Optimal and discriminating birth weights in human populations. A new model for estimating the optimal birth weight of a sample of infants from a human population, based on conditional survival probability, is developed. Also, a method is developed for estimating the 'lower discriminating birth weight' (LDBW), the weight below which an infant has a greater probability of dying than surviving, and the 'upper discriminating birth weight' (UDBW), the weight above which an infant has a greater probability of dying than surviving. These models are tested using previously published human birth weight data from British, German, Indian, Italian, and United States samples. The relationship between LDBW and 'prematurity' is briefly discussed.


Differential growth of human foetal gonads with respect to sex and body side. Measurements have been carried out on the gonads of 54 human foetuses, 29 males and 25 females. Crown-rump lengths ranged between 140 and 212 mm. The criteria used were fresh weight, total protein contents and total DNA contents. It was found that for any given crown-rump length class, the mean values of testes exceeded those of ovaries for all three criteria. It was also found that the mean values of right gonads exceeded those of left gonads. Since in true hermaphrodites, testes are preferentially situated on the right and ovaries on the left side, it is concluded that there is a causal relationship between increased growth rate and testicular differentiation. It is suggested that in normal development this function is performed by the Y chromosome.


A matrix method for calculating recurrence risks of unilocal disorders for genetic counselling. A matrix method to calculate conditional likelihoods in a pedigree and use them to determine recurrence risks for unilocal disorders in genetic risks is presented in this paper. Different matrices are assigned to individual members of the pedigree and combined into matrix expressions. The method is explained for X-linked recessive conditions and autosomal dominant conditions with incomplete penetrance.


The use of matrices in calculating mendelian probabilities. It is shown that the method of calculation of probabilities for genetic counselling developed by Bolling, Chase and Murphy can be generalized to give the relative probabilities for any single individual in any pedigree for any mendelian condition. The calculations only require matrix multiplications (of one kind or another), and the expressions can be written down and evaluated directly, whether by hand or by computer.


Chromatid exchanges in ataxia telangiectasia, Bloom syndrome, Werner syndrome, and xeroderma pigmentosum. The frequency of BrdU-induced sister chromatid exchanges (SCE) in cultured lymphocytes from patients with ataxia telangiectasia, Werner syndrome, and xeroderma pigmentosum was normal. The rate was increased in xeroderma pigmentosum following exposure to ultraviolet light and spontaneously raised in the Bloom syndrome. Quadriradial exchanges between homologous chromosomes in Bloom syndrome not only involve sister chromatids but also homologous (non-sister) chromatids. This could result in the formation of recombinant chromosomes and is viewed as a genetically determined form of increased somatic recombination in man. Endoreduplicated metaphases showed 'twin' and 'single' exchanges in a 1:2 ratio. This suggests a comparable frequency of exchanges at both divisions and provides evidence for the polarity of the chromatid subunits and the presence of a single chain of DNA.


Visual classification of banded human chromosomes. I. Karyotyping compared with classification of isolated chromosomes. Visual karyotyping and visual classification of isolated chromosomes was carried out by seven investigators on 22 trypsin banded metaphases of average quality. The karyotyping experiment resulted in an average error rate of 0-1% (zero-0-4%) and the classification of isolated chromosomes resulted in an error rate of 3% (2-5%). The B and F group chromosomes were found to be most difficult to classify when isolated, while no errors were made of the no. 1 and the X chromosome. Large differences were seen in the resulting error pattern for the individual investigators both with regard to their total error rate and also the chromosome types which they most frequently misclassified. Based upon these error patterns it is suggested that more than 95% of the chromosomes in an average quality material contain features upon which a reliable visual classification can be made. Thus there may be a potential possibility that these chromosomes may be classified by computer on the basis of these features. The fact that visual karyotyping is much more reliable than visual classification of isolated chromosomes indicated that computer classification of chromosomes should include programming capable of making appropriate comparison between the chromosomes in the metaphase and at the same time take into account the expected presence of 23 chromosome pairs for normal cells. This would simulate the human performance of visual karyotyping and make a classification possible of at least some of the remaining 5% difficult chromosomes.


C- and Q-band polymorphisms in the chromosomes of three human populations. The incidence of the various classes of C-band and Q-band polymorphisms on ten pairs of chromosomes in the human complement have been investigated in three Scottish populations, two from the mainland (newborn and 14 year olds) and one, of individuals over 65 years, from an island in the Outer Hebrides. Although there is an overall similarity between the populations, there are some differences, especially with the island group. For all populations, over 90% of the C-band size variants fall within the medium class. Rather more variation is found in the Q-band intensity polymorphisms: the island population appears to have fewer Brilliant and Intense variants than do the other two groups, 2-9 per person as compared to 4-2 and 3-9 for the newborn and 14 year olds respectively; this may be an age difference rather than a population difference.


Expression of a mouse immunoglobulin V gene in homozygote and heterozygotes. Our earlier work had demonstrated a fine-specificity idiotype in anti-NP antibodies of C57Bl/6 mice. It was controlled by a VH gene (VH-NPb). The idiotype could be demonstrated in all anti-NP of the C50Bl/6 mice (IgG, IgA, IgM including natural anti-NP). The VH-NPb gene is condominant with CBA allele F1 hybrid mice in the production of natural antibodies but dominant over the CBA allele in immune antibody formation (92% of F1 mice were like C57Bl/6). Probably the product of this gene has a higher affinity for NP than the average affinity of idiotype-negative antibody in the F1 hybrids. Both the codominance in natural antibodies and the dominance in immune antibodies had the peculiar characteristic that genotypically identical individuals varied a great deal. The share of idiotype-positive antibody in the total natural anti-NP titre of (C57Bl/6 x CBA)F1 mice varied from less than 33% to more than 67%. In immune antibodies individual differences were still greater, in ca 92% of mice only idiotype-positive anti-NP could be detected and in ca 8% only idiotype-negative antibody was detectable. Only few F1 hybrid mice had detectable amounts of both types. Homozygous mice of the LP strain behaved in all aspects like the F1 mice. Of their natural anti-NP titres 50% were due to idiotype-positive antibody and in the immune antibodies the figure was 86%. Individual non-immune sera again contained varying mixtures of idiotype-positive and idiotype-negative antibody, but immune sera contained only one or the other type. The third allotype b strain tested, C57Bl/Ka, took an intermediary position between LP and C57Bl/6. Ca 70% of natural anti-NP titres were due to idiotype-positive antibody but all immune anti-NP was idiotype-positive.


Immunodeficiencies in severe atopic dermatitis. Depressed chemotaxis and lymphocyte transformation. Various reports have indicated assorted immune defects in atopic dermatitis, but the prevalence and degree of the defects remain unclear. We assessed various immunological factors in 14 patients with atopic dermatitis to determine whether immunodeficiencies were present consistently and were reflected by the patients' clinical characteristics. A high incidence of cutaneous infection was noted. Cutaneous delayed-hypersensitivity testing showed anergy in eight (67%) patients. Only the seven patients with the most severe condition showed altered leukocyte function, as determined by polymorphonuclear and mononuclear leukocyte chemotaxis and by lymphocyte responsiveness to phytohemaglutinin. All three cell types where shown to be simultaneously dysfunctional during  severe atopic flares. Chemotactic studies during clinical remissions disclosed notable improvement in cell migration. Serum IgE levels were elevated in each patient, but did not correlate with the degree of cutaneous anergy or altered leukocyte function.


Topically applied thiabendazole in the treatment of scabies. Forty patients were treated for scabies with a 10% suspension of thiabendazole applied externally. Thirty-two patients (80%) had a satisfactory response to one course of therapy, while a second course was necessary in six (15%). Two patients (5%) required intralesional injections of triamcinolone diacetate because of persistent scabious nodules.


Somatic generation of antibody diversity. Hybridization of lambda-mRNAs to excess liver DNA yielded results compatible with gene reiteration frequencies of three or less. Purified mRNA from tumors producing structurally different lambda chains were used in competition hybridization experiments. An unlabeled lambda-mRNA competed with another, labelled mRNA to the same extent as homologous unlabelled lambda-mRNA. Mouse DNA was digested with Eco R-I restriction endonuclease and fractionated by gel electrophoresis. A DNA fragment carrying the V lambda-gene(s) was indentified in this digest. This fragment hybridized with lambda-mRNAs coding for two different lambdaV regions equally well. These results indicate that base sequence homology among lambda-mRNAs is so high that any lambda-mRNA should cross-hybridize with all or most of germ line V lambda genes. From amino acid sequence data, it is argued that there are probably more than 25 different lambdaV regions. Hence it is concluded that the number of germ line genes is too small to account for the diversity of lambda chains.


Vulval epidermoid cysts in the Igbos of Nigeria. Epidermoid cysts are reported to be uncommon on the vulva. However, among the Igbos of Nigeria, the vulva was the most common site of such cysts in a series of specimens examined at a central laboratory. Vulval epidermoid cyssts probably arise as a result of traumatic implantation during ritual circumcision.


Persulfate hair bleach reactions. Cutaneous and respiratory manifestations. Ammonium persulfate is widely used to "boost" peroxide hair bleaches. These persulfates can produce a variety of cutaneous and respiratory responses, including allergic eczematous contact dermatitis, irritant dermatitis, localized edema, generalized urticaria, rhinitis, asthma, and syncope. Some of these reactions appear to be truly allergic while others appear to be due to the release of histamine on a nonallergic basis. Patch tests may be performed with 2% to 5% aqueous solution of ammonium persulfate. Scratch tests may result in asthma and syncope. In some patients, merely rubbing a saturated solution of ammonium persulfate into the skin will evoke a large urticarial wheal. Hairdressers should be made aware that these ammonium persulfate hair bleach preparations may provoke severe reactions and should seek medical attention if the client complains of severe itching, tingling, a burning sensation, hives, dizziness, or weakness.


Epidermal nevus and rhabdomyosarcoma.

Epidermal nevus and rhabdomyosarcoma. A child with an epidermal nevus was diagnosed at the age of 15 months as having an embryonal rhabdomyosarcoma of the bladder. This child also had pigmentary abnormalities characteristic of the epidermal nevus syndrome. The question is again asked whether patients with epidermal nevi have an increased incidence of tumors. It is suggested that the thorough evaluation of these patients as recommended by Solomon should also include an alertness for the development of earlier-than-anticipated neoplasms.


Erosive adenomatosis of the nipple.

Erosive adenomatosis of the nipple. Erosive adenomatosis of the nipple is a rare, usually benign neoplasm of the major nipple ducts. Although morphologic features may distinguish it from Paget disease, histopathological differentiation is simple. Recognition of this tumor may spare needless mastectomy.


Perinevoid alopecia. An unusual variety of alopecia areata. We report three cases of alopecia areata occurring around central, pigmented nevi. The histologic appearance of the central nevus was that of the halo nevus. Removal of the nevus did not appear to alter the natural course of the alopecia. Histochemical studies showed a substantial increase of acid mucopolysaccharides in the dermis in each case.


Umbilical endometrioma (silent type).

Umbilical endometrioma (silent type). Umbilical endometrioma is an uncommon entity and is rarely asymptomatic. A 24-year old black woman had an asymptomatic, spontaneous umbilical endometrioma. The lesion was excised and the diagnosis was histologically confirmed.


Steatocystoma multiplex.

Steatocystoma multiplex. Steatocystoma multiplex is a poorly understood clinical condition characterized by numerous cutaneous cysts. The lesions can be confused with milia, epidermal inclusion cysts, sebaceous cysts, dermoids, and the cysts of acne vulgaris. This patient has hypotrichosis and multiple milia-like cysts on the face and scalp, showing the histologic characteristics of steatocystoma multiplex.


Acquired hypertrichosis lanuginosa. A skin marker of internal malignancy. A 54-year-old woman had acquired hypertrichosis lanuginosa. She developed excessive growth of lanugo-like hair all over her body two years prior to the sudden appearance of a rapidly growing, localized, solid mammary tumor. Of 12 published cases, nine have been associated with an internal malignant neoplasm and obviously, as in the present case, the cutaneous symptoms may serve as a skin marker by preceding the tumor diagnosis for up to two years.


Phototoxic textile dermatitis ("bikini dermatitis"). Phototoxic textile dermatitis with subsequent hyperpigmentation developed in two patients after they wore bikini bathing suits. After extraction of the dye from the bathing suits, 15 fractions could be visualized by two-dimensional thin-layer chromatography. Two of these fractions are found in Disperse Blue 35, an anthraquinone dye known to give rise to occupational phototoxic dermatitis, but which, to our knowledge, has never been reported to cause dermatitis in consumers. One of the two fractions was also found to cause phototoxic reactions in normal subjects.


Hidrotic ectodermal dysplasia in a black mother and daughter. Hidrotic ectodermal dysplasia is a rare genodermatosis with clinical hallmarks of alopecia, nail dystrophy, and palmoplantar hyperkeratosis. This report calls attention to the first reported cases, to our knowledge, of hidrotic ectodermal dysplasia in a black mother and daughter.


Hepatitis and bone destruction as uncommon manifestations of early syphilis. Report of a case. We describe a patient with a painful lytic lesion of the clavicle and a granuloma of the liver in late secondary syphilis. The classic "moth-eaten" alopecia of the scalp as well as eyebrows and eyelashes suggested syphilis, although an initial false-negative VDRL test for syphilis (prozone phenomenon) caused a delay in diagnosis. Bone as well as liver involvement in early syphilis may be more common than previously recognized.


Inhibition of induction of human contact sensitization by topical glucocorticosteroids. Ten healthy human volunteers were exposed to a primary sensitizing dose of 1 mg dinitrochlorobenzene (DNCB) by an open topical technique within an area that had been pretreated with a potent topical glucocorticosteroid compound. Quantitative elicitation testing was performed on the opposite side by an open patch test technique two weeks after the sensitizing application. One (10%) of the ten subjects became sensitized. A matched control group of ten subjects was similarly sensitized without steroid treatment. Eight (80%) of the ten became sensitized. One month later, five of the eight test subjects in whom sensitization had been prevented were retested in an identical fashion without steroid pretreatment, to determine if any degree of tolerance had been induced. All five subjects became sensitized. Topical glucocorticosteroids inhibited the development of sensitization to topically applied DNCB. Tolerance was not induced by this single process.


Allergic contact dermatitis and stomatitis caused by a cinnamic aldehyde-flavored toothpaste. A patient had acute stomatitis and dermatitis due to a popular toothpaste containing cinnamon oil flavor. Cinnamon cassia oil is known as a topical sensitizer and was demonstrated to be the offending allergen. Cinnamic aldehyde and related chemicals are used widely, so that patients having cinnamon allergy may be exposed to many sources. There is difficulty in diagnosing allergic contact stomatitis.


Dermatologists in the United States, 1968 through 1973. From 1968 to 1973, the number of dermatologists in the United States per 100,000 population gradually increased from 1.6 to 1.8, with the West and Northeast regions showing relatively higher rates and the South and North Central regions showing relatively lower rates. The variation in rate, considered by geographic divisions, can be analyzed to identify areas in the United States that may be in need of additional dermatologists. Given the current number of dermatologists being certified by the American Board of Dermatology and given the current death rate, there appear to be a sufficient number of dermatologists to ensure future growth.


Treatment of dermatomyositis in childhood. Analysis of the response to corticosteroid therapy in a personal series of 8 consecutive cases of dermatomyositis in childhood shows that there are advantages in a moderate dosage, short-term treatment schedule, with gradual tapering of the dosage as soon as there is clinical improvement without waiting for full remission, and in trying to stop steroid therapy within six months rather than following the more prolonged regimen currently still in vogue. Clinical response is a more reliable guide to progress than serum enzyme levels. Review of published reports suggests that overtreatment with corticosteroids may be a factor in chronicity of the disease and failure of adequate long-term response.


Association of cystic fibrosis with allergy. Immediate skin hypersensitivity to various inhalant allergens was present in 59% of 123 children with cystic fibrosis (CF), a much higher percentage than in the general population. This is consistent with the idea that atopy arises as a result of impaired handling of antigen at mucosal surfaces. The allergic CF children had more chest infections, a worse chest x-ray appearance, and lower peak expiratory flow rates. Allergic diseases were also frequent in the CF obligate heterozygotes (32% of mothers and 26% of fathers). It is suggested that the heterozygotes may also have a mucosal abnormality resulting in defective antigen handling.


Long-term assessment of children exposed in utero to carbimazole. Twenty-five children aged 3 to 13 years who had been exposed in utero to carbimazole were assessed physically and psychologically to evaluate the long-term effects of the drug on growth and development. 2 children had congenital malformations but all had normal pituitary-thyroid function and appeared to have grown and developed normally.


Plasma renin activity and aldosterone concentration in the human newborn. Twenty-one healthy newborn infants whose mothers had normal pregnancies and deliveries were studied. Plasma renin activity (PRA) and plasma aldosterone concentration (PAldo) were measured by semimicro methods in cord blood and on the 6th day of life. PRA and PAldo were increased in cord blood compared with values previously found in healthy infants between 1 month and 1 year of age. There was a twofold reduction in both values by the 6th day. PRA and PAldo were positively correlated when cord blood and 6th-day values were considered as a whole, but no significant correlations were found between either cord blood PRA or cord blood PAldo and their respective values on the 6th day. The PRA and PAldo findings were not related to birthweight, the infant's sex, weight change, 6th-day urinary sodium, or blood pressure measurements. The type of milk feed did not influence PRA but PAldo was slightly greater in bottle-fed babies on the 6 day. These observations confirmed that the inverse relationship between PRA, PAldo, and age extends into the neonatal period but they suggest that the balance of factors controlling these variables at birth is different to that operating at the age of 6 days.


Follow-up of 13 children after ureterosigmoidostomy. Follow-up of 13 children who had had a ureterosigmoid anastomosis 3 1/2 to 10 years previously and whose initial urogram had been satisfactory, showed that growth was normal and that there was no serious metabolic disorder. In particular whole-body potassium did not differ significantly from normal values (as given by Langham, 1961). Asymptomatic urinary infection is the chief hazard in these cases but is difficult to diagnose and may lead to progressive dilatation of the ureters.


Achondrogenesis type I. A familial subvariant? The clinical, pathological, and radiological features of 2 male sibs with a severe and lethal form of micromelic dwarfism are desribed. The family also includes 2 normal sibs. The histological and radiological appearances suggested a diagnosis of achondrogenesis type I, but the markedly deficient ossification of the skull and the presence of intrauterine rib fractures were atypical. These changes have been observed in two other families with 2 or more infants with suspected achondrogenesis, raising the possibility that these familial cases may be a subvariant of achondrogesis or even a distinct disease entity. The disease appears to be inherited as an autosomal recessive and death occurs shortly after birth because of severe pulmonary hypoplasia.


Homozygous cystinuria and the oculo-cerebro-renal dystrophy of Lowe in same family. The mother and daughter in a family had homozygous cystinuria and were also heterozygous carriers of the oculo-cerebro-renal dystrophy of Lowe. The daughter was also epileptic. The son had Lowe's syndrome and the father an increased urinary excretion of cystine and lysine. This evidence together with other case reports suggests that the defect in cystinuria and that of Lowe's syndrome may be connected.


Pre- and postoperative growth in persistent ductus arteriosus. Children with a persistent ductus arteriosus requiring ligation under 6 months of age show evidence of intrauterine growth retardation. By the time of operation the weight centile of 17 (71%) of 24 such infants had fallen, but 20(84%) of the 24 gained weight postoperatively. Those who did not so were either large-for-dates infants growing towards the normal or small-for-dates infants who remained small postoperatively.


Neonatal thyrotoxicosis is associated with transplacental passage of human thyroid stimulating immunoglobulin (HTSI). A woman who developed thyrotoxicosis during pregnancy had a high level of HTSI at the time of delivery. The baby had high levels of HTSI initially but, unlike the mother, the levels fell, giving a half-life of HTSI of 10 days.


Hypoaldosteronism in three sibs due to 18-dehydrogenase deficiency. Three sibs all presented in the early neonatal period with a salt-losing syndrome. The salt-losing form of congenital adrenal hyperplasia was diagnosed and appropriate treatment with glucocorticosteroids, mineralocorticosteroids, and additional dietary salt started. Although early life was maintained with difficulty, with age all 3 children required decreasing amounts of replacement steroids to maintain normal plasma electrolyte balance. They were reinvestigated at the ages of 15 years and 8 years (twins), when cortisol synthesis and metabolism proved normal, but aldosterone synthesis was blocked by deficiency of 18-dehydrogenase. Rational treatment of these cases of a salt-losing syndrome in which aldosterone synthesis alone is blocked due to lack of the enzyme 18-dehydrogenase requires the administration of a mineralocorticosteroid drug only. Since deoxycorticosterone (acetate or pivalate) requires intramuscular administration, as life-long therapy oral fludrocortisone is preferable. Although fludrocortisone has glucocorticoid activity, the "hydrocortisone equivalent" effect of the small dosage used was unlikely to inhibit either pituitary corticotrophin or growth hormone production.


Lack of breast feeding and early weaning in infants of Asian immigrants to Wolverhampton. Fifty Asian immigrant mothers who would have expected to breast feed their infants had they remained in rural Asia were studied. There was a striking reduction in the incidence and duration of breast feeding on arrival in the United Kingdom, and a fall in the age of weaning. The availability of an alternative to human milk is the most important factor reducing the incidence of breast feeding. Only 2 (4%) of the 46 infants followed prospectively were breast fed. Reasons for not breast feeding were sought and the results indicated that the majority of mothers were frightened, misinformed, or apathetic about breast feeding. If breast feeding is to be promoted, antenatal education and encouragement is essential. The advantages of human milk need to be stressed. Potentially serious mistakes occurred in preparing bottle feeds, and vitamin supplements were often inadequate. Later weaning could be encouraged by the staff of well baby clinics.


Congenital paroxysmal atrial tachycardia. Ten infants who had paroxysmal atrial tachycardia in utero or at birth are reported. Because of apparent fetal distress, caesarean section was performed in 4 cases and labour was induced in 1. Birthweight was generally large for gestational age. Severe ascites and hydrops at birth were manifestations of cardiac failure. Atrial flutter was recorded in 4 infants and supraventricular tachycardia in 5. The WoLff-Parkinson-White syndrome became evident later in 2. Digoxin was given to all 10 infants, and cardioversion was required and was effective in 4. Known recurrences in childhood have occurred in only 1 patient. Congenital atrial tachyarrhythmias may be commoner than generally believed, and fetal electrocardiography may help to avoid unnecessary termination of pregnancy. Blood sugar determinations are important, since neonatal hypoglycaemia was found. Cardioversion should be performed promptly in severely ill infants or if there is no response to digoxin. Care is required to avoid digoxin toxicity.


Arthrogryposis multiplex congenita. Search for prenatal factors in 66 sporadic cases. In a family and epidemiological survey of 66 cases of arthrogryposis multiplex congenita all cases were found to be sporadic and no family association with clubfoot, congenital dislocation of the hip, or hereditary neuromuscular disease was found. The mothers were significantly older than average. Oligohydramnios was noted in only one-third of cases but many other complications of pregnancy, including probable attempts at abortion, had occurred. It is likely that most cases of arthrogryposis are nongenetic and result from a defective intrauterine environment, whether hormonal, vascular, mechanical, or possibly infective.


Alterations in head shape of newborn infants after caesarean section or vaginal delivery. Alterations of head shape in preterm, small-for-dates, and term normal infants were studied by measuring occipitofrontal circumference (OFC), biparietal diameter (BPD), and occipitofrontal diameter (OFD) at intervals after birth. In 9 preterm infants born by elective caesarean section ther was a 5-2% reduction in BPD and 2-0% reduction in OFC at the age of 7 days. In 18 term infants born by elective caesarean section these changes were 2-4% and 0% respectively in BPD and OFC. In 25 preterm infants born by vertex vaginal delivery there was a significant fall in OFC of 0-7% at the age of 7 days and of 2-4% in BPD, but no significant change in OFD. In 19 small-for-dates infants born vaginally OFC increased 1-0% and OFD 2-7% at 7 days, but BPD decreased 2-5%. After the first week all three measurements increased in both groups of vaginal deliveries. The results show that shrinkage and biparietal flattening of the skull occur during the first week of life in preterm and term infants born by caesarean section and in preterm infants born vaginally. This fact should be borne in mind when comparing the measurements of an infant's head size with published norms.


Echovirus 19 infection in infants under six months. Twenty-four infants under 6 months infected with echovirus 19 are described, They were the youngest of the many children admitted to hospitals in Newcastle and Gateshead during an epidemic in the north-east of England in 1974. Generally, the younger the child the more severe the illness, which affected the upper respiratory tract, the gut, the skin, and the meninges, and sometimes caused as state of collapse resembling septicaemic shock. Polymorphonuclear pleocystosis of the cerebrospinal fluid (CSF) sometimes suggested bacterial meningitis, so that antibiotics were given in 38% of cases. The virus was recovered with a high success rate from nasopharyngeal secretions, CSF, and stool.


Severe echo 19 virus infection in a neonatal unit. An epidemic of echo 19 virus infection in a neonatal unit affecting 12 babies with one death is described. With one exception it was confined to the neonatal unit and medical and nursing staff were also affected. The unit was closed for 9 days, then was disinfected, and there was no recurrence.


Organic aciduria. Treatable cause of floppy infant syndrome. A floppy infant is described who has an inborn error of organic acid metabolism due to defective activity of the enzyme beta-methylcrotonyl CoA carboxylase. She presented with hyperventilation, hypotonia, and regression of motor and intellectual development. She responded to treatment with biotin.


Balanced translocation, impaired sperm motility, and offspring anomaly. An infant with multiple physical abnormalities, failure to thrive, and mental deficiency, all probably due to a 22/11 chromosomal translocation is described, and the implications of inducing pregnancies in childless couples are discussed.


Enhancement of sperm acrosin activity by glycerol-pretreatment - quantitative estimations. Acetic acid treatment of spermatozoa, a method suitable for optimal extraction of the acrosomal proteinase acrosin, was used to show the influence of glycerol on sperm acrosin activity. Short-time pretreatment of semen samples with glycerol in concentrations up to 35% (v/v) caused a 1.5-2.5 fold increase in sperm acrosin activity. Higher glycerol concentrations caused a decrease in sperm acrosin activity due to leakage of the enzyme into the suspension medium. A further increase in sperm acrosin activity was observed during aging of semen in the presence of glycerol. In this case, the height of the increase depends on the glycerol concentration applied as well as incubation temperature and time. The acrosin activation pattern induced by glycerol was not influenced by proteinase (acrosin) inhibitors. On the other hand, addition of glycerol to spermatozoa from which the seminal plasma had been removed and substituted by physiological saline caused only a small increase in sperm acrosin activity. This indicates the occurrence of a seminal plasma factor which is either stimulated (activated) by glycerol or which can penetrate the membranes and subsequently activate acrosin only in the presence of glycerol. This seminal plasma factor was not consumed during activation and could be transfered to another sperm sample. However, a protecting influence of such a factor on the sperm head membranes and thus an indirect activation effect, i.e. better extractibility of acrosin, has also to be considered. The glycerol-induced rise of the acrosin activity is not caused by reversible conformational changes of the enzyme molecules: acrosin activity was not diminished if glycerol was removed from semen samples or extracts later on. The possibility that the observed increase in BAEE-splitting activity is due to a so far unknown proteinase may be excluded: the activity completely disappeared by neutralization due to formation of the acrosin-inhibitor complex and appeared again by acidification, a well known characteristic of acrosin and its inhibitors. Factors which are probably responsible for the glycerol-induced activation of acrosin-membrane effects and the activation of a precursor from of acrosin-are discussed.


[Immunological investigations in lichen planus patients (author's transl)]. 30 patients suffering from generalized lichen planus (= L.p.) have been examined by the following methods in order to more precise information regarding their immune-status: 1. Quantitative determination of immuno-globulins including complement fraction (beta 1C/A) 2. Intracutaneous tests with recall-antigens 3. Investigation of cutaneous sensitivity to DNCB 4. Lymphocytemigrationinhibition- and Lymphocytetransformationstests. The results obtained were not statistically significant when comparing the results of this investigation in patients suffering from L.p. with the control group. Therefore, the theory that immunological processes are the basis of these occurences is still under discussion. Further studies applying more specific methods should be conducted in order to clarify this problem.


[Morphological and biochemical investigations of hairs in inborn errors of amino acid metabolism (author's transl)]. The influence of inborn errors of metabolism on the amino acid content, the structure and growth of human hair has been studied in patients suffering from Phenylketonuria, Cystinosis, Homocystinuria and Tyrosinosis. Examiniation of hairs under the scanning electron microscope reveals defects and abnormalities such as a plicated pattern of the cuticula in patients with Phenylketonuria and Cystinosis. The amino acid content of the hydrolized hair keratin of all patients was within normal range and did not reveal significant changes of phenylalanine, cystine, homocystine, methionine or tyrosine. Disturbance in hair growth was determined by evaluation of standardized hair root samples. The results indicate an increase in hair root atrophy with increasing severity of the disorder of amino acid metabolism.


[Penetrations kinetics and distribution of topically applied estrogens (author's transl)]. The penetration into the single layers of human skin in vitro of 17 alpha-estradiol, 17 beta-estradiol and estriol was investigated. The radiolabeled substances were incorporated into 4 standard ointments and into an alcoholic solution mixture. After application to the skin and after different penetration periods, the horny layer was taken off by adhesive tape stripping. The epidermis and the dermis were separated by slicing them down parallel to the skin surface in a freeze microtome. In each single layer, the amount of substance was determined and calculated relative to the applied quantity and in absolute concentrations (mug per tissue weight and molarity). Besides the expected dependence of the penetration on the type of ointment, there is a distinct dependence on the chemical structure: estriol penetrates considerably slower and in less concentrations into the living layers of the human skin than the estradiols. Furthermore, estriol reaches the dermis only in low concentrations so that this substance may be termed epidermotropic. 17 alpha-estriol which has only weak sexhormone properties in humans penetrates as well as the sexhormone 17 beta-estradiol.


Separation, isolation, and amino acid composition of the albumin-like fraction from psoriatic scales. The albumin-like fraction of psoriatic scales was isolated either directly by slab gel electroporesis or after previous treatment with polyethylene glycol6000. After both isolation procedures the amino acid composition was determined. Both proteins were rich of glutamic acid, glycine, and alanine. On the other hand both contained very small amounts of cysteine and tyrosine. Only after the direct isolation procedure the amino-sugar galactosamine could be detected.


Dopa-positive cells and melanin in basal cell epithelioma (BCE). In 47 out of 61 bce's, melanocytes were detectable with the aid of Dopa-reaction. In 24 of these cases, the percentage of tumour cells was less 5%, and in 23 it was more. The melanocytes preferred the periphery of the epithelial tumour formations. Only when the proportion of melanocytes exceeded 5% were they also to be found in the central parts of the tumours. Generally the melanocytes were more numerous in the upper parts of tumours, next to the epidermis. Our findings strengthen the opinion, that bce is a tumour of the primary hair germ.


Enzymes of carbohydrate metabolism in naevoid basal-cell epithelioma. The activities of 27 enzymes of carbohydrate metabolism and the proportions of lactate dehydrogenase isoenzymes were determined in epidermis, in superficial epitheliomas and in several solid tumours biopsied from a patient with basal-cell naevus syndrome. The activity patterns varied from that of normal epidermis to that found in basal-cell epitheliomas. Thickened epidermis, superficial epitheliomas and some of the solid tumours presented an intermediate pattern. Histologically similar lesions sometimes differed markedly in their enzyme activities.


[Experimental inoculation of Leishmaniasis tropical from man to man (author's transl)]. Experimental transformation of leishmaniasis from man to man was demonstrated. The infection occurs through direct inoculation of the leishmania organism in the amastigote form: from an ulcer of a leishmania papule some materials were obtained and were inoculated intradermally in the thigh of one of the authors. Within weeks a red papule has developed in the place of inoculation from which the microorganisms were frequenctly demonstrated. The papule was cured spontaneously within 70 weeks under a formation of a flat pigmented scar. In the electronenmicroscopy the microorganisms were seen to be located intracellular. The microorganism had a double outer membrane, an oval nucleus, and a kinetoplast out of which (in the phlebotomus fly or in the culture) the future flagellum would be formed.


Ultrastructural studies in epidermolysis bullosa hereditaria. III. Recessive dystrophic types with dermolytic blistering (Hallopeau-Siemens types and inverse type). Ultrastructural examination was performed in 42 biopsy specimens from 22 patients with the Hallopeau-Siemens types or with the inverse type of epidermolysis bullosa dystrophica recessiva. The patient group consists of 8 cases of the localized Hallopeua-Siemens type, 9 of the generalized Hallopeau-Siemens type and 5 of the inverse type. The origins of the biopsy specimens are involved, intact and experimentally frictioned skin from blister-predilected sites, as well as clinically normal skin from nonpredilection sites. It is confirmed that all the blisters initiate below the basal lamina. Anchoring fibrils are moderately to markedly decreased in most cases, while they are normal in 3 other cases. It is thought that secondary degradation of anchoring fibrils and/or collagen fibrils plays an important role in blistering mechanism in the Hallopeau-Siemens and inverse types of recessive dystrophic epidermolysis bullosa, whereas a primary aplasia of anchoring fibrils as causative defect has been out ruled.


Early metastases in regional lymph nodes and prognosis of malignant melanoma. Histological and clinical examinations in 104 lymphadenectomized patients. In 104 malignant melanoma patients who underwent lymphadenectomy (67 females, 37 males), correlations were studied between histologically diagnosed lymph node metastasis, the type of malignant melanoma and the depth of invasion according to Clark, as well as other parameters. In 35.6% of the patients, metastases of the primary tumor were found in one or several regional lymph nodes. In about one third of the patients, the clinical and histological lymph node findings were proven to diverge. The female:male ratio of generally about 2:1 shifted to 1:1 in the group of patients with lymph node metastasis, i.e. cases with lymph node metastasis were found significantly increased in the male sex, and also, when primary tumors were localized on the trunk. A prognostic correlation between the two parameters, sex and localization, is suggested by the high incidence of histologicallly diagnosed metastases in 1 or 2 lymph node regions, when malignant melanomas were localized on the trunk in males. As to the types and the micro-stages of primary tumors, the number of cases collected until now does not permit establishing clear correlations with the incidence of lymph node involvement. Calculating the 5-year-survival rates for patients with and without lymph node metastasis according to the "actuarial method", we found the prognosis to depend largely on the presence or absence of lymph node involvement, even at a time as early as at primary tumor excision. Our results support the indication for prophylactic lymphadenectomy in malignant melanoma, provided the primary tumor has reached or surpassed the micro-stage 3.


Fluorescence-microscopic investigations of pigment cells of lentigo maligna (melanosis circumscripta praeblastomatosa Dubreuilh) and lentigo maligna melanoma. With fluorescence-histochemical methods (formalin-induced fluorescence), the different stadia of development of lentigo maligna (Morbus Dubreuih) and lentigo maligna melanoma were investigated. In this way, the special stadia can be clearly characterized using the fluorescence-microscope. In the earliest stadium of malignancy, only the pigment-cells of the basal part of the epidermis seem to be numerous. At this time, these cells are mainly arranged as palisades in the basal layer, and their strongest dendrites are usually directed towards the corneal layer. As the malignancy progresses, the pigment-cells are arranged in several layers in the basal epidermis. In this case, polymorphism of the cells is obvious and their dendrites spread in all directions. A further stadium shows pathological alterations resembling a lentigo with long rete ridges. The atypical cells cluster together into the so-called pseudonests, predominantly at the tips of these rete ridges. With the fluorescence-microscope, dendrites are seldom visible here. In the stadium of tumorous growth, all above-described alterations of the epidermis in lentigo maligna are no longer detectable. Malignant cells in the dermis, which form as a tumor mode, seldom show dendrites. These cells are mainly round or oval-shaped; at best there are some spindle cells in certain areas of the tumor. The epidermis covering the tumor node is infiltrated by some tumor cells but the characteristic alterations as described above for the various stadia of lentigo maligna are no longer visible. Even fluorescence-microscopically, a tumor node of lentigo maligna does not seem to be different from a primary nodular melanoma or a tumor node of a superficial spreading melanoma, if the flat parts of the tumors are not considered in the diagnosis.


Comparison of the surface glycoprotein components in the isolated cells of hamster melanotic and amelanotic melanomas. A suspension of melanoma cells isolated non-enzymatically from tumors (melanotic and amelanotic) of transplantable melanoma in Syrian hamster was treated with trypsin to obtain surface material. In the material released from the cell surface contents of protein, aminosugars, fucose, sialic acids and hexoses were determined. Differences in the composition of the surface material derived from two kinds of melanoma were observed. The differences in the surface glycoprotein composition seem to be related to biological properties of both melanomas.


Which breast to biopsy: an expanding dilemma. To provide insight into the significance of findings reported from screening asymptomatic women for breast cancer, we reviewed 19,928 mammographic studies with the accompanying physical examination and correlated these findings with 554 breast biopsies. Of 83 breast biopsies with suspicious findings on both physical examination and mammography, 72 demonstrated breast cancer (87%). Of 155 biopsies for suspicious  changes on mammography alone, 50 (32%) demonstrated breast cancer. The accuracy of suspicious mammography was independent of findings limited to physical examination, 34 (17%) had breast cancer; 31 were in 152 biopsies of patients with mammography interpreted as normal (20%) and three were in biopsies of 52 patients (6%) in whom a visualized  mass was interpreted as benign. One hundred and twelve breast biopsies were performed for changes interpreted as normal or benign. Six malignancies were discovered (5%). No cancer was found in 31 biopsies for nonpalpable benign mammographic abnormalities. Our results emphasize the importance of discriminating between nonvisualization of a mass and mammographic recognition of either a benign or malignant tumor. The reliability of interpretation is considerably greater for a visualized lesion than a nonvisualized one.


Immunobiology of operable breast cancer: an assessment of biologic risk by immunoparameters. The concept of whether immune function was related to risk of  recurrence was examined in patients with operable breast cancer in whom careful clinical and pathologic staging had been performed. Patients were classified according to the risk of recurrence. The "low risk" group included patients with minimal breast cancer, noninfiltrating cancer, or infiltrating cancer less than 1 cm with negative nodes. The "high ridk" group included patients with lesions greater than 1 cm or who had greater than or equal to 4 nodal metastases or who had macrometastases at Level II or III (apex). In the "intermediate risk" group were patients with infiltrating cancer less than 1 cm or with less than 4 nodal metastases at I only. Immune reactivity was assessed by skin tests, by measurement of absolute lymphocyte count, T and B cells, lymphocyte stimulation by mitogens and a battery of common antigens, serum immunoglobulins and complement levels. There were 134 patients with operable breast cancer and 63 patients with benign breast lesions. The breast cancer patients showed minimal or no impairment of DNCB skin test. Only patients with nodal metastases showed a slight but not significant impairment of DNCB responses (80% were DNCB positive compared to 90% in the controls.) The lymphocyte responses to mitogens were normal in the breast cancer patients, but there was a significant depression of lymphocyte responses to certain recall antigens such as Candida albicans and E coli. The absolute lymphocyte count and the T cell counts were normal, but B cells bearing complement receptors were decreased and B cells bearing sufface immunoglobulins were increased in the breast cancer patients. Analysis of immune function according to the pathologic stage of disease "risk of recurrence" categories showed no correlation with skin tests or lymphocyte levels. A striking and paradoxical finding was the demonstration that patients with  "low risk" cancer overall had markedly lower responses to the battery of stimulating mitogens and antigens than found in patients with "high risk" or "intermediate risk" disease. Only the lymphocyte responses to PHA showed a significant linear correlation with increasing pathologic stage or "risk of recurrence." Current evidence from this study suggests that PHA response is markedly influenced by the primary tumor burdenand thus indirectly reflects the risk of recurrence.


Limb salvage from a multidisciplinary treatment approach for skeletal and soft tissue sarcomas of the extremity. Multimodality management of extremity skeletal and soft tissue sarcomas with preoperative intra-arterial Adriamycin and radiation therapy, radical surgical resection and postoperative chemotherapy or chemo-immunotherapy has resulted in preservation of a functional extremity in 13 or 14 patients. Seven of 8 patients with Stage IIIA and IIIB soft tissue sarcomas, managed with preoperative intra-arterial Adriamycin and radiation therapy, followed by en bloc soft tissue resection and 6 patients with bone sarcomas managed by preoperative treatment, followed by bone resection and replacement with cadaver bone allografts, remained free of disease from 4 to 34 months. The results of the combined modality approach were significantly better than the results obtained in patients managed by surgical resection alone, or by combination of operation with another single modality, both in terms of short term-recurrence free survival and salvage of a  functional extremity.


Risks in therapeutic portacaval and splenorenal shunts. Analyses of the records of 120 patients who underwent portacaval shunting (PCS, 57%) or splenorenal shunting (SRS, 43%) from 1966-1973 disclosed that patients in each group undergoing elective shunts had the same preoperative physical condition and postoperative mortality rates (approximately 20%). Although the post-operative death rate from emergency shunts was 48%, patients having these procedures were poorer risks. Long-term incidences of encephalopathy were the same, irrespective of the type of shunt (PCS, 46%; SRS 36%, P greater than 0.5). Despite comparisons of data most unfavorable for PCS, 5-year survival rates were also the same after either type of shunt (all PCS, 29 +/- 7.5%, SRS, 42.0 +/- 7.4%, P = 0.23). The survival rate after elective PCS was also the same as after SRS during the entire 5-year period. However, the survival after all elective PCS and SRS was significantly greater than after emergency PCS (P range = 0.005-0.038); the poorer results of emergency shunting could be partly attributed to the poorer condition of patients selected. A numerical score based on serum bilirubin concentrations, ascites, and urgency of shunting reliably predicts postoperative mortality. Long-term encephalopathy is predicted by a history of encephalopathy and the urgency of shunting.


Hepatic artery flow improvement after portacaval shunt: a single hemodynamic clinical correlate. We have documented a highly significant increment in hepatic arterial flow following a portacaval shunt in patients with cirrhosis of the liver and portal hypertension. In contrast with other hemodynamic variables, the increment in arterial flow was directly related to morbidity, hospital mortality, and long term survival. Patients with increments smaller than 100 ml/min had the worst clinical results. They accounted for all of the hospital mortality, the largest incidence of encephalopathy, and the worst long term cumulative survival rates. The extent of the increment was not related directly to the type of shunt but, rather, to some intrinsic capability of the cirrhotic liver to increase its arterial flow in response to the relief of sinusoidal hypertension produced by the shunt. This capablilty appears related to the degree of entrapment of the hepatic arterioles by the fibrous tissues of cirrhosis. This encasement of arterioles should change the elastic properties of the hepatic arterial bed and we propose to measure these properties by determining the characteristic input impedance of the arterial bed.


The surgical treatment of constrictive fibrous endocarditis. Constrictive fibrous endocarditis is a pathological entity described by Loëffler in 1936. Its etiology is unknown. The clinical course is characterized by an evolution towards cardiac insufficiency leading rapidly to a fatal outcome. Moderen paraclinical investigations are necessary to assess the diagnostic. Caridac catheterization brings the proof of adiastole and angiogardiography reveals the shape of amputation of the ventricle with auriculoventricular regurgitation. The operative procedure consists of resection of the ventricular fibrosis including the valves and auriculo-ventricular valve replacement by a prosthetic valve. The disease affects both Caucasians and Negros. Our experience includes 5 cases. The indications for operation and their results are discussed.


The treatment of acute traumatic rupture of the aorta: a 10-year experience. Forty-three patients with aortic rupture secondardy to blunt trauma have been treated at the University of Micigan within the past 10 years with an overall salvage rate of 70%. The diagnosis should be suspected in anyone who has sustained a high speed decelerating injury, if the chest roentgenogram shows media-stinal widening, whether or not there is hypertension of the upper extremities; systolic murmur, or external evidence of chest injury. Aortography should be employed to confirm the diagnosis and to determine the site or sites of rupture. Repair of the lesion should be undertaken as soon as possible and takes priority in most instances over associated injuries. Repair in almost all cases can be accomplished safely and quickly using a bypass shunt without the aid of extracorporeal circulation.


Long-term survival after resection for bronchogenic carcinoma. Of 915 resections for bronchogenic carcinoma over a 25-year period (1945-1969), 249 patients survived over 5 years; 127 of the patients eligible survived over 10 years, 61 over 15 years, and 22 over 20 years. The case material was divided into three time periods: 1945-49, 1950-59 and 1960-69, as well as by extent of resection. Lobectomy became the operation of choice, pneumonectomy being reserved for the more extensive lesions. Observed survival rates  at 5, 10 and 15 years for 561 patients in the lobetomy series were 35, 22 and 15%, respectively, but strikingly increased to 41, 28 and 19% in the 1960-69 period. Observed rates  for 354 patients having pneumonectomies were similar for three time periods, being 16, 8 and 6% at 5, 10 and 15 years, respectively. Relative survival rates for the lobectomy series at 5, 10 and 15 years rose from 33, 28 and 26%, repectively, in the 1950-59 period to 50, 39 and 35% in the last  time period, becoming a near horizontal curve segment after 5 years. Dominant factors in survival were extent of the lesion and stage of nodal involvement, histologic type and location being less significant.


Biliary lipid excretion after hepatic portoenterostomy. Since 1974, 16 consecutive infants with biliary atresia have been treated by hepatic portoenterostomy employing an exteriorized Roux-en-Y intestinal segment (Miluliez). Simultaneous, sequential analyses of bile pigments and lipids in serum and biliary drainage were performed. In the 11 patients with sustained bile drainage, progressive increases in bile volume, bilirubin and biliary lipid concentrations correlated well with their subsequent return toward normal in the serum. Despite relief of biliary obstruction, four patients have had progressive liver cirrhosis. The other 7 have residual liver damage which has been stable, or in two instances, improved, at late biopsy. The clinical and biochemical results suggest that both obstructive and parenchymal factors are operative in infants with biliary atresia.


Repair of ventricular septal defect in the first two years of life using profound hypothermia-circulatory arrest techniques. Ventricular septal defect repair had been performed in 57 infants ages 21 days to 21 months and under 10 kg in weight using profound hypothermia-circulatory arrest technics. Severe congestive heart failure was the indication for operation in all but two infants under 6 months of age, and in those under 3 months there was usually an associated moderate or large sized atrial septal defect or patent ductus arteriosus or a coarctation. In infants over 6 months controlled heart failure was accompanied by failure to thrive and often recurrent respiratory infections. The main indication for surgery in three infants was repeated severe respiratory infections and in 7 infants, ages 10-15 months, an elevation of pulmonary vascular resistance of 6 units M2 or more. There were two hospital deaths among the 49 infants without coarctation (ages 6 and 20 months) and two among the 8 with coarctation. Postoperative respiratory and other complications were uncommon. On late review there was no significant residual VSD amongst the 11 recatheterized patients. Psychometric studies in 19  children who had reached the age of three to four years gave no evidence of cerebral damage due to the circulatory arrest period. In view of these results palliative pulmonary artery banding is no longer performed for VSD in infancy unless there is a Swiss cheese septum or an associated severe coarctation.


Informed consent: recall by patients tested postoperatively. When tested for recall between 4 and 6 months following operation, 20 patients failed to remember accurately major portions of their informed consent interview. Documentation of the details of consent in the clinical record is considered advisable.


In vivo evaluation of the Lillehei-Kaster heart valve prosthesis. In vivo evaluation of the Lillehei-Kaster heart valve prosthesis was performed in 28 patients; 22 had undergone aortic valve replacement and 6 had had mitral valve replacement. Mean pressure gradients ranged from 6 to 53 mm Hg in aortic prostheses; valve area varied from 0.83 to 2.9 cm2. The maximum opening angle of 80 degrees was never reached in this group of patients; opening angles ranged from 57 to 74 degrees without evidence of disc malfunction. There was no correlation between the ratio of effective to geometric valve area and the degree of opening of the disc occluder. Similar results were found in the mitral valve group. Gradients ranged from 6.0 to 12.5 mm Hg and valve area from 1.6 to 2.2 cm2. The maximum opening angle was 59 to 63 degrees. It is concluded that incomplete opening of the disc occluder in pivoting-disc valves is not necessarily a sign of disc malfunction. Lillehei-Kaster valves smaller than 18 mm in internal diameter should be avoided in adults, and outflow aortoplasty for implantation of a larger prosthesis should be used in patients who have a narrow aortic root.


Aortic valve replacement with the Hancock porcine xenograft. The Hancock porcine xenograft stabilized with the glutaraldehyde process was used for isolated aortic valve replacement in 71 patients from March, 1972, to July, 1975. Aortic stenosis was the primary diagnosis in 52 patients and aortic insufficiency in 19. There were 52 men and 19 women ranging in age from 18 to 82 years; 14 patients were older than 70 years. One patient was in Functional Class II, 50 in Class III, and 20 in Class IV preoperatively. Seventy-three patients undergoing Björk-Shiley aortic valve replacement during the same period are presented for comparison. The operative mortality was 3% (2 of the 71 patients); 4 of the remaining 69 patients (6%) died in the late postoperative period. No patient was placed on anticoagulation during the postoperative course, and there was 1 postoperative embolus in a patient with chronic atrial fibrillation (1.4%). With a mean follow-up period of 17 months, 60 patients are now in Functional Class I, 4 in Class II, and 1 in Class III. Seven patients have had transvalvular gradients and effective valve areas measured postoperatively that ranged from 32 to 5 mm Hg and 0.9 to 2.9 cm2 in 21 through 25 mm (OD) sizes.


Surgical treatment of large ventricular septal defect with pulmonary hypertension in the first 24 months of life. A total of 74 patients under 24 months of age with large ventricular septal defects (VSD) and pulmonary hypertension were subjected to surgical treatment from 1969 through 1975. Emergency pulmonary artery (PA) banding was performed in 13 patients during the first year of life with 1 death from postoperative respiratory failure. Primary closure of the VSD was performed in 61 patients using simple hypothermia and short-term coronary perfusion, with an operative mortality of 1.6%. There were no late deaths or neurological disturbances. Normal hemodynamic data were obtained in all 7 patients who underwent postoperative cardiac catheterization from one month to five years after the primary correction. It is concluded that primary closure of a VSD in infancy is reasonable and that PA banding is indicated only for those patients less than 6 months old with a complicated defect or in an emergency situation.


The Blalock-Taussig operation: the procedure of choice in the hypoxic infant with tetralogy of Fallot. From 1971 to 1975, 17 consecutive patients aged 1 day to 4 years underwent Blalock-Taussig shunts for severe tetralogy of Fallot. Three infants were under 6 weeks of age and 7 (41%) under 1 year. There were no hospital deaths. Modification of the shunt technique adapts it to any size infant. The subclavian artery is divided at its major branches and the end spatulated to enlarge it. The artery is occluded while the shunt is constructed. No intraoperative complications were encountered; all patients have a shunt murmur with no early or late closure. No child has had heart failure or hypoxic spells. Flows measured at operation equaled one-quarter to one-half of the child's normal cardiac output. Ligation of the shunt at subsequent repair is uncomplicated. One child died three years later at correction from causes unrelated to the shunt. With appropriate modifications in technique, the Blalock-Taussig shunt is the operation of choice, at any age, for palliation of severe tetralogy of Fallot.


The operative problem of small left atrium in total anomalous pulmonary venous connection: report of 5 patients. A moderately small left atrium is a common finding in total anomalous pulmonary venous connection (TAPVC). In most patients in whom the common pulmonary vein is anastomosed to the left atrium, the small size of this chamber does not interfere with good operative results. Recently a patient was encountered in whom the left atrium measured less than 2 cm in its greatest dimension. This atrium was too small to take an anatomosis with the common pulmonary vein. Therefore the common pulmonary vein was anastomosed primarily to the right atrium, the floor of the fossa ovalis was excised, and a pericardial conduit was constructed. Subsequently, 4 additional patients have been similarly treated. The problem of small left atrium in TAPVC is discussed.


Pulmonary venoocclusive disease.

Pulmonary venoocclusive disease. Pulmonary venoocclusive disease has been established as a definite clinical entity characterized by congestive cardiac failure with pulmonary arterial hypertension, chronic interstitial pulmonary edema, and normal wedge pressure on cardiac catheterization. This disease was diagnosed and confirmed in a patient during life. A review of the 32 patients reported earlier has been done in an attempt to fine possible etiological agents. Early recognition and treatment with anticoagulants, methylprednisolone, aspirin, and dipyridamole may improve the prognosis.


Transaxillary minithoracotomy: the optimal approach for certain pulmonary and mediastinal lesions. This report concerns the use of transaxillary thoracotomy for a variety of pulmonary, pleural, and mediastinal conditions in 50 patients. Primary and metastatic carcinomas, pneumothoraces, and benign lesions such as bronchogenic cysts and neurogenic tumors can be identified, evaluated, and treated with confidence. Reduced postoperative pain and morbidity, rapid return of arm and shoulder movements, reduced hospital stay, and excellent cosmetic result are among the advantages of this approach when compared with the usual posterolateral thoracotomy.


Emergency open lung biopsy.

Emergency open lung biopsy. Twenty-eight patients underwent open lung biopsy on an emergency basis. The clinical course in each case was deteriorating rapidly, and all were in respiratory failure. The correct diagnosis was established in 96% of the biopsies (27 of the 28 patients). The clinical diagnosis prior to biopsy was in error or incomplete in 15 (55%) of the patients. Specific therapy was lifesaving in 12 of the 28 patients. The value of the procedure outweighed the complications. Thrombocytopenia and positive end-expiratory pressure ventilation were not contraindications to biopsy.


Mediastinopleuroscopy: a new approach to the diagnosis of intrathoracic diseases. With the advent of modern therapy, it has become essential to obtain a tissue diagnosis in all cases of pulmonary and mediastinal disease. Since it is often necessary to resort to thoracotomy as a final step in making such a diagnosis, we have sought a procedure that is simpler while capable of providing the same information. Through a standard cervical mediastinoscopy incision, the mediastinum is first explored; if the diagnosis is not obtained, the mediastinal pleura is digitally opened and lung or pleural biopsies are taken. In the course of 1,100 mediastinoscopies since 1969, 275 pleuroscopies have been done. We were able to obtain a tissue diagnosis in 102 (78%) of 131 patients with bronchogenic carcinoma, in 92 (91%) of 102 with benign pulmonary disease, and in all 20 (100%) with pleural disease.


Carcinoid tumors of the lung.

Carcinoid tumors of the lung. Resection of typical bronchial carcinoid was carried out in 203 patients. The average age was 48 years, and the sex distribution was approximately equal. Bronchoscopy was the most definitive diagnostic procedure, even though 15% of the tumors were located in the segmental bronchus or beyond. Conservative resection including local removal of the lesion was the treatment of choice, but distal suppuration and location of the tumor necessitated pneumonectomy in 54 (27%) of the patients. The incidence of metastasis was 5% (11 patients), and the overall hospital mortality was 3%. Of patients who qualified for follow-up, 94% survived 5 years, and of those who were asymptomatic preoperatively, 98% survived 5 years. The 10- and 25-year survival rates for the group as a whole were 87 and 66%, respectively.


Reflux control following extended myotomy in primary disordered motor activity (diffuse spasm) of the esophagus. We have previously reported the results of extended esophageal myotomy and Belsey hiatal hernia repair in 21 patients. Reflux was considered to be a late complication of this operation, and gastroplasty has subsequently been added. Thirty-four patients have now been surgically treated, 17 with myotomy and Belsey repair and 17 with myotomy, gastroplasty, and Belsey repair. Eight of the 17 with Belsey repair developed clinical and roentgenographic signs of reflux 6 to 27 months following operation without evidence of hernia recurrence; 5 of the 8 patients have required further operation, with the addition of gastroplasty for reflux control. Seventeen patients were treated primarily by extended myotomy, gastroplasty, and Belsey repair. None of the patients who underwent gastroplasty have reflux symptoms, and only 1 shows a trace of reflux radiologically.


Simplified lateral chest incision for most thoracotomies other than sternotomy. Our experience using the lateral simplified thoracotomy incision for most chest work other than operations requiring median sternotomy is reported. The incision provides adequate exposure, yet preserves major muscle masses and decreases the postoperative morbidity. Return of normal ipsilateral arm function appears to be hastened in the postoperative period. In addition, the incision is easier to open and close than the standard incision.


Vertical axillary thoracotomy: a functional and cosmetically appealing incision. Vertical axillary thoracotomy offers the specific advantages of minimum trauma and maximum preservation of chest wall function. A cosmetically acceptable scar results. The vertical axillary thoracotomy is specifically indicated in patients requiring less than the maximum intrathoracic exposure provided by the most traumatic posterolateral or anterolateral thoracotomy. The surgical technique is presented.


Total spinal anesthesia: a rare complication of intrathoracic intercostal nerve block. Total spinal anesthesia following intrathoracic intercostal nerve blocks with bupivacaine performed for postoperative pain relief during thoracotomy is described. Possible mechanisms for this complication include: (1) inadvertent placement of the needle through an intervertebral foramen, (2) puncture of a long dural cuff, and (3) intraneural injection with central spread. Recognition of this potential complication is important, and facilities for proper support must be available.


Massive pulmonary embolism permitting paradoxical systemic arterial embolism: successful surgical management. The case of a young woman, receiving oral contraceptives, who developed massive pulmonary embolism producing circulatory collapse and paradoxical arterial embolism through a patent foramen ovale is documented.. Limb viability was threatened. Emergency management included removal of arterial and pulmonary emboli, surgical closure of the patent foramen ovale, inferior caval partitioning, ovarian vein ligation, and short-term anticoagulation. Recovery was rapid and complete.


Pulmonary embolism and intracardiac shunt: a unique indication for operation. Pulmonary embolism with right-to-left intracardiac shunt presents a special problem for the clinician. A review of the literature and 4 personal cases, all diagnosed antemortem, are presented. On the basis of this information certain conclusions are drawn, and we suggest the problem to be a unique indication for the consideration of surgical intervention.


Comparative study of 1-cyclohexyl-4-(1,2-diphenylethyl)-piperazine and its enantiomorphs on analgesic and othe pharmacological activities in experimental animals. The analgesic activity of (+/-)-1-cycylohexyl-4-(1,2-diphenylethyl)-piperazine (MT-45) was comparable to that of morphine. The activity of the S(+)-isomer was 1.14 to 1.97 times in mice and 1.00 and 1.23 times in rats as potent as MT-45, and 18.3 to 61.6 times as potent as the R(--)isomer, which was approximately comparable to that of Spa. The hyperglycemic and miotic activities of MT-45 and its S(+)-isomer in rabbits were negligible or very low, though they showed potent morphine-like activites. On the other hand, the R(--)-isomer showed no or very weak effects on those, while Spa showed definite effects. These results suggest that the modes of action of MT-45 and its enantiomorphs are partly different from those of morphine and Spa, and it may be concluded that MT-45 belongs to a new series of compounds having a potent analgesic activity.


The anti-inflammatory profile of proquazone. Proquazone, 1-isopropyl-4-phenyl-7-methyl-2(1H)-quinazolinone is an orally effective anti-inflammatory analgesic and antipyretic compound in animal models. The compound is less ulcerogenic than indomethacin in the rat and appears to potentiate the anti-inflammatory and thymus involution effects of hydrocortisone in this species. That a nonacidic nonsteroidal compound would display a spectrum of anti-inflammatory activity similar to that previously found only with acidic compounds will be the subject of further investigations.


4-nitro-2-phenoxymethanesulfonanilide (R-805): a chemically novel anti-inflammatory agent. The anti-inflammatory activity of the sulfonanilide, 4-nitro-2-phenoxymethanesulfonanilide (R-805) has been demonstrated in conventional models (carrageenan-induced edema of the rat's paw, UV-induced erythema of guinea-pig skin, adjuvant-induced arthritis of the rat). R-805 differs from most currently available acidic anti-inflammatory drugs in that its functional acidic group is not carboxyl. The relative anti-inflammatory potency of R-805 is comparable to indomethacin. Calculation of acute therapeutic indices (LD50/ED50) for 8 acidic anti-inflammatory drugs show R-805 to possess a more favourable index than the other drugs examined.


In-vitro metabolism of etomidate by rat liver fractions. (R)-(+)-etomidate and (S)-(-)-etomidate were found to be metabolized in-vitro by various rat liver homogenization fractions: the 16,000 g supernatant fraction caused a more intensive metabolic breakdown than the microsomal fraction; the 100,000 g supernatant fraction was only slightly active. The metabolism was somewhat more rapid and more extensive for the (R)-(+)-etomidate than for the (S)-(-)-isomer. For both isomers, a dose-dependence was observed: the smaller the substrate concentration, the smaller the relative amount of unmetabolized drug, and the more the rate of metabolic breakdown after a certain incubation time slowed down. Only minor qualitative differences between the metabolic pathways of the two isomers were observed. The main metabolic pathway for the in-vitro metabolism was the hydrolysis of the ethyl ester. Decarboxylation and oxidative N-dealkylation were also observed.


The plasma protein binding and distribution of etomidate in dog, rat and human blood. The interactions of etomidate and its major metabolite  (R 28 141) with plasma proteins were studied by equilibrium dialysis with a multiple cell system. A 4% human serum albumin solution was able to bind 78.5% of the etomidate, and 60.5% of R 25 141, whereas a 1.5% human gamma globulin solution bound etomidate for not more than 3% and did not bind R 28 141 at all. The association constants and free binding energies for the binding of etomidate and R 28 141 to human serum albumin were determined. Plasma protein binding of etomidate was 75.4% in the dog and 76.5% in man; in rat plasma 79.5% of the radioactivity was bound to the plasma proteins, however the etomidate was partly hydrolyzed, even in the presence of sodium fluoride. In the rat 29.7% was distributed to the blood cells, 55.9% bound to plasma proteins and 14.4% was present in plasma water; in the dog the distribution percentages were 42.1%, 43.7% and 14.2% respectively, and in man 37.7%, 47.6% and 14.7% respectively. The major metabolite of etomidate was distributed for 26.3% to the human blood cells, 47.4% was bound to plasma proteins and 26.2% was present in the plasma water; its plasma protein binding amounted to 64.3%. Etomidate was bound at or in the blood cells, whereas R 28 141 was not.


[Comparative activity of ethaverine and papaverine on chronotropic and dromotropic cardiac functions in the anesthetized dog]. Ethaverine inhibits both atrioventricular conduction and heart rate, starting at a dosage of 1 mg/kg, injected i.v. into the anaesthetized dog. In the experimental conditions used, ethaverine is clearly different from papaverine, which stimulates both at a dosage between 1 and 10 mg/kg, and which only produces an inhibitory effect starting at a dosage of 20 mg/kg, with the appearance of cardiotoxic phenomena. After total cardiac denervation the inhibitory action of ethaverine persists partially, especially at the atrioventricular level, which is probably due to a direct effect on the heart muscle. The observed differences can hardly be explained by a more pronounced cardiac toxicity. Consequently, the ethyl-derivative of papaverine constitutes, in certain aspects, a molecule with original pharmacological properties.


Cardiac chronotropic mechanisms of dimethyl sulphoxide: inhibition of acetylcholinesterase and antagonism of negative chronotropy by atropine. The chronotropic effects of dimethyl sulphoxide (DMSO) were studied in spontaneously beating rabbit atria. Low concentrations of DMSO (0.14, 0.42 M) produced slight positive chronotropic (+C) responses; 0.84 and 1.41 M DMSO caused significant negative chronotropic (--C) responses. All concentrations decreased contractile strength. Atropine sulphate (10)-7) to 10(-5) M) antagonized the chronotropic effects, but not the inotropic effects. In the presence of atropine all DMSO concentrations produced significant +C responses. Reserpine pretreatment or propranolol did not affect contractile responses to DMSO in the absence or presence of atropine. DMSO produced concentration-dependent inhibition of acetylcholinesterase (AChE) activity of atrial homogenates. The results indicate that the --C responses are due specifically to AChE inhibition by DMSO and resulting cholinergic influences on the atrial pacemaker. Adrenergic mechanisms do not appear to mediate the +C responses. Data presented here provide evidence that a cardioactive effect of DMSO is mediated by a well-defined receptor-linked mechanism, and that this effect can be modified by a specific receptor blocking agent.


Studies using KWD 2058, a derivative of terbutaline in isolated atrial and tracheal preparations from the guinea-pig. KWD 2058 is a derivative of terbutaline in which the ring hydroxy groups are esterified with isobutyric acid. In guinea-pig atrial and tracheal preparations KWD 2058 produced slowly developing beta-receptor mediated actions which were absent in preparations pretreated with physostigmine. Incubation of KWD 2058 with guinea-pig plasma resulted in the production of a compound which was indistinguishable from terbutaline on both a qualitative and quantitative basis. KWD 2058 produced negative inotropic and chronotropic actions and increased the effective refractory period of guinea-pig atria. In addition, KWD 2058 produced a non-competitive antagonism of chronotropic responses to (--)-isoprenaline in atria. It is concluded that KWD 2058 has no affinity for beta-adrenoreceptors and that any beta-agonistic activity displayed is due to its hydrolysis product, terbutaline.


Effects of dipyridamole on the smooth muscle cells of the guinea-pig's taenia coli. Effects of dipyridamole on the smooth muscle of the guinea-pig's taenia coli were studied using the single and double sucrose gap method. Dipyridamole (10(-5) M) affected neither the non-adrenergic inhibitory junction potential, elicited by field stimulation, nor the membrane hyperpolarization induced with ATP applied exogenously, but did potentiate the accompanying relaxations. The muscle spike activity was reduced by dipyridamole without affecting the membrane potential or the membrane resistance. Carbachol induced a depolarization of the muscle cell membrane and thus a contraction of the muscle. Dipyridamole did not modify the membrane potential change produced by carbachol but decreased the size and time course of the contraction. From these results it is concluded that dipyridamole does not potentiate non-adrenergic relaxations by interfering with the neuromuscular transmission, which has been assumed to be purinergic.


In vivo antispasmodic activity of Sulcotidil. Suloctidil was tested in vivo for its antispasmodic activity on peripheral and cerebral circulations. In the perfused dog hind limb preperation, suloctidil was found to inhibit after 2 and 5 min, the vasospasm induced by norepinephrine or angiotensin; at equal dose, and at the game time intervals, it was more potent than cinnarizine and papaverine. BaCl(2) induced spasms of the pial arterial of the rabbit were also rapidly alleviated by i.a. suloctidil (3.5 mug/kg or more), in conditions where papaverine and vincamine were inactive.


The inhibitory action of dopamine on the anterior tibialis muscle preparation antagonized by pimozide and chlorpromazine. In the cat anterior tibialis muscle preparation dopamine produces a decrease on indirectly evoked twitch contraction when it is administered intraarterially but not on intravenous injection. Edrophonium (0.3 mg/kg) exerts only a brief antagonism to the dopamine-induced inhibition. The phenothiazine derivative, chlorpromazine (CPZ, 400 mug/kg) which possesses both alpha and dopaminergic blocking properties significantly reduces the action of dopamine on skeletal muscle. However, phentolamine (1 mg/kg), an alpha adrenergic blocker is without effect, possibly indicating that the dopaminergic blocking characteristic of CPZ is responsible for decreasing the action of dopamine. A more selective dopaminergic blocking agent, pimozide (100 and 200 mug/kg) is an effective antagonist to the paralysis caused by dopamine on the anterior tibialis muscle. The results of this investigation suggests the possibility that a dopaminergic receptor may be present in or on skeletal muscle.


Factors influencing tolerance to d-amphetamine-induced anorexia in rats. Three experiments were concerned with tolerance to anorexia induced by d-amphetamine. In experiment 1, one group of rats on a 2 hr food deprivation schedule received 2 mg/kg of d-amphetamine 15 min before eating every other day for a month. A second group of rats on a similar schedule received the same dose of d-amphetamine immediately after eating. When compared to a saline-treated control group, the former group showed significant decreases in weight and food intake; tolerance to the amphetamine-induced anorexia began to occur toward the end of the experiment. The latter group showed a significant decrease in food intake on the non-drug days and an overall weight loss when compared to the control group. Experiment 2 demonstrated that tolerance to d-amphetamine-anorexia was related to the duration of drug administration per se. Experiment 3 showed that taste can be a factor in influencing the rate of tolerance to d-amphetamine-induced anorexia. These results indicate that both pharmacological and experiential factors play an important role in determining the rate of tolerance to this action of d-amphetamine.


Indirect and direct depressive effects of morphine on activation of lamina V cell of the spinal dorsal horn induced by intra-arterial injection of bradykinin. Small doses of morphine (0.3-2.0 mg/kg i.v.) inhibited, in the majority of intact rabbits, the unitary activities of the lumbar lamina V dorsal horn neurons induced by intra-arterial injection of bradykinin, a potent pain producing substance, but not in spinal rabbits. A large dose of morphine (5.0 mg/kg), however, inhibited the bradykinin-induced response even in spinal rabbits. These results suggest that morphine, in small doses, inhibits the sensory transmission of bradykinin-induced pain at the dorsal horn of the spinal cord, through its facilitatory action on the descending inhibitory mechanism; in large doses the level of dorsal horn is directly inhibited.


Effects of thyroxine pretreatment and calcium on the isolated perfused rat heart. Phosphorylase a activity was the same in isolated perfused hearts from euthyroid and thyroxine-pretreated rats. Perfusion with 3.6 mM Ca2+ caused an increase in phosphorylase a in hearts from euthyroid as well as those from thyroxine-pretreated animals, but the Ca2+-induced stimulation of phosphorylase activity was similar in both groups over the time course studied. Greater conversion of phosphorylase b to a occurred with 7.2 mM than with 3.6 mM Ca2+ in both groups, but once again thyroxine pretreatment did not significantly influence the conversion of phosphorylase b to a. Isometric systolic tension increased in response to 3.6 mM and 7.2 mM Ca2+ in hearts from normal and thyrotoxic rats, but thyroxine pretreatment did not appreciably alter the nature of this response. While spontaneous heart rate was higher in hearts from thyroxine-pretreated rats, perfusion with 3.6 mM or 7.2 mM Ca2+ had no significant effect on heart rate in hearts from euthyroid or thyrotoxic rats.


Vas deferens desensitization by noradrenaline and other drugs. Desensitization of the isolated rat vas deferens was demonstrated by using noradrenaline, 5-hydroxytryptamine, carbachol, acetylcholine or barium chloride as a test concentration after a large concentration (concentration producing a contraction that was 80% of the maximum) of the same agonist. The large concentration of noradrenaline caused desensitization in response to 5-hydroxytryptamine and acetylcholine but not to carbachol and barium chloride. Desensitization is not altered by reserpine--in pretreatment of rats with reserpine or reserpine in Tyrode solution--imipramine and 6-hydroxydopamine. Surgical denervation or modification of the sodium and calcium concentration of the Tyrode solution did not either alter desensitization. Results show that in the rat isolated vas deferens desensitization is not mediated by an action of noradrenaline on the adrenergic neuron.


Effects of prostaglandins E1, E2 and F2 alpha and polyphloretin phosphate of domestic fowl. The predominant effect of PGE1, E2, and F2 alpha on systemic arterial pressure of domestic fowl is hypotension. PGE1 and E2 are approximately equiactive and PGF2 alpha is about 10 times less active than E1 and E2, PGE1 and E2 produce sudden hypotension with gradual recovery while F2 alpha produces fall in blood pressure with both slow onset and recovery. Polyphloretin phosphate itself produces depressor responses in chickens and antagonizes the depressor responses to the prostaglandins dose-dependently.


Duration of analgesia and hyperactivity in mice after single injections (S.C. and I.V.) of heroin. ED50 values for analgesia (tail-clip method) at 30 min after heroin HCl administered i.v. or s.c. in groups of Swiss-Webster mice were not significantly different. Nor was the duration of the analgesia following various doses of heroin significantly different after i.v. or s.c. injections, although there was a tendency for the latter route to have a longer effect. Hyperactivity (mean levels in groups of 5 mice, measured by an Activity Meter), though variable, was increased after s.c. injections of heroin in a dose-related manner up to doses of 10 mg/kg. Larger doses progesssively prolonged the peak levels of hyperactivity. Because the degree and duration of both analgesia and hyperactivity were parallel over a wide range of doses of heroin HCl in these mice, a close relationship between the two underlying mechanisms seems very likely.


The effect of acetylcholine on bile flow. The effect of acetylcholine on bile flow was studied in isolated perfused rat liver. Acetylcholine added into the perfusion medium altered bile flow in a way analogous to mechanical clamping and opening of the common bile duct. This effect was potentiated by physostigmine and antagonized by atropine. The results suggest that acetylcholine can pass from portal sinusoidal blood into the biliary tract, possibly through the terminal bars of bile canaliculi, and cause an obstruction in the biliary tree. Suggested mechanism could explain the observed decreased and increased bile flow caused by cholinergic drugs or vagal stimulation in the earlier experiments.


Intestinal absorption and biliary excretion kinetics of 14C-labeled methadone in the rat. Intestinal abosrption, biliary excretion and enterohepatic circulation of d,l-methadone were studied in male, female, fasted and fed rats by monitoring the appearance of radioactivity in the portal vein, the inferior vena cava, and the bile following intraduodenal administration of 2-14C-d,l-methadone. An early peak in portal concentration was not reflected in the peripheral blood or in the bile. An enterohepatic circulation exists, but is minimal, accounting for less than 1% of the dose in the first hr. Experimental diversion of the bile flow from the lumen of the duodenum has little effect on the relative percentage of methadone vs. metabolites circulating in the blood. However, bile diversion was associated with a 2 to 3 fold increase in the concentration of methadone and its metabolites in portal and peripheral blood 30 min following administration. Eighty to 90% of the 14C in the portal blood is present as methadone and 60 to 70% of the 14C in peripheral blood is methadone while less than 10% of the radioactive materials in the bile is methadone. The amount of metabolite No. 1, metabolite No. 2 and water soluble metabolites vary with over 60% of the radioactive compounds in recirculated bile in the form of water soluble materials.


[The influence on heart conduction time and refractory period of in vitro and in vivo prostaglandins]. The effects of PGE1, PGE2 and PGF2alpha on conduction time and functional refractory period in the isolated rabbit atrium and in the cat heart in vivo were investigated. In the isolated rabbit atrium the PGs (10(-8)--10(-5) g/ml) were without any effect in this respect. In contrast there was a dose-dependent decrease of conduction time and prolongation of functional refractory period in the cat heart in vivo following PG-infusions (2,0--8,0 mug/kg/min i.v. over a period of 5 min). These findings indicate the absence of a direct quinidine-like membrane action of PGs in the heart. The indirect, depressive effects of PGs on conduction time and functional refractory period in the heart in vivo, should be considered responsible for the antiarrhythmic action of PGs.


Hypertension and renal disease in systemic lupus erythematosus. A retrospective analysis of 235 patients at the National Institutes of Health who met at least five criteria for systemic lupus erythematosus (SLE) indicated that 45% were hypertensive. Approximately two thirds of these hypertensive patients had creatinine clearances of more than 60 ml/min and nonnephrotic range proteinuria. Only 16% of normotensive patients had creatinine clearances of less than 60 ml/m9n. A subgroup of 36 patients with SLE and with biopsy-proved diffuse renal disease were studied. For these patients, the presence of hypertension could not be correlated with the degree of proteinuria or hematuria, with the level of serum complement, or with the presence of casts, focal necrosis, crescent formation, or interstitial inflammation. Hypertensive patients had a median age of 24.5 years; the majority had creatinine clearances of more than 60 ml/min. In SLE, hypertension is not necessarily associated with advanced renal disease, and high blood pressure may occur relatively early in the course of the disease.


Secondary pituitary insufficiency: report of three cases of ectopia or hemiagenesis of the thyroid gland. Three patients with clinical and laboratory manifestations suggestive of pituitary insufficiency due to the presence of a pituitary tumor were found to have long-standing myxedema. The insidious appearance of the signs of hypothyroidism was explained by the cause of their disease--an ectopic thyroid gland in two patients and hemiagenesis of the thyroid in the third. Early recognition and treatment of such cases is important.


Hemolysis caused by factor VIII concentrates. Immune hemolytic anemia is a recognized complication of the use of factor VIII concentrates. Hemolysis is obscured often by the presence of active bleeding. Where hemolysis has been demonstrated, red blood cell (RBC) destruction has been attributed to anti-A antibodies found in the transfused material. We present two episodes of hemolysis associated with the use of factor VIII concentrate. In the first, a high titer of "immune" anti-A (1:256) was present in the factor VIII. In the second, the patient's RBCs were group B, and the hemolysis was caused by anti-B antibody in the factor VIII concentrate. In addition, the antibody titer in the material that was received was much lower than previously described. The RBC destruction presumably occurred because of the massive dosage of factor VIII concentrate administered on order to overcome a factor VIII inhibitor.


Oral-contraceptive-induced hypertension after adrenalectomy and hypophysectomy. The cause of oral-contraceptive-induced hypertension in certain susceptible subjects is obscure. We describe a woman who was receiving replacement doses of fludrocortisone acetate after adrenalectomy and hypophysectomy who developed high blood pressure while ingesting an estrogen-containing oral contraceptive. Renin substrate level was increased, but renin activity was suppressed and unresponsive to tilting. The patient developed a markedly exaggerated natriuresis when infused with saline. Both blood pressure and her responses to infused sodium and tilting normalized after discontinuance of the oral contraceptive medication. In this adrenalectomized patient, the estrogenic component of the pill acting synergistically with a fixed ("nonsuppressible") replacement dose of mineralocorticoid seems to have caused a volume-related hypertension.


Chiasmal syndrome due to intrasellar abscess. A 43-year-old woman had diabetes insipidus and amenorrhea. There was panhypopituitarism on endocrine testing and visual field examination showed inexorably progressive loss to bitemporal hemianopsia. All radiographic findings were normal, but craniotomy disclosed the cause of this chiasmal syndrome to be an intrasellar abscess which, on culture, grew a Gram-positive anaerobe, Peptococcus. Intrasellar or pituitary abscess is rare, but it must always be considered in the differential diagnosis of the chiasmal syndrome, since loss of pituitary and visual function may occur much more rapidly than with the tumors most often responsible for this syndrome and since surgical cure is possible.


Ascaris lumbricoides--a reminder.

Ascaris lumbricoides--a reminder. A Vietnamese refugee was admitted to the hospital with signs and symptoms of an acute condition within the abdomen. Examination ultimately led to the roentgenographic diagnosis of an Ascaris lumbricoides infestation. The patient recovered after medical treatment with intravenous fluids and nasogastric suction, followed by piperazine citrate administration. This ubiquitous parasite has the potential for causing many serious abdominal complications. An awareness of this disease is particularly timely, in view of the recent influx of nearly 150,000 Indo-Chinese into North America.


Ankylosing spondylitis with complete heart block. A patient with complete heart block due to ankylosing spondylitis exhibited an unusually brisk increase in ventricular rate with exercise. Despite broad ventricular (QRS) complexes, His bundle electrograms demonstrated a His deflection before each QRS complex and thus established the level of atrioventricular (A-V) block to be proximal to or localized to the His bundle. A junctional pacemaker accounted for the brisk response to exercise, atropine, or isoproteronol. Left bundle branch block pattern and prolongation of infranodal conduction time (H-Q) suggested additional disease involving the His bundle and/or right fascicle. Wide-spread disease affecting A-V nodal and infranodal conduction was compatible with pathologic changes seen in this disease. Because the pacemaker was able to respond to stress promptly and with appropriate increase in heart rate, the patient appeared not to warrant pacemaker implantation in his present state.


Abnormalities of urinary sediment and renal failure following sulfinpyrazone therapy. A patient with recurrent thrompophlebitis had sterile pyuria with white blood cell casts and transient, mild renal failure during therapy with sulfinpyrazone. These abnormalities resolved on cessation of therapy, but similar changes in the urinary sediment recurred during therapy with sulfinpyrazone. These abnormalities resolved on cessation of therapy, but similar changes in the urinary sediment recurred during a second course of sulfinpyrazone therapy.


Early care of acute myocardial infarction. A fixed life support station (LSS) was established in the emergency department of a community hospital in order to provide early care for patients with suspected acute myocardial infarction (MI). Prospective studies were conducted on 154 patients with verified acute MI. Median time from onset of symptoms to electrocardiographic monitoring was 164 minutes. Overall hospital mortality for these patients was 15.6%. Of 112 patients less than 70 years old, 51 arrived within two hours; only three (6%) of the 51 died. Patients arriving within two hours of the onset of symptoms in clinical class I had an incidence of cardiogenic shock (CS) of 2%, while those arriving two hours or more after the onset of symptoms in clinical class II had an incidence of CS of 26% (P less than .005). A fixed LSS in a community hospital is feasible and effective for early care of patients with acute MI and may facilitate identification of patients at highest risk for development of CS.


Reversal of intractable uremic pericarditis by triamcinolone hexacetonide. Of 74 patients undergoing long-term hemodialysis who were observed during a 21-month period, seven developed uremic pericarditis. Five of these patients developed intractable pericarditis, unresponsive to intensive dialysis and pericardiocentesis, and were treated with prolonged pericardial drainage (16 to 60 hours) by an indwelling polyethylene catheter and instillation of triamcinolone hexacetonide. Evidence of intractability was based on either the recurrence of cardiac tamponade after pericardiocentesis (two patients) or progression in the size of the pericardial effusion despite four weeks of intensive dialysis (three patients). These five patients recovered and subsequently were observed from 1 to 15 months with no evidence of recurrent pericarditis. This procedure may be an effective alternative to the surgical management of intractable uremic pericarditis, particularly in the patient at high risk for anesthesia and major surgery.


Low-dosage heparin in rapidly progressive glomerulonephritis. Two patients developed acute renal failure; creatinine clearances fell to 13 and 34 ml/min, respectively, and one patient was oliguric. Renal biopsies in both patients gave results that were compatible with rapidly progressive glomerulonephritis (RPGN). Both patients were treated with low-dosage heparin sodium infusion (8,000 units/day) and prednisone for two to four weeks, followed by oral anticoagulant (warfarin) and antithrombotic agents (dipyridamole). In the two patients, creatinine clearance rose to at least 60 ml/min, and no bleeding complications were observed. Repeat renal biopsy specimens that were obtained after three to six months of treatment showed no evidence of active glomerulonephritis in either patient, but there was extensive scarring and fibrosis. Low-dosage heparin infusion may arrest and partially reverse the renal failure associated with RPGN in some cases, while avoiding the bleeding complications that are frequently observed in patients treated with larger dosages of heparin.