white children and 48% were girls. Five-year survival rates were 35% for children diagnosed in 1960-64, 34% in 1965-69, and 49% in 1970-74. Girls had consistently better survival rates than boys. White children experienced consistently better survival rates than blacks. Of those who survived the first year, children with supratentorial tumors had better five-year survival rates (46%) than those which with infratentorial tumors (27%). Of those who survived the first year, children with astrocytomas had better survival rates than those with other types of tumors.


Spinal fluid aluminum levels in patients with Alzheimer disease. Spinal fluid from 180 male patients was examined for aluminum levels. Values were coordinated for age and protein determinations. In addition, values were listed according to the patient's diagnosis. Although in most instances no correlation could be made, 10 patients with Alzheimer disease showed significantly low levels of aluminum.


Ia versus K/D antigens in immunological enhancement of tumour allografts. II. Studies with alloimmune sera prepared in recombinant strains. Previous studies have demonstrated that anti-K/D antibodies obtained by specific absorption on and elution from relevant red blood cells were capable of inducing enhancement of tumour cells in allogeneic hosts. Anti-Ia antibodies were not found enhancing except when alloimmune sera prepared by skin grafts were used. In the present report, anti-H-2K and anti-H-2D or anti-H-2I sera were obtained in mouse recombinant strains, in order to obviate such absorption and elution procedures. It has been shown that SaI-tumour cells (H-2a, i.e. H-2k/d) can be enhanced in allogeneic recipients, CBA (H-2k) or C57BL/Ks (H-2d) by antisera directed towards H-2Dd or H-2Kk. Alloimmune sera directed towards H2i-coded antigens prepared by immunization with spleen cells had no enhancing activity on the same tumour allografts in the CBA-A/J strain combination anti-IC'D,Sd,Gd) but caused a transitory effect in the C57BL/Ks-A/J combination (anti-IA'K,IBk,IJk,IEk).


Familial arteriovenous malformation.

Familial arteriovenous malformation. A family is reported in which 3 siblings, 2 with the same and the third with a different father, were demonstrated to have cerebral arteriovenous malformations.


Hypernatremic hemorrhagic encephalopathy. A 12-year-old juvenile diabetic was inadvertently given 500 ml of hypertonic saline intravenously. He developed hypernatremia, hyperosmolality, metabolic acidosis, and hyperglycemia. Seizures and stupor ensued, followed by coma and death. Computerized cranial tomography revealed numerous small subcortical hemorrhages that were verified postmortem.


Mechanism and specificity of action of ribavirin. Ribavirin at a concentration of 30 mug/ml added immediately after infection completely inhibited influenza A/Port Chalmers/1/73 (H(3)N(2)) virus hemagglutinin production in infected MDCK cells. Under these conditions, host cell protein synthesis was inhibited by only 10 to 20%. Polyacrylamide gel electrophoresis of [(35)S]methionine-labeled material from virus-infected cultures confirmed that ribavirin inhibited viral but not host cell protein synthesis. In parallel experiments, actinomycin D also preferentially inhibited viral protein synthesis. The possibility that ribavirin inhibited viral protein synthesis as a result of general inhibition of ribonucleic acid synthesis was therefore examined. In uninfected cells, ribavirin at 30 mug/ml inhibited the incorporation of [(14)C]inosine or [(3)H]uridine into ribonucleic acid but stimulated the incorporation of [(3)H]guanosine. The effects noted are consistent with an inhibition of the host cell enzyme inosine 5'-monophosphate dehydrogenase. This suggestion is supported by the finding that addition of guanosine, but not inosine, to the culture medium substantially reversed the antiviral effect of ribavirin. There was no separation between the concentration of ribavirin causing inhibition of influenza A viral protein synthesis or inhibition of MDCK cell ribonucleic acid synthesis, suggesting that ribavirin is not specifically antiviral in this system but inhibits viral protein synthesis as a result of the general inhibition of ribonucleic acid synthesis.


Antimicrobial susceptibility testing of Mycobacterium fortuitum complex. A total of 24 strains of the Mycobacterium fortuitum complex were tested for susceptibility to antimicrobial agents by the disk diffusion and agar dilution techniques. By comparing zones of inhibition obtained with the disk diffusion technique with results of minimal inhibitory concentration determinations, it was shown that disk diffusion results could predict in vitro susceptibility to selected antimicrobial agents. All of 17 strains of M. fortuitum were susceptible to </=1 mug of amikacin per ml. The corresponding average zone of inhibition around a 10-mug amikacin disk was 37 mm. Seven M. chelonei strains were more resistant to amikacin, with minimal inhibitory concentrations ranging from 1 to 32 mug/ml, and the corresponding average zone size was 21 mm. Susceptibility of both M. fortuitum and M. chelonei to tetracycline was variable and none of the M. chelonei strains was inhibited by polymyxin B, whereas M. fortuitum strains consistently had zones of inhibition around the polymyxin disk. It appears that identification to species of the M. fortuitum complex may be of importance with regard to antibiotic susceptibility. Separation of M. fortuitum and M. chelonei was readily accomplished in the present study by the nitrate reduction and 3-day arylsulfatase tests.


Characteristics of herpesvirus mutants resistant to phosphonoformate and phosphonoacetate. Mutants of herpes simplex virus type 1, resistant to phosphonoformate (PFA) and phosphonoacetate (PAA), have been selected in cell culture. The PFA-resistant mutant (HSV-PFA(r)) and the PAA-resistant mutant (HSV-PAA(r)) were also resistant to PAA and PFA, respectively. This cross-resistance indicates that PFA and PAA interact at the same site. The HSV-PFA(r) had a decreased susceptibility to vidarabine, but no difference in sensitivity to idoxuridine (5-iodo-2'-deoxyuridine) was observed when compared to the wild type. The induced deoxyribonucleic acid polymerases isolated from cells infected with HSV-PFA(r) and HSV-PAA(r) were both cross-resistant to inhibition by PFA and PAA. No increased resistance to vidarabine triphosphate could be observed, but the susceptibility to inhibition by pyrophosphate was about two times lower. None of the mutants showed any increased temperature sensitivity


Rapid antimicrobial susceptibility test using tetrazolium reduction. A rapid method of antimicrobial susceptibility testing has been developed, which uses a modified microdilution procedure and an inoculum of 10(7) bacteria per ml. Results are determined within 4 h with an indicator consisting of 2(p-iodophenyl)-3(p-nitrophenyl)-5-phenyltetrazolium chloride. The precipitation of a red formazan by bacteria uninhibited by antimicrobials is accelerated by the addition of phenazine methosulfate. Isolates are classified as resistant, indeterminate, or susceptible, based on growth in up to two antimicrobial concentrations which conform closely to concentrations which correlate with the millimeter breakpoints used in the Bauer-Kirby method. Results of testing 10 antimicrobial agents against 1,126 isolates were compared with results obtained when the Bauer-Kirby method and the agar dilution procedure were used as reference methods. Enterococci were excluded because of false resistance. Discrepancies were classified as very major (false susceptibility), major (false resistance), and minor (combinations of susceptibility or resistance with indeterminate results). The rapid method versus the agar dilution method yielded 2.3% very major, 0.7% major, and 2.9% minor discrepancies, for a total of 6.0%. Of 58 organism-antimicrobial agent combinations tested, 23 displayed 1% very major discrepancies between the rapid method and the agar dilution method. Six were not therapeutically important. The remainder involved Staphylococcus aureus, Staphylococcus epidermidis, Acinetobacter sp., and most organisms tested with chloramphenicol. It is suggested that adjustments in antibiotic concentrations and/or inoculum size may eliminate these discrepancies. The rapid method appeared economical when compared with Autobac 1 and the Bauer-Kirby procedure.


Therapy of experimental herpes simplex encephalitis with aciclovir in mice. This report is concerned with the capacities of aciclovir to protect mice challenged intracerebrally with multiple lethal doses of type 1 herpes simplex virus and to control multiplication of this virus in the brain. With treatment initiated 12 h after inoculation and continued for 4 consecutive days, aciclovir administered subcutaneously in daily doses ranging from 40 to 100 mg/kg led to 21-day survival rates of from 33 to 73% and reduced virus titers by 1 to (1/2) x 4 logs on postchallenge day 8. The therapeutic accomplishments of the 100-mg/kg doses of aciclovir were comparable to those of 1,000-mg/kg doses of vidarabine (9-beta-d-arabinofuranosyladenine); however, as measured by impact on body weight, aciclovir was better tolerated than vidarabine at these similarly effective doses.


Relationship between aminoglycoside-induced nephrotoxicity and auditory toxicity. We have reviewed our data from 391 patients entered into three prospective, double-blind studies of aminoglycosides and evaluated 127 cases to determine whether aminoglycoside-induced auditory toxicity and nephrotoxicity are independent events. The cases selected for evaluation included all patients treated for greater than 3 days (mean, 7.7 days) who had serial creatinine determinations and were able to cooperate with serial bedside audiograms (250 to 8,000 Hz). Patients received either gentamicin, tobramycin, or amikacin. Drug dosage was altered to keep serum levels 1 h after administration between 5 and 10 mug/ml (gentamicin or tobramycin) or 20 and 40 mug/ml (amikacin). The investigators evaluating auditory toxicity and nephrotoxicity were blind to the aminoglycoside being administered. The incidence of auditory toxicity in the nephrotoxic group (18.2%) was not significantly different from that in the nonnephrotoxic group (15.2%) (P = 0.75; Fisher exact test). There was no statistical difference between the nephrotoxic and auditory toxic groups in patient age, total dose of aminoglycoside, initial creatinine level, duration of therapy, or concurrent use of furosemide or cephalothin. We conclude that aminoglycoside-induced auditory toxicity and nephrotoxicity are independent events when the drug is administered for approximately 7 days and when aminoglycoside levels are maintained within a predefined range.


In vitro activity of furazlocillin (Bay k 4999) compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics. The activity of furazlocillin (Bay k 4999) was compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics against a number of gram-positive and gram-negative organisms. These new expanded-spectrum penicillins were less active than penicillin G against most gram-positive organisms. Furazlocillin, mezlocillin, and piperacillin showed activity comparable to ampicillin and penicillin G against Haemophilus influenzae and penicillin-susceptible neisseriae, respectively. None of the drugs tested was effective against penicillin-resistant gonococci. The activity of furazlocillin was greater than that of mezlocillin, piperacillin, ampicillin, or carbenicillin against many Enterobacteriaceae. However, certain beta-lactam-resistant strains among these organisms were not highly susceptible to any of the three new penicillins. Furazlocillin was less active than piperacillin against Pseudomonas aeruginosa but was more active than carbenicillin or mezlocillin. Inoculum effects and discrepancies between minimal inhibitory concentrations and minimal bactericidal concentrations were observed with furazlocillin, mezlocillin, and piperacillin against several genera. The kinetics of bacterial killing by the new penicillins were often slow and incomplete over 24 h, especially in tests with Enterobacter and P. aeruginosa. Synergy was demonstrated between furazlocillin and aminoglycosides against a variety of gram-negative bacilli and Streptococcus faecalis.


Correlation of netilmicin disk diffusion susceptibility and agar dilution susceptibility. The minimal inhibitory concentration of netilmicin determined by the agar dilution method was correlated with the disk diffusion zone of inhibition against 322 clinical isolates. Regression line analysis revealed good correlation, r = -0.90, and suggested that isolates with zone sizes </=14 mm should be considered resistant.


Comparative pharmacokinetics of cephalexin, cefaclor, cefadroxil, and CGP 9000. In a randomized crossover study, the pharmacokinetics of three new cephalosporin antibiotics, cefaclor, cefadroxil, and CGP 9000, in comparison to cephalexin, were determined after oral administration, by capsules, of 1,000 mg on an empty stomach in 12 normal subjects. Serum concentrations were measured during a period of 8 h, and urine recovery was measured during 24 h. The significant parameters of bioavailability of an orally administered substance were determined. The maximal serum concentrations (y(max)) for cephalexin, cefaclor, cefadroxil, and CGP 9000 (in milligrams per liter) were: 38.8 +/- 8.1; 34.6 +/- 7.8; 33.0 +/- 5.4; and 23.3 +/- 7.3, respectively. The areas under the curve (in hours x milligrams per liter) were: 93.0 +/- 14.8; 74.5 +/- 9.9; 70.1 +/- 9.0; and 108.5 +/- 18.4, respectively. In a further crossover study with six subjects, 1,000 mg of cephalexin and of cefadroxil were given during a standard breakfast. The y(max) of cephalexin decreased to 23.1 +/- 6.6 mg/liter, in contrast to cefadroxil, with an unchanged y(max) of 32.7 +/- 3.4 mg/liter.


Inhibition of cilia regeneration of Tetrahymena by ansamitocins, new antitumor antibiotics. Ansamitocins inhibited cilia regeneration of partially deciliated Tetrahymena pyriformis W, and the activity depended on the acyl groups at the C3 position.


In vitro susceptibility of Ureaplasma urealyticum to rosaramicin. Thirty-two clinical isolates of Ureaplasma urealyticum were inhibited by 0.036 mug of rosaramicin per ml, whereas 25 (78%) and 13 (41%) of the strains were inhibited by this concentration of minocycline and tetracycline, respectively. These results suggest that rosaramicin may be useful for the treatment of U. urealyticum infections.


In vitro of cefotaxime against cephalothin-resistant clinical isolates. Cefotaxime is more active than six other cephalosporins against 150 cephalothin-resistant Enterobacteriaceae strains and is the only drug which is more active than ampicillin against Haemophilus. It shows a potentially useful activity against Pseudomonas.


Comparative in vitro activity of five cephalosporins against Lactobacilli. Of five parenteral cephalosporins tested against 43 lactobacilli, cephaloridine, cefazolin, and cefamandole were the most active inhibitory and bactericidal agents. Timed-kill analysis revealed a slow bactericidal effect, with significant declines in mean minimal bactericidal concentration values at 48 h versus 24 h.


Isolation and properties of metronidazole-resistant mutants of Bacteroides fragilis. Metronidazole-resistant mutants of Bacteroides fragilis, isolated after mutagenesis, had diminished ability to take up and metabolize the drug. All the metronidazole-resistant strains had depressed levels of pyruvate dehydrogenase compared with parent cultures. Their end products of glucose metabolism also differed from normal B. fragilis products and were consistent with deficiencies in pyruvate dehydrogenase activity.


Susceptibility of Campylobacter fetus subsp. jejuni to twenty antimicrobiol agents. One hundred recent clinical isolates of Campylobacter fetus subsp. jejuni were tested by an agar dilution technique for susceptibility to each of 20 antimicrobial agents. Doxycycline and gentamicin were the most active of the drugs examined, inhibiting all strains at concentrations achievable in serum. Although the median minimal inhibitory concentration of erythromycin was low, 8% of the isolates were highly resistant. All isolates of Campylobacter fetus subsp. jejuni were relatively resistant to the beta-lactam antibiotics. Some strains were highly resistant to metronidazole and tinidazole.


Comparison of a micromethod for performance of the serum bactericidal test with the standard tube dilution method. A micromethod for performance of the serum bactericidal test is described, and the results obtained with this method are compared with those obtained with the standard tube dilution macromethod. An agreement within +/- 1 dilution was achieved in 23 of 25 (92%) determinations of the serum bactericidal titer. The micromethod used approximately one-third of the amount of pooled normal human serum and of the technician's time required for performance of the macromethod. The micromethod offers an accurate and economical alternative to the macromethod for the performance of the serum bactericidal test and is particularly useful with infants and children since it minimizes blood loss.


Human fibroblast interferon for clinical trials: production, partial purification, and characterization. The production and partial purification of human fibroblast interferon for performing clinical trials is described. The interferon was produced by superinduction (exposure to riboinosinic-ribocytidylic acid, cycloheximide, and actinomycin D) of large numbers of human diploid fibroblast cultures. The yield averaged 750 units per cm(2) of culture area. The interferon was concentrated and purified by a two-step procedure involving acid desorption from controlled-pore glass beads and dialysis against polyethylene glycol. Human plasma protein was added as a stabilizer. The lyophilized end product had a specific activity of 0.5 x 10(6) to 1 x 10(6) units/mg of protein; it could be reconstituted for injection at a concentration of 2 x 10(6) units/ml. The composition of this interferon was characterized by crossed immunoelectrophoresis with polyspecific antibodies prepared against the principal sources of potential contaminants: human serum, calf serum, and normal human fibroblasts. Several components of each source were detected. Although the major component of calf serum, bovine serum albumin, was absent, other minor components were retained by the production and purification sequence. One of the main contaminants of fibroblast origin was found to be fibronectin.


Human fibroblast interferon for clinical trials: pharmacokinetics and tolerability in experimental animals and humans. Human fibroblast interferon (F-interferon) purified by adsorption on controlled-pore glass was given intramuscularly to patients at daily dosages of up to 20 x 10(6) units. Serum levels of antiviral activity were low or undetectable. In contrast, reasonably high serum titers were found in patients receiving interferon prepared from leukocytes (L-interferon). Similarly, in rabbits lower serum titers were seen with F-interferon than with L-interferon. These results are at variance with those obtained earlier (V. G. Edy, A. Billiau, and P. De Somer, J. Infect. Dis. 133:A18-A21, 1976). Possible explanations for this discrepancy are discussed. The F-interferon evoked febrile reactions, delayed skin reactivity, and transitory lymphopenia in humans. Some patients developed an allergic state of the reaginic type as evidenced by a weal and flare reaction after intradermal challenge. However, these patients did not show allergic symptoms after intramuscular injections. None of the side effects was severe enough to prohibit continuation of the treatment; most of them seemed to be due to contaminants not removed by the purification method. The possibility is considered that some of the side effects, e.g., delayed skin reactivity, are sufficiently specific to justify identification of the active principals.


Ventricular fluid levels of chloramphenicol in infants. Investigation of two infants suggested that peak ventricular fluid levels of chloramphenicol after intravenous administration were achieved after 3 h. The penetration of chloramphenicol into ventricular fluid may be unpredictable. In one patient, the peak ventricular fluid level was 57.5% of the peak serum level, and it was only 22.5% in the other patient. This observation may explain some of the past treatment failures when chloramphenicol was utilized in patients with gram-negative ventriculitis and meningitis.


Pharmacokinetics of cephradine suspension infants and children. The pharmacokinetics of cephradine suspension were studied in 16 infants and children who were 13 months to 8 years and 3 months of age (means age, 3.5 years). Mean peak concentrations of 21.3 and 9.9 mug/ml were achieved at 30 min after administration of 60-mg/kg doses to fasting and nonfasting patients. The area under the serum concentration-time curve was 26% larger in fasting than in fed subjects. The half-life of cephradine in serum was 0.8 and 1.0 h in fasting and fed groups, respectively. Antimicrobial activity was detected in 49% of all salivary samples; in 75% of specimens, the concentrations were less than the 50% minimum inhibitory concentration for most pneumococci and group A streptococci. Urinary concentrations of cephradine ranged from 28 to 8,760 mug/ml and were independent of feeding status.


Effects of dextranases on attachment of Streptococcus mutans to hydroxyapatite. A Fusarium dextranase and a Penicillium dextranase were compared for their relative ability to quantitatively reduce the adsorption of (3)H-labeled Steptococcus mutans cells onto hydroxyapatite. Fusarium dextranase-treated hydroxyapatite disks caused a statistically significant decrease in the hydroxyapatite adsorption of both the OMZ 176 and NCTC 10449 strains of S. mutans relative to untreated control disks. The extent of initial bacterial adsorption was not promoted by sucrose-dependent glucan synthesis. Since the Fusarium dextranase has a much greater affinity for hydroxyapatite than the Penicillium dextranase, it could represent an enzyme with improved decay-preventive therapeutic properties. This was concluded because the Fusarium dextranase may interfere with both the initial attachment and later glucan-dependent accumulation of dental plaque microorganisms.


Thoracic duct cyst in the anterior mediastinum. Case report of a 60-year old asymptomatic male with a chylous cyst in the right anterior mediastinum. It communicated with the thoracic duct through a narrow vessel with a length of 4 cm. During the eight years of pre-operative observation the cyst varied in size. At one time it disappeared completely, though temporarily. The rarity of this type of mediastinal tumor is stressed.


Chylous ascites after resection of an abdominal aortic aneurysm. A case of chylous ascites after resection of an abdominal aneurysm in a 72-year old male is presented. The complication is extremely rare. Therapy should start medically with a diuretic and medium chain triglyceride (M.C.T) diet. This is the ninth reported case of iatrogenic chylous ascites and the second after resection of an abdominal aortic aneurysm.


Cross clamping the lower abdominal aorta during vascular surgery. The effect of cross clamping the lower abdominal aorta on systemic blood pressure and right and left heart pressure was studied in 17 patients requiring surgical treatment for abdominal aortic aneurysm or aortic occlusive disease, in neuroleptanaesthesia. After cross clamping the systemic systolic blood pressure rose 24 mmHg (p is less than 0.01) and the systemic diastolic blood pressure 8 mmHg (p is less than 0.01). There was no influence of cross clamping on the right (CVP) and and left (PCWP) heart filling pressure even in patients with preexistent readings beyond the normal range.


Bladder fistulae in Crohn's disease.

Bladder fistulae in Crohn's disease. Ten patients with various stages of enterovesical fistulization in Crohn's disease are discussed. These fistulae can develop at different times in the course of the disease, but may also cause the presenting symptoms. Cystoscopy and radiologic examination rarely visualizes the fistulae. Conservative treatment by medication can sometimes suppress the symptoms, but cannot cure. Surgical treatment, which can consist of resection of intestine but need not involve resection of parts of the bladder, gives good results at least so far as the urinary infection is concerned.


Neonatal form of dystrophia myotonica. Five cases in preterm babies and a review of earlier reports. Five preterm babies with the neonatal form of dystrophia myotonica are reported. In addition to the generally accepted signs and symptoms of the disease, two other features were present in these patients; oedema was notable in all 5 babies and 4 had unexplained haematomas. It is suggested that premature birth may be a result of severe involvement and that prematurity further aggravates the symptoms.


Plasma 17OH-progesterone concentrations in newborn infants. Plasma concentrations of 17OH-progesterone were determined in 60 normal newborn infants aged between 3 and 36 hours. Mean levels decreased rapidly during this time after removal of the placental contribution of this steroid. A further 70 normal infants, studied between ages 2 and 7 days, showed a mean plasma 17OH-progesterone concentration of 3.5 nmol/1 (1.2 ng/ml). By comparison, plasma concentrations in untreated infants with congenital adrenal hyperplasia were markedly raised. At 36 hours of age, there was an obvious difference between plasma levels of this steroid in normal and affected infants. Determination of plasma 17OH-progesterone concentrations are valuable in the evaluation of disorders of sexual differentiation and electrolyte balance in newborn infants, provided due care is given to the timing of sample collections.


Continuing need for mineralocorticoid therapy in salt-losing congenital adrenal hyperplasia. Four patients with salt-losing congenital adrenal hyperplasia (CAH) who had stopped mineralocorticoid therapy for several years, showed raised plasma concentrations of 17OH-progesterone and plasma renin activity, despite adequate glucoticoid therapy. One patient was able to reduce urinary sodium excretion when the sodium intake was restricted. Another patient who was a salt-loser, developed signs of an adrenal crisis when salt deprived. In comparison, one nonsalt-loser and 2 normal subjects decreased urinary sodium excretion in response to sodium restriction. The addition of fludrocortisone (100 micrograms) to usual maintenance doses of glucocorticoid, resulted in normal levels of plasma 17OH-progesterone and plasma renin activity in all 4 salt-losers. Two female salt-losers, with raised plasma testosterone concentrations, began menstruating when their plasma testosterone concentrations returned to normal after treatment with fludrocortisone. It is recommended that salt-losing CAH patients should be given mineralocorticoid, in addition to glucocorticoid therapy, at least until adult life.


Creatine phosphokinase levels in the newborn and their use in screening for Duchenne muscular dystrophy. The PKU sample, if taken after the 3rd day, is suitable for Duchenne muscular dystrophy screening using creatine phosphokinase (CPK) levels. 101 babies (53 girls and 48 boys) had CPK levels measured on filter paper blood specimens taken by heel prick on the 1st and 4th days of life. The method used was that described by Zellweger and Antonik (1975). The CPK levels were markedly raised on the 1st day of life but by the 4th they had reduced to within 3 times the upper limit of the normal range for adults. 10,000 boys were then screened for Duchenne muscular dystrophy using the PKU sample, and 2 cases were found.


Serum 25-hydroxy-vitamin D in hepatobiliary disease in infancy. Serum 25-hydroxy-vitamin D (25-OHD) concentrations were measured in 49 patients with hepatobiliary disease in infancy. Low mean values were found in groups of patients with biliary atresia, neonatal hepatitis, choledochal cyst, and chronic intrahepatic cholestatic syndrome. In the group of patients with surgically repaired biliary atresia, the mean value did not differ from normal. Parenteral vitamin D increased 25-OHD in serum in patients with biliary atresia, but did not do so in one patient with neonatal hepatitis. In contrast, oral vitamin D did not increase serum 25-OHD concentrations in patients with biliary atresia. It is concluded that the reduction of serum 25-OHD seen in biliary atresia was largely due to the malabsorption of vitamin D, while in neonatal hepatitis it was due to impairment of 25-hydroxylation of the vitamin.


Relationship between urinary and blood glucose in diabetic children. The relationship of urine glucose concentration with 'average' blood glucose concentration for the corresponding period was investigated in 10 juvenile diabetics during the performance of 15 inpatient metabolic profiles. 0% glucosuria was associated with 'average' blood glucose concentrations less than 6.4 mmol/l (less than 115 mg/100ml), 2% glycosuria with concentrations greater than 8.6 mmol/l (greater than 154 mg/100ml), and over 5% glycosuria with concentrations greater than 11.3 mmol/l (greater than 204 mg/100ml). Urinary glucose loss was large (greater than 278 mmol; greater than 5g) when the 'average' blood glucose was greater than 11.1 mmol/l (greater than 200 mg/100ml). Because many diabetics have blood glucose concentrations up to 11.1 mmol/l, it is advantageous if glucosuria up to 5% is detectable by routine home urine tests. The 2-drop Clinitest method detects glycosuria up to 5% without significant loss of accuracy and is recommended in preference to the 5-drop method.


Absorption of chlorhexidine from the intact skin of newborn infants. 34 newborn infants who had been bathed in a standard manner with Hibiscrub were studied to find out whether it was absorbed percutaneously. Low levels of chlorhexidine were found in the blood of all 10 babies sampled by heel prick, and 5 of 24 from whom venous blood was taken. The detection of chlorhexidine varied greatly with the method and timing of sampling, and no correlation was found between gestational or postnatal age and chlorhexidine levels.


Infective pericarditis in Nigerian children. 53 children with infective pericarditis were seen at the University College Hospital, Ibadan, between 1967 and 1976. Their ages ranged from 10 days to 15 years but 53% of them were aged 5 years and below. Cough, fever, and breathlessness were the most common symptoms; cardiac decompensation was evident in over 30% of them, 23% had muffled heart sounds, but a pericardial friction rub was audible in only one. The main pathogens identified were Mycobacterium tuberculosis (11 cases), Staphylococcus aureus (11 cases), Escherichia coli (4 cases), Pneumococcus and Pseudomonas (3 cases each). Most of the patients had some other associated infection--such as, bronchopneumonia (12 cases), empyema thoracis (10 cases), lung abscess (10 cases), septicaemis (6 cases), and osteomyelitis (3 cases). Errors in diagnosis were common, the diagnosis having been missed in 72% of the cases identified at necropsy. Even if the correct diagnosis had been made during life and appropriate treatment given, the mortality rate (36%) was high. It is suggested that the onset of cardiac failure in any child with bronchopneumonia, empyema, or lung abscess should always arouse a suspicion of infective pericarditis.


Adder bites in children.

Adder bites in children. 16 children with adder bites were admitted to hospital in Southampton in the years 1969--77. Two children were severely poisoned; these 2, and a 3rd, fulfilled suggested criteria for antivenom administration but they recovered without it. Three children had no treatment, and 9 children no analgesia. Prolonged morbidity was not seen in these children. Careful observation in hospital was the most important factor in management, with early clinical improvement obviating the need for antivenom.


Pathogenesis of oxytocin-induced neonatal hyperbilirubinaemia. 100 term (gestation at least 37 weeks), vertex presenting, vaginally delivered, and fetomaternal blood-group-compatible neonates were studied to evaluate the pathogenesis of neonatal hyperbilirubinaemia induced by oxytocin. 50 infants were born after oxytocin infusion for augmentation of labour and the other 50 were delivered spontaneously. The babies born after oxytocin induction of labour attained significantly higher serum bilirubin levels at age 72 +/- 12 hours than the controls. Infants born after oxytocin showed significant hyponatraemia, hypo-osmolality, and enhanced osmotic fragility of erythrocytes at birth. These biochemical and physiological alterations can be explained by the antidiuretic effects of oxytocin and concomitant administration of large quantities of electrolyte-free dextrose solutions used to administer it. Our observations suggest that cord serum sodium and/or osmolality should be estimated and infants with serum sodium less than 125 mmol/l and/or osmolality less than 260 mmol/kg should be considered for prophylactic administration of phenobarbitone.


Clinical events relating to intraventricular haemorrhage in the newborn. Continuous measurements of arterial pressures, heart rates, respiratory movements, and respiratory rates were made from birth in 44 infants at risk from intraventricular haemorrhage (IVH). 17 babies died with IVH, in 10 of whom the event was timed objectively. Events in these babies were compared with survivors of similar birthweights, gestational ages, severity of birth asphyxia, and severity of hyaline membrane disease (HMD). IVH followed severe HMD and was associated with cessation of the babies' own respiratory efforts while on a ventilator and also with characteristic cardiorespiratory events. The minimum arterial pressure before IVH was lower than in comparable babies who survived. It is suggested that fluctuations of systemic blood pressure from initial low levels may be important in the pathogenesis of IVH. It is possible that changes in cerebral blood flow are of even greater significance.


Effect of feeding on neonatal oxygen consumption. Oxygen consumption was measured in 9 short-gestation infants before feeding and for an hour after, using a closed-circuit metabolism chamber. Using the same system, O2 consumption of 9 term infants was measured for varying periods, beginning one hour from the end of the last feed. In the short-gestation infants a rise was found in the 15--45 minutes after feeding; O2 consumption then fell, and after 60 minutes had reached prefeed levels. The term infants showed no decrease with time after the first hour, as would be expected if the effect of feeding on O2 consumption extended beyond this. It is concluded that increased O2 demand after appropriate feeding does not extend beyond one hour postprandially.


Hearing loss in very low birthweight infants treated with neonatal intensive care. The hearing of 111 perinatal intensive care survivors of birthweights 1500 g or less was assessed at a mean age of 6 1/2 years (range 4--12). These 111 infants included 86% of the long-term survivors of this birthweight cared for in the newborn unit of University College Hospital, London, during the years 1966--72. All these infants were nursed in commercially available incubators for periods ranging from 2 to 80 days (mean 37) in which the mean noise threshold was 65 dB. Ten (9%) had sensory neural nearing losses, one (1%) infant had a congenital conductive hearing loss, and 21 (19%) infants had exudative otitis media with a mean loss of 25 dB. Apnoeic attacks in the neotal period were the most significant predictors of hearing loss in these infants (P less than 0.05) and an indirect serum filirubin level of at least 170 micromol/l (10 mg/100 ml) in the neonatal period had an additive effect (P less than 0.05). There was no evidence that ambient noise had affected the hearing of these very low birthweight infants.


1028 neonatal electrocardiograms.

1028 neonatal electrocardiograms. Electrocardiograms were recorded from 1028 (99.4%) of 1034 consecutively born babies on the 1st or 2nd day of life. Abnormalities of cardiac rhythm or conduction were found in 49 (4.8%) babies. 17 babies had single or multiple premature beats during the recordings, and 7 babies showed sudden increases in R-R interval possibly due to sinoatrial node dysfunction. One baby had sinus or junctional bradycardia of less than 80 beats/min. One baby had an incessant reciprocating tachycardia and subsequently required digoxin for heart failure. Continuous 24-hour ECG monitoring in 25 babies with abnormalities of the screening ECG, and 25 babies without such abnormalities, failed to show any additional tachyarrhythmias or bradyarrhythmias warranting treatment. In view of the uncertain clinical significance of many neonatal arrhythmias and cardiac conduction disorders, more information concerning their natural history and relationship to sudden unexpected death in infancy is needed before recommending that neonatal ECG screening be generally adopted.


Sinusoidal heart rate rhythms in severe neonatal hypoxia. Sinusoidal heart rate traces were detected in 8 patients, 6 of whom died; the 2 survivors showed evidence of gross cerebral damage. It is felt that the origin of the sinusoidal curve is probably central and reflects loss of central control of heart rate.


Breath hydrogen test for detecting lactose malabsorption in infants and children. Prevalence of lactose malabsorption in Japanese children and adults. The breath hydrogen test (BHT) was adapted for use in young infants and children. The diagnostic criterion of sugar malabsorption in the BHT was determined by oral administration of 0.5 g/kg of unabsorbable sugar (lactulose) to 21 healthy infants and children. A maximum increase in breath hydrogen less than 0.05 ml/min per m2 was observed in all subjects. A good correlation between results by the BHT and by the ordinary lactose tolerance test was obtained after oral administration of 2 g/kg lactose to 21 healthy infants and children, 2 congenital lactase-deficient infants, and 7 adults. Using this test, 80 healthy Japanese infants and children (aged between one month and 15 years) and 18 adults were examined for lactose malabsorption after a dose of 1 g/kg lactose. All infants and children under 2-years old absorbed lactose completely. The incidence of lactose malabsorption was 30% in 3-year, 36% in 4-year, 58% in 5-year, and 86% in 6-year-old children, 85% in schoolchildren, and 89% in adults. Thus the incidence of lactase deficiency gradually increases with age from 3 years, and about 90% of all normal Japanese adults are lactase-deficient.


Defective Candida killing in childhood malnutrition. This study shows that malnourished children have impaired candidacidal activity of leucocytes, a finding which runs parallel to the higher rates of isolation of Candida sp. from throat secretions. In well nournished subjects the mean candidacidal ability was 44.5% in the moderately undernourished group it was 17.6%, and in the severely malnourished group it was 13.7%. This impaired candidacidal capacity may be important in the establishment of large numbers of Candida sp. which are commonly found in the upper intestine and in the pathogenesis of diarrhoea in children with malnutrition.


Bronchial asthma in Nigerian children.

Bronchial asthma in Nigerian children. Clinical and laboratory studies on bronchial asthma in 200 Nigerian children who were seen during a 2 1/2-year period in Ibadan are described. Contrary to reports that the condition is rare in African children, after pulmonary tuberculosis, asthma is the next most common chronic chest disease in Ibadan. While many features of the disease are similar to those seen elsewhere, skin tests indicate that ascaris is the most common antigen associated with asthma, followed by Dermatophagoides pteronyssinus.