[Characteristic features of ischaemic strokes in young adults (author's transl)]. Clinical symptoms, angiographic findings and risk factors were recorded according to a classification system in 28 women and 39 men who suffered an ischaemic cerebral stroke before the age of 40. This enabled correlations to be made within the group of young patients and the discovery--by comparison with a corresponding group of patients over 40--of statistically significant age-specific features of cerebro-vascular disease. Vascular lesions in young patients show a sex-specific distribution and a characteristic relationship to clinical symptoms. The prognosis is more favorable in young patients; risk factors which predispose to stroke and influence its further development are less frequent. It is, therefore, suggested that characteristic features of strokes in young adults can be partially explained by the fact that they are usually caused by single pathological alterations in otherwise healthy persons.


[Orally-administered taurine in therapy-resistant epilepsy (author's transl)]. The anticonvulsive action of taurine, was tested in 9 therapy in 9 therapy-resistant patients with a high incidence of seizures. Taurine was given orally (1.5-7.5 g daily) over a period of 4 to 16 weeks and, despite the high dosage, no appreciable side effects were observed. During this time seizures disappeared temporarily for about two weeks in 5 out of 9 cases. In one case the seizure frequency was transiently reduced by approximately 25%, whilst in the remaining 3 cases no effect of taurine on seizure frequency was observed. The reason for the rapid disappearance of the anticonvulsive action of taurine is not known.


[Comparative bioptic and electrophysiological investigations in polyneuropathies (author's transl)]. Comparative bioptic and electrophysiological investigations were performed in 30 cases of polyneuropathy of varying aetiology. Axonal and demyelinating neuropathies were distinguishable concordantly on the basis of both investigations. Maximum motor nerve conduction velocity (NCV) and compound potential (CP) were regularly examined in several nerves of each patient. Low (NCV) values (critical limit 25 m/sec) and long-standing high CP values were characteristic of demyelinating processes, whereas axonal neuropathies showed a slight to moderate decrease in NCV with early decrease in CP, often rapidly followed by loss of nerve excitability. Nonclassifiable stages and diseases are discussed. In biopsies, ultrastructural examination in particular, not only allowed the differentiation of primary axonal and primary demyelinating lesions and the respective neuropathic syndromes, but permitted moreover, further classification of these heterogenous groups of neuropathies. According to the sequence of lesions of the nerve fibre classes on the one hand, and to the nature of the primary lesion of the nerve fibres on the other hand, the following types of neuropathies were distinguished: in axonal neuropathies of the myelinated fibres, dystrophic and disintegrative forms were differentiated; axonal neuropathies of unmyelinated fibres correlated with sensory neuropathies. Demyelinating neuropathies were represented by hypertrophic, leucodystrophic and paraproteinaemic forms. The correlation of these types of neuropathies to the different clinical and aetiological forms of polyneuropathies is diagrammatically shown. The connection between the electrophysiological data and the basic nerve fibre alterations of the different neuropathies is discussed.


[Raynaud's phenomenon in the carpal tunnel syndrome (author's transl)]. The case is reported of a female patient with bilateral carpal tunnel syndrome, the diagnosis confirmed on surgical exploration, associated with Raynaud's phenomenon. A review is given of the relatively sparse literature on the subject, followed by a discussion of the pathogenetic relationship and therapy.


[Cyclic esotropia (alternate day squint) (author's transl)]. One case of the extremely rare conditioning of cyclic esotropia is reported following a short review of the literature and clinical features of this form of strabism. According to our experience the only effective treatment is operative correction on the day of the squint. It is not advisable to wait until the alternate day squint cycle breaks down and a permanent convergent squint develops.


Myospherulosis of the paranasal sinuses, nose and middle ear. A possible iatrogenic disease. Sixteen cases of myospherulosis, a disease of unknown etiology previously reported only from East Africa, were found in the St. Louis metropolitan area. Although the disease in Africa occurred in the peripheral deep and superficial soft tissues, in St. Louis it involved the paranasal sinuses, nose, and middle ear. All patients had previously had surgical procedures involving the regions subsequently shown to contain the structures of myospherulosis. A common denominator in these cases was the operative use of hemostatic packing containing petrolatum-based ointments and gauze. These ointments, usually containing an antibiotic, were nonsterile. This raised the possibility that the as yet unidentified structures of myospherulosis may be introduced via these petrolatum-based substances.


Prostatic carcinoma and needle aspiration biopsy. Carcinoma of the prostate can be diagnosed definitively only by biopsy. Needle aspiration biopsy obtained with a flexible 20- or 22-gauge needle may provide this diagnosis. This method has been utilized widely in Scandinavia but rarely in the United States. Fifty-one patients were so biopsied with concomitant punch biopsy. Of the 32 cases of carcinoma, there were abnormal cells in 27. There was no false-positive diagnosis. Although complications that occur with routine punch biopsy may be significant, there was no secondary to aspiration biopsy. The procedure should be used as a primary tool in the diagnosis of prostatic carcinoma.


Economic impact of a computer-based centralized organization in a clinical laboratory. The Department of Laboratory Medicine, University of Washington, has explored various management of organizational approaches over the past seven years. The Centralized Processing Area supported by a computerized information system has evolved from these efforts. Despite a decrease in U.W. hospital usage since 1968-69, laboratory volume has steadily increased. The cost of these services is shown in relation both to three successive management systems and to the impact of inflation on laboratory costs. Chemistry and hematology costs per procedure, including administration and computer costs, are compared with microbiology cost per procedure, where the management system was not used. There is growing acceptance of the intangible benefits of computerization in the laboratory. Economic benefits are often presumed but have not been proven. Favorable economic effects of the Centralized Processing Area together with the computerized information system are demonstrated.


An automatic leukocyte analyzer. Validity of its results. A statistical study was undertaken to evaluate the Corning Larc Leukocyte Analyzer by comparing its results with those of 20 medical technologists with regard to reproducibility and degree of agreement. A special effort was made to use statistically quantitative comparisons, large numbers of samples, and a large group of technologists. The results of the Larc are frequently more reproducible than those of technologists, especially for bands and segmented neutrophils. Other comparative studies show that the Larc reports clinically equivalent proportions of the different cell types normal and abnormal. This is true for case by cases as well as cumulative comparisons. All known cases of leukemia was detected by the Larc during the study, although the number of samples from leukemia patients was small (11 of 700).


Acquired factor X deficiency and amyloidosis. A selective acquired Factor X deficiency is an unusual occurrence. Six cases of an acquired Factor X deficiency in association with amyloidosis have been reported. This paper describes two additional cases, suggesting that this relationship may be more than coincidental. The mechanism by which amyloid may affect Factor X levels remains unknown, but suggestions include consumption, inactivation or decreased synthesis of Factor X. Factor II, VII, IX, and X concentrate transiently increased the Factor X level to normal in one of the patients. In an adult patient who has an isolated Factor X deficiency, amyloidosis should be actively sought.


Platelet-derived acid phosphatase isoenzyme in the serum in thrombocythemia. Acid phosphatase is present in platelets and is released during the clotting process. In thrombocythemic conditions, this may increase serum enzymatic activity. An illustrative case in which the determination of plasma enzymatic activity suggested a platelet origin of elevated serum levels, confirmed by isoenzyme fractionation on disk polyacrylamide gel electrophoresis is presented. It is concluded that in the presence of thrombocytosis a plasma sample is preferable to a serum sample for determination of acid phosphatase activity.


Instability of the oxy form of sickle hemoglobin and of methemoglobin in isopropanol. Oxygenated hemoglobin from water-lysed sickle erythrocytes preciptated more rapidly than hemoglobin from normal cells when exposed to 17% isopropanol in 0.1 M tris, pH 7.4, buffer (the isopropanol solubility test of Carrell and Kay). Precipitates became visible after approximately 20 minutes of incubation with SS, AS, or SC blood, while AC hemoglobin and normal adult A hemoglobin required 40-60 minutes of precipitate. Methemoglobin comprised less than 1.5% of the total hemoglobin present in all samples under study. Significant preciptation of methemoglobin did not occur unless methemoglobin levels were greater than 8%. Solubilization of the precipitate in 6M urea-barbital buffer and subsequent electrophoresis demonstrated that the insoluble material was sickle hemoglobin (Betas chain). The results of these experiments confirm previous findings indicating that even fully oxygenated sickle hemoglobin is unstable.


Ecology of 350 isolates of group F Streptococcus. The ecology of 350 strains of group F streptococci isolated from clinical material over a six-year period is described. The respiratory tract, particularly the throat, yielded the largest number of isolates. Wound swabs, mainly appendectomy, ranked second as a source of this organism, followed closely by the genitourinary tract. A significant proportion of strains was recovered from gastrointestinal sites. Dental abscess yielded several strains, often in pure culture, and the external auditory canal was identified as minor locale of the group F streptococcus. A few isolates were also obtained from blood, cerebrospinal fluid, and miscellaneous tissues.


Antimicrobial susceptibility patterns (antibiograms) as an aid in differentiating Citrobacter species. The hydrogen sulfide-negative Citrobacter group represents a taxonomic problem. Various investigators have proposed such designations as Padlewskia, Levinea, atypical Enterobacter cloacae, H2S-negative variants of Citrobacter, Citrobacter koseri and Citrobacter diversus. This problem has been investigated with emphasis on antibiograms as a means of discrimination. Clinical isolates fitting the designation Citrobacter were studied and, using the criteria of Ewing and Davis, separated into two groups: C. diversus (40 strains) or C. freundii (25 strains). Susceptibilities to ampicillin, carbenicillin, cefazolin, cephaloridine and cephalothin were determined by the agar-dilution method. C. diversus strains were resistant to 8 mug/ml ampicillin (97.5%) and 32 mug/ml carbenicillin (87.5%), and were susceptible to 8 mug/ml cephalosporins (greater than or equal to 90%). C. freundii strains were moderately susceptible to 8 mug/ml ampicillin (25%) and susceptible to 8 mug/ml carbenicillin (92%), and were resistant to 8 mug/ml cephalosporin (greater than or equal 92%). Using these data one can separate C. diversus from C. freundii with 90% accuracy.


Assessing the intellectural consequences of early intervention with high-risk infants. Infants at-risk for mental retardation were divided into a group that received early day-care intervention and a matched control group that did not. The purpose of the intervention was to prevent sociocultural retardation. Children were tested at 7 and 18 months on a simple two-choice visual-discrimination task and on the Bayley Scales of Infant Development to assess the impact of the intervention program on their development. Analyses revealed that the experimental group's performance was reliably superior to that of the control group on both measures and that experimental subjects scoring high on the Bayley Scales reached criterion on the discrimination task on fewer trials than low Bayley scorers. The relationship was particularly strong at 18 months.


Self-perception of intrinsic and extrinsic motivation: effects on institutionalized mentally retarded adolescents. Self-perception theory predicts that the introduction of extrinsic rewards for behavior that was intrinsically rewarding may decrease rather than enhance overall motivation. This hypothesis was tested on a group of institutionalized mentally retarded adolescents (34 boys, 10 girls). Intrinsic (high and low task interest) and extrinsic (high- and low-incentive objects) motivation were both manipulated as independent variables, and the dependent variable was task persistence during a free-play period. Results indicated that for a high intrinsically interesting task, the task persistence was greater under the external reward of low- rather than high-incentive value conditions. The opposite trend was revealed for the low intrinsically interesting task. The results provided some evidence that the greater the amount of the reward for an interesting activity, the greater the degree to which the intrinsic interest is undermined.


Deficient acquisition strategies: a proposed conceptual framework for analyzing severe language deficiency. A conceptual framework was proposed for analyzing aberrant or retarded language development. Recent developments in psycholinguistics have led to a view of language acquisition as an interactive process involving external interactions between child and environment and internal interactions between cognitive holdings and processes. The child's active participation in these interactions is conceptualized as a system of language-acquisition strategies. These consist of both information-gathering strategies and information-processing strategies and are distinguished from the adult speaker's facilitation strategies. We suggest that aberrant or retarded language development may be viewed in terms of specific process deficits in one or more of these strategy systems. In the present article three preverbal information-gathering strategies identified as selective listening, establishment of joint reference, and feedback mechanisms were described. Suggestions for future research and implications for intervention were discussed.


Facilitative effects of coin displacement on teaching coin summation to mentally retarded adolescents. Two methods of teaching coin summation to retarded adolescents were compared: one method involved a coin-displacement procedure, the other did not. Displacement was designed to compensate for retarded persons' attention and retention deficits. A pretest-posttest matched-groups design as well as a multiple baseline across coin-counting responses were used. Fourteen retarded subjects were assigned to either displacement or nondisplacement conditions. Subjects in both groups were first taught to count a single coin and then sum that coin in combination with coins previously taught. Both groups used the same finger-counting procedure; however, subjects in the displacement condition were also required to move each coin aside systematically after it was counted. The training methods were modeling, modeling with subject imitation, and independent counting by the subject. Both groups improved from pre- to posttest; however, the displacement group performance was significantly better. Skill maintenance for both groups was evident on follow-up. Displacement subjects required fewer trials and less time to complete training. Coin displacement may compensate for attention and retention deficits of retarded persons.


Evaluation of entertainment materials for severely retarded persons. Research with retarded and nonretarded populations suggest that toys can be an important part of group-care programs. Yet in a review of the literature. Wheman (1976) showed that there was a paucity of empirical data on effective toy utilization with retarded populations. In this study time-sampling measurements were made of the free-play behavior of 11 severely retarded females with 20 different toys and comparison items. Data analysis revealed that (a) the subjects had strong preferences among toys; (b) there was a low, statistically nonsignificant, correlation between toy preference and price; and (c) professional staff were unable to make accurate predictions of toy preference. Subjects were idle 65 percent of the time when only the 10 less popular toys were available, but only 25% of the time when only the 10 more popular toys were available. We concluded that (a) the behavior of retarded individuals is strongly influenced by the particular toys available to them, (b) empirical data are necessary to make maximally effective and economical use of entertainment materials, and (c) the current lack of such data for retarded population makes this an important area for future research.


Mothers' and graduate trainees' judgements of children: some effects of labeling. Graduate students in a clinical practicum in mental retardation and mothers randomly chosen from a university community were asked to rate retarded and nonretarded children on characteristics reflecting social competence and interpersonal attractiveness and also on a social distance scale. The children rated were viewed on videotape in free-play interactions with their mothers. Each retarded child was shown once as an unlabeled child and once as a child labeled retarded. Mothers rated the retarded children as different from the nonretarded children on six of nine measures, regardless of label. When the retarded children were labeled, they were rated by mothers as significantly higher on items related to attractiveness than when they were unlabeled. Graduate student trainees' ratings did not discriminate between retarded children as a function of labeling, with one exception: like mothers, trainees rated retarded children as more likable when labeled. However, both observer groups placed retarded children, regardless of status, significantly farther from themselves on the social distance scale than they placed nonretarded children. The results were interpreted within the theoretical frameworks of Zigler (1971) and Mercer (1973).


Effects of music-listening contingencies on arithmetic performance and music preference of EMR children. A five-phase experiment was designed to investigate (a) whether contingent music-listening would act as a reinforcer to increase arithmetic performance of EMR children and (b) whether this contingent reinforcement would affect preference for that reinforcer. During the three baseline (no reinforcement) phases, subjects returned to their classrooms at the end of the arithmetic work period. During the two treatment phases, experimental subjects meeting criterion were permitted to remain and listen to either rock (high preference) or music classics (low preference). Statistical analyses revealed significant differences between the no-reinforcement and contingent-reinforcement conditions and between the control and four experiment groups during the contingent reinforcement phases. No differential effect between the more or less preferred contingencies was found. Analyses of the music-selection data indicated that the contingencies did not influence music preference.


Comparison of three training procedures for teaching social responses to developmentally disabled adults. Three developmentally disabled adults were taught three peer interactive responses--verbailization, recreation, and cooperation--by three training procedures: (a) modeling, (b) instruction and feedback, and (c) modeling, instructions, and feedback. All three training procedures increased all three responses, but the most effective procedure was modeling, instructions, and feedback. In the two modeling conditions, videotapes of nonretarded adults were used, demonstrating the feasibility of this method for teaching retarded persons.


Effects of preferred stimuli on the free recall of moderately and severely mentally retarded children. The effects of two types of stimuli, preferred and nonpreferred, on the free recall and clustering of 16 moderately and severely retarded public-school children were investigated. An empirical determination was made as to whether to classify a particular conceptual category of stimuli as preferred or nonpreferred. All subjects were presented with 18 objects from 6 conceptual categories in blocked condition. Both the preferred and nonpreferred stimuli were given to each subject in a counterbalanced order using a repeated measures design. Our major finding was that the use of preferred stimuli had a significant facilitating effect on recall but not clustering.


Note on the interpretation of interactions in comparative research. In comparative research it is often the case that attention centers around the existence of an interaction between subject population and an experimental manipulation. Several recent investigators have discussed problems in the interpretation of such interactions. The present paper concerns one particular conceptual difficulty that, although common in research of this type, has received little attention. It was pointed out that dependent variables that are only ordinally related to the construct for which they are a measure are subject to transformations that may create or eliminate statistical interactions.


Serum unconjugated estriol levels in the third trimester and their relationship to gestational age. II. The purpose of this study was to further validate a preliminary report concerning the clinical usefulness of serum unconjugated estriols as a marker of gestational age. Serial estriol values from 50 women with uncertain dates were plotted on semilogarithmic graphs and the gestational age predicted from the timing of the abrupt surge in estriol values which normally occurs between 35 and 36 weeks. The gestational age at birth, as determined by careful neonatal examination, agreed with the age predicted by the estriol surge within +/- 1 week.


The incompetent cervix and accelerated fetal lung maturation. The incompetent cervix is an infrequent but identifiable cause of late midtrimester pregnancy loss. The early diagnosis and surgical treatment of these patients have resulted in successful outcomes in 70 to 80 per cent of patients treated. However, this closure of the cervix may be only partially successful, in that the pregnancy may continue beyond the age of fetal viability, but the fetus may be born prematurely. There are no reports in the literature of the neonatal respiratory status of these infants delivered between 24 and 33 weeks of gestation. Nineteen preterm infants of less than 3-4 weeks' gestation were born to mothers with an incompetent cervix. The incidence of the respiratory distress syndrome was significantly less in infants of mothers with an incompetent cervix than in control infants of similar gestation (p less than 0.001). The incomplete cervix appears to be related to maternal or fetal conditions which result in accelerated fetal lung maturation.


Management and outcome of class A diabetes mellitus. Patients who have a normal fasting serum glucose (FSG) and an abnormal glucose tolerance test, and who require little dietary regulation, have been designated as Class A diabetics by White. During the period 1970 through 1972, 261 Class A women were delivered at Los Angeles County (LAC) Women's Hospital. These patients were managed by a uniform protocol which included dietary supervision and continued surveillance for the onset of overt diabetes. Elective intervention prior to 40 weeks' gestation was to be avoided. Twenty-five per cent of the Class A patients--those who had had a previous stillbirth or who developed pre-clampsia--were considered at greater risk for perinatal death and were managed as if they had overt diabetes. The perinatal death rate for the entire Class A group was 19/1,000 as compared to 32/1,000 in the general population. Five perinatal deaths occurred, three associated with congenital malformations. There were no unexplained stillbirths or deaths due to trauma or iatrogenic prematurity. Our data thus indicate that as long as the FSG remains normal, an unexplained intrauterine death is a rare event. Twenty-five per cent of the infants did experience some morbidity.


Human amnion metabolism. I. In vitro maintenance. The energy stores of human term amnion include glycogen (2.2 +/- 0.3 mumoles of glucose per gram, mean +/- S.E.) and ATP (0.13 +/- 0.2 MM.). Histologic structure and biochemical functions were preserved during incubations of amnion for 120 minutes at 37 degrees C. in a defined medium simulating amniotic fluid; glycogen concentrations were maintained at control values, and the concentration of ATP usually remained at 85 to 100 per cent of control values. Glucose utilization during the first 60 minutes of incubation was linear at a rate of 70.0 +/- 3.0 nmoles per minute per gram of tissue. It is concluded that amnion is a highly metabolically active tissue that can be maintained in a viable state in a suitable medium.


Human amnion metabolism. II. Incorporation of fatty acids into tissue phospholipids in vitro. The rate of incorporation of 3H-arachidonic acid and 14C-palmitic acid into 15 term amniotic membranes was studied during incubation of tissues in an artificial amniotic fluid medium. Phospholipids were extracted from the amnions, separated by thin-layer chromatography, and both the radioactivity and the phosphorus associated with each phospholipid species were determined. The distribution of amnion phospholipids was: lecithin, 47 per cent; phosphatidyl ethanolamine, 30 per cent; sphingomyelin, 7 per cent; phosphatidyl inositol, 5 per cent; lysolecithin, 4 per cent; and other phospholipids, 6 per cent. During incubation, the specific activities of the phospholipids became maximal after 2 hours and remained constant for at least the next 2 hours. Arachidonic acid was incorporated mainly into lecithin (53 per cent) and phosphatidyl ethanolamine (27 per cent) whereas palmitic acid was incorporated mainly into lecithin (70 per cent). Incorporation of fatty acids was 33 per cent higher in amnions obtained after vaginal delivery than in those obtained before labor. From the known fatty acid composition of amnion phospholipids, it is concluded that there is a high rate of turnover of arachidonic acid relative to palmitic acid in lecithin.


Intra-amniotic injection of thyroxine (T4Y to a human fetus. Evidence for conversion of T4 to reverse T3. 131I (150 mCi) was inadvertently given to a woman during week 10 to 11 of her gestation. When referred, fetal size was estimated at 31 to 32 weeks' gestation. Because of the potential risk of fetal hypothyroidism, an amniocentesis, with an injection of 500 mug of thyroxine, was performed weekly from week 33 until delivery. T4, T3, thyrodi-stimulating hormone (TSH), and rT3 were measured in amniotic fluid samples obtained at 33, 36, and 37 weeks. Maternal serum T4 was measured on the day of delivery. T4, T3, and TSH concentrations were measured in cord blood and during the neonatal period. The concentration of T4 in amniotic fluid (AF) was within the normal range at 32 weeks (prior to thyroxine); AF T3 and TSH were not detectable. The concentration of AF rT3 at 32 weeks also was normal (160 ng. per deciliter) and increased markedly after beginning intra-amniotic T4 injections; AF T4 increased modestly, but the AF T3 level remained unmeasurable. The concentration of T4 in cord serum obtained within 24 hours of the last amniotic fluid thyroxine injection, was in the hyperthyroid range and the TSH level was low. The cord serum T3 level was at the upper range of normal. The infant's serum T4 and T3 both increased during the first 24 hours. The male infant developed normally and serum T4 and TSH concentrations were normal at 4 months of age. The data indicate: (1) that T4 injected into AF is absorbed by the human fetus, (2) that AF rT3 concentration increases markedly after the AF T4 injection, whereas AF T3 levels do not increase, and (3) that the neonatal TSH surge is not entirely suppressed by hyperthyroid levels of cord serum T4.


Thermodilution measurement of human umbilical blood flow at delivery. A local thermal dilution technique was used to estimate blood flow in the human umbilical vein during the first minute after delivery of the neonate. Estimates of flow were attempted at 101 deliveries and thermal dilution curves obtained at 52. The mean estimation of all flows recorded up to 20 seconds after delivery was 171 ml. per minute reducing to 58 ml. per minute between 40 and 60 seconds.


Embryotoxicity of bilirubin.

Embryotoxicity of bilirubin. Intraperitoneal injection of bilirubin in a dosage of 25 mg. per kilogram during the days nine to 15 of gestation in bile duct-ligated heterozygous Gunn rats was embryotoxic. Bile duct ligation per se had no gross observable effects on fetal development. Infertility is found in homozygous female Gunn rats that have unconjugated plasma bilirubin concentrations comparable to those achieved in this study (approximately 6.0 mg. per deciliter).


Glucose and oxygen metabolism in normally oxygenated and spontaneously hypoxemic fetal lambs. Whole blood glucose and oxygen concentration were measured in chronically catheterized fetal lambs, some of whom had implanted common umbilical artery flow transducers. Ten of the fetuses were well oxygenated (femoral arterial PaO2 less than 18 torr) and 13 fetuses had evidence of chronic hypoxemia (femoral arterial PaO2 less than 18 torr). The mean glucose uptake (54.0 +/- 7.6 S.E.M. mM. per kilogram per day), umbilical blood flow (230 +/- 13 S.E.M. ml. per kilogram per minute), and glucose/oxygen ratio (0.503) were the same in both fetal groups. The oxygenated fetuses had higher glucose levels at ang given maternal glucose concentration than the hypoxemic animals (p less than 0.001y and showed a correlation between glucose again across the placental circulation and the transplacental driving force for glucose (p less than 0.002). The hypoxemic fetuses, who had a higher per kilogram oxygen consumption than the oxygenated fetuses (p less than 0.05), showed no correlation between the amount of glucose taken up and the transplacental glucose concentration gradient.


Carcinoma of vagina 10 or more years following pelvic irradiation therapy. Gynecologic cancer records of 4,238 patients treated between 1956 and 1974 were reviewed. Sixteen patients developed noeplasia in the cervix or vagina 10 or more years following pelvic irradiation. Three patients had squamous carcinoma in situ; the other 13 patients had invasive squamous cancer involving the upper vagina. Only 1.26 per cent of invasive carcinoma of the cervix treated by radiation therapy from 1956 to 1966 presented with a late or recurrent or new primary tumor involving the vagina or cervix 10 or more years after primary treatment. The authors conclude that the risk of developing radiation-induced carcinoma in the upper vagina or cervix following pelvic irradiation is low. Follow-up Pap smears are indicated for all patients treated for cervical or vaginal malignancies by radiation therapy in order to detect vaginal neoplasia as well as recurrent carcinoma of the cervix.


Increased incidence of postoperative localized osteitis in mandibular third molar surgery associated with patients using oral contraceptives. Current literature has noted the various side effects of oral contraceptives. Oral surgeons have recently encountered an increased incidence of postoperative localized osteitis occurring with removal of manidibular third molars. This article documents the occurrence of this phenomenon among 105 women participating in a recent study at the Clinical Center of the National Institutes of Health.


Implantation of pure crystalline pellets of estradiol for conception control. Estradiol pellet implantation for contraception offers another alternative in conception control. The occurrence of only two pregnancies in 1,668 cycles (Pearl index: 1,42) reflects its efficacy. The advantages over oral contraceptives are: (1) absence of gastrointestinal symptoms, (2) minimal untoward effects, (3) no patient failure, and (4) convenience. Progressive stepdown in dose reduces the total amount of steroid used in long-term contraception. Contraceptive effect may not occur during the first month of implantation; adequate precaution should be taken. Because of the efficacy, minimal untoward side effects, and excellent patient acceptability, this regimen may be considered for contraception in developing countries and when other modalities are contraindicated.


Cold pressor test in women: effect on vaginal blood flow. Vaginal blood flow changes in women were evaluated qualitatively by heat-flow discs mounted on cooled vaginal probe. Statistically significant increases in vaginal blood flow, systolic blood pressure, and pulse rate were found in seven normal subjects during a 4 minute immersion of one hand in ice water.


Coagulopathy with midtrimester induced abortion: association with hyperosmolar urea administration. Coagulation changes, usually subclinical, have been reported in association with the induction of midtrimester abortion by the administration of intra-amniotic hypertonic sodium chloride, hyperosmolar urea, hyperosmolar urea plus prostaglandin F2alpha, and hyperosmolar ura or hypertonic glucose plus prostaglandin E2. In addition, clinically significant coagulopathy has been described in association with the administration of hypertonic sodium chloride. This study details a three-year experience involving 3,034 cases of midtrimester elective abortion and describes six cases of coagulopathy in association with the administration of hypertonic sodium chloride and two cases in association with the administration of hyperosmolar urea. The significance of these findings and etiologic considerations are discussed.


The pigment dispersion syndrome.

The pigment dispersion syndrome. The pigment dispersion syndrome was noted in 10% of white and black subjects with and without glaucoma. This suggested pigment dispersion was not a high risk factor in the development of glaucoma. The HLA-B7 antigen was less prevalent and HLA-B13 and Bw17 antigens were significantly more prevalent in individuals with the pigment dispersion syndrome than in subjects without the syndrome. Either HLA-B13 or Bw17 antigen was found in 23 (77%) of 30 patients with the pigment dispersion syndrome and in only 13 (6%) of the 203 subjects without pigment dispersion. Pigmentary glaucoma was characterized by a significantly higher prevalence of combinations of HLA-B12 and B13 or HLA-B12 and Bw17 antigens as compared to the pigment dispersion syndrome without glaucoma, primary open-angle glaucoma, or the general population. This suggested that pigmentary glaucoma differed genetically from primary open-angle glaucoma and was a separate entity.


Analysis of the systemic corticosteroid sensitivity of patients with primary open-angle glaucoma. Patients with primary open-angle glaucoma have an ocular and systemic sensitivity to corticosteroids. We adapted a cellular assay that used peripheral blood lymphocytes to detect this corticosteroid sensitivity in vitro in a microtiter assay. It reduced the time, cost, and amount of blood required to examine a patient. We examined ten subjects on three separate days and demonstrated that the reliability of one 50% inhibitory concentration was about 76%. We then studied 25 patients with primary open-angle glaucoma and 25 control subjects using this in vitro assay. The patients with primary open-angle glaucoma were significantly more sensitive to corticosteroids than the control subjects (P less than .001).


Trabeculotomy ab externo and trabeculectomy in congenital and adult-onset glaucoma. In one prospective study, 75 eyes (47 children with congenital glaucoma) were treated by trabeculotomy. Intraocular pressures were controlled in 93.4% after one or more trabeculotomy operations. In five eyes the intraocular pressure was not controlled and these had a fibrovascular membrane in the angle, extending over the trabeculum and iris base with finger-like processes over the peripheral iris. The eyes that had successful operations did not have this appearance. In a second study trabeculotomy in adult-onset open-angle glaucoma had a high rate of failure (30%) including the use of postoperative medication. Nineteen eyes (17 patients) were operated on, 13 successfully. Another group of 19 eyes (17 patients) were treated by trabeculectomy, with the same follow-up period. The one failure (5%) occurred in an eye in which the angle appeared to be totally closed on gonioscopic examination. The operation was equally effective in black and white patients.


Cataractogenic factors in patients with primary angle-closure glaucoma after peripheral iridectomy. In this retrospective study we evaluated 154 patients with primary angle-closure glaucoma operated on by peripheral iridectomy to determine the factors contributing to the high occurrence (57%) of cataracts. Cataract formation in an eye operated on by peripheral iridectomy was age-dependent and less related to the time after surgery. The acute attack enhanced the appearance of the lenticular changes but did not influence the overall occurrence of cataracts in older patients.


Dust particles retained in the upper fornix. Minute multiple dust particles enclosed in long stick mucous filaments may remain hidden in the recesses of the upper fornix for considerable periods of time. They produce the subjective sensations of grittiness  or smarting. After repeated maneuvers of eversion of the upper eyelid and blinking, the nasal end of the mucosities lodged in the upper fornix may become visible over the plica semilunaris or caruncle. When drawing them from the lacus lacrimalis with thin moist cotton-tipped applicators, long mucous filaments will be seen gliding out from under the nasal end of the upper eyelid.


Corneal mucus plaques.

Corneal mucus plaques. Corneal mucus plaques adhered to the anterior corneal surface in 17 of 67 advanced cases of keratoconjunctivitis sicca. The plaques were translucent to opaque and varied in size and shape, from multiple isolated islands to bizarre patterns involving more than half the corneal surface. Ultrastructurally, they consisted of mucus mixed with desquamated degenerating epithelial cells and proteinaceous and lipoidal material. The condition may be symptomatic but can be controlled and prevented in most cases by topical ocular application of 10% acetylcysteine.


Modification of the antibiotic system in M-K medium. Corneal endothelial cell function and ultrastructure were studied in rabbit corneas stored in M-K medium with different antibiotics. At concentrations about ten times greater than their minimum inhibitory concentrations, tobramycin, gentamicin, polymixin B, penicillin and streptomycin mixture, cephaloridine, and cephalothin did not damage corneal endothelia. Corneas stored in M-K medium with bacitracin did not have temperature reversals as did other corneas after storage. This is probably not significant since they maintained almost constant thickness and the endothelial layer remained intact.


Reactive corneal endothelialization.

Reactive corneal endothelialization. Results of a study of 100 consecutive enucleated globes showed an incidence of 22% of corneal endothelialization of the anterior chamber angle. Endothelialization had been overlooked in 15 of the 22 eyes in the original pathologic descriptions of the globes.


Keratoglobus and blue sclera.

Keratoglobus and blue sclera. Five patients from two families had similar features including keratoglobus, blue scleras, hyperextensibility of the hand, wrist, and ankle joints, sensorineural conduction hearing alterations, and mottling of the teeth. Keratoglobus had been observed in all patients at, or shortly after, birth. Corneal perforations developed in seven of the ten eyes after minimal trauma. Repair of these perforations was complicated by the extremely thin corneas and six eyes had to be either enucleated or eviscerated. Histopathological examination of two of the enucleated eyes showed the corneal stromas of both eyes to be estremely thin, Bowman's membrane was absent, and Descemet's membrane was unusually thick. This condition has an autosomal-recessive inheritance pattern.


Dominant cystoid macular dystrophy.

Dominant cystoid macular dystrophy. Of 24 examined family members, 14 had an undescribed macular dystrophy. There is a clear autosomal-dominant heredity. Essential features of the disease are pigmentary disturbance, cystoid macular edema, wrinkling of the internal limiting membrane, and vitreous body changes. In this family there was an increased incidence of severe hyperopia (greater than or equal to 6 diopters). As the disease progressed color vision deteriorated (type 1 acquired red-green defect), disturbance of the electro-oculogram became more prevalent, and the electroretinogram was normal. These finding differentiate this dystrophy from other diseases with a bull's eye aspect or cystoid macular edema and from vitreoretinal syndromes.


Clinical and histopathologic observations in severe Vogt-Koyanagi-Harada syndrome. Vogt-Koyanagi (V-K) syndrome is a severe anterior uveitis associated with alopecia, vitiligo, poliosis, and dysacousia. Harada's disease (HD) is primarily a posterior uveitis accompanied by signs of meningeal irritation and abnormalities of the cerebrospinal fluid. The overlapping of clinical manifestations between the two justified considering them as part of a spectrum of one disease (V-K-H). In a clinicopathologic study of nine cases four patients (three with V-K syndrome and one with V-K-H syndrome) histopathologically displayed a granulomatous uveitis. Five patients (two with V-K syndrome and three with HD) showed a nongranulomatous uveitis. We emphasized this latter finding, since in the past the diagnosis of this syndrome has been discarded both clinically and histopathologically because of the absence of a granulomatous uveitis. We established the clinical and histopathologic differences between V-K-H and sympathetic ophthalmia. The designation "uveomeningoencephalitic syndrome" stresses the key features of V-K-H, namely the uveal involvement and signs of meningeal irritation (that is, headaches, personality changes, and cerebrospinal fluid alterations).


The photostress recovery test in the clinical assessment of visual function. To distinguish optic nerve conduction defects from macular disease in patients with otherwise unexplained loss of central vision we first determined the best visual acuity with correction at distance in unilateral defects. The normal eye was tested first and photostressed for ten seconds by looking at an ordinary penlight held 2 to 3 cm from the eye. The time required to read three letters on three Snellen test lines just larger than the best acuity was used as the end point. In 63 eyes with maculopathy the recovery time was prolonged. Prolonged recovery time was not observed in 20 patients who had optic nerve disease.


The coating agent on the corneal contact lens in electroretinography. Two animal groups were subjected to electroretinographic studies under identical circumstances with the exception of the coating agent on the surface of the corneal electrode, which consisted in one group of an ophthalmic artificial tear solution containing 1.6% hydroxyethylcellulose, and in the other group, an ophthalmic artificial tear solution containing 0.2% hydroxyethylcellose. A similar comparative recording was performed on five human subjects. Electrophysiological responses recorded with 0.2% ophthalmic artificial tear solution increased up to 81%, as compared to the values obtained with the 1.6% solution. The difference in electrical conductivity of these two solutions, which is also time dependent, correlated with differences in electroretinographic amplitudes. I cannot explain these observations at the present time.


A corneal electrode for patterned stimulus electroretinography. A corneal contact lens electrode employs a silver-coated hard contact lens placed onto a soft contact lens. The electrode is used without corneal anesthesia and has excellent optical characteristics that allow reliable and convenient recording of patterned electroretinograms.


Digital A-scan ultrasonography used to measure ocular distances. Digital A-scan ultrasonography provided a digital display of intraocular distances with an overall accuracy of 0.05 mm. Since the control setting was easy and calibration was unnecessary, the time of measurement is reduced and hence the apparatus is useful in clinical practice.


Morphologic, biophysical, and biochemical consequences of ligation of the common biliary duct in the dog. Common biliary ducts of 32 adult mongrel dogs were ligated for a period of 2 days to 6 weeks. Sham-operated animals served as controls. Bile ducts were removed at sacrifice, and biophysical, morphologic, and biochemical parameters were measured. Our study shows that biliary duct ligation results in an immediate increase of intraductular pressure and is followed quickly by significant increase in the rate of collagen synthesis and the activity of prolyl hydroxylase. Histologic data show subepithelial inflammation followed by marked increases in periductular fibrosis. This fibroproliferative response is paralleled by peak levels of prolyl hydroxylase activity at 2 weeks prostligation. Paradoxically, bile ducts continuously distend throughout the ligation period despite increased fibroplasia. We present here the first topographic (SEM) study of normal and ligated common bile duct epithelium. Following 2 weeks of ligation large crater-like fenestrae are seen ductular epithelial surfaces. This is followed by focal epithelial sloughing. We speculate that the continuous distention and epithelial necrosis seen in the present study may be due to biliary stasis and/or subepithelial infiltration of bile through epithelial fenestrae. This hypothesis is supported by our studies which show that collagen extractibility is markedly increased by the addition of bile to the homogenate.


Soft tissue calcification in chronic dialysis patients. Autopsy protocols and microscopic slides of 56 dialyzed and 18 nondialyzed chronically uremic patients were reviewed to assess the presence, extent, and severity of extraosseous soft tissue calcification. Calcification was identified in 79% of the dialysis patients and 44% of the nondialysis patients (P iss less than .025). Soft tissue calcification most frequently involved the heart, lungs, stomach, and kidneys. Lesions were severe in 36% of the dialysis patients and, when strategically located within the myocardium, were life-threatening. The deaths of 6 dialysis patients were attributed to severe calcification of the cardiac conduction system and/or myocardium. The presence and severity of soft tissue calcification was not related to duration of dialysis, patients' age, degree of parathyroid gland hyperplasia, radiographic evidence of soft tissue calcification, serum calcium and phosphate levels, Ca X P products, or type or severity of metabolic bone disease.


Reversible inner medullary vascular obstruction in acute experimental hydronephrosis. The pathogenesis of experimental unilateral hydronephrosis was studied in the rat, with emphasis on the role of medullary vascular obstruction. The medullary circulation was evaluated after increasing periods of ureteral obstruction (up to 48 hours) using in vivo perfusion of silicone rubber or colloidal carbon. Evidence of inner medullary hypoperfusion was seen after 1 hour, and by 6 hours, the entire papilla was ischemic. Papillar hypoperfusion was still present at 24 and 48 hours, but significant recirculation occurred in the presence of continued obstruction. Release of ureteral obstruction caused rapid reversal of the perfusion defect. Histologic studies of the renal parenchyma adjacent to the pelvis showed increasing vascular congestion, focal interstitial edema, and extravasation of erythrocytes; these changes were also diminished after release of obstruction. Endothelial swelling or thrombosis in inner medullary blood vessels was not observed. Inner medullary tubules showed degenerative changes in kidneys that had been obstructed for 6 hours or more; at later periods (18 hours or more) focal necrosis was seen, but it never involved the entire papilla. Thus, reversible collapse of inner medullary blood vessels occurs in acute unilateral hydronephrosis and may provide the basis for the development of ischemic tubular damage. The findings suggest that the vascular obstruction may be due to increased intrapelvic pressure, rather than endothelial swelling or thrombosis. The vascular-tubular defect may be relevant to the altered medullary physiology observed in this condition.


The role of the pathologist in environmental medicine and public health. The present paper summarizes the role of the morbid anatomist and clinical pathologist in environmental carcinogenesis. It points out that in the past he has contributed considerably to the identification of rare tumors and their etiology. He has an important role to play in the future in providing more accurate data on which epidemiology studies can be developed. The view is also expressed that it is highly important that modern pathologists have an understanding of toxicologic and pharmacologic techniques and their potential application to biologic material in order that they may be in a position to correlate and develop multidisciplinary approaches to the identification of environmental hazards. Some of these approaches are illustrated and their potential developments outlined.


HLA-B8 and dermatitis herpetiformis in patients with IgA deposits in skin. The association between antigens of the HLA system and dermatitis herpetiformis (DH) using in vivo-bound IgA as an added criteria for diagnosis is reexamined. Twenty-eight of 33 (85%) immunologically proven patients with DH were HLA-B8 positive, whereas only 17 of 92 (18%) controls were HLA-B8 positive.


Cutaneous manifestations of idiopathic hemochromatosis. Study of 100 cases. Skin manifestations of idiopathic hemochromatosis (IH) are presented in 100 cases with emphasis on the previously unrecognized high frequency of ichthyosis-like states and koilonychia. In 50 cases with treated and nontreated groups, histological siderosis and clinical skin pigmentation were found to decrease postphlebotomy whereas melanosis, histologically, did not. By skin biopsy in 50 cases versus controls, the location of siderosis in eccrine sweat glands seems specific for IH providing a strong basis for a probable diagnosis of the disease. There are correlations between skin manifestations and other signs of the disease.


Epidermal mast cells.

Epidermal mast cells. Tissue from 134 patients with neurodermatitis and prurigo, pseudoepitheliomatous hyperplasia, pemphigus, and urticaria pigmentosa was examined qualitatively for epidermal mast cells. Epidermal mast cells were found in all of the diseases that were studied except dermatitis herpetiformis. Pemphigus vegetans and dermatitis vegetans were frequently associated with the presence of epidermal mast cells. In other pseudoepitheliomatous diseases, such as tuberculosis verrucosa cutis, blastomycosis, and bromoderma, epidermal mast cells were present in many cases. Four of eight patients with acral dermatitis with elevated IgE blood levels had intraepidermal mast cells; the number was much lower in patients with usual neurodermatitis and prurigo nodularis. Only two of ten cases of alopecia mucinosa showed epidermal mast cells. A single epidermal mast cell was found in ten cases of urticaria pigmentosa. Chronic inflammation associated with epidermal cell proliferation appeared to correlate with the presence of epidermal mast cell.


Treatment of servere psoriasis with pyrimethamine. Pyrimethamine, a folate antagonist similar to methrotrexate without known hepatotoxcity in man, was administer orally, once a week, to seven patients with severe, long-standing psoriasis. Four patients obtained a good to excellent response; a fifth withdrew from the study early after a partial response; a sixth had minimal response to high doses, and the seventh was withdrawn due to a probable drug-induced hepatotoxic reaction. Hepatotoxic reaction was suspected in another patient with abnormal liver biopsy and experienced severe gastrointestinal toxic reactions and two developed significant thrombocytopenia, which resolved after oral treatment with folic acid or discontinuation of the drug. These did not recur at lower doses. Pyrimethamine appears to be effective in severe psoriasis, but offers no advantage, and several disadvantages over methotrexate. Pyrimethamine is probably hepatotoxic. It should be used with caution in patients with liver disease or impaired renal function; pretreatment liver biopsy is recommended.


Allergic contact dermatitis from topical fluorouracil. An allergic contact dermatitis from fluorouracil developed in two patients 8 and 18 days respectively after institution of topical fluorouracil therapy. The character of the usual irritant dermatitis changed to that of an allergic dermatitis. Epicutaneous patch tests and intradermal tests with fluorourcil were reactive. Histologic specimens of positive test sites revealed the changes expected in allergic contact dermatitis. Twelve control subjects failed to react to intradermal fluorouracil tests.


Pseudomonas cepacia endocarditis and ecthyma gangrenosum. A case of right-sided Pseudomonas cepacia endocarditis in a heroin addict is presented in which septic cutaneous vasculitis (ecthyma gangrenosum) is a prominent feature. Ecthyma gangrenosum, most commonly associated with sepsis due to P aeruginosa, has not been previously described with P cepacia septicemia.


Staphylococcal scalded skin syndrome. Clinical features, pathogenesis, and recent microbiological and biochemical developments. The essential clinical features of staphylococcal scalded skin syndrome (SSSS) and otherforms of toxic epidermal necrolysis (TEN) are contrasted. Whereas TEN is a devastating disease of multiple causes and of high fatality affecting all age groups, SSSS comprises many clinical entitles that occur primarily in early childhood and is caused by certain phage group 2 staphylococci. Because of the high cleavage plane, the barrier is only translently perturbed, and rapid recovery is the rule. Although the early stages of SSSS may resemble other widespread dermatoses clinically, the correct diagnosis is suggested, even prior to frank exfoliation, by the presence of cutaneous tenderness and a positive Nikolski sign. However, rapid bedside confirmation is now possible with exfoliative cytology and frozen sections. Recent availability of in vivo and in vitro animal models of SSSS have advanced the knowledge of the disease: the responsible epidermolytic toxin has been characterized, and the purely extracellular pathogenesis of SSSS has been established. The epidermolytic toxin is strikingly species and tissue specific, attacking only certain keratinizing epithelia of mice, hamsters, monkeys, and man. The lower incidence of SSSS in adults is primarily due to a supreior capacity to metabolize and excrete the toxin, as well as more efficient immune capabilities. The mechanisms of epidermolytic toxin action and the molecular site of action are still the focus of active investigation.


[Immunity against measles in mother-child binomials]. The persistence of passively adquired measles hemagglutination-inhibition (HI) antibody, was studied in a group of 50 mother-child binomials. In this longitudinal study, serial samples of blood were obtained from each infant during the first eight months of life. There was a high correlation between the level of the antibody titer in mothers and in their newborns. Passively antibody titers between 1:20 to 1:80, persisted as late as 8 months in more than 60% of infants. The presence of antibody may have a suppressive effect on the immunogenic response to live measles virus vaccine.


[Surgical correction of acute congenital cardiopathies in the newborn infant]. The experience of the Cardiac Surgery Service at the Hospital del Niño IMAN with the deep hypothermia method and hemodynamic arrest is shown in 30 infants with severe congenital cardiac malformations. The procedures followed before and during the operation are carefully described in their three aspects; anesthesia, extracorporeal circulation and surgery, including postoperative care. Ventilatory assistance is stressed. Results are analyzed considering postoperative evolution; stress is made on the causes of morbidity and mortality. Considering the results of this and other similar reports, we believe that the deep hypothermia method and heart arrest in treating severe cardiac malformations in infants are of outstanding importance since they have significantly improved results in these problems.


[Neonatal meningoventriculitis].

[Neonatal meningoventriculitis]. Clinical and autopsy data indicate that ventriculitis persists despite parenteral and intralumbar antibiotic therapy. In the present study, ventriculitis was documented as postmortem examination in nine newborns. These studies indicate that ventriculitis occurs commonly in neonates with meningitis, particularly when there is delayed sterilization of CSF culture, A clinician has to bear in mind the diagnosis of ventriculitis when: 1) There is poor clinical and/or laboratory response to the usual therapy. 2) He has a critically ill patient with lethargy, convulsions and bulging fontanels. 3) He culture an unusual organism. 4) He faces a suspected complication of meningitis: subdural effusion, ventriculitis or abscess. 5) A CSF from ventricular puncture with more than 150 WBC, glucose less than 50 mg. and protein more than 200 mg.


[Choledocal cyst. Surgical treatment].

[Choledocal cyst. Surgical treatment]. Experience at the Hospital del Niño IMAN in choledochus cysts is reviewed in 13 patients with ages ranging from 3 months to 13 years. Nine were female patients and four were male. Seven cases were managed with cystoduodenostomy and six with cystojejunostomy using Roux's Y operation. Two patients from the cystoduodenostomy group died probably due to the serious hepatic lesion present before surgery and not to the surgical procedure itself. There were no deaths in the group with cystojejunostomy using Roux's Y operation and all patients are asymptomatic at 6 months to 5 years after surgery. Stress is made on the high incidence of cases in our country. Disadvantages of cystoduodenostomy due to the reflux of food contents of the biliary ducts, documented in these cases, are discussed. The possibility of a complete cyst resection is considered, based on reports of late malignancies and poor functioning of the anastomoses mentioned by other authors.


[Epidemiology of skin diseases in 10,000 patients of pediatric age]. Ten thousand new patients were seen between January 1971 and January 1975 at the Department of Pediatric Dermatology, "Hospital del Niño IMAN" in Mexico City. The patients were between 0 and 18 years old. They represented 10.4% of the entire pediatric population attending the general out-patient clinic of the hospital. The results of our study showed no significant difference among the sexes of patients. The highest proportion of patients in the sample were under one year of age. The most frequently observed groups of dermatoses were: parasitic, cutaneous reactions, viral and bacterial. The ten diseases most frequently observed were: papular urticaria (16.3%); atopic dermatitis (12.9%); scabies (10.4%); viral warts (8.4%); impetigo (6.8%); pitiriasis alba (6.6%); vitiligo (2.6%); acne (2.5%); dermatophytosis (2.4%) and numular eczema (2.3%). The 20 skin diseases most frequently recorded accounted for 85.8% of the sample. The ten most frequent skin diseases in each group of age were also recorded. The monthly and annual frequency for the more frequent dermatoses was studied. The present study provides epidemiological information for a rational development of programs on care, education and investigation in pediatric dermatology in Mexico.


[Treatment of chronic osteomyelitis].

[Treatment of chronic osteomyelitis]. Levels of Cephaloridine and Cefazoline were measured in serum, pus and bone in 20 patients with chronic osteomyelitis and the efficiency of these drugs in the treatment of osteomyelitis was evaluated.


[Site of BCG vaccine administration and development of hypertrophic scars]. In this preliminary report, two groups of children were vaccinated with subcutaneous BCG, one on the deltoid area and the other one on the area between the spine and the scapula. The number of hypertrophic scars on the deltoid area was significantly higher that in the area between the spine and the scapula. Vaccination on this area is as effective in turning the P.P.D. positive as on the deltoid area and the risk of hypertrophic scars in minimized.


[Outpatient surgery].

[Outpatient surgery]. The authors describe their experience in 778 patients under an ambulatory surgical program at the Hospital del Niño, IMAN. All were operated with general anesthesia; the child arrives in the morning to the hospital and is released in the afternoon. This report suggests that ambulatory surgery is a procedure which can be carried out in Mexican hospitals, saving time and money, since it decreases the number of beds in use; consequently, a better service can be provided. If it is duly fulfilled, the procedure is safe and an effective surgical care can be given to pediatric patients.


[Disease due to gastroesophageal reflux]. Disease due to gastroesophageal reflux is one of the most important of the esophagogastric union; Depending on the time of diagnosis is the severity and prognosis of the disease. It is obvious that the collaboration of a skilled nurse is essential for the recovery of the patient as well as a timely medical evaluation.


[Strongyloidiasis in children. Report of 17 cases]. Results from the study of 17 strongyloides infections without other associated parasitoses seen at the Hospital del Niño, IMAN between January 1971 and June 1976 are reported. The most affected age groups were of pre-school children with no sex predominance. Patients came from the states of Veracruz, Guerrero, Hidalgo, Michoacín, Morelos, San Luis Potosí and Sinalos. Different degrees of malnutrition were found in 10 out of the 17 patients. Predominant signs or symptoms were as follows: paleness, nausea, vomiting, diarrhea, bloody and mucous stools, hyporexia, hyperthermia, pain and abdominal distention. Ferreira's method for coproparasitoscopic examination was the most efficient to show Strongyloides sterocarlis larvae. Moderate eosinophilia from 10 to 14% was found in most of the patients. Treatment was carried out with thiabendazole in most of the patients. This drug proved to be quite effective in the treatment for strongyloidoisis.


[Ataxia telangectasia. Probability of damaging immune mechanisms]. Twelve patients suffering from ataxia telangiectasia and relatives of three of them were studied. A late diagnosis prevailed and the neurological symptoms in some turned worse after suffering recognizable viral infections. The cellular and humoral immunodeficiencies were evaluated in each case as well as the simultaneous presence of hyperimmunoglobulinemia and/or auto-antibodies. Among the relatives, there were frequent cases of immunological and neoplastic alterations; cellular immunodeficiency was not detected. Five cases showed lung disease; four with absence of IgA, and histologic interstitial lesion detected in three of them. The hypothesis that the defect of cell immunity predisposes mulisysthemic disease and that an early diagnosis with immune reconstructive treatment can modify the evolution of the disease was considered.


Relation between apex cardiogram and changes in left ventricular pressure and dimension. The relation between the apex cardiogram and changes in left ventricular pressure measured by micromanometer, and dimension measured by echocardiography, was studied in 12 normal subjects and 64 patients with heart disease. In 12 patients, the apex cardiogram was delayed with respect to simultaneous left ventricular pressure by 17 +/- 18 ms during the upstroke and 28 +/- 16 ms during the downstroke. In the normal subjects, changes in left ventricular dimension during the upstroke and downstroke of the apex cardiogram were small, amounting to 6 +/- 5 and 21 +/- 7 per cent total excursion, respectively. In 10 patients with mitral regurgitation, there was significant inward wall movement during the upstroke and in 10 patients with aortic regurgitation, significant outward movement during the downstroke, both reflecting valvular regurgitation. In 20 patients with ischaemic heart disease and segmental abnormalities on left ventricular angiography, apex cardiogram-echo dimension relations were abnormal in all, because of inward or outward wall movement during the upstroke, increased outward movement before the 'O' point, or abnormal inward movement during the downstroke. These disturbances were displayed by constructing apex cardiogram-echo dimension loops, which appear to be a sensitive means of detecting incoordinate left ventricular contraction, analogous to those between pressure and dimension.


[Teaching of pediatric surgery in Mexico]. This is a brief presentation of the way in which a large number of Mexican pediatric surgeons have been made from the beginning of this specialty at the Hospital Infantil de México to the present time, stressing the medical pediatric basis in pediatric surgery and on their lack of training in general surgery. Results are presented from a survey made among pediatric surgeons, highlighting the fact that the pediatric surgeon limits his role to only one type or surgery which always seems to be abdominal, disregarding vascular, gynecologic or urologic surgery. A noteworthy fact is that pediatric surgeons dedicate most of their time to medical pediatrics. A vicious circle in which the pediatric surgeon seems to have fallen in is presented. A series of steps are set forth to end this vicious circle such as improving training of pediatric surgery, establishing training objectives according to reality and avoiding frustration of those who are trained to operate on children and turn out dedicated to medical pediatrics.


[Mucocutaneous lymph node syndrome. Report of a case]. The first case of mucocutaneous lymph node syndrome (MLNS) seen at the Hospital del Niño IMAN and probably in Mexico City is described. The guidelines for the diagnosis of the syndrome are outlined as well the differential diagnosis with other diseases.


Echocardiographic assessment of left ventricular function in coronary arterial disease. This investigation was designed to determine the role of echocardiography in the assessment of left ventricular function in patients with significant coronary arterial disease. Satisfactory echocardiograms were obtained in 43 patients with coronary arterial disease. The ventriculographic ejection fraction was determined by the area length method. The echocardiographic left ventricular end-diastolic dimension was increased to more than 5-4 cm in 17 patients. Fifteen of these patients had an ejection fraction of 0-45 or less. Three patients had a normal left ventricular end-diastolic dimension but an ejection fraction of less than 0-45. Twenty-three patients had an ejection fraction of more than 0-45 and a normal left ventricular end-diastolic dimension. The left ventricular end-diastolic dimension index was increased (greater than 3 cm/m2) in 15 patients, all of whom had ejection fraction of less than 0-45. Three patients had a normal left ventricular end-diastolic dimension index and an ejection fraction of less than 0-45. Twenty-five patients had a left ventricular end-diastolic dimension index of less than 3 cm/m2 or less and an ejection fraction of more than 0-45. The percentage fractional shortening of the echocardiographic left ventricular dimension was reduced in 25 patients. In 18 of these the ejection fraction was 0-45 or less. The percentage fractional shortening of the left ventricle was normal in 18 patients. In 2 of them the ejection fraction was less than 0-45. In summary, increase of the left ventricular end-diastolic dimension or left ventricular end-diastolic dimension index is usually associated with a critical reduction of the ejection fraction as determined by ventriculography. Since the ejection fraction is an important determinant of mortality related to bypass graft surgery, echocardiography should be useful in the detection of patients with a poor prognosis.


Learned voluntary control of heart rate and rhythm in two subjects with premature ventricular contractions. Two people with frequent premature ventricular contractions and bigeminal rhythm not associated with other signs of heart disease, learned to suppress the arrhythmia using a biofeedback technique. In both cases, physical exercise and atropine suppressed the arrhythmia, and in both the learned control was related to the development of tachycardia. In Case 1, it appeared to depend on something more than speeding alone, for sinus rhythm could be maintained during voluntary control at a lower heart rate than during physical manoeuvres such as exercise. In Case 2, the premature ventricular contractions could be induced by a sudden fall of heart rate, e.g. after a Valsalva manoeuvre, and could be suppressed by voluntary increase of heart rate by up to 40 beats/minute produced with little change in breathing or muscle activity.


[Community participation patterns in health programs]. The study of some Latin American experiences of participation of the community in health programs allows us to consider the following as minimum requirements to establish interrelationships between local health organisms and the community: a) To have a local health system. b) To have a participating health them. c) To show respect for the community. d) To have contact with community organizations. e) To have contact with private and government organizations at a local level. The models for participation of the community in health are manifold and the experiences have been countless. For teaching purpose and based on Latin American experiences, some considerations are made regarding: 1) Community health volunteers. 2) Local health councils. 3) Local councils for community development. 4) Health brigades. Finally, it is concluded that the active participation of the community organized in health activities is the best guarantee of success in implementing integral health programs.


[Torsion and infarct of the spleen with benign lymphoid hyperplasia of the colon]. A case of an infant with vomiting and a palpable abdominal mass is discussed. His preoperative studies showed a double right collecting system and a benign lymphoid hyperplasia of colon. The laparotomy showed a spleen in an abnormal position with total ischemic necrosis due to torsion of a pedicle. Emphasis is made on the complementary studies to help the diagnosis.


[Surgical treatment of pleuropulmonary infection in children]. Pleural empyema is most frequently seen in surgical pathology of the chest at the Hospital del Niño IMAN. Decortication has been necessary, with or without pulmonary resection, in 58% of the cases, contrasting with the limited number of cases in series published in countries with a high standard of life and where a conservative criterion for treatment is held by the authors and some national pediatric groups. Thus, a retrospective analysis is made with 118 patients who underwent surgery between 1971 and 1976 with ages ranging from 3 months to 17 years. The strict management procedure followed in all cases in mentioned, as well as the criterion to perform thoracotomy, to establish the irreversible nature of the anatomical lesions and to evaluate the results. 114 patients were discharged following recovery; 11 of these showed complications such as bronchopleural fistula, atelectasis and postoperative fever, which were treated with pleural drainage and bronchoscopy. Four patients died: one from upper gastrointestinal bleeding and three from sepsis. With the clinical and radiological, as well as the bronchoscopic evaluation, the destructive and irreversible nature of the lesions was determined. This was confirmed by the histopathological study of the resected parts. It is concluded that there should be no doubts or disagreements when surgical treatment is indicated.


Improvement of symptoms in patients with sick sinus syndrome by spontaneous development of stable atrial fibrillation. Fifty-six patients with symptomatic chronic sinus bradycardia because of sick sinus syndrome (SSS) were followed for periods from one month to 11 years (average 3-2 years). Eleven developed stable atrial fibrillation persisting for 8 to 61 months; 52 had permanent demand pacemakers implanted before atrial fibrillation commenced. In the 11 patients with atrial fibrillation, 10 had adequate ventricular rate, 8 with rates greater than 100 beats/min requiring digoxin for rate control. The 8 patients with atrial fibrillation with pacemakers remained asymptomatic for 13 to 18 months without requiring reimplantation; battery failure occurred in 2 whose rapid ventricular rates were controlled by digoxin. In the other 6 patients with pacemakers who developed atrial fibrillation, adequate ventricular rates persisted resulting in overdrive suppression. No patient had systemic embolisation. The previous duration of symptomatic sinus bradycardia was longer in patients developing atrial fibrillation (average 5-5 years) compared (P less than 0-01) with patients without atrial fibrillation (1-9 years). Further, premature atrial contractions occurred in all 11 patients before atrial fibrillation in contrast to only 21 of the 45 patients without atrial fibrillation. It is concluded that occurrence of atrial fibrillation in SSS with symptomatic sinus bradycardia provides a natural cure of symptoms caused by bradycardia. These data indicate that permanent ventricular pacing may not be necessary if persistent atrial fibrillation develops in SSS.


Circulatory reflexes in myocardial infarction. The Valsalva manoeuvre was used to examine circulatory reflexes in 22 patients with acute myocardial infarction. Four patients had the 'square wave' response of cardiac failure and two responded normally to the manoeuvre. In the remaining 18 patients there was a 20 per cent or more fall in pulse pressure during the manoeuvre, but no ensuing rise in diastolic pressure, implying impairment of vasoconstriction. This impairment cannot be explained by acidosis, hypocapnia, or arterial hypoxaemia but may be explained by reflex inhibition of vasoconstriction. This abnormal response has important implications when transporting patients; furthermore, it could explain the rapid deterioration sometimes seen in patients with arrhythmias.


[Surgical treatment of pulmonary valve stenosis]. "Open" pulmonary valvotomy with vena cava occlusión and normothermia was first performed by Varco in 1950, but the procedure was abandoned with the arrival of extracorporeal circulation. This paper compares two groups of patients who were operated with Varco's procedure and extracorporeal circulation. Similar data of both procedures are analyzed as well as their advantages and disadvantages. It is concluded that Varco's proceduce is useful in well selected patients with no associated anomalies in which the possibility of complications of extracorporeal circulation is avoided. Also, equipment, personnel, surgical time and stay in the Intensive Care Unit and in the hospital are reduced, saving cost as much as 50%.


P loops during common and uncommon atrial flutter in man. Atrial flutter has never been satisfactorily defined. The 'common' pattern of flutter was originally described by Lewis in 1913. Less frequently observed forms of flutter are termed 'uncommon'. Sixteen cases of the 'common' and 6 of the 'uncommon' type have been studied using isolated P loop vectorcardiography. All patients had some degree of atrioventricular block but none had evidence of digitalis excess. The atrial rates were regular and were in a range between 250 and 330/minute. Vagal manoeuvres increased AV block in each instance. All those with the 'common' type of flutter had P loops with a caudad-cephalad orientation and fifteen of the sixteen had forces which descended over the right atrium and ascended over the left atrium. The 6 cases of the uncommon type of flutter had rates which ranged between 250 and 300/minute and did not fulfil both of the criteria for 'common' flutter; namely continuous baselineu ndulation and prominent negative P deflections in the inferior leads. The cases with the 'uncommon' type of flutter had a variety of loop patterns. The most frequent type was oriented inferior slightly to the right and anterior. One patient satisfied criteria for left atrial flutter. In another the loop was oriented inferior leftward and anterior. The vectorcardiogram provides a rich source of descriptive data but does not identify the underlying mechanism(s) of flutter.


[Cryptococcosis of the central nervous system]. The steps for diagnosis and treatment and the clinical course followed in three patients with Cryptococcus meningitidis are discussed. One of them was treated with 5-flurocytosine alone. Two consecutive patients were treated with a combination of 5-flurocytosine and amphotericin B. The objectives of the study were: a) to achieve a therapeutic response better than that which might be obtained with either drug alone, b) to use lower doses of 5-fluorocytosine and amphotericin B in order to reduce toxicity, c) to extend treatment only for a period of four weeks, thus decreasing the period of hospitalization. None of the patients has relapsed. A shorter time of hospitalization and reduction in toxicity, suggests that combined therapy is a safe and effective alternative to other regimens.


Initial care of hypertensive patients. Influence of different types of clinical records. The initial record of history and clinical findings has been studied in 278 patients attending three hypertension clinics. Half of these were randomly allocated to standard case notes and the other half to a special structured questionnaire record. The investigations carried out in a total of 521 patients with raised arterial pressures were examined. The records derived from the structured questionnaire were much more complete than the standard case notes but the difference was less obvious for a positive record than a negative one. None of the investigations was carried out in all patients, even though it was the policy of the clinics that most of them should be. A possible aetiological diagnosis was made in 28 patients and, at the time of writing, 3 patients had benefited from a surgical operation carried out as a result of investigation. These results raise the question of the quality of the initial care of hypertensive patients and suggest that the structured questionnaires might lead to an improvement. It remains to be established whether all the information collected does influence the outcome in patients with hypertension.


Long-term prognosis after acute anterior infarction with atrioventricular block. The purpose of this study was to evaluate the need for permanent pacing in patients who have survived the effects of anterior myocardial infarction with complete heart block and have returned to sinus rhythm but who are left with impairment of intraventricular conduction. We have reviewed 52 patients with complete heart block complicating recent anterior myocardial infarction. Temporary pacing was instituted in all patients. There were 25 hospital survivors who were followed for an average of 49 months. Long-term pacing was established in 4 patients. Of the 21 patients in sinus rhythm, 14 had partial bilateral bundle-branch block with either right bundle-branch block and left anterior hemiblock or right bundle-branch block and left posterior hemiblock; at the end of the follow-up period, 10 of these 14 were alive and well. Furthermore, permanent pacing failed to prevent sudden death in 2 patients. At the present time, therefore, we conclude that long-term pacing is not justified in patients, otherwise asymptomatic, with partial bilateral bundle-branch block persisting after transient complete heart block in anterior myocardial infarction.


Formes frustes of Marfan's syndrome presenting with severe aortic regurgitation. Clinicogenetic study of 18 families. Eighteen patients who presented with severe aortic regurgitation and dilatation of the ascending aorta were found to be formes frustes of Marfan's syndrome and formed the basis for this clinicogenetic study. All had aortic valve replacement and reconstruction of part of the ascending aorta. The diagnosis was confirmed by histological examination of the aortic tissue. There were 126 first degree relatives; 85 were living and 67 (78-8%) of these were examined. Limited information was available about 32 of the 41 relatives who had died. No relative had the classical clinical features of Marfan's syndrome but stigmata of the disease were found in 25 (37-3%) of the 67 first degree relatives examined. In 21, the abnormality was confined to the cardiovascular system, the skeleton, or the eye, but in 4, abnormalities involved 2 systems. Cardiovascular abnormalities affecting the aortic valve or aortic wall were present in 6 (9-0%) of the 67 first degree relatives examined. One or more of the skeletal indices measured (height-span difference, metacarpal index, phalangeal index) was abnormal in 18 (26-9%) and ocular abnormalities were found in 5 of 51 (9-8%) examined. There were no relatives with dislocation of the lens or iridodonesis. Using strict diagnostic criteria, a minimum of 37-3 per cent of the first degree relatives examined were affected; this involved 12 of the 18 families studied. There was nothing in our data to suggest that the formes frustes of the disease had a different mode of inheritance from the classical syndrome.


Experience with counterpulsation in cardiac surgical patients. At Sheffield Regional Cardiothoracic Unit, the AVCO intra-aortic balloon pump has been used on 25 occasions in 21 months. Of the 25 patients, 12 survived and left hospital. The procedure is particularly beneficial in patients who have suffered some failure of myocardial protection during operation and to those who are suffering from acute ischaemia or the sequelae of myocardial infarction. The place of preoperative counterpulsation is discussed. Patients with long-standing cardiac disease who have emergency surgery benefit less from counterpulsation. Those patients with chronic ischaemic damage to the heart have nothing to gain from the use of counterpulsation.


Chronic bilateral bundle-branch block. Long-term observations in ambulatory patients. During a period of 28 months, all patients (79) who presented with bilateral bundle-branch block were selected for study from a private practice outpatient population. They were followed prospectively from the date of entry into the study and their charts were reviewed retrospectively. The average age of the participants was 73-3 years and they were observed clinically for a cumulative period of 4237 months (353-08 years). A high incidence of severe heart disease and death was noted among the study group. Twenty-four (30-3%) had a New York Heart Association functional classification of 3 or 4. Eight (10-1%) died. Only one patient died suddenly and he had had a stable electrocardiographic pattern of bilateral bundle-branch block for a period of 118 months (9 years 10 months). Seven patients required permanent pacemakers. In 6 instances death resulted from pump failure; in one it was the result of lung cancer. In none of these 7 individuals did rhythm disturbances contribute to death. In most cases vertigo was not of cardiac origin (88-2%). Eight patients had 11 major surgical procedures with no significant cardiac sequelae. Our observations suggest that elderly patients with chronic bilateral bundle-branch block should be managed conservatively. The prognosis in these patients appears primarily to be related to the degree of myocardial disease rather than to the conduction disorder.


The normal electrocardiogram as a predictor of left ventricular function in patients with coronary artery disease. Fifty-five consecutive patients with a normal resting electrocardiogram and coronary artery disease were examined to determine left ventricular function. Fifty-two (95%) had no evidence of left ventricular asynergy; 3 patients had only mild hypokinesis. Of this group of patients, 25 (47%) had one vessel disease, 17 (30%) had two vessel disease, and 13 (23%) had three vessel disease. Significant left ventricular asynergy was not found in patients with coronary artery disease and normal electrocardiograms. In addition, a normal electrocardiogram was not related to the number of coronary arteries involved.


Bradycardia-dependent interatrial block with retrograde left atrial activation. A patient with a peculiar interatrial block is reported. The electrocardiogram showed a short PR interval and negative P waves in II, III, and aVF, which were preceded, 0-07 s earlier, by another positive P wave present in the right praecordial leads which were absent in the limb leads. From the study with His bundle electrograms, high right atrial electrograms, and bipolar oesophageal electrocardiograms, it could be proved that atrioventricular, His-Purkinje, and right intra-atrial conduction were normal, and that P waves recorded in limb leads represented left atrial depolarization; whereas the ones in the right praecordial leads corresponded to right atrial activation. The vectorial analysis from both P waves and atrial potentials showed that the left atrium was activated in a retrograde fashion, because of an interatrial block. This block was bradycardia dependent and it disappeared in the cycles shorter than 800 ms.


Controlled ventilation with the Mapleson D system A theoretical and experimental study. A theoretical analysis has been performed to show the interrelationships between alveolar carbon dioxide concentration, carbon dioxide output, alveolar ventilation and fresh gas flow during controlled ventilation with the Mapleson D system. The model and forms of equation used have been substantiated by experiments in which dogs were ventilated through a coaxial version of the Mapleson D system at varying levels of fresh gas flow and alveolar ventilation. By assuming that man ventilated with this system behaves as does the dog, a nomogram has been produced to predict alveolar carbon dioxide concentrations at any levels of fresh gas flow and minute volume.


Halothane solubility in human blood.

Halothane solubility in human blood. In a study of the influence of nutritional state on halothane anaesthesia, results were obtained which showed how the blood/gas partition coefficient for halothane varied with blood chemistry in 20 patients undergoing elective surgery. For each patient the partition coefficient lambda was measured by equilibration at 37 degrees C  of a blood sample with a 1% halothane in 5% carbon dioxide in air mixture, followed by chemical extraction and estimation of the halothane content by gas chromatography. The haematocrit and haemoglobin, serum albumin, total protein, triglyceride and cholesterol concentrations were measured by routine laboratory methods. Regressions were sought of lambda on each of these, and on the globulin concentration and the ratios of albumin: globulin and albumin: total protein, deduced from these determinations. The only statistically significant regression (P = 0.0004) was that of lambda on the serum triglyceride concentration (T) (mmol/litre): lambda = 1.83 + 0.424T. The dependence of lambda on haemoglobin concentration was not statistically significant, but the slope of the regression was consistent with those of previous investigators. The regressions of lambda, corrected to the mean triglyceride concentration, on the ratios of albumin: globulin and albumin: total protein were not statistically significant but were not significantly different from an earlier reported result.


The effect of thiopentone on enflurane-induced cortical seizures. The effect of thiopentone 0.5 and 1.0 mg/kg on the enflurane-induced cortical spike discharge has been examined. Seven cats were anaesthetized with enflurane in oxygen and ventilation was controlled to maintain eucapnia during e.e.g. recording. End-tidal enflurane concentrations of between 1.2 and 2.2% provoked dose-dependent spontaneous spike discharges reproducibly. It was found that, during light enflurane anaesthesia, intravenous thiopentone could exacerbate e.e.g. signs of seizure activity. However, at a greater depth of anaesthesia spike activity was suppressed. The e.e.g. changes following thiopentone resembled the effects of still greater concentrations of enflurane.


Feed-back monitoring in anaesthesia. IV. The indirect measurement of arterial pressure and its use for the control of halothane administration. A technique of indirect determination of arterial systolic pressure using a photoelectric pulse monitor signal to indicate arterial occlusion has been applied to the feed-back control of halothane administration. In normotensive patients, the inspired halothane concentration had little influence on arterial pressure; in about 25% of patients a periodic pattern between the low and medium outputs of the vaporizer occurred. In hypertensive patients, the arterial pressure was more sensitive to the depressant effects of halothane and the concentration administered was reduced automatically as the operation proceeded.


The pharmacokinetics of metabolism of inhalation anaesthetics. A simulation study. The non-steady state metabolism of inhalation anaesthetics during anaesthesia and recovery was simulated with a linear and non-linear whole body compartmental model. These two models were studied for nine anaesthetics during 1-MAC anaesthesias lasting 1, 4 and 8 h and recovery from 5 to 10 days. Both models demonstrated significant metabolism for several days following anaesthesia. For the linear model, both the percentage and the molar quantity of anaesthetic metabolized increased with increased duration of anaesthesia, increased anaesthetic fat solubility and increased assumed rate of hepatic metabolism. For the non-linear model, the duration of anaesthesia had little effect on the percentage metabolized but demonstrated increased molar quantities of anaesthetic metabolized with increased duration of anaesthesia and increased fat solubility. The agreement between the results obtained from the non-linear model and experimental data in the literature suggests that many inhalation anaesthetics belong to a class of xenobiotics whose biotransformation is limited by the same or similar non-linear rate-limiting step(s). A difference in the quantities of anaesthetic metabolized would be a direct consequence of the tissue solubilities of the anaesthetic.


Screening for malignant hyperpyrexia.

Screening for malignant hyperpyrexia. Skeletal muscle from normal human subjects produced linear contracture responses in vitro to caffeine at concentrations of between 4 and 32 mmol/litre. In the presence of 0.4% halothane, caffeine contractures were greater but the magnitude of halothane potentiation decreased as the caffeine concentration was increased. The contractures produced by caffeine 4 and 8 mmol/litre at 37 degrees C were significantly reduced by decreasing the temperature of the incubation solution to 25 degrees C. Among 57 normal subjects, 18% had fibres which responded to halothane treatment with contracture. On the basis of these findings, it is suggested that screening for malignant hyperpyrexia by in vitro pharmacological testing of skeletal muscle should be carried out at 37 degrees C, and should include exposure of the sample to halothane, caffeine, suxamethonium and potassium rather than to halothane alone.


Anaesthetic management for children with alveolar proteinosis using extracorporeal circulation. Report of two cases. This report demonstrates the results following massive simultaneous lavage of both lungs in two brothers suffering from pulmonary alveolar proteinosis with severe hypoxaemia, using partial extracorporeal bypass.


A hazard of the pollard endotracheal tube. Two patients are described in whom failure of the Pollard endotracheal tube produced complete respiratory obstruction. Comparisons are made of external diameters, resistance to gas flow and resistance to compression between Pollard tubes and several conventional tubes. It is concluded that the Pollard tube is not satisfactory for microlaryngoscopy.


Inhibition, by anaesthetic agents, of human leucocyte locomotion towards chemical attractants. The effects of local, i.v. and volatile anaesthetic agents on locomotion of human blood leucocytes were studied in vitro. Blood neutrohpils and monocytes and PHA-activated lymphocytes were allowed to migrate in filters towards standard chemotactic agents and the effect of adding anaesthetic agents to the system was measured. The results showed that locomotion of all cell types was depressed reversibly by all classes of anaesthetics used at clinical concentrations. The pattern of depression varied according to the cell type under study and the class of anaesthetic used. The action of anaesthetics on chemically stimulated locomotion of leucocytes was analysed. It was concluded that the principal action of these drugs is primarily on the mechanism of locomotion itself, rather than on the capacity of the cells to detect and respond to concentration gradients of attractants. Serum albumin can protect against the inhibitory action of anaesthetics.


A cell line from an anaplastic transitional cell carcinoma of human urinary bladder. A cell line, TCCSUP, derived from an undifferentiated, Grade IV transitional cell carcinoma is described. The karyotype showed an abnormal distribution of chromosomes, with no obvious modal number. Distinct marker chromosomes were observed in both early and late in vitro passages. These cells have been subcultured over 50 times during a 20-month period. TCCSUP differs in certain morphological and immunological features from other cell lines from transitional cell carcinomas.


Comparison of autochthonous and allogeneic breast-tumour cells in tests for lymphocyte immunity to human tumours. Lymphocytes from 10 patients with breast carcinoma were seeded in autologous serum, on autochthonous tumour cells and allogeneic tissue-cultured breast tumour cell lines. In 4 patients, the anti-tumour cell cytotoxicity against at least one of 3 breast tumour cell lines differed significantly from that against autochthonous tumour cells. Further study of these 4 individuals (using their previously frozen lymphoid cells and sera) showed that these differences occurred because serum which decreased ("blocked") lymphocyte anti-tumour cytotoxicity when applied to one tumour cell line, could either have no effect or potentiate it when applied to another, without any consistent pattern vis-à-vis target-cell susceptibility to these different humoral effects.


Sensitivity to cytotoxic agents of the EMT6 tumour in vivo: tumour volume versus in vitro plating. 1. Cyclophosphamide. Growth curve measurements on the EMT6 tumour following treatment with cyclophosphamide indicate a growth delay of about 3 days for each 100 mg/kg of the drug. Tumours treated whilst still microscopic show a rather longer delay for the same dose. Data for the surviving fraction of cells in the tumours measured by in vitro plating at 2 h after cyclophosphamide are not compatible with the measured growth delay and realistic values for the doubling times of surviving clonogenic cells; It is concluded that there is considerable "repair of potentially lethal damage", and that there is probably no single time after cyclophosphamide treatment at which the surviving fraction of cells can be correctly measured by the in vitro plating technique. Cell loss from cyclophosphamide-treated tumours is increased only slightly over that from untreated tumours, and the regeneration of surviving cells is very rapid. In this situation, only marginal regressions in tumour volume are caused by the highest doses of the drug.


Mechanism for the incorporation of S-(1,2,3,4-tetrahydro-2-hydroxy-1-naphthyl)-L-cysteine into protein. Evidence is presented which indicates that S-(1,2,3,4-tetrahydro-2-hydroxy-1-naphthyl)-L-cysteine (THN-cysteine), formed by the reaction of 1,2-epoxy-THN with cysteine, can be incorporated into protein; The position of incorporation of THN-cysteine into protein would depend on whether the epoxide of THN reacts with cysteinyl-tRNACyS or with cysteine. In both cases, the mechanism of incorporation of THN-cysteine into protein is the same as for the natural amino acids. For example, the incorporation of THN-cysteinyl-tRNACyS is stimulated by Poly-UG, the code for tRNACyS, and would be expected to be substituted for cysteine in protein being synthesized, whereas THN-cysteine not previously esterified to tRNA is activated by the isoleucyl- and valyl-RNA synthetases, and its incorporation is stimulated by Poly-AU and Poly-UG, respectively. Consequently, in this case, THN-cysteine would substitute for isoleucine and valine during protein synthesis.