The development of experimental brain tumours a sequential light and electron microscope study of the subependymal plate. II. Microtumours.

Pregnant BD-IX rats were given a single intraperitoneal injection of 30 mg of N-ethyl-N-nitrosourea (ENU) per kg of body weight on the 15th day of gestation. The offspring were killed at fortnightly intervals between 2 and 20 weeks of age. The subependymal plate region adjacent to the lateral ventricles was examined by light and electron microscopy to study the early stages in the development of brain tumours. Microtumours, composed of subependymal plate cells, glioblasts and various glial cells at different stages of maturation, were found in 16-, 18-, and 20-week-old rats. The most common site for microtumours was the angle of the lateral ventricles between the corpus callosum and caudate nucleus; others were located at the lateral aspect of the ventricles. It is suggested that most, if not all, cerebral gliomas originate from the undifferentiated cells of the subependymal plate: these mitotically active stem cells provide a susceptible target for the carcinogenic stimulus. The morphology of the gliomas developed is determined by the diverging processes of differentiation and anaplasia resulting in a pleomorphic cell population. The relevance of this experimental model to the pathogenesis of human gliomas is discussed.


Subarachnoid hematoma in staphylococcal septicemia. A report of two cases.

Two cases of subarachnoid hematoma, due to a Staphylococcus aureus septicemia are described. The clinical as well as the pathological findings suggest a two-step evolution, consisting first in the appearance of a small to moderate stroke, due to a septic embolic occlusion of a leptomeningeal artery and to cerebral infarction, followed by rupture of the artery and the formation of the subarachnoid hematoma, acting as a mass-lesion and leading to death by uncal herniation and brain stem compression. The typical location of the hematoma over the convex surface of a cerebral hemisphere suggests that local factors, such as the vicinity of patent leptomeningeal anastomoses and the fibrosis of the leptomeninges, are probably predisposing factors for its occurrence.


Cell origin of human adenovirus type 12-induced subcutaneous tumor in Syrian hamsters.

Single subcutaneous inoculation of human adenovirus type 12 (Ad.12), 0.05-0.1 ml of 10(8.0) TCID50 HEK cells/0.1 ml, was made on the back of 0-day-old hamsters. In 21 of 25 hamsters (84.0%), multiple solid tumors developed close to the inoculation site within 3 months. No control hamsters developed tumors. Tumor histopathology revealed the characteristic Homer Wright rosettes of neuroblastoma. Ad. 12-specific tumor antigens were demonstrable in both the primary and the cultured tumor cells by the immunofluorescein technique. Histochemical demonstration of cholinesterase and NADH oxidoreductase gave rise to a predominantly positive intracytoplasmic granule within the tumor cells. Electron microscopy showed remarkably uniform cell morphology: small, undifferentiated neuroblastic cells with poorly developed intracytoplasmic organelles; many possessed characteristic solitary cilia in a 9 + 0 tubules pattern. Intercellular junctions were poorly developed. Search for an incipient tumor cell aggregate by means of immunofluorescein T-antigen detection was carried out through a 240-h period following Ad. 12 inoculation. A sequential study in parallel with electron microscopic examination of the normal subcutaneous tissue proved that neuroblastic cells closely associated with the muscle spindle anlage could preferentially become the most sensitive target for Ad. 12 tumorigenesis.


[Intensity of spontaneous activity and mean visual evoked response during calculation of variable mean. New technique for measuring retinocortical time (author's transl)].

Various statistical discrimination indices reveal deflections regarded as significant before the 20th ms after stimulation (probably equivalent to Bickford responses or subcortical activity) and between the 20th and 23rd ms (early fractions of MVER). The independence of signal and noise is discussed. Considerations concerning the calculation of retinocortical time are developed.


Quantitative analysis of the size distribution of target- and targetoid fibres employing the method of Daeves and Beckel for mixed distributions.

An analysis of frequency distribution is performed in 250 target and targetoid fibres each from the anterior tibial muscle of a case with rapidly proceeding denervation atrophy. Following plane measurements on cross sections the size data were analysed according to the method of Daeves and Beckel [1] for mixed distributions. Three homogeneous normally distributed populations could thus be extracted from the mixed distributed sample. The largest population represents target fibres with a normal size range, while the second one encloses hypertrophic fibres, and the third and smallest one consists of fibres ranging within atrophic size limits. These findings support the previous presumption that targets predominantly occur in fibres of normal size and can therefore be regarded as manifestations of an early stage of denervation atrophy. The targetoid fibres, on the contrary, are of an atrophic size by 84%, while only a small population of about 15% contains targetoid fibres of a normal size on cross section.


[The evolution of motricity after a stroke (author's transl)].

A hundred and one patients undergoing rehabilitation for hemiplegia due to hemispheric cerebrovascular accident were observed for a period of  six months after the accident. Detailed records of the analytical and functional aspects of motricity enabled the extent of the deficiencies and the progress of the patients to be evaluated. The results illustrate certain classic neurological concepts and show how much time is required before significant improvements can be obtained. Progress is more satisfactory with right hemiplegics than with left ones.


Production of myelin by neoplastic cells.

Formation of myelin sheaths by neoplastic cells was found in a spinal ganglioneuroma. All phases of initial myelination were observed including the formation of a mesaxonal spiral and the fusion of its lamellae into a major dense line. A unique aspect of neoplastic myelin formation was the formation of sheaths around bundles of extracellular fibrils rather than axons or cell processes. Formation of myelin sheaths around extracellular material has never been observed before. The findings have implications on the mechanisms controlling initial myelination.


Skin and conjunctival biopsies in infantile neuroaxonal dystrophy.

The diagnosis of infantile neuro-axonal dystrophy (INAD) in a 5-year-old patient was confirmed by the ultrastructural study of neuromuscular, skin and conjunctival biopsy specimens. Abnormal networks of smooth membranous, lamellar and tubular profiles were found in presynaptic terminals and in conjunctival and dermal axons. INAD is the first neurological disease outside the group of storage disorders in which skin and conjunctival biopsies contribute significiantly to the diagnosis.


Present status and future directions of the Ear Research Institute cochlear implant program.

Thirty-three adult subjects have been implanted with single-electrode cochlear implants at the Ear Research Institute. This paper outlines the current status of the subjects; the rehabilitation and testing program; results found with the implant; and future directions of the implant program. Results indicate that implant subjects can score significantly above chance on a variety of discrimination tests. Implant subjects also score significantly better than hearing aid subjects on these tests. Research is continuing on engineering and signal-processing improvements for the single-elecrode implant. Multiple-electrode implants and binaural implants are being considered for future research at the Ear Research Institute.


Neurophysiological requirements for implanted cochlear prostheses.

Regarding the neurophysiological requirements for implanted cochlear prostheses, we have discussed (i) the complexity of speech sounds, (ii) problems of intensity, then (iii) the frequency problem, and (iv) finally the possibility of a frequency transposition to the genuine frequency range of a single fibre of any mechanoreceptor and its connecting nerve fibre (less than 1 kHz) for the construction of an intracochlear prosthesis. In general it would seem necessary to seek compromises based on the fact that speech, at least the vowels, contains redundancy and that the use of additional sensory channels might be helpful for cochlear implants. Certainly besides other preprocessing techniques for speech information, the multichannel stimulation set-up of special electrodes has to be used to convey a sufficient amount of speech information to restore the faculty of speech perception in completely deaf patients. Decompression of intensity range and compression of frequency range might be especially useful.


Indications and results of the multichannel cochlear implant.

In the case of total deafness, the multichannel cochlear implant prosthesis constitutes a substantial improvement. It allows known words to be recognized without lip reading, with a great percentage of good responses. Clinical and phoniatric results are reported in 21 cases of patients with implants.


Designing of and experience with multichannel cochlear implants.

The technology of two different multichannel cochlear prosthetic devices is described. The clinical results after electrical stimulation in five implanted patients are discussed.


A functioning multichannel auditory nerve stimulator. A preliminary report on two human volunteers.

This paper is a brief progress report on our work with two volunteers, each with 4 electrodes placed in his auditory nerve. We are performing stimulation studies to find out if multielectrode stimulation is more effective as a communication aid than single-electrode stimulation, and to gain insights on stimulus coding of environmental sound using sophisticated digital signal processing techniques.


Fundamental considerations in designing auditory implants.

The usual premise underlying developmental work on cochlear prostheses as prospective cures for profound deafness is that the auditory nerve can be electrically stimulated in such a manner that communicative skills can be developed or maintained. Physiologic recordings from single fibers in the cat's auditory nerve and attempts to model these responses have generated a description of how the auditory nerve codes complex sounds such as speech. This work suggests that certain minimal cues might have to be present at the level of the auditory nerve in order that adequate discrimination of specific speech signals can take place. The prospects for achieving a useful prosthesis in the near future will be evaluated in terms of what can be expected from current attempts to code the artificial stimulation properly.


[Physiology of taste].

The various types of taste papillae, in and on the tongue have been studied, together with its role in discriminating between the basic tastes (sweet, sour, bitter and salt). The importance of the other factors associated with taste is also discussed.


Preneural phase of taste.

The preneural phase of taste has been studied, describing first the pit region of taste buds and its dynamics. The biochemical regulation of the preneural phase is then analyzed, with emphasis on thiol and metal (certain metals) interactions: the first inhibit and the second facilitate. The equilibrium between thiol and metal ions regulates the flux of tastants, probably at the level of the microvilli membrane. The hypothetical role of the pore and dense substance is considered.


[Standardized examination methods for smell and taste and their clinical value].

The diagnostic of disturbances of the chemical senses is from a clinical standpoint still insufficient, as the literature of the whole world shows. Ten years of experimental and clinical investigations as well as the collection and evaluation of the experiences at the University ENT-Clinic Halle/S., GDR--have helped to develop some new tests and tools like a big and a small smell-case, two electrogustometers, the documentation by means of olfacto- and gustograms and so on. Now in the whole GDR a special group of ENT-scientists, members of our ENT society, are working on standardisation. The experiences will be official in our country. After the representation of our diagnostic system from to-day, as we are using them in our clinic, we are giving clinical examples as the diagnosis of the cranial nerves, the control of the treatment and so on, which are showing the usefulness of such examinations in smell and taste.


Occupational hearing loss. The significance of asymmetrical hearing thresholds.

In 1873 consecutive patients referred for compensation assessment for presumed industrial hearing loss, 281 (15%) had an average difference in hearing threshold between the ears of 15 dB at 1/2, 1, 2 and 4 kHz. An unrelated cause was found in 115 (6%). It was due to trauma in 37 (2%), unexplained in 32 (1.7%) and attributed to noise exposure in 97 (5.2%). The possible mechanisms for noise as a cause are discussed and include shielding of one ear from noise, unequal recovery after severe noise exposure, and unequal sensitivity of the ears. After extensive investigation, including X-rays, vestibular tests and some myelograms, no treatable disorder was discovered.


Experimental exposure to impulse noise in the especially pathogenic impact frequency range.

The pathogenicity of impulse-induced noise depends not only on its intensity, but also on the repetition rate of the individual sound impacts. The reason is the effect exercised by the acoustical reflex. Its protective function is said by some experts to last for only little more than 2 seconds. For this reason, two groups of young persons were exposed to noise impacts whose repetition rates were 2 and 3 seconds, thus falling within the period of time in question. The resulting auditory fatigue (TTS) is analysed. The results of the measurements suggest that the activity of the acoustical reflex lasts less than 2 seconds under these test conditions.


Tectorial membrane: a possible sharpening effect on the frequency analysis in the cochlea.

Excitation of cochlear hair cells is believed to be produced by radial deflection of their stereocilia as a result of shear motion between the reticular lamina and the tectorial membrane. The shear motion must depend on the mechanical coupling between the organ of Corti and the tectorial membrane. It is shown that, because longitudinal stiffness of the tectorial membrane, the shear motion must be enhanced as the wavelength decreases toward the cochlear vibration maximum. The resulting sharpening of the vibration maximum agrees with the frequency selectivity found in the inner hair cells and cochlear-nerve afferents.


Auditory nerve and brainstem responses in the newborn and in preschool children.

The practicability of recording auditory nerve and brainstem responses during early childhood is demonstrated. This paper reports our experience with two different electrode locations: ear-canal/ear-lobe and ear-lobe/vertex. The test is performed with a light portable stimulus-generating and response-recording system that can easily be brought into wards and nurseries. In most instances, the presence of responses can be assessed using ear-lobe/vertex recordings. There is seldom any need for sedation or general anaesthesia. Testing personnel can be limited to one trained technician. If responses are not detected, ear-canal/ear-lobe recording may be used to clarify the results. General anaesthesia may then be necessary and the presence of a physician will be required for the placement of the canal electrode.


Fully objective ERA by phase spectral analysis.

A method of ERA using the Vertex potential is presented which is entirely objective. The result is given by means of a statistical evaluation which is derived automatically. The method is based on pattern analysis of the V-potential, the technique relying essentially on analysis of the phase spectrum of the appropriate Fourier components.


Auditory brainstem potentials in man evoked by electrical stimulation of the round window.

In normal subjects, round-window electrical stimulation provides a sound sensation and supplies brainstem-evoked responses whose form is just the same of those evoked by sound stimulation. This electrical stimulation also provides a sound sensation in more than 90% of cases of total deafness, which means that at least a few auditory nerve fibres are still present. Thus, this test is indispensable when considering surgical rehabilitation with a multichannel cochlear implant. The diagram of this response to an electrical stimulus differs completely in the case of total deafness and in normal subjects. The correlation between the form of these diagrams and the supposed etiology of the deafness is not significant.


First observations on treatment of cholesteatoma with (N-acetyl)cysteine.

In a series of cholesteatoma patients the benefit of local application of acetylcysteine was demonstrated. Chemical studies and fractional analyses were used to reveal the breakdown of keratin. Histochemically the influence of acetylcysteine on keratin is confirmed.


The high position of the jugular bulb.

The relationship between the bottom of the hypotympanon and the jugular bulb has been investigated on the basis of a histological analysis of 815 temporal bones. A high position of the jugular bulb has been found in 3.5% of the temporal bones examined. Only exceptionally does it occur bilaterally and is more often found on the right than left side. We distinguish two localizations of the high position of the bulb in the hypotympanon: the lateral and the medial. In either case the bulb may be damaged during myringotomy or during the removal of granulation tissue in middle ear surgery. Injury at myringotomy can be avoided only if there is a reinforcement of the bony wall. In the lateral position, the jugular bulb may be damaged when the tympanomeatal flap is being elevated. The bulb can occasionally be mistaken for a jugular glomus tumour. There is hardly any difference between cases where the bone between the bulb and the middle ear space is dehiscent or only very thin. The thickness of the bony shell is only 0.1-0.3 mm--thus there is no real protection against instrumental injuries.


Experimental surgery on the nose. Changes of the epithelium in the vestibular region at altered airflow.

In 20 rabbits one nostril was closed surgically and the nasal mucosa lying anteriorly in the vestibule was studied 4--90 days postoperatively. On the occluded side, without air-flow, the epithelium--which at this site is normally thickened due to hyperplasia of basal cells--gradually returned to a normal thinner, regular epithelium with increased number of goblet cells. On the patent side, where the airflow was doubled, the cilia were damaged. As early as the 4th day, a process of repair had been initiated, with hyperplasia of basal cells and differentiation of these cells into ciliated and goblet cells. As a result of continued trauma, similar processes continued, but there were no signs of a permanent transformation of the epithelium into squamous epithelium, not even on the 90th day.


Nasal polyposis. Relationships to allergy and acetylsalicyclic acid intolerance.

Allergological, clinical and histological findings in 109 unselected patients, treated for nasal polyps during the period Feb. 1977 to Feb. 1978 are reported. The material was divided into three groups according to clinical findings: 1) Atopy Group; 18 patients with positive history and skin test; 2) ASA Intolerance Group; 25 patients with a definite history of acetylsalicylic acid intolerance; and 3) Intrinsic Disease Group; 66 patients in whom specific etiological factors were not found. On skin testing, positive reactions were obtained in 42 patients. In 23 of the patients, the skin test result agreed with the history. Secretion and tissue eosinophilia, noted in 97 and 102 patients, respectively, correlated in 88% of the patients, whereas correlation with blood eosinophilia was poor (30%). The mean IgE level was 140 in the serum and 731 in the polyp fluid, serum values above 150 occurring in 28 out of 105 patients and fluid values above 150 in 58 out of 84 patients. The predominant histological finding in the polyp biopsies was tissue eosinophilia, which was most abundant in the ASA intolerance group. Squamous metaplasia was seen in 30% but it was marked only in 5 cases. In 10 patients ASA intolerance was confirmed by oral provocation.


Growth mechanisms in skulls with facial clefts. Descriptive and experimental studies on the facial skeleton.

During postnatal growth, skulls of patients with untreated unilateral clefts of the alveolus and palate develop additional anomalies of the facial skeleton. Similar anomalies--a deviation of the upper jaw to the non-cleft side and retropositioning of the maxilla on the cleft side--develop in rabbits with the same type of cleft, surgically produced in the fourth week after birth. Based on a quantitative study of the postnatal growth of the rabbit skull under normal and various experimental conditions, a mechanisms is proposed for the late developement of anomalies of the facial skeleton in cleft-affected skulls.


Perilymph production and cochlear blood flow.

In rodents at least, the main sources of the perilymph fluid are (1) influx of CSF through the cochlear aqueduct, and (2) blood flow dependent local production within the cochlea. Experimental data are presented that give a ratio of 22:78 percent for those sources. The perilymph production thus derives mainly from the cochlear blood flow. It is concluded that measurements of the perilymph production can be used as indirect measurements of the inner ear blood flow under various experimental conditions. Two experimental examples are referred to.


A new method for the identification of cerebrospinal fluid leakage.

Apart from the use of anamnestic data the most common techniques for the diagnosis of CSF leakage have included X-ray studies, and chemical analysis of glucose, protein, and electrolytes of the fluid obtained from the nose or ear, intrathecal staining, and radioactive cisternography. These studies, although useful, have not always succeeded in demonstrating the CSF leakage, especially when the leak is delayed, small, or contaminated. A new immunochemical technique for the identification of the CSF leakage is described. It is based on demonstration of an extra band of transferrin located in the beta 2-fraction of protein electrophoresis of CSF. This beta 2-transferrin is pathognomonic for liquor and could not be demonstrated in serum, nasal secretions, saliva, tears, or peri- and endolymph. After routine protein electrophoresis on cellulose acetate membranes, the transferrins are identified by application of anti-transferrin on beta-regions. Stained precipitates in both beta-regions demonstrate clearly the presence of CSF. Compared with other methods, the new technique offers many advantages. The amount of sample needed for the procedure is small, moderate contamination does not invalidate it, it makes it possible to localize the leak by differential suction, and it is absolutely safe for the patient.


Nystagmus alternans.

Alternating nystagmus is a spontaneous nystagmus which changes in direction without any external influence. In the literature this phenomenon has so far been described in 90 cases; in 12 of these, the nystagmus had a congenital origin. In contradistinction to the congenital type, the acquired type of alternating nystagmus is in most cases caused by a central nervous system disorder. We found the phenomenon of alternating nystagmus in 21 cases, in 15 of which it was congenital. The nystagmus was observed by means of electronystagmography. Differences were found between the two nystagmus types. The characteristics of alternating nystagmus are discussed.


Neural connections of the outer haircell system.

The afferent innervation of the outer hair cells consists of a special type of neuron, distinguished by its characteristic structure and particular degeneration behavior. The connections of these neurons to the sensory cell, the central nervous system and the other cochlear neurons have been studied from different aspects and under various experimental conditions. There is evidence that the neurons are not effectively connected to the central nervous system, have no functional interconnections to other neurons and their functional significance in the adult animal is only rudimentary.


Family aggregation in Bell's palsy.

Some authors have reported a familial aggregation in Bell's paralysis. However, the information so far forthcoming is unsatisfactory and even contradictory. Our survey consisted of 115 patients, 30.5% of whom had an affected first-degree relative, which, compared with the control group figure of 3.6%, is highly significant. The frequency of 30.5% of families with an affected first-degree relative is the highest reported in literature.


Immunological investigations in laryngeal cancer.

The authors carried out immunological investigations in 96 patients with laryngeal cancer. The following tests were applied: DNCB, PPD, phyto-test and the lymphocyte count. The patients were divided into three groups: 1) cured, one year following treatment; 2) relapses; 3) died during the first year. The separate group of 13 patients tested twice in first year was analysed too. The immunological tests were also performed in 24 patients with no relapses of laryngeal cancer in the period between 3 and 10 years after treatment. This group was used for a comparative analysis with laryngeal relapses. In our opinion each individual test has its relative merit. According to our results patients with normal and elevated test values have the best prognosis of cancer disease.


Menière's disease: etiology and natural history.

Fifty-three carefully selected patients with Menière's disease were studied. Unlike Pulec, who describes a specific etiology in Menière's disease in 48% of the cases, we found no specific etiology in this study, except in one case (syphilis). The sequence of the development of the symptoms showed marked individual differences. In 16 patients, cochlear and vestibular symptoms started at the same time. In 26 patients the vestibular symptoms started after the cochlear symptoms and in 11 patients the reverse occurred. The meaning of these findings for the mechanism of the Menière attack is discussed.


Quality of care: a tracer diagnosis study of acute otitis media, comparing a district paediatric service with paediatric and otolaryngology emergency departments.

Acute otitis media was used as a tracer condition for comparing patient care as regards patient satisfaction, compliance and medical outcome in a district paediatric office, an otolaryngological and a paediatric hospital emergency department. The initial work-up of the 216 patients studied at the three units was in good agreement with predefined standards. However, while the district paediatrician arranged a follow-up for all patients, the hospitals did so only in 10--30% of the visits. Parent satisfaction was significantly higher at the district office when the time spent waiting and the time the patient was with the doctor were kept constant. Urinary penicillin was not detected in 1/17 of district paediatric and in 6/19 of otological patients. Compliance with follow-up was also much higher at the district paediatrician. Medical outcome did not differ between the units. The majority of the parents expressed preference for the type of care given in a neighbourhood service. It is suggested that the criteria for adequate treatment of acute otitis media adapted for emergency departments may be revised in case easy access is provided to a medical centre offering continuity of care and proper follow-up. Studies of the quality of care have so far not managed to demonstrate a definite and positive relationship between the process of care, patient satisfaction and final medical results.


Clinical course of whooping cough in children younger than six months.

The patient records of 59 children aged 2--26 weeks with culture-verified pertussis were analysed. Twenty-four of them were hospitalized, in most cases for social reasons. Only one child with hypothyroidism and a complicating pneumonia was critically ill. Seventeen of the 35 non-hospitalized patients had a mild disease without developing typical whooping attacks. Thirteen children were treated with erythromycin in the catarrhal stage. There was a tendency towards milder disease in this group but the differences compared to untreated children were not statistically significant.


Diagnostic value of symptoms and clean-voided urine specimen in childhood urinary tract infection.

In diagnosing urinary tract infection (UTI) the symptoms of 477 infants and children and the findings in their clean-voided urine specimens were evaluated. 322 patients were considered infected, when a bacterial culture of suprapubic aspirate was used as a diagnostic reference. No diagnosis was attempted on the basis of symptoms only. Numerous bacteria or greater than or equal to 200 leuc./mm3 in an uncentrifuged clean-voided urine specimen or greater than or equal to 10(5) bact./ml in quantitative bacterial culture were found in 59%, 42% and 81% of the infected symptomatic patients. The diagnostic accuracies of these indices were 88%, 94% and 95%, respectively. In asymptomatic patients the accuracies were considerably lower. Among these infected patients normal or equivocal isolated findings in the clean-voided urine specimens were frequently seen, and could not markedly be reduced by the various related factors, such as technique of urine collection, urine specific gravity or pH of urine. None of the above mentioned indices of the clean-voided urine specimens seems to be alone accurate and sensitive enough for diagnosing UTI, and therefore these should be used in combination. The advantage of immediately obtaining results supports the use of urine microscopy as a primary diagnostic method in symptomatic UTI of childhood in particular.


Mitral and tricuspid valve vegetations in infancy diagnosed by echocardiography.

The use of echocardiography in diagnosing intra-cardiac vegetations is described in two infants. The condition is unusual in infancy, but can be suspected from the clinical picture and positive blood cultures. Using echocardiography it is possible to localize the vegetations exactly and estimate the extent of valvular involvement. In one of the cases presented a vegetation on the anterior mitral leaflet was diagnosed and a gradual increase in size could be demonstrated. In the other case a large echo-producing mass was found attached to the tricuspid valve, protruding into the right ventricular outflow tract. This mass represented a fungal vegetation. In both cases autopsy later verified the echocardiographic findings.


Renal sodium excretory capacity in infants under different dietary conditions.

An evaluation of dietary effects on sodium (Na) homeostasis was performed in 28 healthy infants 7--13 weeks of age. Each infant received during one week an ordinary formula where either the Na and/or the protein content was increased twice. The high Na diets induced a significant elevation of the natriuretic response to an oral Na load. The response was most pronounced in those infants receiving a high Na as well as a high protein diet. The diet that was only high in protein resulted in an increased osmotic load to the kidneys but did not affect the Na excretion. The maturation of renal Na excretion thus seems to be accelerated by a high Na intake and further potentiated by a high protein intake. The Na excretory capacity was, even after the period of a high Na diet, well above the level of Na then given.


Serial measurements of thoracic impedance and cardiac output in healthy neonates after normal delivery and caesarean section.

Thoracic electrical impedance measurements were serially performed during the 1st, 2nd, 8th and up to the 32nd hour of life in two groups (V and S) of healthy infants. In group V, all 24 infants were delivered vaginally, in group S, all 24 infants were delivered by caesarean section for obstetrical reasons. Basal thoracic impedance (Zo), heart rate (HR), stroke volume (SV) and cardiac output (Q) were determined on each examination. In group V, Zo increased from 31.9 to 34.0 ohm between 2 hours and the last recording between 8 and 32 hours. SV decreased from 4.1 to 3.4 ml between 2 and 4 hours and was accompanied by a decrease of Q from 560 to 450 ml/min. Heart rate slowed from 129 to 115 beats/min between 2 hours and the last recording at greater than or equal to 8 hours. In group S, Zo increased from 32.2 to 35.9 ohm between 2 and 8 hours. Mean SV increased from 3.6 to 4.4 ml between 8 and 32 hours and heart rate slowed from 131 to 113 beats/min between 1 and 8 hours. No significant differences were observed between the groups. The accuracy of the impedance--SV and Q data cannot be validated. For the most part they compare favourably with values previously obtained by soluble gas methods. Serial changes may reflect not only decreasing shunts and/or increasing aeration but also changes in total fluid volume of the lungs, intra- or extravascular. The precision of the measurements is good since reproducibility of single SV and Q determinations is higher than with standard dilution techniques. The data obtained may serve as baseline values for comparison with data in infants of the same age with various anomalies.


Transepidermal water loss in newborn infants. II. Relation to activity and body temperature.

Using a method described in a previous article the transepidermal water loss (TEWL) was studied in 10 healthy newborn infants at rest and during activity. On the average TEWL was 37% higher during activity than during rest although no sweating was observed. In 9 infants placed in incubators with an ambient temperature slightly above the thermoneutral range measurements were made as the body temperature rose. TEWL was almost constant until a temperature of 37.1 degrees C was reached whereupon the water loss suddenly increased as the infant started sweating.


Human colostral and breast milk cells. A light and electron microscopic study.

Colostrum and breast milk samples were obtained from 74 women, 18 of whom gave sequential samples. The mean total leukocyte count in colostrum was 3190 cells/mm3. Proportions of macrophages, polymorphs and lymphocytes varied widely; macrophages usually predominated. Serial sampling showed (1) a small fall in total counts through delivery, (2) a fall in total counts and the proportion of PMNs at the onset of lactation, (3) after 1 to 2 weeks of lactation the appearance of cytoplasmic fragments together with epithelial cells which later constituted the main cell type. It was estimated that the total number of leukocytes available to the neonate remained approximately constant during the first 2 weeks of lactation and fell thereafter. Functionally, morphologically and histochemically macrophages in colostrum and breast milk resembled macrophages elsewhere. Their ultrastructure was characterized by filiform surface projections, numerous endocytic vacuoles and lipid droplets in the cytoplasm.


Incidence of coeliac disease and transient gluten intolerance in children in a Swedish urban community.

The incidence of coeliac disease in children in the city of Malmö, South Sweden, was 1 : 982 during 1966 to 1975. The diagnostic criteria were: flat intestinal mucosa on gluten-containing diet, free of symptoms, and improvement in mucosal morphology on gluten-free diet, and morphological and/or evident clinical relapse (three times) on gluten challenge. 6 (12%) of 49 children with initially a flat mucosa still had a normal mucosa on a gluten-containing diet for two years or longer, having so-called transient gluten intolerance.


Effect of long-term GH administration on pituitary-thyroid function in idiopathic hypopituitarism.

Twenty-four euthyroid children with idiopathic pituitary dwarfism were studied. The euthyroid state for seven of these patients was determined by negative physical examinations, normal plasma T4 assays and normal 131I uptakes. For the other children, thyroid function was evaluated with T3 and T4 assays and on the basis of the TRH test. Each of the children was treated with HGH in one of three different ways. The first group (five cases) was given a HGH dose, ranging from 12.4 to 17.2 IU/m2//week. The second and third groups (nine and ten cases, respectively) were treated with 10 and 20 IU/m2/week, respectively. Treatment was carried out for periods ranging from 6 months to 6 years. After no less than 6 months of treatment, and at intervals of 6 months (or some multiple of 6 months) plasma T3 and T4 assays, as well as a TRH test were performed in each patient. In some patients one of the indices was once beyond the upper or lower limit of the normal range (none of the children presented simultaneous abnormal levels of more than one index during the controls). This value, however, returned to within normal limits at the following control. There was no correlation between T3, T4 and TSH with the duration of HGH therapy. There was no significant difference between the groups of children treated with the different HGH doses. These data seem to demonstrate that the risk of inducing an alteration in thyroid function in hypopituitary patients during HGH treatment is very slight, and that the irregularly abnormal thyroid indices observed in some of the children during one of the controls might be an expression of their metabolic status at that moment.


Pharmacokinetics of amikacin in infants and pre-school children.

The pharmacokinetic properties of amikacin sulfate in infants and children aged from three weeks to 6 years were studied during treatment with doses of 7.5 mg/kg every 12 hours using standard assay methods and technique of two compartment open model kinetic analysis. Peak serum concentrations of amikacin were measured 30 or 60 min after the first intramuscular injection. These ranged from 11.8 microgram/ml to 23 microgram/ml in infants and from 9.0 microgram/ml to 29 microgram/ml in children. Five minutes after the first intravenous bolous injection they varied from 16 microgram/ml to 29.8 microgram/ml in infants and from 34 microgram/ml to 42 microgram/ml in children. Twelve hours after injection serum concentrations were less than 0.8 microgram/ml in all patients. Mean serum half-lives of amikacin in infants and children were 2.1 hours and 2.0 hours after intramuscular, and 2.2 and 2.0 hours after intravenous administration respectively. No evidence of accumulation was observed after four days treatment. The amount of antibiotic recovered within 12 hours from the urine in all patients ranged from 34.5 to 65% of an intramuscular dose, and from 45.8 to 63.3% of an intravenous dose. The dosage regime of 7.5 mg/kg body weight given every 12 hours should be safe and effective for the treatment of infections in the age groups studied.


Correlation between age and plasma level/dosage ratio for phenobarbital in infants and children.

123 plasma concentration measurements of phenobarbital were obtained from 82 children (2 months - 6 1/2 years old) at steady-state conditions. The plasma level/dosage ratio has been found to have a highly significant correlation with the age of the patient both for dosage in mg/kg and in mg/m2. The ratio increases with the increase in the age of the patient at a rate which is greater for dosages expressed on the basis of body weight. Moreover, at least for body weight related dosages, this increase is relatively high in the first year of life, becoming less marked after. Practical indications are given about the required dosage of phenobarbital in different groups of ages from 2 months to 6 1/2 years. It is recommended however to regularly measure the plasma level of the drug in infants and children treated for long periods of time.


Serum concentrations of theophylline in children following the administration of doses generally recommended: new dosage regimen required.

Serum concentrations of theophylline following intravenous and oral administration of aminophylline were studied in asthmatic children, 2--17 years of age. The biological half-life (t 1/2 beta) of theophylline varied between 165 and 495 min. The results revealed that an intravenous loading dose of 6 mg of aminophylline per kg body weight was necessary in order to obtain therapeutic concentrations in children who had not received the drug for the last 6 to 8 hours. The maintenance dose should be determined and controlled by use of serum concentration determinations. In a group of children receiving 5 mg of aminophylline per kg body weight 3 times a day orally, none had concentrations within the therapeutic range in the morning, and only 39% reached therapeutic levels 2 h after the morning dose. No correlation was found between the serum concentration of theophylline and the amount of drug given per kg body weight. The results show that theophylline concentration analysis is necessary to obtain adequate therapeutic levels in children without risking toxic effects.


Regional deficiency of secretory IgA in a patient with combined immunodeficiency of the ADA deficient type.

The IgA system in a patient with SCID and ADA deficiency showed heterogeneity. Serum IgA and stool secretory IgA (SIgA) levels were normal, but with altered kappa/lambda and A1/A2 subclass ratios; IgA in saliva and urine was deficient. Amounts of secretory component were normal. Jejunal and rectal biopsies showed prominent lymphonodular hyperplasia, but no cells containing IgA. A normal serum IgA level therefore does not always predict an intact secretory IgA system.


A virilizing adrenal tumor with borderline elevation of urinary 17-ketosteroids and histochemical demonstration of a deficiency in the delta 5/delta 4-isomerase, 3 beta-hydroxysteroid dehydrogenase enzymatic system.

A 3-year-old girl affected by a virilizing tumor of the adrenal gland, without significant elevation in the levels of 17 ketosteroids (17-KS) urinary excretion, was studied clinically. Her symptoms started abruptyly at the age of 2, with progressive enlargement of the clitoris and the appearance of pubic hair. In various tests, the 17-KS levels barely exceeded the upper normal limits and at times remained within normal limits. The retropneumoperitoneum X-ray suggested an enlargement of the right adrenal gland and the presence of a neoplasm, which was actually discovered during surgery. Histopathological examination revealed a well-defined neoplasm, without capsule invasion and with accentuated cell polymorphism. Histoenzymology showed that the tissue lacked the enzymatic system involving 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Indoxylesterase (I.EST-A) activity identified the tumor as originating from the internal layers of the adrenal cortex. The histochemical findings were correlated to the clinical picture and the levels of urinary 17-KS.


Affinity chromatography of influenza virus on immobilized alpha- and beta-ketosides of neuraminic acid derivatives.

In order to purify influenza viruses which contain neuraminidase as a constituent of the virus-coat surface, a study was made of the affinity of formaldehyde-inactivated viruses for immobilized ketosides of neruaminic acid derivatives. Attempted desorption of viruses bound to columns of the conjugates was performed by addition of the benzyl alpha-ketoside of N-acetylneuraminic acid to the eluent. The conjugates with alpha-ketosidically bound neuraminic acids adsorbed virus which could be desorbed with the enzyme substrate. When beta-ketosidically immobilized N-acetylneuraminic acid was saturated with virus and the conjugate was washed with buffer until it was free from neuraminidase activity, no more virus could be desorbed with neuraminidase substrate-containing eluents. However, addition of substrate to the buffer during the washing procedure resulted in a neuraminidase activity peak in the effluent. All conjugates bound firmly a portion of the viruses, which remained on the sorbents even after excessive treatment with eluent containing the neuraminidase substrate. When the conjugates were saturated with virus, all sites which bound the viruses strongly were blocked, and the remaining binding sites could be utilized for reversible adsorption of the viruses. Using this method, crude influenza virus vaccine could be separated into allantoic-fluid components and pure virus. Centrifugation of the virus preparation in a sucrose gradient indicated that this column procedure did not solubilize the viral neuraminidase. Using freshly prepared non-inactivated influenza virus, the portion of gel-bound viruses which could not be desorbed by neuraminidase substrate was diminished.


Cytotoxicity to tumour cells induced in human monocytes cultured in vitro in the presence of different sera.

Rodent macrophages can be stimulated in vivo and in vitro to become cytotoxic to neoplastic cells. It is shown in the present paper that cytotoxicity to a human tumour cell line is induced in human monocytes cultured in vitro in the presence of human serum. The cytotoxic ability is defined as including cytostatic ability, measured as inhibition of 3H-thymidine (3H-TdR) incorporation in tumour cells, and cytocidal ability, measured as release of radioactivity from 3H-TdR-labelled tumour cells. Monocytes cultured in medium containing 25 per cent human serum (HS-M) developed both a cytostatic and a cytocidal ability. When tumour cells were separated from these monocytes by a membrane, allowing factor-mediated interactions, a cytostatic effect was found, thus indicating that secretion of soluble factor(s) may be an important mechanism. The development of cytotoxic ability in the monocytes was accompanied by development of high capacity for phagocytosis of 125I-labelled Candida albicans, increased protein synthesis in the monocytes and microscopically observed alteration into large, well-spread monocytes with accumulation of phase-dense granules in the perinuclear region. Culture of monocytes in the presence of bovine sera induced less cytotoxic and phagocytic ability, as well as a smaller increase in protein synthesis and less morphological alterations, as compared to culture in HS-M.


In vitro effect of R 17934, a new drug with antitubulin activity, on neutrophil granulocyte locomotion and orientation.

R 17934 is a new synthetic antimicrotubule drug, which binds to tubulin at the same site as does colchicine. The interaction of this drug with human neutrophil granulocyte locomotion and orientation was examined, using a modified reversible Boyden chamber and a gradient chamber offering a direct visual assay of cell orientation. R 17934 at concentrations as low as 5 x 10(-6) M was found to inhibit chemokinesis to an equal degree in gradient chambers, and in Boyden chambers using checkerboard experiments, in which the absolute concentrations and the concentration gradients of the chemotactic agent were varied. At higher concentrations (10(-5) M) R 17934 also inhibited chemotaxis in Boyden chambers. Much lower concentrations of R 17934 (10(-7) M) were found to affect the ability of neutrophils to orient in gradient chambers. This finding may show that filters form a more suitable substrate for oriented pseudopod formation of microtubule-deficient cells than do glass or plastic slides. In conclusion this study has provided evidence that in the absence of functioning microtubules neutrophils can still orient and migrate directionally towards the source of a concentration gradient, but that they do so less precisely. The finding that R 17934 inhibited chemokinesis suggests that this drug may interfere with the mechanism translating a recognition signal into locomotion. The previous finding that colchicine also had this effect supports the hypothesis that this process may be microtubule-dependent.


Purification and characterization of rabbit anti-mouse renin specific Fab fragments.

Antibodies, raised against pure renin from the submaxillary gland of mice, were used to obtain renin specific Fab fragments. The purification steps were DEAE-chromatography, followed by papain digestion with separation of the undigested IgG preparation from the Fab/Fc fragments on a Sephadex G-100 column. Finally the Fab fragments were subjected to affinity chromatography on a CH-Sepharose 4B column with submaxillary renin attached. The purified Fab fragments revealed only a single band in SDS-polyacrylamide gel electrophoresis and a single precipitation line in cross immunoelectrophoresis. The association constants for the reaction of renin with the purified Fab fragments compared to the divalent antibodies were of the same magnitude, 0.7 x 10(11) l/mol and 1.0 x 10(11) l/mol, respectively. Comparison of the affinity of the Fab fragments for the antigenic determinants and the enzymatic inhibition of renin were determined to be approximately the same. Thus, the pure specific immunoreactive Fab fragment of antirenin, with an inhibitor constant of 1.5 x 10(-11), is the most potent inhibitor of mouse renin, so far.


The Spitzbergen reindeer--a winter-dormant ungulate?

Seasonal changes in serum levels of growth hormone, cortisol and thyroxine in calves and adult Spitzbergen reindeer (Rangifer tarandus platyrynchus) were measured and compared to those previously found in Norwegian reindeer (R.t. tarandus). Cortisol did not differ significantly between summer and winter, or between the subspecies. Growth hormone and thyroxine exhibited highly significant seasonal changes and subspecific differences: winter levels of growth hormone were much higher than summer levels in the Spitzbergen reindeer, while Norwegian reindeer differed very little from season to season. Both Spitzbergen and Norwegian reindeer had markedly reduced thyroxine levels during winter, but the values from the former were much lower than those from the latter. In summer, however, the levels were equal. The high levels of growth hormone and low levels of thyroxine in the Spitzbergen reindeer during winter are indicative of high lipolytic activity and a reduced metabolic rate, respectively.


Apparent and true vascular resistances to flow in SHR and NCR kidneys as related to the pre/postglomerular resistance ratio.

In maximally vasodilated SHR and NCR kidneys, perfused with filtrable and non-filtrable perfusates, analyses have been performed concerning the extent of average renal tissue pressure (Pt) elevation which occurs upon glomerular filtration and causes passive autoregulation of flow. The results illustrate the great importance of distinguishing between 'apparent' (PA--PV/flow) and 'true' (PA--Pt/flow) renal resistance to flow. This is particularly so when the compared SHR and NCR renal vascular beds differ not only in true total renal resistance but also concerning the structurally determined ratio between the pre- and post-glomerular resistances. The combined results show that this ratio is considerably elevated in adults SHT kidneys because of structural vascular changes, which is perhaps the most efficient way of resetting the 'long term barostat function' of the kidneys in hypertension. It is also illustrated how the altered pre-/post-glomerular ratio in SHR in combination with Pt rises can so markedly distort the results of apparently precise in vitro comparisons of SHR and NCR renal vascular beds as to give entirely misleading results, with underestimations of the structurally based vascular hyperreactivity of the preglomerular section in SHR.


Cardiac receptors with non-medullated vagal afferents in the rat.

The characteristics of 22 atrial receptors in 15 normotensive adult male Wistar rats were investigated. All the receptor afferents were included in the C-fibre group with conduction velocities from 0.4 to 1.2 m/sec. No atrial medullated receptors or ventricular C-fibre endings were found. Two receptors were located in right atrium and 2 receptors throughout left atrium. Upon elevation of the left atrial pressure the receptor discharge was markedly elevated with thresholds from 2.5 to 9 mmHg in mean left atrial pressure. Ten of the atrial receptors displayed a clear cardiac rhythmicity upon activation and the discharge correlated with the v-wave, indicating distension as the cause of receptor activation. The maximal firing rate in most receptors was very high (up to 70 Hz), but 8 receptors had maximal firing rates below 25 Hz. These low frequency receptors had higher threshold and showed a more irregular firing. Thus, there is a substantial population of atrial receptors with vagal non-medullated afferents in the rat heart and the thresholds for many of these receptors are so low that they are likely to be active during normal conditions.


Hepatic portal vein infusion of glucose on sodium excretion in the rat.

Anesthetized rats were prepared with catheters in the hepatic portal (HPV) and femoral (FEM) veins and in the bladder or ureters. In some experiments the left kidney was denervated. HPV infusion of 1 M glucose at 2 ml/h for 20 min increased Na excretion by the kidney when given as a second infusion. Bilateral cervical vagotomy eliminated the increase in Na excretion during glucose infusion and uncovered a delayed decrease in Na and K excretion. Renal denervation attenuated the increase in Na excretion to HPV glucose. FEM infusion of glucose had variable effects, increasing Na excretion only after vagotomy. The results are interpreted to suggest that central and vagal receptors tend to enhance Na excretionwhereas splanchnic nerve afferents and humoral mediator(s) have the opposite effect.


Lipoprotein-lipase activity of human skeletal-muscle and adipose tissue after intensive physical exercise.

Seven young, healthy subjects performed bicycle exercise with a working load leading to exhaustion after one hour of work. The tests were done in the afternoon in the fed state. The serum insulin concentrations decreased from 22 to 4 mU/l and plasma glucagon increased from 241 to 340 pg/l already after 30 min of work. The level of adipose tissue lipoprotein lipase activity (LPLA) did not fall as had been expected, but increased. The skeletal muscle LPLA was unchanged. The results indicate that during the first hour of heavy exercise the heparin-releasable LPLA in tissues is not influenced by the work induced changes in serum hormone levels.


The effect of water temperature on the hormonal response to prolonged swimming.

The relationship between thermoreception, hormonal secretion and muscular activity was studied. 6 men swam 60 min in 21, 27 and 33 degrees C water at a speed requiring 68% of VO2 max (determined in 27 degrees C water). Rectal temperature increased in 33 degrees C (1.3 +/- 0.2 degrees C, mean and S.E.) and 27 degrees C (0.7+/- 0.1 degrees C) expts. but decreased in 21 degrees C expts. (0.8 +/- 0.3 degrees C). Changes in esophageal and muscle temperatures parallelled changes in rectal temperature. Plasma noradrenaline was higher in 33 degrees C than in 27 degrees C expts. and growth hormone, cortisol and glucagon concentrations increased in 27 degrees C and 33 degrees C expts. only. Insulin concentrations were uniformly depressed during swimming at the different water temperatures. In 21 degrees C expts. noradrenaline and adrenaline concentrations were higher than in 27 degrees C expts. VO2, carbohydrate combustion and peak lactate were slightly lower in 33 degrees C expts. Plasma glucose decreased slightly and FFA and glycerol concentrations increased identically in all expts. Heart rate increased continuously during swimming in 27 degrees C and 33 degrees C expts., but not in 21 degrees C expts. In conclusion the rise in body temperatures normally observed during exercise enhances the exercise induced increases in the plasma concentrations of noradrenaline, cortisol, growth hormone and glucagon. Decreased body temperatures may elicit catecholamine secretion as a direct consequence of thermoreception. Shivering may account for previously observed decreases in insulin secretion during cold stress but not for increases in cortisol and growth hormone.


Release of 3H-noradrenaline from the rat vas deferens under various in vitro conditions.

The release of 3H-(-)-noradrenaline (NA) from rat vas deferens in vitro was examined under various experimental conditions. It was found that in normal and reserpinized vas deferens the release of NA evoked by (+)-amphetamine (5 X 10(-6) M) or low external Na+ (26 mM) was antagonized by imipramine methiodide and desipramine, inhibitors of the NA uptake, but was not dependent on the presence of Ca2+ in the medium and was not antagonized by the potent local anaesthetic agent bethoxycaine. The release evoked by veratridine in reserpinized tissue was antagonized by the uptake inhibitors but was in normal tissue only partially inhibited in presence of Ca2+ but almost completely in absence of Ca2+. The release by high K+ (117 mM)+low Na+ (26 mM) in normal tissue was dependent on the presence of Ca2+ and was antagonized by the muscarinic agonists carbacholine and metacholine and by high concentrations of desipramine. In the reserpinized vasa the corresponding release was not dependent on Ca2+ and was not antagonized by the muscarinic agents but was inhibited by high concentrations of desipramine.


Different effects of furosemide on urinary excretion of prostaglandin E2 and F2 alpha in rabbits.

The effect of a constant infusion of furosemide (130 micrograms/min i.v. for 60 min, n = 8) was studied on urinary excretion of water, electrolytes and immunoreactive prostaglandin E2 (iPGE2) and iPGF2alpha in chloralose-urethane anesthetized rabbits. During the furosemide infusion sodium and water excretion increased ten-fold and the excretion of potassium and iPGE2 two to three times. The excretion of iPGF2alpha (0.06 +/- 0.03 micrograms/min/100 g kidney weight) was not significantly changed during the furosemide infusion but increased markedly after the infusion and reached a maximum (1.0 +/- 0.6 microgram/min/100 g) 30 to 45 min later, while the small increase in iPGE2 excretion at this time could be attributed to cross-reaction with PGF2alpha. The results indicate that PGE2 might possibly be involved directly in the action of furosemide, while PGF2alpha might participate in sodium and water conserving mechanisms in the rabbit kidney, activated by the drug induced diuresis.


Fasting and prolonged exercise increase vasoactive intestinal polypeptide (VIP) in plasma.

6 young men had venous blood drawn during 4 experiments. The concentration of VIP in plasma increased markedly (from 1.8 (0--4.5) to 22.3 (7.8--43.8) pmol.1(-1), mean and range) during 3 h of mild bicycle exercise but not at all during an equivalent period of rest or during short term submaximal and maximal exercise. During 59 h of fasting, VIP increased from 3.6 (0.6--6.6) to 10.2 (6.6--13.8) pmol.1(-1) (p less than 0.05). The concentration of glucose in plasma decreased significantly during the prolonged exercise as well as during fasting. The known metabolic actions of VIP and the demonstrated increases in its plasma concentration during negative energy balance indicate that VIP is "a polypeptide of substrate need".


A simple test for autonomic neuropathy in juvenile diabetics.

The reproducibility of a simple method for determining the beat-to-beat variation during maximal respiration (duration of inspiration = duration of expiration = 5 sec), using an ordinary ECG apparatus and a ruler, was tested in 10 normals and 40 insulin-treated diabetics. The results were reproducible and beat-to-beat variation was found to be independent of a 25-minute period of rest. The method was subsequently applied to 126 insulin-treated diabetics and the results are in accordance with previous investigations on cardiac vagal neuropathy. The method is applicable as a clinical routine test for cardiac vagal neuropathy.


Effect of clinical bed rest for seven days on physical performance.

Twenty-two healthy men were confined to bed in a hospital ward (clinical bed rest) for one week. Variables related to physical fitness were measured before and immediately after the bed rest period, as well as one and three months thereafter. As a result of bed rest, maximal oxygen uptake, W170 and total Hb decreased to 94%, and calculated blood volume to 93% of the initial value. Hb concentration and Hct were unaltered. Thus, red cell and plasma volumes were proportionately reduced. No significant orthostatic dysfunction developed. The blood lactate peak at maximum work remained unchanged (14.0 mM/l). The resting exertion of noradrenaline decreased moderately during the bed rest period, whilst that of adrenaline was unchanged. Body weight decreased by a mean of 0.7 kg.


Self-therapy for haemophilia in Norway. Effect on transfusion frequency and days lost from work.

During the years 1975--77, 35 patients with haemophilia A or B (factor level of 1% or less) were instructed to administer concentrates of the deficient factor (mean dose 14 U/kg) i.v. in case of episodic, uncomplicated bleedings without prior consultation with a physician. At Dec. 1977, 33 of these patients (29 with haemophilia A, 4 with B) were taking part in the program. They represent 35% of all Norwegian patients above 7 years of age with severe haemophilia in whom high-titered antibodies have not been demonstrated. For 13 patients, records from 2 years on self-therapy have been compared with records from the last year before self-therapy. During the first year on self-therapy the number of days lost from work dropped by 77%, while the number of transfusions increased by 22%. During the second year, days lost from work were still low (68% decrease compared to the year preceding self-therapy) and the transfusion frequency remained unchanged. Significant side-effects of antihaemophilic concentrates were not observed and vein damage was not a problem. Joint motion studies did not indicate progress of haemophilic arthropathy during self-therapy. Properly supervised self-therapy is practical and safe and improves considerably to quality of life.


Biochemical variables related to calcium metabolism in epileptics.

Five biochemical variables, S-Ca, U-Ca, S-P, U-P and S-ALP, all involved in calcium metabolism, have been investigated in 86 epileptics on long-term medication. We found hypocalciuria in half of the epileptics and increased S-ALP in one third. In contrast to earlier reports there was no hypocalcemia, whereas hypercalcemia was found in 7 epileptics. We have previously reported a high frequency of fractures in these epileptics. An increased fracture rate was found in the 13 epileptics with both hypocalciuria and increased S-ALP, indicating osteomalacia.


Fractional intestinal calcium absorption in epileptics on anticonvulsant therapy. Short-term effect of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol.

Fractional intestinal 47Ca calcium absorption (alpha) in 12 epileptic outpatients receiving chronic high-dose anticonvulsant therapy was reduced (p less than 0.05) compared to 12 matched normal controls. Six of the epileptics were treated orally with 0.5 microgram of 1,25-dihydroxycholecalciferol (1,25-DHCC) per day and six with 10 microgram of 25-hydroxycholecalciferol (25-HCC) per day for 10 days. The alpha was determined before and after treatment and compared with the effect of 0.5 microgram of 1,25-DHCC per day given for 10 days to 6 controls. An increase of the same order in alpha was found in all groups (p less than 0.05). No changes were observed in the serum levels of calcium, phosphorus, alkaline phosphatase or iPTH during treatment. Urinary calcium excretion was low in the epileptic patients and rose during treatment. The investigation demonstrates that the sensitivity of the intestine to 1,25-DHCC is normal in epileptic patients on anticonvulsant therapy and that 1,25-DHCC and 25-HCC in the given doses had an equal effect on the reduced intestinal calcium absorption.


Mexiletine in treatment of ventricular arrhythmias. A long-term follow-up.

Maxiletine, a new drug effective in the treatment of ventricular arrhythmias, was given to 20 patients for approximately 2 years. The study was designed to investigate the nature and prevalence of side-effects during long-term therapy, and the degree of correlation between such effects and the serum levels of the drug. The methodology used to determine the serum level is described. Mexiletine was well tolerated and serious side-effects were not seen. In particular, antinuclear factor was not detected during the treatment period. The serum level of mexiletine was easily maintained within the therapeutic range, and most side-effects correlated closely with the drug level. Mexiletine appears to be an effective alternative to currently available antiarrhythmic agents.


Kinetics of hemodynamic and electrocardiographic changes following intravenous disopyramide.

Changes in hemodynamic and ECG variables following disopyramide (1.7 mg = 3.9 mmol/kg b.wt.) were studied in 9 patients with ventricular arrhythmias. All patients displayed a marked reduction in the number of ventricular ectopic beats, all except one exhibiting complete abolition of the arrhythmia for at least 30 min. QT and QRS intervals showed statistically significant prolongations, and thereafter decreased exponentially with time. Above a certain concentration threshold that varied between the patients, systolic time intervals and aortic (dp/dt)max showed linear changes with increasing drug serum levels. Changes in diastolic pulmonary artery pressure showed no simple relationship with disopyramide concentration or time after injection. In 3 out of 4 patients studied, there was a good correlation between the lowest level of disopyramide that elicited both an antiarrhythmic effect and a demonstrable decrease in cardiac contractility.


Arrhythmias in patients with acute cerebrovascular disease.

Cardiac disease is common in patients with cerebrovascular disease (CVD) and cerebral lesions as such may influence cardiac activity and rhythm. To study the indication for continuous ECG surveillance of patients with CVD, 100 consecutive patients admitted to a medical stroke unit were investigated with 24-hour Holter recordings. The patients' mean age was 73 years and 70% of them had a history of heart disease. Twenty-three patients had chronic atrial fibrillation and 55% of the remainder showed ventricular ectopic activity. Serious ventricular arrhythmias were comparatively rare and mainly seen in association with signs of congestive heart failure and acute myocardial infarction. A prolonged Q-T interval was registered in two-thirds of the patients but there was no significant association between this finding and ventricular ectopic activity. Close observation for cardiac complications is important in patients with CVD and continuous ECG surveillance is indicated in selected high-risk patients.


Temporal arteritis--progressive affection of vision during high-level corticosteroid therapy. A case report.

A case of giant cell arteritis (temporal arteritis) is presented in a 73-year-old male patient in whom lasting reduction of vision developed during high-level prednisone treatment (60 mg daily) at a time when clinical improvement in other respects had appeared.


Adolescent and postadolescent asthmatics' perception of their mothers as overcontrolling in childhood.

One of us (HSR) reported that adolescent and postadolescent patients with well-controlled bronchial asthma coming to a university health services clinic were more likely to arrive late for an appointment, or not to show up for it at all, than non-allergic healthy patients, patients with perennial rhinitis, patients with seasonal rhinitis, or patients being investigated for cardiac disease. He wondered whether such behavior might be a reaction against an overcontrolling mother. To determine whether patients with bronchial asthma perceived their mothers as having overcontrolled them in their childhood, we asked adolescent and postadolescent patients coming to a university health services clinic to answer a questionnaire anonymously. Three disease groups were studied: 1) bronchial asthma, 2) perennial rhinitis, 3) seasonal rhinitis; and a group of non-allergic healthy controls. Asthmatics significantly more often than the other groups reported that when they were children their mothers (but not their fathers) had overcontrolled them (p less than .001).


Parent-peer influence as a predictor of marijuana use.

Although there is some literature which discusses adolescent reference groups, none have utilized reference group theory to examine the relative impact of the parent and peer reference groups and to attempt to predict behavior among teenagers from this knowledge. This study attempts to correct this deficiency by examining the frequency of marijuana use in a nonrandom sample of college students from a large southwestern university. Ordinal type scales and tau-b provide a statistically strong degree of association between the type of reference group orientation and marijuana use. The results of this study show that the influence of the most salient reference group appears to be an important predictor of whether or not an individual may engage in the use of marijuana.


Factors in adolescent rebellious feelings.

To verify the existence and determine some sources of 15- and 16-year-old youths' (midteens') antisocial feelings, 174 midteens (89 males and 85 females) from two small Tennessee towns were administered L. Srole's Anomia Scale and two author-devised tests, the Inventory of Midteen Rearing Theories and the Rebellion Scale. As their parents' levels of education rose, midteens' feelings of anomie and rebellion decreased significantly: fathers F (3, 160) = 4.77,p less than .01; mothers F (3, 163) = 2.77, p less than .05. Midteen feelings of anomie and rebellion correlated positively with midteen perception of parent-midteen disagreement about how the midteen should be reared: Anomia r (172) = .25, p less than .01; Rebellion r (172) = .37, p less than .01. Probable causes of extremely rebellious feelings in midteens include parent-midteen conflict over how the midteen should be reared and the midteen's rejection of attending school as a worthwhile occupation.


The effects of self-management of school attendance by problem adolescents.

Self-management of attendance by problem adolescents was shown to improve attendance in an alternative school. The use of biased measures to investigate change is discussed as well as the utility of frequent measures. The effect of improved attendance on academics is presented and future research in this area is suggested.


Sociological correlates of alienation among adolescent suicide attempts.

The purpose of this research is to assess the relationship between adolescent alienation and a number of sociological factors in a sample adolescent suicide attempts from a northern metropolitan area. First, Dean's alienation scale is employed and the distribution of responses of the adolescent suicide attempts are analyzed. Second a number of sociological variables are examined by means of multiple regression procedures. In the regression analysis, eight variables were found to be statistically significant-in descending order: social contact with peers in the neighborhood, conflict with parents, broken romance, economic status of parents, communication blockage with parents, school performance, stepparents, and broken romance, These variables have been salient in previous research and theorizing about adolescent suicidal behavior. The fact that adolescence, by itself, seems to be a good predictor of whether or not a person will attempt suicide strongly suggests that there is something about the condition of adolescence which underlies this type of behavior. One possibility is that biological maturation is itself the crucial variable. Alternatively, the argument which follows concentrates on a major sociological aspect of adolescence-the adolescent's relative alienation from institutionalized social life. Alienation may be endemic to the period of adolescence.


Self-esteem and institutionalized delinquent offenders: the role of background characteristics.

Some of the delinquency literature sustains the assumption that inept persons doing unworthy things is the self-view held by youth offenders, "Disadvantaged" or "adverse" background characteristics are often assumed to account for low self-esteem among delinquent offenders. However, the implications of control theory suggest that youths having few bonds to people and institutions are relatively "free" to drift into delinquency without serious damage to self-esteem. The hypothesis we examined was derived from the work of control theorists: that self-esteem would be higher for offenders "removed" from conventional ties, lower for those who maintained conventional attachments. Data from 75 male delinquent offenders incarcerated at a correctional youth institution are used in testing this relationship. Our hypothesis received strong support. The implication drawn from these results is that the impact of the correctional process on self-esteem may be far less important than the myriad relationships previously established with people and institutions. These results pertaining to a special category of youth are in keeping with the reported findings on the link between deprivation and self-esteem of general youth populations.


Internal control and success orientation in a token economy for emotionally disturbed adolescents.

Forty-one emotionally disturbed adolescents were tested at each of three token economy levels on Rotter's Internal-External Locus of Control Scale and Guevar's Success-Failure Inventory. Delay of reinforcement (immediate, daily, weekly) was the primary differentiation between levels. One-way analyses of variance indicated a change across levels in the direction of more perceived internal control of behavior (p less than .025) and a greater success orientation (p less than .005). Change scores were not correlated with length of time in the program. Results suggest that the token economy as an external source of control is not necessarily incompatible with increasing patient expectancies of present and future control of the environment.


Creative thinking and juvenile delinquency: a study of delinquent and nondelinquent youth on the Torrance Tests of Creative Thinking.

Using the T.T.C.T. this study examined the creative thinking of 32 delinquent and 32 nondelinquent adolescent males. The delinquent group was composed of juveniles on parole status. The nondelinquent group was composed of public school students. On the variables of IQ, age, and socioeconomic class, t-test results indicated no significant differences, except on socioeconomic class, between the groups. Analysis of variance procedures were performed to determine the possibility of an interaction between levels of intelligence and delinquent status with regard to verbal and figural creativity test scores. There were no significant main effects or interaction between IQ and adjudication status with respect to figural creativity. There was a significant main effect due to adjudication status for the dependent variable of verbal creativity scores, respectively while blocking on the intelligence variable. The results were parallel to the ANOVAS which did not specifically control for the intelligence variable between the two groups.


Developmental aspects of hopelessness.

Developmental aspects of hopelessness were studied within a holistic-organismic framework. It is suggested that for an individual to become hopeless, cognitive-affective development and the development of the concept of time have to reach a certain level. The developmental readiness to experience hopelessness is considered necessary for an adolescent to present a clinical picture of depression similar to that of the adult.


Sexual identity and personality variables in normal and disturbed adolescent girls.

Disturbed and normal adolescent girls from a working class background were compared on three measures of sex role as well as self and ideal personality characteristics. Both disturbed and normal girls had an appropriate sex-role identity on two of the measures. An association was found between normal status and high self scores on nurturance, affiliation, and endurance, and between pathological status and succorance. Although differences existed on some self reported traits between pathological and normal status, all groups tended to see the ideal female teenager as having an equitable balance among the personality variables and higher than they rated themselves on deference, nurturance, and affiliation and lower on autonomy. It was concluded that the presence or absence of certain adaptive personality traits may be more important than sex role disturbance in pathology.


A study of sexual offenses against females.

The objective of this study was to obtain information on sexual offenses against females. Data were obtained from 103 females in two university classes. Eighty-four percent reported having been the victim of a sexual offense. The offenses experienced were obscene telephone calls (61%), sexual molestation (44%), exhibitionism (27%), being followed (24%), attempted rape (16%) and rape (1%). Most offenses were discussed with friends while very few were reported to parents, police or social workers.


Clinical and administrative synthesis in adolescent treatment: search for a sane integration of thought and action.

In working as administrator and clinician (co-director and head psychologist) of a day and residential treatment facility for disturbed adolescents, I have become acutely aware of some of the difficulties of integrating both roles. To keep rooted in the concrete, I have described the program with which I am involved in particular as to crucial client and staff dynamics. By drawing on concepts from systems theory (as system integrity and cross-boundary interactions) and psychoanalytic theory (unconscious testing), I have tried in this paper to sketch a framework for bringing the two separate roles into a single way of thinking and give some examples of how this kind of synthesized approach can be useful and powerful. The two concrete examples focus (1) on the more administrative issue of program design, and (2) on a more clinical case of child abuse.


Seriousness of adolescent problems.

Two hundred and forty white middle class adolescents in a four year high school were administered a 14-item questionnaire designed to assess the seriousness of typical adolescent problems. The three most worrisome problems were physical appearance, careers and grades. Sex, year of high school and college vs. work bound differences were analyzed and discussed.


Fractured proximal femur in Newcastle upon Tyne.

Using Hospital Activity Analysis (HAA) data as a diagnostic index followed by record linkage procedures, a retrospective survey was carried out of patients aged 65 and over from the Newcastle area admitted to hospital with fractures of the proximal femur. Annual incidence rates for the Newcastle area of 5.6 per 1000 in females and 2.3 per 1000 in males were observed. These rates are probably 7% lower than true rates owing to patients with multiple fractures being allocated to diagnostic codes other than fractured proximal femur in HAA files. Incidence rates increased steeply with age, and rates in the sexes tended to converge at higher ages. Proportionately large numbers of patients were admitted in the winter months. The mean length of hospital stay was 75.2 days of which an average of 47.8 were spent in acute orthopaedic units: this was equivalent to the continuous occupation of 51.1% of acute orthopaedic beds in Newcastle. At one hospital, mean length of stay was 64% greater than at the other and the weekly discharge rates were suggestive of partly prescriptive discharge. Of the patients studied 35.6% died in hospital, and actuarial analysis shows that risk of death fell from initially high values to a nadir at four to six weeks and then showed a secondary rise.


Oral and dental discomfort--a necessary feature of old age?

A socio-dental study was conducted among an elderly population living at home. The dental status of the sample was generally poor; 74% were edentulous and only 10% of the full denture wearers had appliances which were clinically satisfactory. Nearly 60% of the subjects had pathological lesions of the oral mucosa, mainly associated with the wearing of dentures. Many of the subjects were handicapped either socially or functionally by their oral conditions; 40% had oral pain, 30% had difficulty chewing and 20% were embarrassed by their dentures dropping during social contact. Although 78% were assessed as needing treatment only 19% had tried to obtain it. Various reasons were mentioned for not obtaining dental treatment, including immobility, fear and prohibitive cost. Reasons for the present state of the dental health of the elderly are discussed.


Economic aspects of the demand for total hip replacement in the elderly.

Approximately 1--3% of people attaining the age of 65 will eventually require a hip replacement. At present the elderly account for about half the total hip replacements performed annually under the National Health Service. Although this may appear to be difficult to justify on economic grounds, there may be minor financial gains and a saving of medical and community resources, in addition to the relief from symptoms and dependence upon others, which results from a successful operation.


Prediction of outcome of patients admitted to a geriatric department.

The reliability of a clinical prognosis of outcome at six weeks has been investigated in a series of 1092 consecutive admissions to a geriatric department. The prognosis was made within a day of admission and made use only of the history and clinical findings. The results for discharge were good but categorization of patients who died or who stayed longer than six weeks was less reliable. Unpredicted deaths were often sudden or related to disease with developed after assessment. Other errors were due to over-optimism in forecasting response to medical treatment or rehabilitation. In other cases progressive deterioration had not been clearly recognized at our assessment based on a single point in time.


Urodynamic studies in the management of urinary incontinence in the elderly.

An outline is given of simple urodynamic investigations applicable to elderly subjects. The type of patient presenting primarily to geriatric departments with urinary incontinence, whose management is aided by such studies, is described under various clinical groupings. The requirement for urodynamic studies and the best means of providing these for the elderly patient is discussed.


A geriatric psychiatry day hospital service: a five-year review.

Psychiatric day hospitals for the elderly have been regarded either as an alternative to in-patient care or as a long-term supportive facility for patients with chronic psychiatric disabilities. In a five-year review of such a unit it was found that the unit's main function had become that of providing an immediate short-term supportive facility to demented patients, mainly in the 75-years-and-over age group, and to their relatives, until such time as beds in the long-stay psychogeriatric wards of the hospital became available. The implications of this change in role of day hospitals are discussed in the light of present facilities and the predicted increase in the size of this section of the population.


Capillary fragility in the elderly.

Within-subject variation of capillary fragility with a 20 mmHg change in blood pressure has been studied in a series of elderly patients. Capillary fragility is increased by an average of 48% by a 20 mmHg rise in blood pressure. The reported association of capillarly fragility and blood pressure is thus artefactual rather than an indication of a higher prevalence of vascular abnormality in subjects with higher blood pressure.


Selection of occupational therapy students.

A research study on the selection of students for entrance into the basic professional four-year occupational therapy curriculum at Elizabethtown College is presented in this paper. The study has tow primary objectives: the determination of factors that could serve to discriminate between prospective students who would remain in the program from those would withdraw; and the development of a mathematical model that could be used in future years for student selection to the occupational therapy program. It is suggested that the model can be applied to any educational setting, can effectively streamline the usual admissions process, and can ensure that qualified students enter occupational therapy programs and thus be an additional indicator for the success and continuation of the profession.


A prediction of internship performance.

Previous studies of predictors for occupational therapy internship performance were based on the Report of Student Performance, the tool used before 1974 to evaluate students' clinical performance. The instrument was never tested for validity or reliability. No studies for prediction of clinical performance used the present Field Work Performance Report (FWPR), which was tested for validity and reliability before its adoption late in 1973. Thus, new studies using the FWPR were indicated. Grades from 16 selected college courses and the pre-occupational therapy grade-point average were studied to determine significant relationships with the physical disability intership grades of 72 students from Colorado State University. Neurology was significant at the .0004 level. Further study is necessary to confirm the present findings and to determine additional predictors for clinical performance of Colorado State University students.


Role of the asymmetrical tonic neck reflex in hand visualization in normal infants.

Fourteen infants were each videotaped 7 times within the first 12 weeks of life to determine whether or not the asymmetrical tonic neck reflex had a role in placing their hands within their fields of vision. Infants' arms were more frequently out of the reflex position. Hands were within the peripheral visual field more often than in the focal visual field or not within the visual field. The proportion of observations that hands were in a particular visual field varied in accordance with the presence or absence of the reflex. A higher proportion of reflex observations occurred in the focal visual field, whereas a higher proportion of observations made when the infants were not in the reflex position occurred in the peripheral visual field. Further, the proportion of focal field observations in the reflex position was greater than the proportion of observations out of the reflex position for the first six of the seven ages. This study confirms that when infants are in the asymmetrical tonic neck reflex position, their hands are more likely to be in a position in which they can be visualized.


Advising the mastectomy patient about reconstruction.

Breast reconstruction deserves critical consideration and discussion in each patient's case. The psychologic benefits from the procedure are enormous. Reconstructive goals are: skin coverage, contour restoration and formation of the nipple-areola. The prospect of reconstruction must have no effect on the procedure for extirpation of the cancer. Breast reconstruction is now possible even after the removal of large amounts of skin and muscle.


In-toeing gait in children.

Torsional deformities in the lower extremities, resulting from constrained intrauterine position, tend to spontaneously correct toward the adult configuration during growth. Internal tibial torsion, metatarsus adductus and femoral anteversion are clinically evident conditions that occur because of arrested normal postnatal development. An understanding of the dynamics of spontaneous correction permits assessment of the child with in-toeing gait as well as the selection of proper treatment.


Infection of glutaraldehyde-preserved porcine valve heterografts.

Gross, histologic and ultrastructural changes associated with bacterial infection are described in four porcine valve heterografts that had been in place in patients for 6 days to 28 months. In one patient, culture of the aortic tissue tag included in the heterograft container grew Mycobacterium chelonei; however, examination of the heterograft, recovered at necropsy 6 days after implantation, revealed small colonies of bacteria that differed morphologically from mycobacteria. A second heterograft was the site of staphylococcal infection associated with extensive destruction of collagen in the leaflets. Similar destruction was observed in a third heterograft, which was found to have organisms on ultrastructural study even though bacterial cultures of the valve were negative. The fourth heterograft, from a patient who died of coronary embolism secondary to dislodgment of vegetative material, contained structures resembling lysed bacteria. Observations in these 4 patients and review of published reports of infection involving 43 other patients with porcine valve heterografts indicates that infection in these valves: (1) develops in the fibrin layer that covers the cusps, (2) can involve the collagen in the leaflets, and (3) is uncommonly (three patients) associated with valve ring abscesses.


Effect of diltiazem, a calcium antagonist, on myocardial ischemia.

In line with studies on the metabolism of the ischemic myocardium, the effectiveness of diltiazem hydrochloride, a potent calcium antagonist, in reducing the effects of ischemia was evaluated. Nonischemic and ischemic tissue samples were examined in two groups of dogs--Group I, dogs receiving no drug and killed after 60 minutes of regional ischemia, and Group II, dogs given diltiazem after 10 minutes of ischemia and killed 50 minutes later. Administration of diltiazem proved beneficial in several ways: The decrease in adenosine-5'-triphosphate in the ischemic region was halved, inhibition of anaerobic glycolysis was reduced, tissue levels of lactic acid and free fatty acids were lowered and the contractility of glycerinated heart muscle fibers was improved. However, administration of the drug did not influence mitochondrial function. Mitochondrial oxygen consumption and respiratory control were reduced by equal amounts in both groups, as was mitochondrial calcium ion binding. These observations demonstrate that diltiazem is capable of minimizing the consequences of acute ischemic, although the beneficial effects do not extend to all aspects of myocardial metabolism.


Canine electrophysiology of encainide, a new antiarrhythmic drug.

Encainide, a new benzanilide derivative with high potency and a good therapeutic/toxic ratio, was evaluated with the use of standard His bundle recording techniques to determine its effects on the cardiac conduction system in closed chest animals. Twenty mongrel dogs weighing 18 to 29 kg were anesthetized with 4 percent chloralose and classified into groups: group 1, a control group and groups 2, 3, and 4, which were given 0.3, 0.9 and 2.7 mg/kg body weight, respectively, of encainide in an intravenous infusion over a 15 minute period. Plasma concentration, blood pressure, surface electrocardiogram and atrial and His bundle electrograms were recorded before, during and after drug infusion for a total of 120 minutes. Heart rate, A-H and H-V intervals, the QRS complex and Q-Tc interval were measured every 5 minutes during sinus rhythm and with constant atrial pacing. In addition, sinus nodal recovery time and atrial, atrioventricular (A-V) nodal and left ventricular refractory periods were measured before and immediately after infusion and every 30 minutes for 2 hours. Peak plasma concentration averaged 450 ng/ml in group 2, 1,300 ng/ml in group 3 and 4,000 ng/ml in group 4. Blood pressure was not altered at any dose level throughout the study. The QRS complex and H-V interval were significantly prolonged (P less than 0.005) at doses of 0.9 mg/kg and greater. These effects correlated well with plasma concentration. There was no significant change in heart rate, corrected sinus nodal recovery time, A-H interval, Q-Tc interval atrial, A-V nodal or left ventricular refractory period. It is concluded that, unlike other antiarrhythmic agents, encainide prolongs His-Purkinje system conduction without significantly affecting conduction or refractoriness of other parts of the cardiac conduction system in animals.


Effects of thioridazine (Mellaril) on ventricular electrophysiologic properties.

The effects of therapeutic and toxic doses of thioridazine (Mellaril) (10 and 50 mg/kg body weight, respectively) on ventricular electrophysiologic properties were studied in 12 anesthetized dogs. Threshold pacing currents (diastolic threshold), effective refractory period and conduction time were significantly increased, and idioventricular automaticity was suppressed after administration of 10 mg/kg of thioridazine; the effects were much more pronounced after administration of 50 mg/kg. Rapidly repetitive responses or tachycardia could be induced in the ventricle by two early premature beats in 9 of the 12 dogs after the 50 mg/kg dose, but they did not occur before drug administration or after the 10 mg/kg dose. These results indicate that the antiarrhythmic and arrhythmogenic effects of thioridazine are dose-dependent and that careful monitoring with frequent electrocardiograms is needed for patients receiving large doses of this drug.


Multiple gated cardiac blood pool imaging for left ventricular ejection fraction: validation of the technique and assessment of variability.

The intrinsic variability and accuracy of left ventricular ejection fraction determined by multiple gated cardiac blood pool imaging was evaluated in 83 patients. Ejection fraction by gated studies correlated well with data from first pass radionuclide angiocardiography (r = 0.94) and from contrast angiography (r = 0.84). Intra- and interobserver variabilities of absolute ejection fraction were minimal (mean +/- standard deviation 1.4 +/- 1.2 and 1.6 +/- 1.5 percent, respectively) and were not different for normal (ejection fraction 55 percent or greater) and abnormal patients. Ejection fraction was determined twice in 70 patients: on the same day at intervals separated by 1 to 2 hours (41 patients) and on 2 different days (29 patients). Ejection fraction ranged from 18 to 91 percent and was normal in 37 patients. There was no difference in mean serial variabilities of absolute ejection fraction for all repeat studies performed on the same and separate days (3.3 +/- 3.1 versus 4.3 +/- 3.1 percent (not significantly different). The mean variability of absolute ejection fraction for repeat studies in normal patients was significantly greater than in abnormal patients (5.4 +/- 4.4 versus 2.1 +/- 2.0 percent, P less than 0.01). The incidence rate of absolute interstudy changes of 5 percent or more was significantly higher in normal than in abnormal patients (P less than 0.01). This differential variability should be considered in interpreting sequential changes in left ventricular ejection fraction. To be attributed to nonrandom physiologic alterations, the absolute change in ejection fraction should be 10 percent or more in normal patients and 5 percent or more in abnormal patients.


Management of surgical complete atrioventricular block in children.

Because there is disagreement concerning the efficacy of and indication for permanent pacemaker implantation in children with postoperative complete (third degree) atrioventricular (A-V) block, experience in the management of this problem at one institution was reviewed. Thirty-four patients with postoperative complete atrioventricular block were identified. They ranged in age from 4 months to 22 years and in weight from 4 to 60 kg and were evaluated from 1 month to 20 years postoperatively. Complete A-V block developed within 24 hours of operation in 28 of the 34 patients. A permanent pacemaker was implanted in 13 of the 28. Death occurred in 4 of these 13 patients and in 5 of the remaining 15 patients who did not have an artificial permanent pacemaker. Complete A-V block developed later than 1 day (2 days to 4 months) postoperatively in 6 of the 34 patients; all 6 of these patients survived, and only 3 required permanent pacemaker implantation. Intracardiac electrophysiologic studies were performed by 14 of the 34 patients. The site of complete block was above the His bundle in 5, within the His bundle in 2, and below the His bundle in 4; it was undetermined in 3. The results of intracardiac electrophysiologic studies are important in delineating the natural history of surgically induced complete A-V block and in the clinical management of this lesion. Permanent pacemaker implantation is indicated if complete A-V block persists longer than 2 weeks postoperatively and if the site of the block is within or below the bundle of His.


The fast-slow form of atrioventricular nodal reentrant tachycardia in children.

An unusual form of atrioventricular (A-V) nodal reentry is described as the underlying mechanism for incessant tachycardia in two children. During tachycardia a fast pathway was utilized for anterograde conduction and a slow pathway for retrograde conduction. This is the reverse of the usual form of A-V nodal reentrant tachycardia, in which the slow pathway is utilized for anterograde conduction and the fast pathway for retrograde conduction. One patient had a smooth ventriculoatrial (V-A) conduction curve demonstrating exclusive utilization of the slow pathway for retrograde conduction. The other had a discontinuous V-A conduction curve demonstrating failure of retrograde fast pathway conduction with resultant slow pathway conduction. In both cases the retrograde effective refractory period of the fast pathway was longer than that of the slow pathway, resulting in the establishment of this unusual reentry circuit. Both patients had a superior P axis with a P-R interval shorter than the R-P interval during tachycardia, features described in a significant number of children with incessant tachycardia. This unusual form of reentrant tachycardia can be suggested by its electrocardiographic pattern and is another mechanism for reentrant tachycardia not previously documented in children.