Complications of laryngectomy and neck dissection following planned preoperative radiotherapy.

One hundred sixty-nine patients with carcinoma involving the larynx treated with surgery, combined preoperative radiotherapy plus surgery, or failed curative radiotherapy with surgical salvage have been evaluated with respect to complications. Major complications occurred at approximately the same rate with all three modes of therapy. Major complications had generally a later onset and healed less rapidly in the preoperative radiotherapy group. Minor complications occurred more frequently in irradiated patients than in nonirradiated patients. When evaluating postoperative complications in irradiated patients the time interval must be extended beyond the immediate span because of delayed onset.


Papillary adenocarcinoma of the thyroid invading the upper air passages.

The clinical course of papillary adenocarcinoma of the thyroid is delayed but aggressive and lethal in an estimated 11-16% of the patients. Death results in the majority of patients from respiratory obstruction produced by a collar of tumor that has proliferated from residual or multicentric thyroid disease. Review of a large series of cases reveals an incidence of invasion of the aerodigestive tract of 1-6.5%. Six such cases are presented in which resection of the larynx, trachea and pharynx were performed along with total thyroidectomy with local control of the disease and prolonged survival. In five cases conservation surgery was done. Three patients had prior thyroid lobectomy with recurrence and invasion of the air passages 2-5 years later. Intraluminal thyroid carcinoma may be confused with a primary lesion of the larynx, trachea or hypopharynx.


Esthesioneuroblastoma: diagnosis and treatment.

Esthesioneuroblastoma is a nasal tumor which arises from cells of neural crest origin. It is a difficult tumor to diagnose clinically and histopathologically. First described in 1924, approximately 160 cases have been reported with over 125 of these in the last 15 years. This reflects an increased awareness of the tumor by physicians rather than an icreased incidence. In the past 17 years, 12 cases of esthesioneuroblastoma have been treated at the Department of Otolaryngology and Maxillofacial Surgery of the University of Virginia Medical Center. Reviewing these cases and the literature leads us to make the following recommendations for diagnosis and treatment: The diagnosis of esthesioneuroblastoma can be made by 1) the clinician who suspects it in any patient with a nasal mass causing unilateral obstruction; 2) the finding of plexiform intercellular fibrils by light microscopy (rosettes and pseudorosettes are not as common as reported); 3) the finding of secretory granules and neurites by electron microscopy of the highly undifferentiated tumors; and 4) formaldehyde-fume-induced fluorescence. Combined therapy with preoperative irradiation followed by craniofacial resection of the tumor to include the cribriform plate is recommended. This treatment should result in a five-year survival in excess of 50% of patients.


Anatomy and development of the cricoid: serial-section whole organ study of perinatal larynges.

Whole organ serial-section study contributes to our understanding of neonatal intubation injury by demonstrating the previously undescribed "V" configuration of the posterior cricoid lamina; this may be readily correlated with subarytenoid paramedian intubation injury. This technique also permits detailed study of an anomalous larynx and permits the precise identification of a "tracheal" anomaly as a cricoid malformation. The need for a fetal staging system is reemphasized.


Localization of adductor and abductor motor nerve fibers to the larynx.

Knowledge of the location of motor nerve fibers to the adductor and abductor muscles of the larynx may be useful in the diagnosis and treatment of innervation disorders in this organ. Anterograde degeneration and retrograde tracer anatomical techniques have demonstrated the central and peripheral positions of these two groups of motor nerve fibers in the cat. Traditional nerve fibers degeneration methods applied following intracranial transection of the vagus nerve rootlets indicated that: 1) Most of the fibers in the recurrent laryngeal nerve (RLN) are motor; 2) Almost all of these motor fibers leave the brain stem in the most rostral rootlet(s) of the vagus nerve; and 3) Motor fibers to the larynx form a discrete bundle within the trunk of the vagus nerve before forming the RLN. A tracer (horseradish peroxidase) of retrograde axoplasmic flow in motor neurons has been employed to demonstrate: 1) Dorsoventral division of the adductor and abductor neurons in the nucleus ambiguus; and 2) Diffuse arrangement of both adductor and abductor nerve fibers in the vagus nerve but collection of these fibers into abductor and adductor halves of the RLN prior to entering the larynx. These findings dispel theories of differential cord paralysis (Semon's law) based on a vulnerable position of abductor fibers at the periphery of the RLN. Furthermore, the diffuse arrangement of these fiber groups explains the usually mixed functional results obtained following reimplantation of the RLN into a laryngeal muscle.


Preservation of the laryngeal nerves during total thyroid lobectomy.

A technique of exposure and preservation of the recurrent laryngeal nerve at the very onset of thyroidectomy and preservation of the external branch of the superior laryngeal nerve at the close of the procedure is described, which is believed to afford maximum protection to these nerves during total thyroid lobectomy and isthmusectomy as well as total thyroidectomy. At the same time, preservation of the parathyroid glands is achieved. In 120 exposures and preservations of the recurrent laryngeal nerve there have been no instances of a single permanent paralysis of this nerve. In 111 total thyroid lobectomies in which the external branch of the superior laryngeal nerve was placed in jeopardy, only one patient had a slight bowing of the vocal cord with excellent voice function during a limited follow-up period.


Reinnervation of the unilaterally paralyzed larynx.

Because of early success with reinnervation of the abductor musculature of bilaterally paralyzed larynges, experimental work and ultimately surgery in human patients has been undertaken to endeavor to apply the same basic concept to reinnervation of the unilaterally paralyzed larynx. A nerve-muscle pedicle is obtained from the omohyoid muscle in a manner identical to that previously reported. The lower 50% of the thyroid ala is carefully removed outside the perichondrial envelope and the lateral fibers of the thyroarytenoideus muscle (major laryngeal adductor) is exposed. The previously repaired nerve-muscle pedicle is inserted into this muscle to complete the procedure. The procedure has been undertaken in nine cases to date where the degree of posterior glottic chink, usually because of a concomitant superior nerve paralysis, was felt to be too great to be adequately managed by Teflon injection. Some degree of spontaneous return of adduction was accomplished in all nine cases.


Management of the dying patient with head and neck cancer.

The management of a patient with head and neck cancer and the psychological effect on the patient and his or her family is a subject frequently avoided in scientific assemblies. Yet, it is a fact that many physicians silently look for better understanding in themselves to be better able to understand the possible responses in patients and their respective families so that confrontations between all parties may be more comfortable for all concerned. I have tried to verbalize in this presentation such processes that affect the patient, his family and the physician himself so that we, as physicians, may better manage those unpleasant situations associated with the care of a patient with incurable head and neck cancer.


Histopathological observations on the cochlear changes in otosclerosis.

Alterations in the dimensions of the basilar membrane and spiral ligament have been implicated in the pathogenesis of sensorineural hearing loss in otosclerosis. The histopathological findings in nineteen temporal bones with otosclerotic involvement of the cochlear endosteum are reviewed. Hyalinization and decrease in the width of the spiral ligament are the only consistent findings related to the otosclerotic focus in these temporal bones. The width of the basilar membrane is normal. The hair cell population and the stria vascularis are normal for the age group.


Recurrent laryngeal nerve histopathology in spastic dysphonia: a preliminary study.

Spastic dysphonia is a severe voice disorder ordinarily described as psychogenic. Organic-neurologic changes secondary to central or peripheral nervous system involvement have also been postulated and led recently to the surgical treatment of spastic dysphonia by unilateral section of the recurrent laryngeal nerve (RLN). This study reports the histologic findings from these resections of the RLN from patients with an average 9.5 years duration of spastic dysphonia. Thirty percent of the RLNs examined demonstrated significant abnormalities as compared to age-matched controls. Although no reactive changes were noted by light microscopy, groups of fibers which did not stain for myelin or axons were found in RLNs from patients with spastic dysphonia. A preliminary ultrastructural study of these areas in one RLN revealed sheets of unmyelinated axons. These findings suggest an organic basis for spastic dysphonia at least in some patients.


Temporary threshold shift following 24-hour noise exposure.

Nine men were exposed to 24 hours of continuous noise in a sound field. The noise was an octave band centered at 4 kHz at levels 80 and 85 dB. Hearing thresholds were measured monaurally at 11 test frequencies ranging from 250 to 10000 Hz before, during, and after exposure. Temporary threshold shift (TTS) reached maximum levels at 8 to 12 hours of exposure. Maximum TTS occurred at 4 and 6 kHz. Mean asymptomtic threshold shifts (ATS) resulting from the 80 dB exposure level were 9.3 dB for 4 kHz and 7.2 dB for 6 kHz. For the 85 dB noise level, these threshold shifts were 17.8 dB and 14.6 dB respectively. The increase in ATS with increase of noise level for these two frequencies could be fitted with a straight line having a slope of 1.6.


Transtympanic electrocochleography in patients with syphilis and hearing loss.

Transtympanic electrocochleography was carried out on 18 syphilitic patients (30 ears were tested) most of whom were suffering from the late onset congenital form of the disease. A diphasic action potential with a large negative summating potential on the descending limb was found in 77.7% of ears; the cochlear microphonic potential was always of small amplitude. While these findings are not pathognomonic of syphilis, they are characteristic and may be explained on pathological grounds.


Magnesium absorption in the caecum of rats related to volatile fatty acids production.

Rats were fed with a semi-synthetic diet with or without raw potato starch. (The level of minerals was the same in the two diets.) Because of its special structure raw potato starch was not attacked by rat enzymes. The rats fed on the raw potato starch diet showed increase in caecal weight. The increase in caecal volatile fatty acids (VFA) and decrease in pH were evidence of increased microbial fermentation from the presence of substrate in the caecum. There was also an increase in the arteriovenous difference in VFA and Mg in the caecum. Nutritional balance study was performed and confirmed the better Mg absorption in rats fed on the raw potato starch diet. The lower parts of the digestive tract seem to play an important role in Mg absorption and further studies on the relations between caecal volume, pH, VFA, microbial activity and Mg absorption are necessary.


Experimental animal model of subglottic stenosis.

An animal model of subglottic stenosis has been developed. The results of this pilot study show evidence to suggest that injury to the cricoid cartilage leading to perichondritis is the important factor in the development of subglottic stenosis.


Lingual thyroid: review, case reports, and therapeutic guidelines.

The literature on lingual thyroid is reviewed. The incidence is relatively rare and sex incidence is four or five to one in favor of females. The embryology and development of the thyroid gland is discussed and some evidence presented to suggest that the lateral thyroid primordia are not involved in the formation of functional thyroid tissue. The pathologic findings of lingual thyroid tissue are similar to that of cervical thyroid tissue, including goiter formation. Diagnostic measures include mirror examination, I-125 scan, and tomography. Thyroid function studies are helpful in evaluating the level of thyroid function. Treatment includes surgical removal, transplantation, I-131, and thyroid replacement. Since the first three methods usually require supplemental thyroid treatment afterward, it is believed that initial thyroid replacement is the treatment of choice since it is simple, safe, effective, and noninvasive. Four new cases are reported.


[Production of patulin in a liquid medium by moulds belonging to the genera: Aspergillus and Penicillium (author's transl)].

The toxinogenesis of 10 strains of Penicillium granulatum, 5 of P. expansum, 4 of Aspergillus terreus, 2 of A. clavatus, P. thomii, P. urticae, P. italicum and 1 of P. claviforme was tested at 26 degrees C in Czapek's enriched liquid medium (8 p. 1000 glucose + 2 p. 1000 yeast extract). 6 strains of P. granulatum, 5 of P. expansum, 1 of P claviforme and P. thomii produced patulin after 9 days of culture. Mycotoxin concentrations recovered was between 0.2 ppm and 3127 ppm. Highly toxinogenic strains are Penicillium granulatum; but patulin in silages was not associated with P. granulatum.


Bilateral first branchial cleft cysts: case report and literature review.

Instances of first branchial cleft anomalies are quite uncommon. A patient with a first branchial cleft cyst was seen and surgically treated at UCLA Hospital in 1972. Three years later he developed a similar lesion on the opposite side of his neck and this also was surgically excised. A review of the literature has revealed only one prior report of bilateral first branchial cleft anomalies. The embryogenesis, diagnosis, and surgical management of these lesions are discussed in this paper.


Metabolism of 19 nortestosterone-14C associated with oestradiol in mice and calves.

Metabolic study of 14C-19 Nortestosterone has been carried out in mice by macroscopic autoradiography and in calves by liquid scintillation counting. From the results, it is obvious that radioactivity is quickly eliminated mainly in urine and faeces. Ten weeks after administration, residual levels are very low.


Late recurrence of a frontal sinus cholesteatoma.

The longest recorded recurrence of a frontal sinus cholesteatoma with involvement of the orbit, frontal bone, and floor of the anterior cranial fossa is presented. Radical surgery is required and often craniotomy is necessary. Bony reconstruction of defects should not be undertaken until recurrence has not been present for at least a year. A review of the literature and a discussion of the origin of cholesteatomas is given.


[Saliva ammonia and urea in the sheep. Effects of alimentary nitrogen additives (author's transl)].

The salivary elimination of ammonia and urea was studied in 4 permanently salivary duct fistulated sheep. Sheep were fed either a regular diet or the same diet with addition of non protein nitrogen (NPN). Individual saliva ammonia levels vary from 34 to 71 microgram N/100 ml. After intra-ruminal dosing with urea (10 g) or ammonia (2 g), the values may rise up to 1000 microgram N/100 ml. Saliva ammonia and blood ammonia changes follow the same direction. Daily saliva urea variations are correlated with feeding behaviour. NPN administration increases saliva urea and blood urea; both concentration curves are parallel.


Comparison of the immune response in serum and bucco-pharyngeal secretions following immunization by different routes with a live hog cholera virus vaccine (Thiverval strain).

The influence of vaccination route on local and systemic immune response was studied with hog cholera virus vaccine. Kinetics of antibody synthesis in serum and bucco-pharyngeal secretion was observed. Results show that, whatever the vaccination route (intranasal or intramuscular) a good systemic and local immune response were induced and pigs resisted to a virulent challenge. However the highest local immune response was obtained by intranasal vaccination with large vaccine dosage (10(7) P.F.U./pig). After a virulent challenge performed by intranasal route, no clear anamnestic immune response was detected in bucco-pharyngeal secretions.


Effect of terramycin in balantidiosis of pigs.

In an industrial pig farm in Lubumashi, Zaïre, Balantidium coli produced severe clinical and fatal disease. Terramycin at a dose rate of 15 mg/kg body weight administered twice daily with concentrates gave clinical recovery in all the pigs treated. The complete parasitological recovery was obtained in 14 out of 20 animals. In the remaining 6 there was significant reduction in the number of B. coli. Keeping in view the large spectrum of activity of terramycin in various infections as well as B. coli, terramycin can be useful in the treatment of balantidiosis of pigs.


Effect of intravenous infusion of glucose and/or fructose on the composition of blood plasma and the clinical response of the calf.

Intravenous infusions of glucose (0.4 g/kg) or glucose (0.4 g/kg) + fructose (usually 1 g/kg) to calves were followed by various clinical reactions from absence of reaction up to death of a few calves. Fructosemia. After fructose + glucose infusion, the blood fructose concentration reached a level inferior to the highest value observed after only glucose infusion, except in the calves dead after the perfusion and in the newly-born calves (the initial fructose concentration was not nil). Glycaemia. In any case, fructose associated with glucose, did not eliminate the rebound of hypoglycaemia following usually a perfusion of glucose. In calves where the death occurred, the hypoglycaemia was specially marked.


Effect of irradiation (gamma rays) on the biology of Eimeria tenella oocysts.

Effect of gamma rays on the biology of the progeny of the irradiated Eimeria tenella oocysts was investigated. The parent inoculum of sporulated oocysts was exposed to 5 to 60 kR (gamma rays). These oocysts were fed to chicks. The oocysts voided by the chicks were collected and sporulated. The sporulation rate, pathogenicity, immunogenicity and reproduction potential of these oocysts--the progeny of the irradiated oocysts--were compared with those of the unirradiated oocysts. It was observed that increase of irradiation dose caused progressive decrease in the pathogenicity of the oocyst suspension. The oocysts exposed to 30 and 40 kR produced only mild infections whereas those exposed to 50 kR and above, were noninfective. No difference in pathogenicity, immunogenicity and reproduction potential of unirradiated oocysts and the oocysts progeny of the irradiated oocysts, was seen. It was concluded, therefore, that the effect of irradiation was limited to the inoculum exposed to it, and was not transmissible to the progeny of the irradiated oocysts.


[Allergic diagnosis of bovine brucellosis. 2. Use of the allergic test in infected herds (author's transl)].

Four hundred and eighty-one cows, in 27 herds, were injected intradermally with a brucella purified protein allergen in order to study the value of the skin test in the diagnosis of bovine brucellosis. The serology was done on the serum or plasma from 444 of these cows. Two hundred and nine cows showed an allergic reaction and 174 were positive in serology. One hundred and twenty-three were simultaneously positive to both tests, 52 were positive in serology but did not show any allergic reaction and 66 showed an allergic reaction but were negative in serology. In general, brucellosis was certainly detected at the herd level with this test. In newly-infected herds, the skin test gives a more complete and earlier result than serological tests. The use of the skin test is recommended as a supplemental test when unknown animals are to be introduced in non-infected herds, to improve the detection of contaminated animals in newly-infected herds and to solve the case of problem herds.


Myocardial protection by continuous coronary perfusion during aortic valve replacement.

The coronary perfusion system used at Oulu University Central Hospital is described and the importance of physiological coronary perfusion stressed. Our method of protecting the myocardium from ischemic injury during aortic valve replacement included the following: phasic constant-pressure coronary perfusion, maintenance of coronary perfusion pressure larger than or equal to 80 mmHg, maintenance of the heart in a beating, empty, oxygenated state, and the use of the largest possible coronary canula. Under these circumstances, autoregulation of the coronary vascular bed was maintained. When small coronary cannulae were used a significant pressure drop occured across the tubing system, especially at high flow rates. Flow measurements recorded by an on-line electromagnetic flowmeter proved reliable.


Results of treatment of carcioma of the cervix, 1964--1969. A report of 768 cases.

A series of 768 cases of primary invasive carcinoma of cervix was collected during the six years 1964--1969. This unselected material represents nearly one third of all new cases in Finland. The percentages of different stages (St) were: St I 49%, St. II 26%, St III 22% and St IV 3%. In comparison with earlier materials from our clinics an increase of St I was seen at the expense of St II. This probably results from increased use of the Papanicolau smear technique examinations. The incidence of St III and St IV was unchanged. Operative treatment combined usually with radiotherapy was used in 85% of the St I and in 38% of the St II cases. The remainder including those of St III--IV were treated by irradiation. The 5-year observed survival rates and relative survival rates (in brackets) were: St I 88% (92%), St II 51% (54%), St III 28% (31%), -t IV 0% and all stages together 63% (67%). A significant improvement in the 5-year results was found in the stages I and III when compared with the earlier material.


Significance of increased fibrin/fibrinogen degradation products and presence of fibrin monomers in pregnant women.

Fibrin/fibrinogen degradation products (FDP) and fibrin monomers might occur as a sign of "athological proteolysis" in complicated pregnancies such as toxaemia, hepatosis and placental insufficiency, eut also in otherwise clinically uncomplicated pregnancies. 18 pregnant women with increased proteolysis, but without any other clinical symptoms of complications were therefore investigated to determine the outcome of their pregnancies. The investigation showed that proteolysis with moderately increased serum FDP and fibrin monomers but without any other clinical signs of complications of pregnancy need not necessarily imply any risk to the mother or the foetus.


The role of different components of balanced anaesthesia in tolerance to endotracheal intubation.

In order to demonstrate the role of anaesthesia, analgesia and muscle paralysis in suppressing the responses to nociceptive stimuli during balanced anaesthesia, the effect of tolerance to endotracheal intubation was used as a model during recovery from a suxamethonium block after different combinations of thiopental and fentanyl. The induction groups were: Thiopental, 4, 6 or 8 mg/kg, and thiopental, 4 mg/kg, supplemented with fentanyt, either 1 microgram/kg or 2 microgram/kg. All 107 patients received suxamethonium 1.5 mg/kg, after precurarization and recovery of muscle strength had been recorded by measuring the twitch tension of thumb adduction caused by indirect supramaximal stimulation of the ulnar nerve. With 4 mg/kg thiopental 60% of the patients reacted against the tube before the suxamethonium block had subsided. Increasing the dose to 8 mg/kg or supplementing the 4 mg/kg thiopental with 1 microgram/kg fentanyl reduced the reactions to about 30%. After supplementing with 2 microgram/kg fentanyl, 90% of the patients tolerated the tube. Reactions against the tube, if any, usually occurred before the twitch tension had recovered by more than 30%. After 4 and 6 mg/kg thiopental, about 10% of the patients started reacting before there were signs of recovery of twitch tension. The results show that if bucking or coughing are used as an indication of inadequate muscle paralysis overcurarization can easily occur. Tolerance to the endotracheal tube is more rationally achieved by small doses of narcotic analgesics (e.g. fentanyl, 0.5 to 1 microgram/kg) than by increasing the dosage of thiopental. This simple model has been found useful in demonstrating the basic principles of balanced anaesthesia at the beginning of training in the specialty.


Renal blood flow and intrarenal oxygen tension in haemorrhagic hypotension.

The changes occurring in renal cortical and medullary tissue oxygen tensions and in renal total blood flow (RBF) were studied during haemorrhagic hypotension in six dogs. The flow was measured with an electromagnetic flowmeter, and tissue oxygen tension with IBC (Ineternational Biophysics Corporation, USA) oxygen electrodes. Haemorrhagic hypotension led to a considerable decrease in cortical tissue oxygen tension. The decrease in the medullary tissue oxygen tension was smaller, while the renal total flow decreased considerably during haemorrhage. The role of perfusion pressure alone in the redistribution of renal blood flow during haemorrhagic hypotension is discussed.


Data processing in pathology laboratories: the Phoenix system. 3. Further programs, staff training, and system performance.

This paper completes the description of the Phoenix system by outlining the additional programs necessary to maintain the data files in a satisfactory condition and prevent them from becoming overfilled. The standards of training required by the operating staff are discussed an assessment is made of the system performance in terms of cost/benefit. This was achieved by observing the time spent by staff during a period when the throughput of work was accurately measured. From these figures it is possible to estimate the needs of another laboratory. Finally, the continued extension of the computer facilities into other pathology disciplines and the provision of terminals in the hospital is described.


Comparison of maternal serum and urinary oestrogen determinations as indicators of fetal well-being.

Serum oestrogen concentration and urinary oestrogen excretion were measured in 134 women in the last trimester of pregnancy. An automated fluorimetric method was used for urinary oestrogens and a radioimmunoassay which measures both free and conjugated oestrogens, with the exception of sulphates, was employed for serum. Pregnancies were classified into a 'normal' or 'abnormal' group according to the clinical state of the baby at birth. The range of values for both serum and urinary oestrogens was wide at each stage of gestation and the mean values in the two groups were not significantly different. It was concluded that for a valid indication of fetal well-being serial determinations were essential, and that serum and urinary oestrogens were of comparable predictive value. Expressing the urinary results in terms of creatinine excretion did not improve their predictive value.


Determination of cortisol in human plasma by radioimmunoassay. Use of the 125I-labelled radioligand.

A radioimmunoassay for plasma cortisol featuring the gamma-emitting radioligand 125I-iodohistamine, coupled to cortisol-3-(O-carboxymethyl)-oxime, is described. The new procedure retains much of the specificity associated with the use of anti-cortisol-3-BSA sera with tritium-labelled radioligands, and has the further advantages that running costs are lower and there is a greater potential for automation. Cortisol values obtained by this procedure agree well with those obtained by a published specific radioimmunoassay using the tritiated cortisol radioligand. Specificity of the procedure was checked by comparing values obtained with and without thin-layer chromatography purication: correlation was excellent (r = 0.96). Satisfactory levels of sensitivity, precision, and accuracy were obtained.


National study of health and growth: standards of attained height, weight and triceps skinfold in English children 5 to 11 years old.

The National Study of Health and Growth (NSHG) was set up in 1972 to monitor growth in primary schoolchildren. Each year 8000 children in England (most parts except the south-east) and 2500 in Scotland are measured. Data from the first year have been used to obtain standards of height, weight and triceps skinfold for ages 5 to 11 inclusive, and ellipse contours of weight by height for each year of age. The distributions of weight and triceps skin fold were positively skew; logarithmic transformations led to satisfactory Normalized distributions. Centiles within each age group, calculated from the mean and standard deviation of the transformed variables, were closely similar to the observed centiles. Scottish children were lighter and shorter than English children in all age-sex groups. The heights and weights of English children in the NSHG were very similar to those published by Tanner, Whitehouse and Takaishi (1966). Triceps skinfold agreed closely with the data of Tanner and Whitehouse (1975) for the 50th and 97th centiles in boys, but our 3rd centile was well above its counterpart. Girls had higher skinfolds than girls in Tanner's data at the 3rd and 50th centiles. The triceps skinfolds of Scottish children were lower than those of English children throughout the age range and for all the centiles in both sexes. An example is given of the use of our ellipse contours of height and weight for surveillance of a population of children. Children's height is discussed in relation to variability over time and between different parts of the country.


A model for the prediction of energy balance and body weight.

A model for changes in energy balance and body weight is described which can be written as an iterative computer program. Medium and long-term changes in body weight resulting from random daily fluctuations in energy balance are quantitatively predicted. Body weight varies periodically about a mean value to to the extent of +/- 1 kg over a span of a few weeks. Long-term weight stabilization is the result of a dynamic equilibrium between energy intake and output which depends on activity and tissue metabolism. A lean : fat tissue deposition ratio defines the metabolic type of individual. This ration, which is constant for each individual, governs the proportions in which these tissues are both deposited and mobilized. In the model, the ratio has an important effect on the magnitude and composition of the weight gains resulting from over-eating. It is suggested that the differences in response which have been observed in over-eating experiments result from inter-individual differences in this ratio.


The distribution of body fat in relation to habitual activity.

42 young female subjects aged 19-24 years were selected to form 3 groups based on the estimated hours of physical activity taken each week. They represented 1. very active, 2. active, and 3. sedentary people. Their body fat and fat-free mass (FFM) were estimated from densitometry (corrected for the lung residual volume present during total immersion) and the distribution of subcutaneous fat mass (SFM) was examined by measuring skinfold thickness at 11 sites. The regression of body density on log sigma 4 skinfold was significantly different between the 3 groups for a given skinfold value of up to 40 mm, which corresponded to a higher density value for the very active subjects. The possibility that this observation might be explained by differences in the distribution of fat between subcutaneous and internal fat stores was examined, using empirical calculations of SFM. The proportion of fat situated subcutaneously was higher than previously reported (0.65), with a range of individual values (0.41-0.87), but no significant differences in fat distribution between the 3 groups. Group differences in the relationship between body density and log sigma 4 skinfolds might be explained by variation in the composition of the FFM which may result from differing levels of habitual physical activity. The implication of this possibility in estimating total body fat from density measurements are discussed.


Age of menarche in Oaxaca, Mexico, schoolgirls, with comparative data for other areas of Mexico.

Status quo menarcheal information was collected for a mixed urban colonia and rural sample of 315 girls in the Valley of Oaxaca, Mexico. Comparative status quo data for girls from four major urban centres in Mexico, and for a rural sample were also analysed. Median age at menarche (estimated by probit analysis) for Oaxaca girls was 14.27 +/- 0.20 years, about 0.5 year later than that for the rural sample from Tampico-Altamira, Tamaulipas (13.79 +/- 0.20 years), and approximately 1.5 years later than that for girls from the four urban centres in Mexico (12.55 +/- 0.10, 12.61 +/- 0.08, 12.75 +/- 0.10, 12.76 +/- 0.07 years). The timing of menarche in Oaxaca girls is similar to that for rural Mayans in Guatemala. Ages at menarche for urban Mexican girls are somewhat lower than those for girls of North-west European ancestry and of North American girls of European ancestry.


Anthropometric determination of body volume, body density and segmental volume in adult Indian women.

Body density, total body volume, leg volume and arm volume of 65 young Indian women 20-25 years were measured experimentally. In addition, a series of 61 anthropometric measurements were also taken on each subject. Correlations of leg volume with total body volume and body density were 0.91 and -0.73 respectively and of arm volume with total body volume and body density were 0.84 and -0.66 respectively. Hip girth alone showed a very high positive correlation (r = 0.94) with body volume and on selective stepwise multiple regression analysis, a combination of even four anthropometric measurements, namely, hip girth, lower thigh girth, ankle girth and shoulder diameter gave an extremely high positive multiple correlation coefficient (R = 0.98) with body volume. Selective stepwise multiple linear regression analysis was conducted also to estimate leg volume, arm volume and body density and stepwise regression equations up to 4th step for estimating each parameter are given.


A Monte Carlo test of weight as a critical factor in menarche, compared with bone age and measures of height, width, and sexual development.

The correlation coefficients for each of nine traits measured at menarche (bone age, pubic hair and breast stages, and five physical measurements) have been calculated. These have been compared with the corresponding correlation coefficients obtained by using a Monte Carlo technique, where the ages of menarche are randomly redistributed over the sample. The difference between the random and actual results are most pronounced for bone age, sitting height and the development of pubic hair and breasts, showing that these characteristics may indeed be critically related to menarche, while the same differences for weight, height, sitting height/height, and biacromial and bi-iliocristal diameters show that these latter are only moderately related to menarche. These results do not support the exclusivity of body weight as a critical factor in menarche (critical body weight hypothesis).


Assignment of the DIA1 locus to chromosome 22.

Human/rodent hybrid cell cultures were examined for the presence of DIA1 and other marker enzymes. Many of these hybrids were also analysed for human chromosomes. Complete concordance was found only with chromosome 22.


The frequency in Japanese of genetic variants of 22 proteins. III. Phosphoglucomutase-1, phosphoglucomutase-2, 6-phosphogluconate dehydrogenase, adenylate kinase, and adenosine deaminase.

Five enzyme systems, PGM1, PGM2, ADA, 6-PGD and AK, were examined by electrophoresis in over 4000 samples from Hiroshima and Nagasaki for the frequencies of common and rare variants. In the PGM1 system, the PGM2(1) allele and PGM7(1) allele were found in polymorphic proportions, In addition, five kinds of slow variants and three types of fast variants of PGM1 were detected. The PGM3(1)NGS1 allele was found in five individuals from Nagasaki, but was not observed in samples from Hiroshima. There were no variants of PGM2. Three kinds of fast variants of 6-PGD were detected. No variation in AK was observed. There were no rare variants of ADA. The 6-PGDc allele had a frequency of 0.084 in Hiroshima and 0.093 in Nagasaki, and the ADA2 allele frequencies of 0.025 in Hiroshima and 0.032 in Nagasaki.


Relative importance of the effect of family environment and heredity on obesity.

In a study using data from 254 families with 546 non-biologically related children and 10 337 families with 25 554 biologically related children an analysis of variance technique was used to evaluate the effect of family environment and heredity for children ages 4-11. Family environment accounted for 32% of the variation in obesity if all children were used and more than 39% of the variation in obesity using subgroups of children similar with respect to sex and age. The estimate of heritability was quite low, only 11%. These results suggest that family environment, which consists of such things as parental example and child rearing techniques, has an important effect on childhood obesity.


Absence of triradius d on the palms of normal people.

Absence of the digital triradius d is a very rare phenomenon, previously only reported in abnormal XXXXY males. During the past few years the anomaly has been found on the palms of three normal females, namely a young English woman and two sisters in the Nicobar Islands in the Indian Ocean. These cases are described and illustrations of the palmar dermatoglyphics presented. The occurrence of such a rare phenomenon in two sisters suggests that it is genetically determined.


Multivariate studies on the genetics of dermal ridges.

In order to investigate the inheritance of the series of ten ridgecounts, factor analysis was used to reduce the dimensionability to two. These two factors are inherited more or less independently and the heritability of the first is 0.97.


Selection at a multiallelic locus: Feller's transformation.

An explanation of Feller's result enabling the contours of mean viability at a triallelic locus to be rendered circular is offered, and a proof given which does not involve the direct use of homogeneous coordinates. In a subsequent paper we propose to use the fact that the same transformation also maps the contours of equal average effect for each gene into circles to establish further results.


F-statistics and analysis of gene diversity in subdivided populations.

It is show that Wright's F-statistics can be defined as ratios of gene diversities of heterozygosities rather than as the correlations of uniting gametes. This definition is applicable irrespective of the number of alleles involved or whether there is selection or not. The relationship between F-statistics and Nei's gene diversity analysis is discussed.


The correlation between estimates of familial frequencies.

For the determination of the mode of inheritance of a disease or disorder familial data is often used and is usually presented in frequency form. This data has usually been obtained from a single set of nuclear families and so the estimates of the frequencies in relatives of those affected are not independent of one another and this makes inference concerning the mode of inheritance difficult. The exact degree of the correlation between estimates is not easy to determine. In this paper expressions are derived for the asymptotic variances of estimates and for the covariances and correlations between the basic pairs of intrafamilial frequency estimates for families of a given structure, and the extension to families of different sizes and structures is outlined. It is shown that these correlations are not necessarily negligible and should be taken into consideration when testing hypotheses concerning the mode of inheritance.


Selection and mutation at an X-linked locus.

The most general mutation-selection model with discrete non-overlapping generations is formulated for a multiallelic X-linked locus. The difference equations for the gene frequencies, though dependent on the female genotypic proportions, are shown to have a simple form. If mating is random and the rates at which various unions produce females may be expressed as products of factors depending on the male and female parental genotypes, then the female zygotic frequencies are proved to be generalized Hardy-Weinberg proportions with respect to the male and female gametic frequencies. As the main application of the formalism, assuming only that mutation is much weaker than selection, the total frequencies of mutant alleles in males and females at equilibrium are related to the mutation rates and mean selection coefficients in the two sexes.


Bioassay of kinship in northwestern Europe.

Kinship of Barra (Outer Hebrides) is bioassayed as 0.0096 relative to northwestern Europe, in reasonable agreement with prediction of 0.008 relative to Britain. The exponential decline of kinship with distance is similar to Scandinavia. Kinship of larger populations is consistent with predictions from isolates. Kinship is largely due to local drift rather than Norse admixture, the estimate of which is obscured by drift and appears highly unreliable. Other populations in northwest Europe, including Iceland, Lewis and Orkney, give estimates of kinship which reflect drift and geography, but also do not provide reliable estimates of admixture. Bioassay of kinship from gene frequencies gives observations to be explained in terms of migration and drift, but contributes nothing to the question of whether polymorphism in the species is maintained by neutral mutation or selection. Although the latter is on various grounds more likely, no calculations based on gene frequency distribution can provide critical evidence.


Physical properties of mouse peripheral lymph node cells: changes during development.

Lymphocytes from axillary and brachial lymph nodes (LN) were fractionated on the basis of electrophoretic mobility (EPM) differences by means of free-flow electrophoresis and the fractions were analysed for size distribution with a "Coulter" counter. The data were combined to form a contour map (fingerprint) representative of the various LN cell types. LN fingerprint from adult mice exhibited a distinctly bimodal pattern with a low-mobility (LM) population corresponding to B cells and a high-mobility (HM) population (80%) corresponding to T cells. These 2 populations peaked 8 to 10 electrophoretic fractions apart. In marked contrast, LN fingerprint from neonatal mice regularly presented a single peak in the HM region which was by 3 electrophoretic fractions slower than in adult mice. These neonatal HM(T) cells possessed a larger modal volume (Coulter channel no 44) than that of adult HM(T) cells (Coulter channel no 37). Moreover, these early appearing LN-T cells were found to be endowed with the same EPM as OHC-resistant thymocytes which might suggest some connection between both populations.


[Sensitivity of Sherman's propionic acid bacilli to antibacterial preparations and vitamin B12 synthesis].

Sherman propionic acid bacilli were sensitive to benzylpenicillin, ampicillin, ceporin, tetracyclines, oleandomycin, oletetrin, tetraolean, sigmamycin, levomycetin and furadonine. Methicillin, oxacillin, monomycin, kanamycin, polymyxin and furazolidone had an insignificant effect on the above organism. The subbacteriostatic concentrations of methicillin, oxacillin, streptomycin, monomycin, kanamycin, neomycin, tetraolean, sigmamycin, polymyxin M and ristomycin increased the biosynthesis of vitamin B12 by Sherman propionic acid bacilli, while benzylpenicillin, ampicillin, tetracyclines, oleandomycin, oletetrin, levomycetin and furadonine in the subbacteriostatic concentrations inhibited this process.


[Inflammation and host resistance against tumours. II. -- Antagonism between bradykinin and a fraction isolated from the supernatant of cultured malignant cells on the spreading of macrophages (author's transl)].

When murine peritoneal macrophages are incubated in presence of 10(-6) to 10(-8) M of bradykinin, their spreading is increased. When macrophages are incubated in presence of a low molecular weight fraction of the supernatant from cultured Lewis carcinoma's cells (AP) their spreading is decreased. When macrophages are incuated first with bradykinin and later on with AP, no inhibition of spreading is observed. When macrophages are incubated first with AP and later on with bradykinin, the increase of spreading is not observed.


[Thymectomy and lymphocyte mediated cytotoxicity in the chicken (author's transl)].

Spleen and blood lymphocytes from non-thymectomized chicken immunized with sheep red blood cells are cytotoxic in vitro against 51Cr-labelled sheep red blood cells with specific lysis values in the order of 40%. Complete Freund's adjuvant is necessary to obtain a measurable degree of specific lysis. Spleen and blood from immunized thymectomized chicken yield little or no cytotoxic lymphocytes, with specific lysis values inferior to 15%, whatever the number of added lymphocytes.


[Combined antibiotic therapy following heart surgery].

In vitro efficacy of combinations of broad and narrow spectrum semi-synthetic penicillins, broad spectrum semi-synthetic penicillins with macrolides or aminoglycosides and tetracyclines with other biosynthetic antibiotics was studied with respect to the causative agents of surgical infections. Correlation between the sensitivity of the isolates and the antibiotics levels in the organism of the surgical patients was shown. The role of the etiological factor in the development of the post-operative complications in the patients after surgical operations on the heart was elucidated. The most rational schemes of the antibiotic use in therapy of the patients with purulent complications after operations on the open heart were developed and the maximum doses of different semi-synthetic penicillins for the treatment of patients with purulent processes after operations under conditions of artificial blood circulation were determined.


[Formation of new antibiotic, virenomycin, by a culture of Streptomyces virens sp. nev].

A culture of a new species Streptomyces virens was isolated from a soil sample. It produced an antibiotic designated as virenomycin. The antibiotic was mainly synthesized in the mycelium. Only insignificant amounts of it were found in the culture fluid. The optimal nutrient medium for production of virenomycin contained glycerol, soybean meal, ammonium sulphate, sodium chloride and calcium carbonate. Crystalline virenomycin had a comparatively low antitumor activity and narrow spectrum.


[Elevated CEA levels in a group of polyvinyl workers (author's transl)].

Carcinoembryonic antigen was assayed in plasma from a population of polyvinyl chloride workers from the same industry. We have found 56% of elevated levels in a group of workers as compared to 9.2% for a normal population including smokers and non-smokers.


[Physico-chemical characteristics of the new antitumor antibiotic virenomycin].

Virenomycin, a new crystalline antitumor antibiotic was isolated from the mycelium of Streptomyces virens. The antibiotic contained: C 64.87 per cent, H 5.66 per cent, methoxylic groups 9.5 per cent. The melting temperature was 255-260 degrees (dec.), [alpha]20D=-17 (c 0.142, chloroform). Virenomycin had a complex UV spectrum with lambdamax. 245 (677), 265 (453), 275 (542), 287 (507), 395 (222) nm. A chromofor fragment and carbohydrate (C7H14O5) were found in the methanolysis products. Virenomycin was close to antibiotic c B-21085 BY THe physico-chemical properties and differed from it in the character of the UV spectrum and the values of the specific absorption, as well as by the optic rotation in dimethyl sulphoxide and acetic acid.


Influence on certain amino acids on steps leading to DNA synthesis in concanavalin A-treated guinea-pig lymphocytes.

When guinea-pig lymph node cells were exposed to ConA in a culture medium lacking glutamine or cysteine, no DNA synthesis occurred. The addition of the missing acid to ConA-treated lymphocytes submitted to glutamine or cysteine starvation for 40 h allowed the synthesis of DNA to take place after a period of only 10-12 h. The synthesis of DNA is preceded by a rapid increase of 3H-uridine incorporation into RNA and of 3H-leucine incorporation into protein which occurred a few hours after addition of the missing amino acid. When cycloheximide was added to lymphocytes exposed to ConA in a glutamine or cysteine deprived medium, a relative enhancement of uridine incorporation was observed. No such effect was provoked by puromycin. These results suggest the possibility of a control system in lymphocytes similar to those described in microbial cells for amino acid control of RNA synthesis.


[Component composition and admixtures of related compounds in commercial preparations with an erythromycin base].

Chromatographic purity of erythromycin base preparations manufactured in the USSR with various technological procedures and those of 4 foreign firms was studied. All the preparations studied in addition to the main component of erythromycin A contained 5 to 7 per cent of erythromycin C and about 1.5 to 3.5 per cent of a non-identified component possessing a somewhat lower chromatographic mobility than erythromycin C. The admixture of 0.5--1 per cent of anhydroerythmycin was found in many erythromycin preparations. The preparations of some foreign firms contained also a number of additional substances. It was shown that the antimicrobial activity of anhydroerythromycin was 50-60 times lower than that of erythromycin. Direct correla;ion between the level of the antimicrobial activity of the market prepaetions of erythromycin and the level of its chemical purity was noted.


[Formation of peroxide compounds and their role in the inactivation of polyene antibiotics levorin and mycoheptin].

The kinetics of peroxide formation in the process of levorin and mycoheptin oxidation at a temperature of 57 degrees C was studied. It was shown that the peroxide compounds actively participated in the processes of levorin and mycoheptin inactivation as intermediate products of their transformation. Addition of the peroxides increased the rate of the antibiotic degradation even if there was no oxygen and subsequently decreased the periods of their storage. Conditions for the use of the iodometric method for determination of the peroxides in the poyenic compounds are discussed.


[Effect of mutagenic factors on the variability of cultures of Actinomyces griseus--preducer of the antibiotic grisin].

The study of the lethal and mutagenic effect of ethylenimine, nitrozoguanidine, nitrozomethylurea and nitrozoethylurea on Act. griseus Krainsky 15, producing grisin, an antibiotic widely used in agriculture as a stimulator of domestic animal growth showed that induction of mutants with increased antibiotic production levels was most favourable under the effect of ethylenimine. The above mutagens were highly active with respect to induction of morphological mutants. No clear correlation between the colony morphology and antibiotic production property was observed. However, it was noted that the dwarf colonies had a significantly decreased antibiotic activity.


[Cellular test system for studying the biological properties of preparations with L-asparaginase activity].

L-Asparaginase sensitivity and asparagin-deficiency of 5 tumor cell populations, i.e. mouse lymphoma L-1210, LI0-1, LTL, Berkitt lymphoma and human ovary cancer, line CaOv were studied. Radiometric estimation of 3H-thimidine incorporation into the cells of DNA served a criterion of cytotoxicity. "Krasnitin" (FDR) was used as L-asparaginase. The cells of leukemia L-1210, lymphosarcoma LIO-1 and line CaOv were asparagine-independent and non-sensitive to L-asparaginase. The cells of mouse lympholeukemia LTL and the cultures of Berkitt human lymphoma proved to be asparagin-dependent and highly sensitive to L-asparaginase. In concentration of 50 IU/ml the drug inhibited incorporation of 3H-thimidine in the cells of LTL and Berkitt lymphoma by 97-98 and 75-80 per cent respectively. Inhibition of 3H-thimidine incorporation in the cells of LTL and Berkitt lymphoma was more pronounced after incubation with the drug for 8 and 24 hours respectively. Two out of the 5 tumor cell populations were chosen as a result of the study. One of these 2 populations, i.e. the cells of Berkitt lymphoma was asparagin-dependent and highly sensitive to L-asparaginase, the other, i.e. the cells of line CaOv was asparagin-independent and resistant to the specific antitumor effect of the enzyme. The use of a system of these two cell lines provided estimation of the ratio of the specific cytostatic (antitumor activity) and non-specific cytostatic properties in the preparations with L-asparaginase activity.


[New species of Actinoplanes cyanea sp. nov. and its antagonistic properties].

An actinomycete stain 1569 isolated from a Siberian soil sample is described as a representative of a new species, designated as Actinoplanes cyaneus sp. nov. The actinomycete cell wall contains meso-diaminopimelic acid, arabinose, xylose and a non-identified analogue of diaminopimelic acid. The actinomycete forms spherical sporangia with mobile spores. The aerial mycelium is absent. The isolate produces a soluble blue pigment on synthetic media. The pygment investigation showed that it belonged to the group of celicomycin-actinorodine.


[Biological characteristics of culture 6734-21 and the conditions for isolating the antiviral antibiotic it produces].

An actinomyceteous strain No. 6734-21 was isolated from a soil sample of Central Asia and classified as Actinomyces bottropensis. It inhibited the development of the phage of the lysogenic culture of Micrococcus lysodeicticus 53-40 (No. 5) and the variolovaccine DNA-containing virus. Actinomyces bottropensis, strain No. 6734-21 produced an antiviral antibiotic classified as one belonging to the actinorodine group.


[Isolation and substrate specificity of neomycin (paromomycin)--phosphotransferase from Actinomyces fradiae, a producer of neomycin].

Neomycin (paromomycin) phosphotransferase was isolated from the mycelium and fermentation broth filtrates of Act. fradiae. The substance was partially purified by means of fractionation with ammonium sulphate followed by gel-filtration through Sefadex G-100. The extracellular and intracellular forms of the enzyme had the same substrate specificity and used only neomycin and paromomycin as substrates. The other aminoglycosides, including kanamycins A and B, lividomycin and ribostamycin were not used. The both forms had the same thermolability. The intracellular form of the enzyme was detected in the mycelium at the early stages of the organism development, while the extracellular form was found in detectable amounts in the culture medium only at the late stages of the actinomycete development. Therefore, the neomycin-producing organism, i.e. Act. fradiae had one enzyme which phosphorilated neomycin and paromomycin and was excreted from the mycellium into the culture medium during the fermentation process.


[Carbohydrate bond to the hydroxyaromatic amino acids in actinoidins A and B].

The method of exhaustive methylation with diasomethane was used as applied for actinoidines A and B and their glycosides for elucidation of the problem of connection between the carbohydrates and oxyaromatic fragments of the antibiotics followed by analysis of the acid hydrolyzates of the methoxy derivatives. It was found that the disaccarhide branch, i.e. 2-O-(L-acozaminyl)-D-glucose was connected in actinoidines A and B through the phenol group of the triaminotricarbonic fragment V, while the residue of D-mannose was connected through one of the phenol groups of the actinoidinic amino acid. The other two phenolic groups of the actinoidinic amino acid, as well as the phenolic groups of the N-end amino acids did not participate ion formation of the glycoside bonds. Actinosamine was probably connected through the alcohol group of the aglycone.


[Synthesis and properties of carminomycinone derivatives].

The possibility of chemical modification of carminomycinone-aglycone (II) of carminomicin, a side product in the antibiotic production was studied. The methyl group C-14 was functionilized by introducing the bromine atom and performing a number of exchange reactions with the bromine atom. It was found that under definite conditions (1. 1 equiv. Br2in dioxane, 20 degrees, 24 hours) carminomycinone (II) was subjected to selective bromination into the side acetyl group with formation of 14-bromcarminomycinone (III). On interaction with anhydrous potassium acetate 14-bromcarminomycinone (III) yield 14-acetoxycarminomycinone (IV). In its turn the latter compound (IV) easily hydrolized to 14-oxycarminomycinone (V) in treatment with aqueous alkali or acid. 14-oxycarminomycinone (V) was also prepared with a high yield (80 per cent) by direct alkaline hydrolysis of 14-bromcarminomycinone (III) in treatment with 0.1N solution of sodium carbonate in a mixture of dioxane and water. The structure of 14-substituted derivatives of carminomycinone was proved by analytical and spectral data and confirmed by their transformation. Thus, according to the data of mass-spectrometry 14-oxycarminomycinone (V) had a molecular weight of 400 c. u. In treatment with an excess of acetic anhydride in pyridine it formed a hexa-acetyl derivative, i.e. 4, 6, 7, 9, 11, 14-hexa-acetyl-14-oxycarminomycinone (VI). The aglycones (III-V) prepared by us may serve a starting material in chemical synthesis, as well as biosynthesis of semi-synthetic preparations of the carminomycin series.


Auxotrophic mutants in the selection of the rubomycin producer, Actinomyces coeruleorubidus.

A total of 351 auxotrophic mutants with different antibiotic activity, including several mutants with activity higher than that of the parent prototrophic strains were obtained under the effect of gamma-rays from 3 prototrophic strains of Act. coeruleorubidus. It was shown that most of the auxotrophic mutants did not preserve the property of biochemical insufficiency on passages on complete media. A mutant strain 1059-32 with activity 2 times higher than that of the prototrophic strain 2-39 and the parent auxotrophic culture was obtained from the revertants. Requirements in 29 growth factors including 17 amino acids, 4 nitrous bases, 8 vitamins and coenzymes were determined in 46 stable auxotrophic mutants isolated. The effect of the specific and non-specific growth factors on the culture antibiotic production was studied.


[Development of bruneomycin and rubomycin resistance in mouse lymphadenosis tumor cells and Staphyloccus when these preparations are used separately or together].

Two sublines of mouse lymphadenosis (L-5178) resistant to bruneomycin and rubomycin used alone, as well as a subline with induced resistance to the combination of these drugs were employed in the study. The studies showd that in separate use of rubomycin and bruneomycin the tumor cell resistance to the respective drug was evident at the 10th passage. After 30 passages neither bruneomycin nor rubomycin produced reliable inhibition of the tumor growth in the respective subline of lyphadenosis. When the antibiotics were used in combination, no significant decrease in sensitivity of the tumor cells to either of the drugs or their combination was observed. The experiment with Staph. aureus also showed that the rate of the resistance increase to the drug combination was lower than that to the drugs used alone. Therefore, it was shown that the combined use of bruneomycin and rubomycin provided a means for preventing to a significant extent of development of the resistance in lymphadenosis tumor cells and Staph. aureus. This may be considered as an indication for clinical trials of the above combination.


[Penetration of polyene antibiotics into human embryonic kidney tissue cell cultures].

Penetration of 14C-amphotericin AM-2 into the cells of the tissue culture of the human embryon kidneys was studied by means of light autoradiography after incubation with the antibiotic. Microscopic examination of the autographs of the cell slices revealed the presence of the radioactive label in the cytoplasm and nucleoplasm of the cells. The revealed intracellular localization of the label was evident of the antibiotic penetration into the cells.


Effects of growth conditions on the lipid composition of Bifidobacterium bifidum subsp. pennsylvanicum.

Lipid-phosphorus and lipid-galactose content and phospholipid and fatty acid composition of Bifidobacterium bifidum subsp. pennsylvanicum were examined under a wide variety of growth conditions. Cells from 29-C cultures contained less lipid-phosphorus than did cells from 37-C cultures, but their lipid-galactose content and phospholipid composition did not differ. At both temperatures, the growth phase influenced the lipid composition similarly. Phosphate, Mg2+ and K+ concentrations in the medium did neither significantly change the cellular lipid-phosphorus content nor the phospholipid composition. Only Mg2+-deficiency markedly reduced growth and lowered the content of cellular lipid-galactose. Omission of Tween 80 from the medium did not affect growth, but lowered the content of lipid-galactose and augmented those of lipid-phosphorus and diphosphatidylglycerol in the cell. Increased osmolarity and substitution of other Tween for Tween 80 caused the same changes in lipid composition, and besides inhibited growth. Omitting Tween 80 and replacing it by other Tweens dramatically reduced the percentage of unsaturated fatty acids. C12- and C14-fatty acids made up about 50% of total fatty acids in cells from Tween 20 cultures and 12-14% in cells from Tween 40 and Tween 60 cultures. The differences in the decline of unsaturated fatty acids and in the degree of replacement of these acids by C12- and C14-fatty acids may be related to the variations in growth in cultures with various Tweens by way of changes in the physical state of the membrane lipids.


Effects of growth conditions on the ion composition of Bifidobacterium bifidum subsp. pennsylvanicum.

The cation content of Bifidobacterium bifidum subsp. pennsylvanicum was markedly influenced by the washing procedure of the cells, by the growth phase and the temperature, and by the composition of the culture medium. Optimal retention of cations was achieved by washing with 0.25 M MgCl2 at 20C. The intracellular Na+ concentration rose during growth in normal medium to a constant value in the stationary phase, the K+ concentration rose in the exponential phase, but fell in the stationary phase. Cells from 29-C cultures contained more Na+ and less K+ in the stationary phase than did cells from 37-C cultures, but the total cation content was the same at 29 and 37C. Intracellular Na+ and K+ concentrations were dependent on the concentrations in the medium and on its osmolarity. The intracellular Na+/K+ ratio varied from 0.04 to 2.3. The concentrations of Na+,K+ and phosphate in the medium hardly affected growth. Mg2+-deficiency of the medium markedly decreased the concentration of Mg2+ within the cell; its concentration in the cell sap was greatly affected, but the amount of sedimentable, bound Mg2+ only slightly. The content of K+ within the cell decreased in Mg2+-deficient medium, but the concentration of Na+ did not. Omission of Tween 80 as well as its substitution by Tween 20 caused a decrease of intracellular K+. Cells from Tween 40 and Tween 60 cultures additionally contained markedly less Na+.


Killer-sensitive relationships in yeasts from natural habitats.

Yeast strains (157) belonging to at least 9 genera were isolated from natural habitats and screened for killer-sensitive relationships. Killer and sensitive characteristics were exhibited by 17 and 11% of the isolates, respectively. The strains belong to either one of two mutually exclusive killer-sensitive groups.


The occurrence of Pseudomonas spp. in surface water and in tap water as determined on citrate media.

Citrate-utilizing bacteria were counted in 289 samples of tap water derived from either surface water or ground water and in 32 samples of raw or partially treated surface water by using media containing ferric ammonium citrate as the carbon and energy source. The citrate-utilizing bacteria constituted only small minorities of the colony counts on Lab-Lemco agar at 25 C in both tap water and surface water. A total of 1071 isolates were obtained, of which 979 were able to utilize citrate. Characterization of the citrate-utilizing isolates revealed that 90% of these bacteria were arginine dihydrolase-positive and belonged to the genera Pseudomonas (84.3%) and Aeromonas (5.7%). The genus Pseudomonas was represented by fluorescent pseudomonads (66.3%), non-fluorescent glucose-utilizing pseudomonads (12.1%) and P. alcaligenes (5.9%). None of the isolates was identified as P. aeruginosa. It is suggested that the pseudomonads and the aeromonads are not adapted to low substrate concentrations. Enumeration of the citrate-utilizing bacteria in tap water therefore may give information on the efficiency of water treatment techniques as regards the substrate removal.


Ploidy, ascus formation and recombination in Torulaspora (Debaryomyces) hansenii.

X-ray inactivation studies on the type strain of Torulaspora hansenii carried out to determine ploidy, provided proof that the species has a haplontic life cycle, a fact which hitherto has only been presumed. Observations on the genesis of the ascus by light microscopy and transmission electron microscopy provide no evidence for, what some earlier workers in this field have presumed to be, heterogamous conjugation between a mother cell and its bud. They do, however, show that asci, bearing obliquely-attached, vestigal, bud-like appendages, arise from some cells to form single, non-abstricting, and frequently, recurving protuberances which enlarge. These could, conceivably, be responsible for the impression that abstricted buds are connected to the mother-cells by bent copulatory tubes. The formation during sporulation of elongated protuberances and the presence of a medial, electron-dense line within the electron-translucent layer of the walls of ascospores fixed with OsO4 preclude the possibility of using these features to differentiate between the genera Torulaspora and Debaryomyces. Furthermore, recombinant studies, which involved the use of auxotrophic mutants, indicated that during sporulation the fusion of independent cells accounted for only 0.03-0.6% of the asci formed. The conclusion was reached that somatogamous autogamy must be the main agency of diploidization and that the species is largely inbreeding.


Kloeckera apis st. nov.; the imperfect state of Hanseniaspora guilliermondii Pijper.

K. apiculata var. apis (nom. nud.) was found to be the imperfect state of H. guilliermondii Pijper by a high degree of DNA reassociation. The name is validated and raised to species rank, K. apis Lavie ex Smith, Simione and Meyer. K. apis and H. guilliermondii could be distinguished from H. uvarum and H. valbyensis by a low DNA reassociation and by growth at 37 C.


Ultrastructure of Hanseniaspora ascospores.

A comparative study of the ultrastructure in sections of the ascospores of six Hanseniaspora species showed three types of spores: (1) hat-shaped in H. valbyensis and H. guilliermondii, (2) spherical with an equatorial or subequatorial ledge, smooth or rough in H. occidentalis and H. uvarum, (3) spherical with warts in H. osmophila and H. vineae. Development and germination of the spores of Hanseniaspora guilliermondii is described in more detail.


Spontaneous mutation of polysaccharide production in Alcaligenes faecalis var. myxogenes 10C3.

Alcaligenes faecalis var. myxogenes 10C3, which produces large amounts of succinoglucan and small amounts of curdlan, was genetically unstable and mutated spontaneously to a form producing more curdland than succinoglucan when stocked on nutrient agar slants. The mutation occurred in the absence of cell division when the cells were incubated in saline and was enhanced by treatment with N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methane sulfonate, or ultraviolet light. Mutant strains were genetically stable and did not revert spontaneously for at least 1 year when stocked on nutrient agar slants.


Histidine production by a regulatory mutant of Streptomyces coelicolor.

Streptomyces coelicolor mutant RF-59, isolated as a revertant of a histidine auxotroph after mutagenic treatment with N-methylN'-nitro-N-nitrosoguanidine, was found to accumulate L-histidine. The mutant was sensitive to 2-thiazo-lealanine and L-2,4-diaminobutyric acid and partially sensitive to alpha-methylhistidine but resistant to 1,2,4-triazolealanine, indicating that repression of the histidine operon was modified in the mutant. Culture conditions were investigated, and optimal media for L-histidine production were developed, resulting in L-histidine accumulation of 2.1 to 3.5 g/liter.


Effect of growth substrate on thermal death of thermophilic bacteria.

The heat sensitivity of gram-negative, hydrocarbon-utilizing thermophilic bacteria was altered by a change in growth substrate. Thermophilic strains CC-6, BI-1, and LEH-1, grown with acetate or n-heptadecane as the carbon source, had a higher survival rate when incubated 5 degrees C above their maximum growth temperature than cells of the same organism after growth on glucose or glycerol. There was a correlation between the growth substrated, heat resistance, and the ratios of cellular n-hexadecanoic acid/branched hexadecanoic acid and n-heptadecanoic acid/branched heptadecanoic acid. The bacterial cells that were more heat resistant had ratios of straight-chain/branched-chain fatty acids above 1.0, whereas the heat-sensitive cells had ratios below 0.6.


Value of the K+ salt of carageenan as an agar substitute in routine bacteriological media.

The K+ salt of carageenan has no distinct advantages as a gelling agent, but it compared favorably with agar in most of the media tested. The difficulty involved in the preparation of blood plates and the results obtained with this medium prohibit its complete acceptance as a substitute for agar in routine solid media. However, it could be a suitable substitute for agar in all other routine bacteriological media.


Isolation and identification of pathogenic Naegleria from Florida lakes.

Five cases of primary amoebic meningoencephalitis associated with swimming in freshwater lakes have been recorded in Florida over the past 14 years. The present study demonstrated that pathogenic Naegleria, the causative agent, is relatively widespread. Twelve of 26 lakes sampled only once yielded the amoeba. Populations in three of five lakes sampled routinely reached levels of one amoeba per 25 ml of water tested during the hot summer months. Overwintering in freshwater lake bottom sediments was demonstrated, showing that thermal-discharge pollution of waters plays a miniscule, if any, role in the maintenance of pathogenic Naegleria in nature in this semitropical area.


Temporal study of the staphylococci and micrococci of normal infant skin.

Staphylococcus and Micrococcus populations were collected from the healthy skin of 10 infant subjects. Infants were sampled from 1 day to 32 weeks of age. Species were characterized by approximately 30 different morphological, physiological, and biochemical characters. Staphylococci were the predominant inhabitants of normal skin, whereas micrococci were found only occasionally in this environment. Staphylococcus epidermidid, S. haemolyticus, and S. hominis were the predominant and persistent staphylococci. These species constituted a high percentage of the total aerobic bacterial flora of infant skin. Micrococcus luteus and M. kristinae were the prevalent micrococci found on infant skin. Only limited correlation between Staphyloccus and Micrococcus populations and infant age or body area sampled was indicated by this study.


Isolation of the etiological agent of primary amoebic meningoencephalitis from artifically heated waters.

To determine whether artificial heating of water by power plant discharges facilitates proliferation of the pathogenic free-living amoebae that cause primary amoebic meningoencephalitis, water samples (250 ml) were taken from discharges within 3,000 feet (ca. 914.4 m) of power plants and were processed for amoeba culture. Pathogenic Naegleria fowleri grew out of water samples from two of five lakes and rivers in Florida and from one of eight man-made lakes in Texas. Pathogenic N. fowleri did not grow from water samples taken from cooling towers and control lakes, the latter of which had no associated power plants. The identification of N. fowleri was confirmed by pathogenicity in mice and by indirect immunofluorescence analyses, by using a specific antiserum.


Production of thermophilic actinomycete-hay aerosols for use in experimental hypersensitivity pneumonitis.

An investigation of the factors that influence the production of dense aerosols of Micropolyspora faeni and Thermoactinomyces vulgaris from hay cultures revealed that the density, freshness, and moisture content of the hay were important influences. Dry aerosols were produced under optimum conditions from hay cultures of either actinomycete and from sterile hay for inhalation challenges to unimmunized rabbits. Depressions in arterial oxygen tensions and hemolytic complement were monitored after such challenge. This investigation showed that hay cultures are capable of inciting a hypersensitivity-like reaction in the lungs, even in the absence of immunization to the organisms contained within the hay, but the entire hypersensitivity reaction cannot be attributed to M. faeni and T. vulgaris alone. Hay itself or other microbial or chemical components appear to have some heat-stable component that possibly contributes to the pathogenesis of the disease.


Influence of CH4 production by Methanobacterium ruminantium on the fermentation of glucose and lactate by Selenomonas ruminantium.

A method is described for increasing the production of H2 from glucose or lactate by Selenomonas ruminantium by sequential transfers in media containing pregrown Methanobacterium ruminantium. The methanogen uses the H2 formed by the selenomonad to reduce CO2 to CH4. Analysis of fermentation products from glucose showed that lactate was the major product formed from glucose by S. ruminantium alone. Several sequential transfers in the presence of the methanogen caused a marked decrease in lactate production, which was accompanied by an increase in acetate. When lactate was the fermentation substrate, S. ruminantium alone produced propionate, acetate, and CO2. Addition to the pregrown methanogen in the sequential transfer procedure caused a significant decrease in the production of propionate and an increase in acetate formed from lactate. These results are interpreted in terms of the influence of H2 utilization by the methanogen on the production of H2 versus lactate or propionate from reduced pyridine nucleotides by S. ruminantium.


Metabolism of dibenzothiophene by a Beijerinckia species.

Beijerinckia B8/36 when grown with succinate in the presence of dibenzothiophene, accumulated (+)-cis-1,2-dihydroxy-1,2-dihydrodibenzothiophene and dibenzothiophene-5-oxide in the culture medium. Each metabolite was isolated in crystalline form and characterized by a variety of chemical techniques, cis-Naphthalene dihydrodiol dehydrogenase, isolated from Pseudomonas putida, oxidized (+)-cis-1,2-dihydroxy-1,2-dihydrodibenzothiophene to a compound that was tentatively identified as 1,2-dihydroxydibenzothiophene. The same product was formed when crude cell extracts of the parent strain of Beijerinckia oxidized (+)-cis-1,2-dihydroxy-1,2-dihydrodibenzothiophene under anaerobic conditions. Further metabolism of 1,2-dihydroxydibenzothiophene by heat-treated cell extracts led to the formation of 4[2-(3-hydroxy)-thionaphthenyl]-2-oxo-3-butenoic acid. The latter compound was metabolized by crude cell extracts to 3-hydroxy-2-formylthionaphthene. Further degradation of this metabolite was not observed.


Patulin production by Byssochlamys spp. in fruit juices.

Ten strains of Byssochlamys fulva and three strains of B. nivea were cultured in a laboratory medium and tested for their ability to produce patulin. Two strains of B. fulva and all three strains of B. nivea produced the mycotoxin. One strain of B. fulva produced patulin in 11 of 13 processed fruit juices, with greatest amounts being produced in blueberry, red raspberry, and boysenberry juices, whereas no patulin was detected in prune or tomato juices. Grown in Concord grape juice at 18, 25, 30, and 38 degrees C, this strain produced the highest patulin concentration at 18 degrees C after 25 days, whereas biomass production was greatest at 25 and 30 degrees C after 20 and 25 days.


Microbial conversion of DL-2-amino-delta2-thiazoline-4-carboxylic acid to L-cysteine and L-cystine: screening of microorganisms and identification of products.

Microorganisms able to form L-cysteine from DL-2-amino-delta2-thiazoline-4-carboxylic acid (DL-ATC), a chemical intermediate in the synthesis of DL-cysteine, were isolated from soil samples and classified as Pseudomonas sp., Pseudomonas cohaerens, P. desmolytica, and P. ovalis. Thirteen L-cysteine-producing bacteria were also found in among 463 stock cultures representing 37 genera. These were Achromobacter delmarvae. Alcaligenes denitrificans, Bacillus brevis, Brevibacterium flavum, Enterobacter aerogenes, Erwinia carotovora, Escherichia coli, Micrococcus sodonensis, Myocoplana dimorpha, Sarcina lutea, Serratia marcescens, Flavobacterium acidoficum, and Pseudomonas ovalis. In the presence of intact cells of Pseudomonas sp. AJ 3854, 6.1 mg of L-cysteine and/or L-cystine per ml was produced from 10 mg of DL-ATC-3H2O per ml in a molar yield of 100%. This finding suggests that racemization and asymmetric hydrolysis occurred simultaneously in this incubation mixture. After the complete oxidation of cysteine to cystine by aeration in the presence of ferrous ion, crystalline cystine was isolated; its configuration was the L isomer based on data from X-ray diffraction, microbioassay, and optical rotation studies.


Antialgal substances for iodine-disinfected swimming pools.

Forty substances were tested for antialgal activity against Chlorella pyrenoidosa (Wis. 2005) and Phormidium inundatum (Wis. 1093). C. pyrenoidosa exhibited greater resistance to adverse effects of test compounds than did P. inundatum. Although several structurally unrelated compounds were inhibitory to both alga species, even at an initial concentration of 1.0 mg/liter, methylthio-s-triazines, ametryne, prometryne, and terbutryne, at 0.1 mg/liter, restricted growth to less than 25% of control (untreated) cultures. The methylthio-s-triazines were virtually chemically unreactive with free iodine. Inhibition of Staphylococcus aureus by free iodine dosages of 0.25, 0.5, 0.75, and 1.0 mg/liter was unaffected by the presence of 2.0 mg of terbutryne per liter.


Use of an organoleptic tracer (mercaptan) for testing for leaks in safety equipment.

A safe, rapid, sensitive, and economical method is presented for detecting leaks in gas-tight laboratory cabinets and other apparatus. This method, using no fluorocarbons and requiring no prior decontamination, is effective under negative, neutral, or positive chamber conditions.


Photochemotherapy for psoriasis.

Photochemotherapy for psoriasis combining orally administered methoxsalen and long-wave ultraviolet (UVA) light was used in 186 patients with severe psoriasis. Several different phototherapy units with various numbers of GE high-output black lights were used. Excellent (90% to 100% clear) and good (80% to 90% clear) results were obtained in 77% of the patients. The average UVA dose at clearing was between 7 and 8 joules/sq cm. The majority of patients required one weekly maintenance UVA dose of their last clearing dose (joules per square centimeter) to remain clear. Side effects and abnormal laboratory findings were minimal.


Necrobiosis lipoidica. An immunofluorescence study.

Biopsy specimens from 12 patients with necrobiosis lipoidica (diabeticorum) were studied by direct immunofluorescent microscopy. The immunoglobulin IgM was present in blood vessel walls of involved skin from six patients, and the third component of complement (C3) was present in the blood vessel walls of involved skin from seven patients. The immunoglobulin IgA was similarly observed in two patients. In addition, IgM, C3, or fibrinogen were observed at the dermal-epidermal junction of involved skin from seven patients. Necrobiotic areas invariably contained fibrinogen. These findings suggest that an immunecomplex vasculitis may be involved in the pathogenesis of necrobiosis lipoidica.


Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons.

In a sibship of nine, six members had hereditary medullary carcinoma of the thyroid. Two of those with thyroid neoplasms and two without had numerous small papular skin lesions. These proved to be a type of pilar tumor that we named fibrofolliculoma. Further investigation of the total kindred of 70 showed no other evidence of thyroid neoplasm. Skin tumors only appeared after the age of 25 years. Fifteen of 37 members older than the age of 25 years exhibited the typical skin lesions. Obviously, the original sibship was the repository of two dominantly inherited traits. The fibrofolliculoma is characterized by abnormal hair follicles with epithelial strands extending out from the infundibulum of the hair follicle into a hyperplastic mantle of specialized firbrous tissue. Associated skin lesions in this kindred were trichodiscomas and acrochordons.


Urinary ammonia and ammonia-producing microorganisms in infants with and without diaper dermatitis.

Free ammonia was determined in diaper squeezings from 26 infants with "ammoniacal dermatitis" and in 82 controls. No significant difference was found (402 ppm in diaper dermatitis compared to 465 in controls). The groups did not differ with regard to the incidence of organisms capable of splitting ammonia from urea. Experimental application of highly ammoniacal urine on intact infant and adult skin failed to provoke a dermatitis. Erythema could be induced only when ammoniacal urine was applied occlusively to scarified skin. These findings do not support the notion that ammonia is a primary factor in common diaper rash, but do not exclude a possible role for further irritation in an already existent condition.


Histologic, ultrastructural and histochemical studies of granuloma annulare.

We reviewed and reclassified the histology in 207 cases of granuloma annulare from our files. The most common pattern found was mononuclear infiltrative type (72%) in contrast to the palisading group (25%) and the epithelioid nodules (3%). Indeed, and entire spectrum from mononuclear infiltrates to the epithelioid sarcoidal types is seen. The electron microscopic findings include histiocytes with membrane activity, well-developed rough endoplasmic reticulum, large mitochondria, and numerous lysosomes. Pathcy damage of collagen and elastic fibers with the presence of vesicles, lysosomes, and cytoplasmic debris are demonstrated. The histochemical and ultrastructural studies localized acid phosphatase in the primary lysosomes and the routh endoplasmic membrane. The presence of fibrin deposition confirmed our previous immunofluorescence results.


Hyperkeratosis of nipple and areola.

Hyperkeratosis of the nipple and areola is a rare condition that may occur in association with various forms of ichthyosis or as the result of extension of an epidermal nevus. The nevoid form is extremely rare and appears most commonly in women in their second or third decade of life. It is characterized by verrucous thickening and brownish discoloration of both nipples and areolae. Thirteen cases of this type have been reported. We are describing two additional cases to bring the total to 15 instances.


On the cause of green hair.

Two silver-blond young women developed green, tinted hair from exposure to tap water containing excessive amounts of copper. Results from analyses of tracemetal content of hair as an indication of excessive ingestion, systemic toxicity, or metabolic derangement should be interpreted with caution in view of the demonstrated ease of external contamination from common sources.


Ichthyosiform dermatosis, keratitis, and deafness.

Two patients had an unusual ichthyosiform dermatosis, neurosensory deafness, and vascularizing keratitis. There was no family history of the disorder and no consanguinity. A squamous cell carcinoma of the tongue developed in one child. The association of such an eruption and deafness in previously reported cases is reviewed.


Vesicular lesions in adults due to echovirus 11 infections.

Echovirus 11 was recovered from vesicular lesions in two adults. Patient 1 had a severe disseminated vesicular exanthem. Patient 2 had a mild vesicular enanthem. Both were clinically suspected of having herpesvirus hominis lesions. Serologic studies indicate that these viruses were similar to each other and also to the "U" prime strain.


Newcastle survey of deaths in early childhood 1974/76, with special reference to sudden unexpected deaths. Working party for early childhood deaths in Newcastle.

All early childhood deaths within a total population of 297 000 were studied by prospective methods. 70 deaths of children aged 1 week to 5 years occurred during a 27-month period; 36 died at home, 29 suddenly and unexpectedly. An extensive standardized necropsy showed a disease process clearly or probably related to death in half the sudden unexpected deaths; in the remainder no recognized disease process was identified. The events preceding sudden unexpected death, and the child's environment, were investigated by a controlled parental interview. Symptoms of serious illness within 24 hours of death were identified in 9 of the 29 children, but in the majority symptoms were thought to have been absent or no more severe than those of the control children. Most children with major symptoms had been seen by a doctor within a few days of death. The two most striking social findings were that 16 of the 29 sudden unexpected deaths occurred at a weekend or bank holiday, and that 45% occurred in three adjacent city wards which contain only 13% of the under-five study population. The additional support and explanation provided during the home visits was greatly appreciated by the bereaved families.


Neurological complications of childhood leukaemia.

We have reviewed the neurological complications not directly attributable to leukaemic infiltration in a group of 438 children with leukaemia or lymphoma. 61 children had one or more complications due chiefly to bleeding, infection, or drug toxicity. Early death from intracranial haemorrhage occurred in 1% of children with lymphoblastic leukaemia and 7% of children with myeloblastic leukaemia. Measles and chicken pox were the most serious infective complications; one child remains severely retarded after presumed measles encephalitis, one child with chicken pox died, and a second remains disabled. 2 additional cases of measles encephalitis and one of progressive multifocal leucoencephalopathy are described. Drugs which caused neurotoxicity included vincristine, cytosine arabinoside, L-asparaginase, and phenothiazines, but most problems were caused by methotrexate. Methotrexate toxicity was more prevalent and more serious in children who had had previous central nervous system leukaemia. We conclude that viral infections and methotrexate pose the greatest neurological hazards to children with leukaemia.


The place of radioisotopic lung function studies in paediatrics.

An analysis of the clinical value of radioisotopic lung function (RLF) tests has been carried out on the results of studies in 123 children with heart or lung disease. The overall incidence of useful RLF tests was 53%, but in children between 6 months and 6 years the incidence was higher (69%). The incidence of useful RLF test was similar whatever the question to be answered, although rather higher when information about differential pulmonary blood flow was required. Lists of conditions are presented for which the incidence of useful RLF tests is likely to be high (72%), moderate (46%), and low (14%).


Aural temperature of the newborn infant.

The aural, oesophageal, and rectal temperatures of 10 term infants were monitored during changes in environmental temperature. The aural temperature in normal infants was found to be consistently higher than at any other site. It is suggested that this finding is due to the local heating effect of brain metabolism and shows the important contribution to total body heat production made by the brain. The depressed aural temperature found in an infant with hydranencephaly is cited as supporting evidence and may indicate the potential of aural temperature measurement in the investigation of cerebral metabolism.


Limitations of diagnostic value of the sweat test.

The sweat test, even if carried out by an experienced technician, sometimes lacks reproducibility owing presumably to physiological variations (patient's diet, temperature, and other factors at present unrecognized). Some patients are particularly prone to exhibit this variability and in them a single sweat test is almost valueless. The aldosterone status is believed to be responsible for a reciprocal relationship between sweat sodium and potassium concentrations: tests done on 8 patients show that a high sweat potassium is associated with a correspondingly lower sodium--a circumstance which must be borne in mind when interpreting a patient's sweat sodium. Of 30 patients presenting with a variety of symptoms compatible with a diagnosis of cystic fibrosis and with sweat sodium ranging from 50 to 75 mEq/1 (50-75 mmol/1), only 4 have proved to have cystic fibrosis after several years of observations; 13 have later been diagnosed as having asthma. The problem of the 'grey area' of uncertainty is aggravated by the heterozygous state which is also associated with a sweat sodium in this range. Repeated sweat tests are indicated if the sweat sodium lies within the 'grey area', and the diagnostic importance accorded the test should diminish as the sodium value approaches this area. The diagnosis of cystic fibrosis must remain in doubt unless there is strong supportive clinical evidence.


Gentamicin dosage in preterm and term neonates.

Pre-dose and peak serum levels of gentamicin were measured in 82 neonates (25-42 weeks' gestational age), and for comparison in 10 infants and 9 children. Dosage was 2-2.5 mg/kg twice daily for the neonates, and three times daily for infants and children. Neonates were subdivided according to gestational age and weight. Serum levels of gentamicin were very variable in all groups. Preterm neonates of low gestational age (25-30 weeks) showed a 66% incidence of pre-dose levels exceeding 1 microgram/ml, indicating possible accumulation. In the less premature neonates this incidence was still 20-29%. The level of 4 microgram/ml, the minimum concentration required to inhibit most of the bacteria sensitive to gentamicin, was reached in increasing numbers of neonates as their gestational age rose (from 30% in the 31- to 35-week gestational age group, to 60% at term); those small-for-gestational age had consistently lower levels. It is concluded that term neonates require dosage to be individualized and serum levels of the drug to be monitored.


Test meal for assessing intraluminal phase of absorption in childhood.

A test meal for assessing the intraluminal phase of absorption in childhood has been validated. 132 test meals were administered to 110 patients aged 2 weeks to 18 years (mean age 4.3 years). 10 children with suspected malabsorption, who were proven to be normal after extensive investigation, constituted the control group. The activities of pancreatic enzymes, and the total and individual bile salt concentrations are presented for the control subjects, and pancreatic enzyme levels in this group are compared with those seen in children with pancreatic insufficiency (cystic fibrosis). The test meal has been designed so that it can be administered to children with suspected gluten, cows' milk, or disaccharide intolerance. The control data provided a basis for the interpretation of information obtained from the application of such a test meal to the clinical investigation of children with suspected malabsorption.


Bladder emptying in neonates.

Ultrasound scanning was used to determine whether bladder emptying is complete when a newborn baby micturates. Residual urine was detected in 6 females and 9 males while one female emptied her bladder completely. The residual volume was estimated in 11 subjects and ranged from 3.9 to 13.9 ml. Incomplete bladder emptying cannot be the main factor in explaining the sex incidence of urinary tract infection in neonates.


Total intestinal aganglionosis. An autosomal recessive condition?

A case of total intestinal aganglionosis in a sib of a previously recorded patient is presented. The number of cases now reported is 9 in six families. The possibility that this condition is a distinct entity inherited in an autosomal recessive manner is discussed.


Lung function in children after repair of congenital diaphragmatic hernia.

Sixteen children who had had congenital diaphragmatic herniae repaired either in the neonatal period (11), or in early childhood (5), were reviewed at between 7 and 19 years of age. Only minor abnormalities were shown in their chest x-rays and in a variety of lung function tests. This suggests that the long-term prognosis in this condition is good.


Lipid droplet of sebaceous carcinoma. Electron microscopic study utilizing glycol methacrylate-glutaraldehyde-urea procedure.

The ultrastructure of lipid droplets of sebaceous carcinoma (Meibomian gland carcinoma) was studied by conventional methods and a lipid-retention procedure. Two different structures were clearly differentiated by the latter technique. The peripheral part of the lipid droplet was composed of whirled lamellar structures (myelin-like structures) while the interior appeared to be continuously homogenous. The lamellar structures were presumed to have come from smooth-surfaced endoplasmic reticulum, and to transform to the amorphous material-triglyceride-during maturation of the lipid droplets. A true limiting membrane or membranous shell around the lipid droplet was not deceted.


Paraproteinaemia in erythema elevatum diutinum.

Paraproteinaemia (IgGkappa) was observed in a 68 year-old patient with erythema elevatum diutinum. The association of this skin disease with paraproteinaemia as already reported by other authors may indicate a pathogenetic relationship.


Toxic effects of 8-methoxypsoralen on lymphocyte division.

Cultured human leucocytes have been used to examine the toxicity and phototoxicity of 8-methoxy psoralen (8-MOP). It has been shown that 8-MOP depresses cell turnover at concentrations of 10(-10) M or above. In black light (UVA), 8-MOP inhibition begins at concentrations of 10(-14) M. Patients treated for psoriasis with 8-MOP show concentrations of 10(-6)-10(-7) M. The inhibition of cell turnover observed with the present technique is at this concentration 40% for 8-MOP alone and 70% for 8-MOP and black light. These results can be related to the micronuclei and chromosome abnormalities seen in dividing cells.


Biochemical characterization of connective tissue macromolecules derived from cutaneous fibrosarcoma.

Tumor tissue of cutaneous fibrosarcoma was solubilized with salt, acetic acid and salt-extracted after pepsin treatment. Type III collagen was observed in neutral soluble collagen, 1.5 M and 2.4 M NaCl precipitated fractions after pepsin treatment. Type III collagen fraction precipitated with 1.5 M NaCl eluted in the alpha2 region when chromatographed on CM-cellulose without reduction, while the type III collagen partially purified with 1.5 M NaCl eluted between the position of alpha1(I) and beta12 after reduction and alkylation. Analysis of amino acid showed the presence of cysteine and the high content of hydroxyproline following CM-chromatography of 1.5 M NaCl precipitated type III collagen fraction. Acidic glycosaminoglycans were composed of hyaluronic acid, chondroitin sulfate, dermatan sulfate and heparan sulfate, and the first two were major components of fibrosarcoma.


Movement and persistence of aldicarb in certain soils.

When the rate of movement and the persistence of aldicarb in 4 types of soils were investigated in laboratory and field studies some leaching was detected in coarse sand; however, leaching was quite limited in clay loam and muck soils. These data indicated that aldicarb degraded quite rapidly in the selected soils and most of the applied radioactivity volatilized from these soil columns as 14CO2. The evolution of 14CO2 from the treated soil suggested severe degradation of the aldicarb molecule and consequently provided indirect evidence against the accumulation of significant quantities of toxic metabolites in the soil types evaluated. Under field conditions this toxicant appeared to have a half-life of about 7 days in loam soil.