Outcome of pregnancy in the presence of intrauterine device. The outcome of 196 pregnancies with Lippes Loop in situ was studied. In 102 cases with inaccessible thread, the IUD was left in place. Ninety-four women had the IUD removed when the thread was still visible. The incidence of spontaneous abortion and premature delivery was 56.8% in the group of 102, and was significantly higher than in those women whose loop was removed. No serious complications occurred in any of the cases. The results suggested that the IUD should be removed early in pregnancy when the string is still accessible.


Scintigraphic studies of uterine and placental growth and placental migration during pregnancy. Placental scintigraphy with 113mIn (Indium) combined with cervical marking with a shielded 57Co (Cobalt) radioactive source was used to study uterine and placental growth in human pregnancy and placental location and migration in a total of 176 patients. Uterine length measurements can be used for selecting growth retarded fetuses. There was an approximately constant ratio between placenta diameter and uterine length (0.68 +/- 0.03). When the placenta was located on the ventral uterine wall, low implantation occurred in 61%. The corresponding figure for low implantation when the placenta was located on the dorsal uterine wall was 30%. The difference was highly significant. Placental migration was studied in 20 patients. Significant migration occurred in 11 cases. The placental margin closest to the internal cervical os migrated outwards about 3 cm on average.


Feto-maternal bleeding. During pregnancy and at delivery. Blood samples from pregnant women and from mothers before and after delivery were tested for the occurrence of feto-maternal bleeding (f.m.b.) using Kleihauers acid-elution technique and a counting technique described by Schneider. It was assumed that f.m.b. had occurred, when there was a clinically significant difference between the values of hb-F cells per million cells in two blood samples. F.m.b. had occurred in nearly 2/3 of the mothers after pregnancy and delivery. The f.m.b.'s were most often less than 0.1 ml and only a few per cent had f.m.b.'s between 0.1 and 1 ml. Abortion, complicated pregnancies, amniocentesis, pre-eclampsia, caesarean section and other kinds of complicated deliveries increased the risk of especially larger f.m.b.'s.


Serum HCG and HPL in twin pregnancies.

Serum HCG and HPL in twin pregnancies. Serum HCG and HPL levels were determined in 154 samples derived from 39 twin and one triplet pregnancies. Compared with singleton gestations, these levels were respectively 2.5 and 1.5 times higher throughout gestation. Analysis of these data in terms of predictive accuracy for the existence of a twin indicates that neither assay can serve for screening purposes though simultaneous determination of HCG and HPL may provide a fair index of suspicion.


The cervical balloon method for induction of labor. The cervical balloon (Embrey & Mollison) was used to induce labor in a study group of 87 patients. The control group included 97 patients, where induction of labor was performed using oxytocin-drip. In the study group oxytocin-drip was added in 34 patients. The cases of the study and control groups were classified as "favorable" cervix. The patients classified as "unfavorable" cervix showed a shorter mean induction-delivery interval in the study group, and a shorter mean duration of oxytocin-drip in the cases of the study group where it was needed. It was concluded that the cervical balloon is a convenient method for the induction of labor, for its effectivity, simplicity and innocuity, especially in the "unfavorable" cervix cases.


Evaluation of a feto-pelvic scoring system in the management of breech presentations. A feto-pelvic scoring system comprising maternal pelvimetric data, estimated fetal weight, type of breech presentation and previous obstetric history was used in selecting patients for cesarean section of vaginal delivery. A maximum score of 20 points was possible. Twelve points or less indicated cesarean section. During 1973-1975 224 singleton breech deliveries were evaluated. In 29.5% cesarean section was performed and in 83% of these it could be planned in advance. In 70.5% of cases, patients were allowed to deliver vaginally under continuous electronic monitoring of the fetal heart rate. There was one intrapartum death and only one early neonatal death of a small premature child. In two cases intrauterine death had occurred already in the antepartum period. The uncorrected perinatal mortality was 17.9 per 1000 but not significantly different from the uncorrected perinatal mortality of 8.0 per 1000 for all patients delivered at the Danderyd's Hospital during the period 1972-1975 (12832 births). The corrected mortality resulting from breech presentation was 8.9 per 1000. The infants exhibited similar and excellent 5 min Apgar scores whether delivered vaginally or by cesarean section or matched with a randomized control series of 1000 cephalic presentations.


Immediate post-partum insertion of the Antigon. The results of intrauterine contraception using the Antigon inserted into 364 women immediately post partum are submitted. The patients were followed for 24 months, total number of woman months 5225. The follow-up was 96.7% after 3 months, 92.9% after 12 months, and 89.7% after 24 months. Four types of Antigon were used, having surface areas from 785 to 2740 mm2. Type I and the wing model (type IV), which have the smallest surface area, proved best suited. The continuation rates for types I and IV after 12 and 24 months were 77.4--59.2 and 76.4--54.5 respectively. These rates are on a level with those for Antigon inserted 6--8 weeks post partum. It is notable that the expulsion rates (12.8 and 12.7 after 12 months) were no higher than those for Antigons inserted 6--8 weeks post partum. The incidence of puerperal complications was not increased, and no perforations occurred.


Incidence of sterility in women operated on in childhood for perforated appendicitis. Of 80 women who had appendicectomy in childhood 78 were reviewed with reference to sterility. Thirty-nine of them had been operated on for acute perforated appendicitis (APA) and 39 for acute non-perforated appendicitis (ANPA). There was no statistically significant difference in the incidence of sterility between the two groups. In the APA group the incidence of sterility differs from that in sterility models with the same age composition. It may therefore be advisable for young girls to have appendicectomy at at the least indication.


Management of carcinoma in situ of the uterine cervix by selective local excision. Local excision of severe dysplasia or carcinoma in situ of the uterine cervix by punch biopsies was the treatment in 366 cases. In 61%, cervical cytology reverted to negative or slight atypia. 153 patients have been followed from 1 to 7 years. Failures to remove the entire lesion were discovered within the first year of follow-up in all cases but 10. Complications were negligible and no patients have subsequently developed invasive cancer of the cervix. Selective local excision as an alternative to other minimally traumatic techniques, e.g. cryotherapy is discussed. Although the failure rate is slightly higher with local excision, an obvious advantage is the availability of all removed tissue for histopathologic diagnosis. Thus, the risk of overlooking microinvasive disease is reduced to a minimum.


Distribution of serum amylase isoenzymes in cystic fibrosis homozygotes and heterozygotes. A simple method has been elaborated for the routine separation and quantitative determination of amylase isoenzymes. The ratio P/S, the quotient of the activity values obtained by densitometric evaluation of the pancreatic and salivary isoenzymes, is used to characterize their distribution. In healthy adults and children the value for P/S is above 1 in 80% of the cases, with a mean of 1.87 +/- 0.23. In 90% of heterozygote CF gene-carriers, the P/S is below 1 with a mean of 0.68 +/- 0.13. In addition to the higher total amylase activity, in MV homozygote patients P/S is less than 0.1, and even 0.001. The phenomenon is explained by a compensatory enhancement of salivary activity. The method is a suitable diagnostic test of the exocrine function of the pancreas and for evaluation of the serum amylase isoenzymes. The P/S value allows to differentiate heterozygote CF gene-carriers from homozygotes and healthy individuals.


Cystic fibrosis: a HLA associated hereditary disease? Twelve homozygote patients and thirty-two heterozygote gene carriers from families with cystic fibrosis were HLA-typed. Diagnostic criteria were sweat electrolyte concentration, pancreatic enzyme levels from duodenal juice and stool, Szczepanski's bromide test in the group of homozygotes, and the latter only in the cases of heterozygotes. In comparison with 130 healthy blood donors typed for 29 HLA antigens. B18 proved to be more frequent in the group of patients and gene carriers, with 50 and 31%, respectively, and 14% in the normal population. The association seems to be stronger in the homozygotes than in the heterozygotes (p less than 0.02, respectively).


Paraneoplastic syndrome in childhood.

Paraneoplastic syndrome in childhood. The case of five-year old boy is reported who at the age of 18 months had successfully been operated upon for neuroblastoma and who had subsequently signs of cerebellar encephalopathy. The paraneoplastic conditions of childhood are discussed in connection with the reported case. Opsoclonus was not observed in the patient, and symptoms showed rapid improvement on methotrexate, carmustine and CCNU treatment. Six months later the child was free of neurological disturbances and only displayed a slight mental retardation (IQ: 88). Cytological alterations observed in the CSF during the cerebellar encephalopathy are described in detail. At present, 41 months after the operation the child is well and free of symptoms.


Oxygen therapy and massive pulmonary haemorrhage in newborn infants. A significant rise in the frequency of neonatal pulmonary haemorrhage was observed in the year when intensive oxygen therapy by CPAP and IPPV ventilation was started. To clarify the role of oxygen therapy the neonatal deaths occurring in two periods of different oxygen treatment were analysed and compared in respect of all clinical features which may be involved in the pathogenesis of pulmonary haemorrhage. In conclusion it is suggested that the local effect of oxygen is probably an additional but significant pathogenetic factor in the condition.


A simple score to facilitate detection of congenital disorders. A simple score has been constructed to facilitate the selection of apparently normal newborns at risk or hidden congenital disorders. Components of the score are family history of previous malformations, stillbirth or infantile death of unknown origin, intrauterine growth retardation (2 points each), and six minor malformations: antimongoloid palpebral slant, hypertelorism, preauricular fistula, simian crease, mammillary and hallucal abnormality (1 point each). Out of 1000 consecutive neonates screened with the method 28 scored 3 or more, in 6 of whom hidden congenital abnormalities were discovered at later reexamination. At the same time only 2 hidden defects were found in the children with a neonatal score of 2 or less. Although the follow-up was incomplete, the results suggest that the score is useful in selecting infants for more complicated clinical and genetic investigations.


The effect of birth asphyxia on plasma free amino acids in preterm newborn infants. The postnatal plasma amino acid pattern was compared in 16 asphyxiated and 13 non-asphyxiated preterm newborn infants. The lactic acidosis induced by asphyxia was associated with a marked rise in the total amino acid content of the plasma. Among the 17 individual amino acids determined the concentrations of alanine, proline, taurine, glutamate, valine, methionine and lysine were significantly elevated. The accumulation of alanine was particulary marked and its concentration showed a significant linear correlation with that of lactate (p less 0.001). A similar relationship was observed between other potentially glucogenic amino acids and lactate. It is suggested that an impaired gluconeogenesis may be responsible for the accumulation of glucogenic amino acids. The response of the plasma aminogram to asphyxia resembles that associated with hypoglycaemia in the small-for-gestational-age infant, where a delay in the maturation of key gluconeogenic enzymes seems to account for the reduced hepatic disposal of glucose precursors.


A teratological evaluation of anticonvulsant drugs. Reviewing the important teratological data on anticonvulsants, the Hungarian experiences are reported. In the Hungarian Congenital Malformation Register use of the anticonvulsants diazepam and phenobarbiturates during pregnancy was determined in infants delivered with cleft lip with or without cleft palate, posterior cleft palate and, as a control, anencephaly and spina bifida. The teratogenic effect of diphenyl-hydantoin was confirmed, while that of diazepam and phenobarbital was not supported.


Peridural lipomatosis.

Peridural lipomatosis. Fifteen cases of peridural lipomatosis are presented. All patients were treated surgically in the years 1965 to 1974 and reexamined in 1975. In 5 cases of condition improved, in 4 cases it was unchanged and in 6 patients it deteriorated. It is emphasized that the question of surgical therapy must be decided individually.


Amyloidosis in ageing obese-hyperglycemic mice and their lean litter-mates. A morphological study. The occurrence of amyloidosis in obese-hyperglycemic mice (genotype obob) about 18 months old and their lean litter-mates was studied. Amyloidosis of varying degrees was found in 60 per cent of the mice and was equally common in both groups. Large amounts of amyloid were usually seen in the adrenal glands, liver, spleen and kidneys. In the kidneys, the amyloid was found mainly in the glomeruli, in the mesangial region. Electron microscopy of isolated amyloid fibrils showed that these consisted of two filaments about 40 A thick, twisted around each other. It is concluded that the distribution of the amyloidosis in these mice is similar to that seen in secondary or experimental murine amyloidosis.


Tumours of urinary bladder and ureter associated with abuse of phenacetin-containing analgesics. Forty-two patients with a bladder tumour and 4 patients with a ureteral tumour and a history of abuse of phenacetin-containing analgesics were studied. The sex ratio was 1:1, and the mean age 63 years. The estimated amount of ingested phenacetin was 7.1 kg, the estimated mean exposure time 21 years, and the estimated mean induction time 30 years. Renal papillary necrosis and impaired renal function were found in 34 patients. A history of recurrent urinary tract infection was found in 80 per cent of the patients, suggesting that the combination of phenacetin-abuse and chronic inflammation might be responsible for the localization of the tumours to the bladder. The majority of the bladder tumours were of low grade (1 and 2); muscular invasion was seldom found and metastases were rare. The patients were followed for 1.5-13 years. Twenty-six patients died; the mean survival time was 46 months. Uremia due to analgesic nephropathy was the main cause of death in 14 patients and contributed to death in another 7 patients. Three of the patients with ureteral tumours had received radiological treatment against the pelvic region, 15-20 years prior to the diagnosis of the ureteral tumour.


Liver ultrastructure in psoriatics related to methotrexate therapy. 1. A prospective study of findings in hepatocytes from 24 patients before and after methotrexate treatment. To show what damage occurs in the hepatocytes of psoriatics receiving Methotrexate (MTX) therapy liver biopsies from 24 psoriatics with severe psoriasis before and after MTX therapy were studied blind by light and electron microscopy. We also aimed to determine the severity of lesions and find possible correlations, and to seek a relationship of these observations with light microscopical and clinical findings. The present study has shown that MTX probably caused damage to the hepatocytes reflected in the membrane whorls (p less than 0.05) and the accumulation of lipid droplets (p less than 0.05). There was an increase (p less than 0.05) in autophagic vacuoles, which mostly contained glycogen and cell sap with residual bodies. These residual bodies were then found in an increased number in the nearby Kupffer cells. Crystals were found in megamitochondria in most patients before and after MTX therapy. Some of these crystals were found free in the cytoplasm. Mitochondria containing crystals were shown in autophagic vacoules, representing possible pathways of their breakdown. Bile canaliculi commonly contained debris but only one patient had evidence of cholestasis. There was no significant change in nuclei, Golgi apparatus, or the endoplasmic reticulum and no statistically significant correlation between the shown changes and the total dose of MTX given.


Liver ultrastructure in psoriatics related to methotrexate therapy. 2. Findings in bile ducts from 11 methotrexate treated psoriatics and 2 controls. To determinate what damage occurred in the bile ducts of psoriatics receiving Methotrexate (MTX) therapy liver biopsies from 11 patients were studied with the light and electron microscope and compared with normal material. Thick sections (1 micrometer) showed light and dark cells in biliary epithelium and lipofuscin granules. At the ultrastructural level these were confirmed. The lumen of the bile ducts contained debris. The microvilli were decreased in number and damaged forms appeared. Damage to the biliary epithelial mitochondria was widespread and there were foci of intracellular oedema. The Golgi apparatus was hypertrophied and dilated. Atrophic cells were seen. The lateral intercellular spaces were dilated and contained debris and the basement membrane showed zones of duplication. Similar changes were found in the ducts of Hering.


Ancient neurilemmoma (schwannoma).

Ancient neurilemmoma (schwannoma). A clinical and light microscopic study of 11 patients with ancient neurilemmoma is presented. Ancient neurilemmoma is a cellular form of ordinary neurilemmoma, showing nuclear polymorphism and hyperchromasia. Seven patients were female and 4 were male; their ages ranged between 37 years and 81 years, with a median of 59 years. Seven tumours were 2.5 cm or larger in the widest diameter, and had been slowly enlarging for one year or more. All tumours were solitary, encapsulated showing nuclear polymorphism and hyperchromasia without any mitotic activity. The differential diagnosis is discussed. Follow-up information available on all patients confirmed that the clinical course is benign.


Epithelial mucosubstances and argyrophil cells in Brenner tumours. Brenner tumours of various degree of malignancy were investigated by histochemical methods. The cells lining the cystic cavities in the benign Brenner tumours contained various amounts of PAS-positive, diastase resistant secretory material mixed with small amounts of sulpho- and carboxymucin. The borderline and malignant tumours contained more acidic mucins than the benign tumours. All tumours contained glycogen. Argyrophil and argentaffin cells have not earlier been detected in the Brenner tumours but in this study they were detected in twelve of the 18 Brenner tumours. These cells were not proliferating and therefore Brenner tumour should not be included in the group of APUDomas.


Ultrastructure of the benign and borderline Brenner tumours. One benign Brenner tumour and one Brenner tumour of borderline malignancy were investigated by electron microscopy. The cells of the benign Brenner tumour nests and the cells in the borderline tumour were similar in ultrastructure. The intercellular spaces were large and reinforced by a moderate number of desmosomes. The nuclei were round or oval. The nuclear membrane was irregular in shape with deep infoldings corresponding to the characteristic nuclear groovings seen by light microscopy. Only few secreting cells could be found in the benign of Brenner tumour. The cystic cavities of the borderline Brenner tumour were lined by nonciliated secreting and ciliated nonsecreting cells. The secretory granules were PAS-positive and diastaseresistant. The granules stained homogeneously and strongly with the PASM-method at the electron microscopical level indicating the presence of 1.2-hydroxyl groups. The Brenner tumours have many similarities to the transitional epithelium and to the Muellerian-derived tubular structures. The findings support the theory that Brenner tumours are  of coelomic origin and develop by direct metaplasia from the ovarian surface epithelium.


The effect of D-galactosamine on LCAT secretion and ultrastructure of isolated rat hepatocytes. The effect of D-galactosamine on secretory activity and morphology of isolated rat hepatocytes was investigated: Galactosamine was found to reduce the secretion of lipoproteins (as indicated by the release of free cholesterol and triacylglycerol) as well as the secretion of lecithin: cholesterol acyltransferase (LCAT) and [14C]-labelled proteins from the isolated cells. The secretion of LCAT was inhibited much more than that of the other secretory products studied. Transmission electron microscopy revealed that galactosamine induced morphological changes in RER, mitochondria and nucleoli. The most striking feature of galactosamine-treated hepatocytes, however, was the appearance of swollen lysosomes. Some of these organelles measured up to 3 mumicrometer in diameter. Uridine did not abolish the effect of galactoosamine upon the secretory activity of hepatocytes. The most conspicuous ultrastructural feature in cells that had been incubated with both uridine and galactosamine was the appearance of large amounts of glycogen. The possibility that galactosamine inhibits glycogenolysis is discussed. The rather selective effect of galactosamine on LCAT secretion suggests the use of this compound for the study of the interrelationship between LCAT and lipoprotein secretion.


Löffler's endocarditis and endomyocardial fibrosis--a nosologic entity? The problem whether Löffler's endocarditis and endomyocardial fibrosis belong to the same disease spectrum or are separate entities is still under debate. Until recently it was believed that endomyocardial fibrosis was a disorder restricted to tropical areas. Three Danish patients are presented, two showing a continuous disease spectrum, one patient showing the fully developed endomyocardial fibrosis which is indistinguishable from endomyocardial fibrosis described from the tropical areas. Eosinophilia was present in all three patients. The findings described in these three patients lend support to the unitarian hypothesis that Löffler's endocarditis and endomyocardial fibrosis belong to the same disease spectrum, and that the eosinophilic granulocyte may be the underlying cause.


Transthoracic aspiration biopsy. A study on diagnostic reproducibility. Based on a randomized material of 100 histologically verified transthoracic aspiration biopsies an inter- and intraobserver variation study was carried out by the two investigators. The results showed a high degree of diagnostic reproducibility pointing towards the value of the aspiration biopsy per se. It is concluded that this diagnostic method is reliable in the hands of the expert and useful even in the hands of a pathologist only given a short introduction to--and a reasonable amount of correction within--this special field.


Clinical, histological and ultrastructural features of a possibly virus-induced oral leukoplakia. Two male patients with oral leukoplakias exhibiting a peculiar type of apparent dysplastic changes have been followed for 4 and 6 years, and a series of biopsies have been examined by light and electron microscopy. The apparent lack of normal epithelial stratification below the keratinized cell layers was mainly caused by the frequent appearance of large ballooned cells and multinuclear giant cells. The centre of the large ballooned cells contained aggregations of chromatin and evenly-dispersed microtubulus surrounded by a thick rim of tonofibril bundles. In the peripheral cytoplasm large numbers of smooth-surfaced endoplasmic reticulum were found, but no Golgi apparatus was observed. In addition, several autophagocytic bodies were recorded. Along the cell membrane only a few desmosomes were present, whereas aggregations of digested desmosomes were found in the cytoplasm. On the basis of the ultrastructural findings, it is suggested that the large ballooned cells represented epithelial cells arrested in early stages of mitotic division. The epithelial cells in interphase exhibited a normal ultrastructure except for large nucleoli with varying degrees of condensation of nucleolonema and vacuolization. Further, atypical dense granular aggregations and strands of fine fibrillar material were recorded in the nuclei. It is suggested that this new type of oral leukoplakia has a viral etiology.


A quantitative study of glomeruli in idiopathic nephrosis with minimal or no glomerular lesions. A quantitative investigation was performed of glomeruli in renal ibiopsies from patients with nephrotic syndrome or persisting proteinuria associated with normal light microscopic findings or slight changes not considered significant ("minimal change disease", lipoid nephrosis). The mesangial area was widened (+ 26 per cent, p less than 0.05) and there was an increase in the mean of the total number of cellular nuclei per glomerulus, the number of mesangial (+ 16 per cent) and edothelial nuclei (+ 23 per cent), but of these only endothelial hypercellularity was significant (p less than 0.025).


Pseudosarcomatous lesions of the soft tissues reported as sarcoma during a 6-year period (1958-1963). Pseudosarcomatous lesion of the soft tissues is a term used in the present study for various soft tissue lesions and tumours easily clinically or histologically, or both, misinterpreted as sarcoma. Eighty-one cases, that is to say 10 per cent of all tumours classified and reported to the Swedish Cancer Registry as malignant soft tissue tumours during the 6-year period studied (1958-1963), were reclassified as pseudosarcomatous lesions of the soft tissues. Forty-seven cases were classified as pseudoarcomatous proliferative lesions of the soft tissue with or without bone formation; 38 cases of nodular fasciitis, 1 of proliferative fasciitis and 8 of proliferative myositis. In 3 of these cases there were mixed forms of proliferative fasciitis and proliferative myositis with areas compatible with the diagnosis of nodular fasciitis evident in all cases. Twenty-two cases of atypical fibroxanthomas of the skin were next in frequency, followed by 7 ancient neurilemmomas, 2 spindle cell lipomas, 1 pseudomalignant osseous tumour of the soft tissues, 1 pigmented villonodular synovitis and 1 juvenile xanthogranuloma. An attempt is made to explain the reasons for these erroneous diagnoses of sarcoma and it is stressed that for these lesions the conventional histological criteria for malignancy are not valid. The awareness and knowledge of the existence of these particular entities are therefore considered mandatory for an accurate diagnosis.


Focal pregnancy-like changes in the breast. The aetiology of focal, preganancy-like mammary changes in non-pregnant and non-lactating women is discussed on the basis of the literature and a material of 31 patients. Such changes were found in one or more glandular lobules in 3 per cent of the breast tissue specimens received in our departments. As a rule, this finding was made in women who had been pregnant and who had been or were on oestrogenic or on contraceptive medication. They occurred in fertile, menopausal, as well as in post-menopausal women. Often they were seen many years after the pregnancy and/or intake of hormones. They were observed also in women who had never been pregnant or on hormone medication, and even in men on oestrogen therapy. It is likely, therefore, that focal pregnancy-like changes in non-pregnant and non-lactating women indicate a selective susceptibility of the mammary glandular tissue to oestrogen. Accordingly, we interpret the change as a normal histological variant.


Effects of the nonapeptide SQ 20.881 on the blood pressure of conscious normotensive and chronic hypertensive mice. Prevention of conversion of angiotensin I to angiotensin II by means of a converting enzyme inhibitor, the nonapeptide SQ 20.881, in chronic hypertensive mice was followed by a drop in blood pressure in all mice independent of the ethiology of hypertension; in conscious normotensive mice was observed a significant decrease in blood pressure, which, however, was less than that observed in the hypertensive mice.


Studies on mycobacteria isolated from animals, with special reference to the agglutination test. Ninety-three strains of slowly-growing mycobacteria were studied biochemically. Ninety of these were isolated from animals (pigs, cattle, dog and poultry) and three from dust and sawdust-bedding in a pighouse. One strain from a lymph node of a pig was identified as M. gordonae. Ninety-two strains fitted into the M. aviam-intracellulare complex. Of the 92 biochemically confirmed M. avium-intracellulare strains, 78 were tested serologically ad modum Schaefer. Of 73 strains from pigs, one was serotype 1, fifty serotype 2 and eight serotype 8, while two could not be type and twelve were autoagglutinable. Three strains from pighouse environment were serotype 8 and two from cattle and a dog were both serotype 2. A slight modification of Schaefer's agglutination method, using smaller amounts of antigen and antiserum, was developed.


Interaction of hydroxyapatite and protein-coated hydroxyapatite with Streptococcus mutans and Streptococcus sanguis. The present study showed that S. mutans and S. sanguis behaved like negatively-charged particles in their interaction with hydroxyapatite in vitro. Phosphate in the system inhibited bacterial uptake by apatite, whereas calcium increased the uptake. A layer of acidic protein inhibited the uptake of bacteria by hydroxyapatite. The opposite was true when a basic protein was first adsorbed to the apatite. A saliva film on the apatite decreased the uptake of bacteria, supporting the view that acidic proteins are selectively adsorbed by hydroxyapatite from saliva. The results indicate clearly that electrostatic forces may be involved in bacterial interaction with tooth surface.


Treatment of Mycoplasma hyorrhinis contaminated tissue cultures with a mixture of antibiotics. Results obtained using a combination of antibiotics to control mycoplasmas in tissue cultures are described. Cell strains and established cell lines from several mammalian species grown in tissue culture were found to be highly contaminated with M. hyorrhinis. Cultures were treated with a mixture of three antibiotics consisting of gentamicin, tetracycline and chloramphenicol, and since that time tests for mycoplasmas in the treated cultures have consistenly yielded negative results. Apart from a transient cytostatic effect on the cells during the treatment, no apparent unwanted effects were observed. The mixture of three antibiotics appeared to be superior to treatment with antibiotics singly or combinations of two antibiotics.


Small spherical viruses in faeces from gastroenteritis patients. Faecal samples from 238 patients with gastroenteritis were examined by direct electron microscopy using grids with thin carbon film. Of these samples 18 were found to contain Norwalk agent-like particles, calicivirus, astrovirus and parvovirus-like particles. Immune electron microscopy was performed on a serum pair and faeces from one of the patients with astrovirus. An antibody response was demonstrated, suggesting that the virus was the etiological agent of the infection.


[Evaluation of the therapeutic performance of an integral program of neuroses as applied to an outpatient clinic]. 1. During 1976, it was evaluated the treatment of 45 cases of neurosis, carried out by monitors (D4) of the External Consultation of Barros Luco-Trudeau Hospital. 2. It is emphasized that the cost of the program in terms of professional hours and economic resources is low. 3. From 156 patients referred to therapy, 88 deserted (56,4%); 23 attend without finishing therapy (14,7%), and 45 completed it (28,8%). 4. It seems important to carry out studies about the factors that influence the desertion to the psychotherapy offered by our psychiatric services. To establish comparisons between the attendance to the group therapy, and also between the attendance to the group therapy carried out by professionals and carried out by monitors. 5. In the patients that complete therapy (12 sessions of 1,5 hours, once a week) the total improvement is 79,1%, the partial, 11,3%, and there is no modification in 9,3%.


Complement C1-inactivator in the serum of patients with malignant disease. Complement C1-inactivator (C1-IA) in serum was determined in 423 individuals. The normal range for the concentration of C1-IA in serum was calculated from values in 94 blood donors and the concentrations in the sera of 329 patients were determined in relation to this range. A significant correlation was found between widespread malignant neoplastic disease and increased quantity of C1-IA in serum. Determination of C1-IA may be used to evaluate the extent to which a malignant disease is disseminated.


Effect of 50 kV roentgen rays and cobalt-60 gamma rays on the activity of ciliated cells. A method capable of continuously recording the changes in the physiologic activity of ciliated cells during irradiation has been used to analyse the importance of photon energy for the early biologic effects of ionizing radiation. Gamma rays from 60Co and 50 kV roentgen rays were used. Important differences were demonstrated and conventional RBE values are not valid for early effects. The results are discussed and RBE for 50 kV roentgen rays has been calculated in respect to early effects of irradiation.


Behavioral modification psychotherapies in the autistic child. Behavioral modification psychotherapies, largely diffused in the anglo-saxon countries, are used here for treating severely autistic children, hospitalized in a child psychiatry service for at least one year. Using Kanner's clinical study on childhood autism, the same syndrome is being described in behavioral terms. This new approach is the basis for the therapeutic project, both on practical and theoretical grounds. To illustrate the method and its application, three observations of children hospitalized between 1976 and 1977 are presented. The results are summarized and discussed (Acta psychiat. belg., 1977, 77, 549-586).


Prognostic relevance of immunologic variables in breast carcinoma. A series of 203 consecutive patients with operable carcinoma of the breast was analysed with regard to correlations between a set of immunologic and clinical variables existing at the time of the diagnosis. No major correlations were revealed between immunologic variables on the one hand and clinical features or the course of the disease on the other. The well-known prognostic relevance of tumour size, involvement of the axilla and the histological grade of malignancy was evident.


[Infant-juvenile psychiatry in Algeria (author's transl)]. Psychiatric problems of the child and the adolescent in Algeria are discussed in light of traditional psycho-social factors and in the modern world. The emphasis is on the frequency and severity of troubles of organic origin. Parallely, the impact of new aspects, coming from consequences of socio-cultural mutations, is understressed. This study underlines relationships between psychiatric aspects and socio-economical and cultural factors, and the role of the psychiatrist, with the heavy responsabilities he has to face in all areas if he wants to remain in his therapeutic role (Acta psychiat. belg., 1977, 77, 587-622).


Biochemistry of late effects in rat lung after hemithoracic irradiation. The right hemithorax of rats was exposed to 1 kR of roentgen rays, the animals were killed at different times, and various physiologic and biochemic parameters (DNA, protein, collagen, sialic acid, lysosomal enzymes, fibrinolytic activity, peroxides and blood flow ratio between irradiated and non irradiated lung) were determined from 1 day until 11 months after irradiation. A decrease in relative blood flow was observed from 2 weeks until 11 months, a decrease in phospholipids from one to 3 months and a decrease in fibrinolytic activity from 1 day to 11 months after irradiation. At several times a decrease in sialic acid and cathepsin D was also noted. The changes are discussed with respect to the pathogenetic mechanisms of late lung damage.


[Emergency and psychiatric emergency at the General Hospital (author's transl)]. First, the author examines the requests made on the consulting psychiatrist (Prof. Luminet Service) within a 1.000 beds' hospital, administered by the Public Assistance and with a university status. He compares data on three months to a similar study done in the same hospital four years ago and lasting for six months. There is an important increase in the number of requests. He examines the reason for the requests, the distribution in age of the patients and their outcome after the psychiatric consultation. The comparison of both studies does not show any improvement in the failure already emphasized in the 1970 study. Secondly, the functioning of the psychiatric emergency unit (11 beds) is examined for a period of four months. The 59 patients in transit in this unit are examined for age, diagnosis, place of origin, length of stay. Some factors in favor and against this type of stay are discussed, in relation to the teaching role of the unit for the students and in relation to the type of hospitalised patients (Acta psychiat. belg., 1977, 77, 639-652).


Distribution of 169Yb microspheres and colloidal 198Au following injection into the rectal submucosa in dogs. A comparison between two tracers, the one colloidal suspension of 198Au, the other 169Yb-labelled microspheres of 8 to 10 micron has been made concerning lymphatic and hematogenous spread from the submucosa in the rectum in dogs. Both tracers have, in principal, the same distribution. It was therefore considered that a colloidal suspension of 198Au is a useful tracer for functional anatomic investigations of lymph drainage.


[Space, time and identity in migrant (author's transl)]. An understanding of the psychology and psychopathology of the migrant is possible from the phenomenological description of his living world, by utilizing categories of space, time and identity. The clinical preponderance of depressive, paranoïd and psychosomatic symptoms and the symptomatic polymorphism are integrated in this perspective. This includes the subject and the social structure as elements of the total picture. The constant relationship of the subject with the social structure can point to the sociogenic reactive character of some troubles (Acta psychiat. belg., 1977, 77, 623-638).


Comparative studies on the soluble proteins of adenovirus type 1. The soluble proteins of adenovirus type 1 have been separated and purified. Their antigenic characteristics were compared in different precipitation experiments performed in electric field. Both two-dimension immune electrophoresis and rocket electrophoresis can successfully be applied for quick diagnostic purposes. Quantitative determination of virus proteins is also feasible by rocket electrophoresis. The isoelectric point values of hexon, penton and fibre were pI 4.55, pI 4.69 and pI 7.07, respectively. The amino acid composition of type 1 adenovirus and its capsid components was determined from separated and purified protein preparations. The former differed in amino acid composition from the tissues used for virus propagation.


The use of ion exchange chromatography for demonstration of rubella-specific IgM antibodies. IgM and IgG immunoglobulins of human sera were separated by stepwise column chromatography in QAE-Sephadex A-25 ion exchanger gel bed. The procedure resulted within 30 min in a fraction suitable for direct titration of rubella-specific IgM antibodies by haemagglutination inhibition test. The method proved to be a useful diagnostic tool for primary rubella. Serum samples of 13 individuals with previously acquired immunity, 152 patients with a recent rubella-like illness, and 194 pregnant women exposed to rubella infection were tested for the presence of rubella-specific IgM antibodies. Sera of individuals with previous immunity proved to be negative for specific IgM antibodies. Specific IgM titre was demonstrated in the blood of all the 25 patients with significant titre-rise tested because of rubella-like illness, and also in the sera of additional 8 patients whose serum samples were taken too late for demonstration of a rise in titre. Significant titre-rises were found in 5 women exposed to rubella infection, but only two of them exhibited rubella-specific IgM antibodies. The absence of specific IgM antibodies refers presumably to subclinical reinfection in the other three cases.


Morphology of Salmonella typhi in different inactivation techniques. Heat-phenol treatment of Salmonella typhi results in a denaturation of the cytoplasm and a smoothing of the cell wall with numerous ruptures. Following acetone inactivation the cell wall changes similarly, the cytoplasm is shrunken and its structures remain intact. Destruction is more intensive following heat-phenol treatment than after acetone precipitation. In both cases three contrasting layers of the cell wall can be seen.


Changes in the surface layer (sheath) of the cell wall of streptomycetes during sporulation. Fine structural changes of the sheath, occurring during spore formation in strains Streptomyces finlayi ATCC 23 340 and Streptomyces coeruleorubidus FBUA 328 were investigated by means of electron microscopy of air-dried whole mounts and thin sections. The results suggest that in the strains the process of sporulation is not strictly synchronized spatially with the molecular arrangements and re-arrangements (formation of hairy or spiny surface ornaments) occurring outside the wall of the sporulation hyphae, in the sheath. On the contrary, the intensity of transformation induction in the sheath may show a gradually decreasing tendency from the tip of the sporulating hypha towards its sterile basal part, resulting in the formation of both ornamented and smooth spores in the same chain. This suggests that the morphogenetic changes occurring in the sheath during spore formation are probably controlled by a "functional centre", located near the tip of the sporulating hypha, and this centre is perhaps indentical with the cell unit at the tip.


Sex chromatin scores in oral mucosa and hair root sheaths of human females. The preparation and the utility of oral mucosa and hair root sheaths for quantitative sex chromatin studies is discussed. In buccal smears requirements for reliable scoring are frequently not fulfilled. Counting is time-consuming and disturbing measurement errors cannot be avoided. On the other hand, hair root sheath slides can be quickly prepared, the method yields preparations of good quality, and sex chromatin is displayed with considerable clarity. This procedure thus provides a high degree of accuracy and simplicity and counting can be quickly done with a relatively small measurement error. The incidence of sex chromatin in hair nuclei is observed to be about 20 per cent higher than in oral mucosa of the same female. In hair root sheaths non-peripheral sex chromatin can easily be recognized; including these into the scores significantly increases the actual incidence of sex chromatin positive nuclei.


Biochemical investigation of lens induction in vitro. I. Induction properties of the eye cup and ectodermal response. 1. Optic cups of 48, 72 and 96 hours old chick embryos were prepared, cultured and recombined with ectoderm. With the optic cups of 48 hours old embryos, lens formation occurred in 16% of the cases. With the optic cups of 72 hours old embryos, lens formation occurred in 28% of the cases. Optic cups of 96 hours old embryos were not able to induce a lens. 2. The optic cup proved to be able to induce a lens more than once. 3. Ectoderm of the head of 72 hours old embryos was still able to form a lens. 4. Using homogenized eye cups of 72 hours old embryos, lens induction occurred only in a few cases. When the optic cups were cut into small pieces, lens induction occurred in 30% of the cases. This suggests that intact cells are necessary to obtain lens induction.


Distribution, composition and possible functional significance of lipids in the follicular epithelium of growing oocyte in the snake Lycodon aulicus ovary. A histochemical study. A histochemical study has been made of the distribution, composition and possible functional significance of lipids in the follicular epithelium of growing oocyte in the snake (Lycodon aulicus) ovary. Lipid bodies composed mainly of phospholipids, and diffusely distributed lipoproteins are formed in the polymorphic and multilayered follicular epithelium of previtellogenic oocyte. The lipid bodies are apparently transported into the oocyte which simultaneously develops several such phospholipid bodies in the cortical ooplasm. It is suggested that the lipids contributed by the polymorphic follicular epithelium meet the nutritional requirement of growing previtellogenic oocyte for the construction of various ooplasmic organelles which simultaneously multiply in their numbers.


Electron microscope study of two types of cells in the anterior lobe of the Chinese quail adenohypophysis with special reference to their cytological features after photostimulation. Two types of cells in the adenohypophysis of the Chinese quail, Excalfactoria chinensis, were studied by electron microscopy in birds receiving nine hours of light per day, and birds exposed to continuous light. Type-I cells of photostimulated quail have a well-developed vacuolar system consisting of cisternae and perinuclear spaces confluent with each other. The cytoplasm is restricted to small strands enclosing cell organelles. Secretory granules reaching 150-250 nm in size are scattered at the secretory pole of the cell. Exocytotic vesicles are not often observed. A circular Golgi apparatus with immature secretory granules in its neighbourhood is characteristic for this type of cell. Type-II cells of photostimulated quail present analogous features: distended endoplasmic reticulum and perinuclear spaces. A cup-shaped Golgi apparatus is often observed, with secretory granules, ranging in size from 80-150 nm. Exocytosis is regularly observed. Evidence is provided that the Type-I cell could be a LH-like cell (gamma-cell), and Type II, a FSH-like cell (beta-cell) in birds. The existence of relationships between gonadotrophs and thyrotrophs did, nevertheless, not exclude the possibility that one of the two types could be a thyrotroph.


Factors affecting the incidence of wound infection in Neurosurgery. A prospective survey of wound infection in a continuous series of 357 patients undergoing operations at a neurosurgical unit was made. The incidence of wound infection was 4.7 percent. Causative organisms were isolated in only 29.4 percent of the clinically infected cases. The type of suture material used did not affect the infection rate and neither did the coincidental use of steroids in the high doses employed in neurosurgical practice. Re-exploration does not carry an increased risk of infection. Use of systemic or topical antibiotics or both was not found to confer any protection against wound infection.


Hydrothorax: unusual complication of ventriculoperitoneal shunts. A case is presented in which puncture of the pleura and hydrothorax occurred during placement of a ventriculoperitoneal shunt. Treatment of this complication is outlined.


The surgical risk in the treatment of Arnold Chiari malformations. The authors describe a series of 26 patients (28 operations) with Arnold Chiari malformations who were admitted during a 4 year period. In 20 the malformation was treated by direct surgery on the posterior fossa. Seven were treated by ventriculoatrial shunting. An analysis of the surgical risks of each procedure is given. In addition a helpful guide in the choice of the proper surgical procedure is outlined.


Developmental arachnoid cysts of the posterior fossa-an analysis of 13 cases. Thirteen cases of posterior fossa arachnoid cyst are described. Presenting features were usually headache, vomiting, lethargy, and delayed development in infants. Association with congenital defects is sometimes noted. The cysts are considered to result from abnormalities occurring in foetal life.


Long-term intracranial pressure monitoring in comatose patients suffering from head injuries. A critical survey. On the basis of a series of 75 patients, the practical use of Icp continuous long-term recording in severe head injuries without mass lesions or remaining deeply comatose after surgical procedures is critically analyzed. ICP monitoring alone seems to be not essential for prognosis. Conversely it is of much greater use as a guide to management (respirator treatment, osmotics, CSF drainage). If the pros and cons of the procedure are carefully weighed, it would appear that, for the time being, ICP long-term monitoring is justified only in comatose patients on intensive care.


Advances in management of severe head injuries in childhood. An analysis of the clinical courses of 205 children with severe head injuries is given. In addition to the use of modern intensive care methods, advances are due to monitoring intracranial pressure directly, steroid therapy in very high doses, and early activation in the subacute stage after injury. By this it is possible to lower mortality and to achieve better clinical results.


Electroencephalographic investigations of traumatic apallic syndrome in childhood and adolescence. Reports of electroencephalographic changes in cases of the traumatic apallic syndrome in children and adolescents are very rare. We tried to correlate special electroencephalographic patterns with the three different stages that are usually seen. We found high voltage subdelta and delta activity in the initial symptom complex, an EEG with dominating delta-theta activity and voltage of medium height corresponding to the fully developed stage, and a flat theta EEG in the stage of remission. The difficulties in interpretation of the changes, especially in children, are discussed. Longitudinal electroencephalographic studies are recommended for diagnosing complications, such as haematomas or palsies, and for prognosis.


Unusual intracranial foreign bodies. Report of five cases. Five patients surgically treated for unusual intracranial foreign bodies are presented. They include representative cases of the three most commonly encountered types of these injuries: industrial accidents, suicidal attempts and the result of criminal assault. Immediate radiological examination is mandatory because the deceptively small entrance wound is usually in no way commensurate with the large size of the foreign body the presence of which is frequently not suspected. The surgical removal of these foreign bodies requires careful pre-operative assessment to avoid hemorrhages and undue injury to the surrounding normal brain tissue.


Arachnoid diverticula: a unitary approach to spinal cysts communicating with the subarachnoid space. The authors report six cases of so-called spinal subdural arachnoid cysts, emphasizing the clinical and myelographic findings which, if not properly evaluated, may be misleading diagnostically. The literature of so-called perineural cysts and of extradural arachnoid cysts is likewise reviewed. Their clinical, roentgenological, and pathological features are examined. A common pathogenesis for all these lesions is proposed. It implies disruption and secondary proliferation of the arachnoid membrane. Hence, the term arachnoid diverticulum is advanced to include all lesions communicating with the subarachnoid space. Their varying relations with the subarachnoid space depend on the sites of the primary abnormalities and on hydrodynamic factors. Numerous observations of associated arachnoid diverticula, either perineural, subdural, or extradural, further favour a common pathogenesis.


Angiographic features of upper cervical extradural neurinoma. Case Report. A case of upper cervical extradural neurinoma in a teenage girl is reported. The value of investigating the spinal arteries in such lesions is stressed.


The infant and hepatitis B virus infection. HBV has been shown to be responsible for a broad spectrum of disease in infants although most are asymptomatic carriers with mild transaminase elevation and unresolved hepatitis on liver biopsy. Maternal-infant transmission is responsible for most infections. Blood product infusion should become less significant. Acute maternal hepatitis in the perinatal period results in asymptomatic infant infections at rates far exceeding transmission from asymptomatic carrier mothers. Carrier mothers with the e-antigen or HBV-associated DNA polymerase transmit infection more readily than do carrier mothers without these HBV markers. The presence of maternal anti-e may be protective. Intrapartum and postpartum transmission occurs more often than transplacental infection. For this reason attempts at prophylaxis with immune serum globulin administered in the newborn period should be further evaluated.


[Performance at school in children suffering of cerebral-convulsion-disease (author's transl)]. Investigations were performed into school-certificates of 226 school-children suffering of cerebral-convulsion-disease (Controlgroup 306 healthy children). Differences between the two groups were significant, the results of the ill children were worse than those of healthy. The differences increased to the elder children. Also in schools of backward children the school-certificates between children with and without cerebral convulsion diseases were very different. The influence of social factors is discussed, hints are given to improve the situation.


[Dust-measurements in the air of school-sporthalls (author's transl)]. Corresponding to the importance of sport in infancy and youth there were made experimental studies to examine the load of dust in school-sporthalls. In one selected school-sporthall of Erfurt 900 dust-measurements with Zeiss-Conimeter type 10 were carried out for a half-year in winter, and supplementary it was measured with the soviet conimeter type A 3-4 some days. The statistical evaluation allowed a break down of the sport-exercises in 3 groups dependent of the lot airborne dust in the sporthall: 1. gymnastic with apparatus 2. physical training on-floor 3. running and plays. The average quantities of dust during these three above mentioned exercises increase from group 1 to group 3, and they differ significantly. The results are discussed in connection with the literature which for the greater part originates from Poland and Soviet Union.


[Methodology of out-of-school sexual-ethical education of youths (author's transl)]. The experiences of out-of-school sexual education with about 5000 youths in the district of Magdeburg are reported. The joining of a strange educator, e. g. a physician, in sexual-ethical education is always unfavourable when this is the only form of influence on youths. But at present it is still necessary to do so because of the lack of a sufficient and continuous sexual education at school. It is important here to take part in the discussion of the problems: "friendship-love-sexuality". Discussions are more effective than lectures in the usual sense. But a special course of the talk must be observed and the youths must also get the possibility of single talks. Altogether the cycle should consist of 2 discussions: -juvenile partnership -marriage and family planning.


Effect of histidine on morphine-induced changes in brain histamine. Chronic morphine administration to rats resulted in a significant decrease in the hypothalamic and cerebro-cortical histamine concentrations. These low histamine values were restored to control levels when L-histidine was administered daily along with morphine treatment. Chronic treatment with L-histidine prevented the midbrain and cerebro-cortical histamine depletion in morphine-withdrawn rats, whereas in the hypothalamus the histamine level remained significantly decreased. The present data suggests that histamine may play a role in morphine dependence and withdrawal.


Comparison of the inhibition of histamine- and pentagastrin-stimulated gastric acid secretion by somatostatin in the cat. The effect of cyclic somatostatin on pentagastrin- and histamine-stimulated gastric acid secretion in conscious cats was studied. Evidence is produced that somatostatin competitively inhibits pentagastrin-stimulated gastric acid secretion whereas it inhibits histamine-stimulated secretion by a mechanism which is not competitive in nature. The vagus nerves seem to be involved in the mode of action of somatostatin as the inhibitory effects are greater in vagotomized than in vagus intact animals.


The effect of hexamethonium on gastric acid secretion in the conscious rat. Evidence against a role for histamine in pentagastrin-stimulated acid secretion has been obtained previously using hexamethonium in gastric fistula rats. This possibility has been re-examined in conscious rats provided with gastric fistulae or Heidenhain pouches. Hexamethonium (20 mg/kg s.c.) inhibited basal acid secretion and acid secretion stimulated by histamine and pentagastrin in gastric fistula rats. The same dose of hexamethonium failed to produce a significant inhibition of acid secretion stimulated by bethanechol, pentagastrin or histamine in the presence of a low dose of bethanechol in Heidenhain pouch rats. These results provide no evidence to oppose the view that pentagastrin-stimulated acid secretion in the rat is mediated at least in part through the mobilization of gastric mucosal histamine. The inhibition of secretagogue induced acid secretion in the gastric fistula rat is mainly the result of a reduction in the basal acid output.


Edema formation and neutrophil mobilization in the neutropenic rat. The relationship between leucocyte mobilization and edema formation was evaluated in the carrageenan pleurisy model. In normal rats carrageenan was able to mobilize between 80 and 100 million cells per ml of fluid. In neutropenic rats the concentration fell to between 20 and 50 million cells per ml, suggesting the edema formed after carrageenan injection is not directly correlated with cellular mobilization.


A polyether sponge constituent which is antioxidant, anti-inflammatory and increases prostaglandin concentrations at the inflamed site. Granuloma formation was studied in rats following s.c. implantation of polyether sponges soaked in carrageenin. Sponges, which had been boiled in ethanol, produced larger granulomata and more exudate than unboiled sponges, but prostaglandin (PG) concentrations were lower in exudates from boiled sponges. Sub-cutaneous injection of the ethanolic sponge extract inhibited the delayed phase of carrageenin-induced rat hind paw oedema. A counter irritant action was ruled out by the demonstration that local administration of the extract also inhibited hind paw oedema. Ultra-violet spectrophotometry of the anti-inflammatory extract indicated that the main constituent was probably a phenolic material, commonly used as an antioxidant in the manufacture of polymers. The antioxidant nature of the extract was confirmed by its inhibition of the autoxidation of adrenaline. The results are discussed in the light of recent reports on the anti-inflammatory properties of phenolic antioxidants and their effects on the PG biosynthetic pathway.


Administration of anti-inflammatory compounds in silastic capsules. Eleven compounds, within hollow capsules of polydimethylsiloxane (Silastic), have been studied with regard to their rate of release and anti-inflammatory activity in the Adjuvant Arthritic (AA) rat. All of the compounds diffused through the capsule wall to some extent with cortisone acetate exhibiting the slowest and ibuprofen the fastest release rate. Of the eleven encapsulated compounds, only phenylbutazone, indomethacin, ibuprofen and naproxen significantly reduced right and left paw volume below that of control value. Silastic encapsulation increases efficacy of phenylbutazone and indomethacin two to three times over subcutaneous or oral administration. Based on potency and duration of constant release, indomethacin and naproxen should exhibit anti-inflammatory activity in excess of 12 months.


The effects of colchicine and its derivates on the collagen biosynthesis in vitro. Recent evidence shows that colchicine decreases collagen production and favourably influences some fibroproductive processes in experimental animal and clinical practice. In our study we investigated the influence of two colchicine derivates--demecolcine and desacetylcolchiceine--on the synthesis of collagen and non-collagen proteins in new born rat skin after the incubation of tissues slices with 14C-proline for 2 h. Collagen was separated in fractions soluble in either 0.45 M NaCl or 2% semi-carbazide that in an insoluble residue. Demecolcine (10(-3)--5.10(-5) M), desacetylcolchiceine (10(-2)--5.10(-4) M), as well as colchicine (10(-4)-10(-6)), inhibited the synthesis of soluble collagen, depending on the drug concentration in the incubation media. Higher concentrations of tested agents also decreased the formation of insoluble collagen. Significant inhibition of non-collagen protein synthesis was ascertained only in the presence of desacetylcolchiceine.


A comparison between the prostaglandin releasing effects of angiotensin II and angiotensin III. Angiotensin II and its natural fragment (des-aspartic acid)1-angiotensin II (angiotensin III) induced a dose-dependent contraction in the isolated rat stomach fundus strip and rat colon. 1-Acetyl-2-(8-chloro-10,11-dihydrodibenz(b,f)(1,4)oxazepine-10, carbonyl) hydrazine (SC 19220), a widely used competitive-blocker of prostaglandins and acetyl salicylic acid, a well-known inhibitor of prostaglandin biosynthesis, partially abolished the contraction induced by both peptides in the rat stomach fundus but not in the rat colon. The inhibition induced by SC 19220 and acetyl salicylic acid was found to be higher for angiotensin III than angiotensin II when the dose-response curves and equipotent concentrations of the peptides were compared before and after the drugs. These results were taken as evidence that some component of the contractile effects of angiotensin II and angiotensin III on the isolated rat stomach fundus involves the release of prostaglandins by the peptides and in this respect angiotensin III has higher potency than angiotensin II.


The comparative gastric ulcerogenic activities of non-steroid anti-inflammatory drugs. A new gastric assay was employed to screen for the ulcerogenic activity of non-steroid anti-inflammatory (NSAI) analgesic drugs. The technique involves exposing rats to brief periods of cold stress, which is not itself sufficient to cause mucosal damage, but does specifically sensitize the stomach to irritant or ulcerogenic actions of NSAI drugs. The assessment of gastric ulcerogenicity of some well-known anti-inflammatory/analgesic drugs using this new assay was shown to agree well with clinical reports of the occurrence of gastric ulceration and haemorrhage. This assay was employed to screen for the ulcrogenicity of some new anti-inflammatory drugs and for potential drug interactions resulting from administration of certain frequently used combinations of these drugs.


Interaction and pH dependence of effects of nicotine and carbon monoxide in cigarette smoke inhalation experiments with rats. In view of subacute inhalation studies with cigarette smoke at high concentrations, the toxic properties of combinations of carbon monoxide and nicotine were investigated. Treating rats with fresh diluted cigarette smoke in an inhalation chamber, we established a smoking schedule that resulted in a certain death rate after 13 days. The mortality under the experimental conditions was taken as a measure for the toxicity of different combinations of carbon monoxide and nicotine. Since the absorption and therefore the toxicity of nicotine is pH dependent, the factorial experiments were performed under two pH conditions. The first experiments were conducted between pH 6.5 and 6.9 and then between pH 6.6 and 7.8 where the higher pH is due to the addition of nicotine base to the cigarette filler. After extensive mathematical treatment of the data, the following results were established: (a) Equations for the dose-response surface of CO and nicotine were computed. (b) R2 values (square of the multiple correlation coefficient) for the respective dose-response surfaces were between 87% and 94%. (c) From the respective equations the dose-response surfaces were drawn in the form of several computer plots. From the equations it becomes evident that, under the experimental conditions, there are no synergistic effects between carbon monoxide and nicotine. A simple additivity of the toxic effects was therefore postulated. On the other hand, it has been demonstrated that smoke pH plays an important role, because only from alkaline smoke does the absorption of nicotine seem sufficiently rapid for it to add to the acute toxicity of CO. The total particulate matter apparently does not contribute significantly to the toxicity of the smoke aerosol.


Computer-assisted pathology encoding and reporting system (CAPER). An on-line computer-assisted pathology encoding and reportying system (CAPER) has been developed by the Department of Pathology and Laboratory of Computer Science of the Massachusetts General Hospital for a department of surgical pathology that processes more than 25,000 specimens yearly. CAPER performs clerical functions, including the accessioning of specimens, monitoring their state of completion, production of log books, billing, statistics, and transfer of diagnoses to other hospital departments. It also permits instantaneous display of all diagnoses rendered within two years, printout within 24 hours of all older diagnoses for any patient, and retrieval of all specimens with any given diagnosis, further defined by any data item (e.g., age) stored in the computer file.


Identification of semen in 500 patients seen because of rape. Of 500 patients seen because of rape, semen was identified in vaginal secretions by the identification of spermatozoa in 61%, by an acid phosphatase value of 50 units or more in 40%, and by the identification of a foreign blood group substance or a high titer of own blood group substance in 16%. The addition of the determination of the acid phosphatase to the search for spermatozoa identified semen in only 1.4% more patients, or a total of 62.4%. Identification and titers of blood group substance were confirmatory only, but further characterized the source of the semen in 25% of those patients with spermatozoa. Spermatozoa were identified for as long as 48 hours, and elevated acid phosphatase was not found after 18 hours. Acid phosphatase was elevated in only 62% of patients with spermatozoa.


Platelet satellitism as a cause of abnormal hemalog D differential results. Platelet satellitosis resulted in an elevated high-peroxidase-activity value (9.9% versus normal range 0 to 3.65%) of the automated leukocyte differential count performed by the Technicon Hemalog D. Platelet satellitism occurred in Wright-stained smears of EDTA-anticoagulated blood, as well as in the effluent of the peroxidase channel of the Hemalog D. All platelets took up the perosidase stain. The rosette-like clusters of platelets and neutrophils were interpreted as single, large, intensely stained leukocytes resulting in the elevated high-peroxidase-activity value.


The zeta sedimentation ratio (ZSR) and activity of disease in rheumatoid arthritis. Zeta sedimentation ratios (ZSR) and modified Westergren erythrocyte sedimentation rates (ESR) were compared with an independent clinical assessment of disease activity in 100 patients with rheumatoid arthritis. The correlation between ZSR and ESR was good. Both methods correlated well with disease activity. The ZSR was more frequently elevated than the ESR in each category of disease activity, but the differences were slight. In addition to its practical advantages, the ZSR appears to be a satisfactory method for monitoring the activity of rheumatoid arthritis.


An improved method for purification of lymphocytes. A method that combines glass-bead column filtration, Ficoll-Hypaque gradient separation, discontinuous sucrose gradient, and drastic reduction of cell transfers is described. The procedure gives a high yield of pure human lymphocytes from small amounts of blood, good preservation of B cell/T cell ratio, and sufficient material for subsequent biochemical studies.


An evaluation of the Guest method for determining erythrocyte sedimentation rate. The Guest method for determining erythrocyte sedimentation rate was compared with the standard Westergren method. The Guest method consists of disposable plastic tubes with a method of filling with potentially infectious blood to avoid contact between the technician and the sample. Erythrocyte sedimentation rates were determined for samples containing normal and elevated fibrinogen levels. On the basis of the results of this study, the Guest method performed as well as the Westergren method in the population of healthy volunteers with normal fibrinogen levels and in the population of diseased individuals whose serum fibrinogen levels were elevated.


Laboratory evaluation of an automated antimicrobial susceptibility system. A newly introduced automated method for antibiotic susceptibility testing, AUTOBAC 1, has been evaluated by comparison with the disk agar diffusion method (Bauer-Kirby). A total of 2,518 strains of gram-positive (540) and gram-negative (1,978) organisms isolated from clinical specimens was examined by both methods with eight or ten antibiotics, including Tobramycin. An overall agreement of 97.4% was obtained when results were compared by individual antibiotic. However, many discrepancies were observed when individual genera or species were analyzed. Of 2,518 strains examined, 651 (26%) showed discrepancies in response to one or more antibiotics. Strains, showing discrepancies were re-examined by the broth dilution susceptibility method. The results obtained favored the disk agar diffusion method. Reproducibility experiments revealed a greater inconsistency in the AUTOBAC 1 system than in the agar diffusion test. It is concluded that although a rapid automated system for antibiotic sensitivity testing is desirable, the conventional disk agar diffusion method is easier to perform, more reliable, and a less expensive procedure for antibiotic sensitivity determination.


Report of a case of gross thymic hyperplasia in a child. A large thoracic mass and a mediastinal lymph node were excised from an infant with a peripheral blood and bone marrow lymphocytosis. The 224-mass was composed of histologically normal thymus, and the lymph node architecture was partially effaced. Hypogammaglobulinemia was detected two years after thymectomy. The enormous thumus in this case fits the classic gross pathologic definition of hyperplasia. The possibility of associated thymic hyperfunction in this case is discussed.


Further findings on assaultiveness and alcohol use in interpersonal disputes. In a previous study uniform observational data were collected regarding family disputes managed by police officers; those data contradicted views commonly held by social scientists and by police about the roles of assaultiveness and alcohol use in these events. In the present study police officers employed systematic naturalistic observation during their interventions as third parties in disputes between nonfamily members as well as those between family members. Tentative conclusions about assaultiveness, based on the data of both studies, are that it: does not usually precede the arrival of police in such disputes; is associated with interpersonal closeness of the disputants; is associated with poverty rather than race; and is as likely in a middle-class small city as in a poor inner-city area. Tentative conclusions about the use of alcohol in police-managed interpersonal disputes are: that these disputes are not usually influenced by alcohol use; and that assaultiveness is not related to alcohol use in such disputes.


Nonprofessional and professional help-agents' views of interventions with young maladapting school children. The expectations of nonprofessional and professional help-agents about helping interventions with young children experiencing different types of school adjustment problems (i.e., aggressive-acting out, shy-anxious, and learning problems) were studied. The two groups responded similarly. Shy-anxious children were seen as most appropriate for the intervention, the easiest and most enjoyable group to work with, and as having the best prognoses. These four sets of judgments were relatively independent of each other. A connection was made between the current data and prior findings suggesting that shy-anxious children have more favorable treatment outcomes than other groups.


Erythrocytic glutathione reductase deficiency in a hospital population in the United States. In the USA, erythrocytic glutathione reductase (GSSG-R) deficiency is significantly more common, and can be considerably more pronounced in hospitalized patients (118/3198) than in outpatients (37/1639) or in apparently healthy persons (12/849). Retrospective analysis of illnesses found in 118 inpatients with erythrocytic GSSG-R deficiency revealed a striking and previously unsuspected association of the enzyme deficiency with a variety of chemotherapeutically treated hematological or nonhematological malignancies (51/118 patients, 43.2%, or 51/170 diagnoses, 30.0%). The prevalence of erythrocytic GSSG-R deficiency also increased in malnutrition, liver disease, and sepsis. Drugs of the nitrosourea class, particularly BCNU [1, 3-bis(2-chloroethyl)-1-nitrosourea] are causally implicated in the association of GSSG-R deficiency with malignancies. Severe of complete GSSG-R deficiency may handicap host response to infections.


Hb Leiden-beta (0) thalassemia in a Chinese with severe hemolytic anemia. The first case of Hb Leiden (alpha2beta2 6 or 7 Glu---O)-beta (0) thalassemia in a young patient with chronic severe hemolytic anemia, which improved after splenectomy, is described. His parents were Chinese. The patient's blood showed no Hb A or normal beta chains when no blood transfusion was given. His mother was heterozygous for beta(0) thalassemia, and his father and brother had a trait for the unstable Hb Leiden. The Hb Leiden level of the father was 22.6% and that of the brother was 19.3%. It is probable that the abnormal hemoglobin in this Chinese family resulted from an independent gene mutation, unrelated to the one found in 2 Caucasian families reported earlier.


Differential in vitro sensitivity of marrow erythroid and granulocytic colony forming cells to chloramphenicol. The effects of chloramphenicol (CAP) and thiamphenicol (TAP) on mouse and human in vitro erythroid (CFU-E) and granulocytic (CFU-C) colony forming units have been studied. Both drugs inhibited CFU-E growth in a concentration-dependent, stereospecific, manner. Complete inhibition of human CFU-E growth was observed at a CAP concentration of 10 microgram/ml while a concentration ofer 50 microgram/ml was required to inhibit CFU-C growth. Furthermore, whereas the inhibition of CFU-C growth could be blocked in vitro by high colony stimulating factor concentrations, inhibition of CFU-E growth was not affected by increased erythropoietin (ESF) levels. The lack of protection by ESF may account for the apparent vulnerability of erythroid cells to CAP in vivo.


The effects of splenectomy and glucocorticoids on survival and hepatic uptake of damaged red cells in the mouse. We have studied the effects of splenectomy and glucocorticoids on the survival and sequestration of Heinz body-containing red blood cells (RBC-HZB). Mice were injected with phenylhydrazine damaged 51Cr labeled isologous red blood cells (RBCs). The spleen removed 36% and the liver 19% of the injected dose after 120 hrs. Red cell survival (T 1/2) fell from 180 hrs for undamaged red cells to 16 hrs for RBC-HZB. Splenectomy resulted in an increase in hepatic uptake of damaged RBCs (36% of the injected dose) and a modest improvement in red cell survival (T 1/2 54 hrs). Treatment of non-splenectomized mice with glucocorticoids reduced the splenic uptake to 16% and the hepatic uptake to 14% of the injected dose. The reduction of splenic upatke was associated with a decrease in splenic mass rather than a decrease in uptake per unit weight of splenic tissue, while reduction in hepatic uptake was associated with both a decrease in hepatic mass and uptake per unit weight. A marked decrease was observed in hepatic uptake and in phagocytosis by Kupffer cells in glucocorticoid-treated splenectomized mice. These data suggest that increased hepatic uptake may decrease the effectiveness of splenectomy in RBC-HZB hemolytic anemia and that glucocorticoids may decrease the hepatic uptake by reducing phagocytosis by Kupffer cells.


Partial trisomy of the long arm of chromosome 1 in myelofibrosis and polycythemia vera. We have identified partial trisomy 1q in 2 patients with different hematologic disorders. The first patient was a 55-year-old female with myelosclerosis and myeloid metaplasia diagnosed at age 38 years presenting with anemia, fatigue, bruising, fever, and splenomegaly. At age 56, she had 50--95% myeloblast cells and 95--100 nucleated RBC precursors per 100 WBC. Chromosome analysis of unstimulated leukocytes with Q, G, and C banding showed 46,XX,-6,+t(1;6) (q25;p22) in all metaphase cells. In vitro incorporation of Fe55 was demonstrated 90% of metaphases by autoradiography. The second patient, a 49-year-old male, was diagnosed as having polycythemia vera at age 30 during a regular checkup. He since developed hepatosplenomegaly. Chromosome analysis from a direct bone marrow preparation at age 44 and 45 showed grossly normal karyotypes. At age 49, his marrow by Q and G banding showed almost 100% of cells with 46,XY,-13,+t(1;13) (q12;p12). Eleven cases of trisomy of 1q have been reported in various hematologic disorders. It is apparent that partial trisomy 1q represents another nonrandom chromosomal abnormality, in addition to the most common nonrandom chromosomal aberrations, such as the Philadelphia chromosome, trisomy 8, trisomy 9, and monosomy 7 in hematologic disorders.


Kaposi's sarcoma presenting as autoimmune hemolytic anemia. A case of Kaposi's sarcoma which presented as a warm type of immune hemolytic anemia is described. The malignancy was discovered at the time of splenectomy, which was required for control of the hemolytic anemia. Three other cases of immune hemolytic anemia in patients with Kaposi's sarcoma have been reported. An association between Kaposi's sarcoma and immune hemolytic anemia is suggested. Careful examination of the skin for Kaposi's sarcoma seems appropriate in cases of immune hemolytic anemia.


Secondary gout in hemoglobinopathies: report of two cases and review of the literature. Although patients with hemolytic hemoglobinopathies characteristically are over-producers of urate, and hyperuricemia is frequently recognized, clinical gout has rarely been reported in such patients. Our evaluation of 2 premenopausal women with gout led to the diagnosis of previously unrecognized hemoglobinopathies (SC disease and CC disease). Investigation of these 2 patients and review of the reported cases of gout in patients with hemoglobin S or C disorders suggest that relatively minor abnormalities of renal function in these patients may lead to early development of significant hyperuricemia. With increasing lifespan of patients with hemolytic hemoglobinopathies and the likelihood of increased occurrence of renal function abnormalities, it is anticipated that gout will more frequently be responsible for joint symptoms in such patients.


Continuous flow method for determination of erythrocyte osmotic fragility. A simple and accurate micromethod for the determination of erythrocyte osmotic fragility is introduced. The method uses a laminar parabolic flow pattern, together with gravity, to retain cells in a long, small-diameter tube while a solution with decreasing osmolarity is passed through the tube. As the cells hemolyze, hemoglobin released from the cells is quickly removed by the axial flow pattern and monitored with a 547 nm optical detector for recording the hemolysis curve. Consequently, a continuous curve is obtained, with a peak occurring at the salt concentration that produces the maximum hemolysis rate. The advantages of this method are simplicity, accuracy, and small sample size (2 microliters of whole blood). The small sample size is of particular importance for infants. A comparison is made with the Parpart method using samples from 18 normal adults. Results are also given for a few abnormal adults and for a series of 26 normal newborns.


Cholelithiasis in Jamaican patients with homozygous sickle cell disease. The prevalence of cholelithiasis in Jamaican adults with SS disease was studied by plain abdominal radiograph in 206 patients and by oral cholecystogram in 126 (61%) of these patients. Gallstones were found in 57 (28%) of patients, were more common in females than males, and increased with age and hemolytic rate. The majority of gallstones were visible on the plain abdominal radiograph, only 17% of patients with gallstones having only radiolucent stones. Nonfunctioning oral cholecystograms were common (10%) in agreement with observations by previous workers. Gallstones were noted in the common bile duct in 2 patients. In general there was no clear relationship between the presence of cholelithiasis and clinical symptomatology. Complications, such as pancreatitis and malignant change in the gall bladder, recognized to be associated with cholelithiasis in the general population, have not been clearly related to cholelithiasis in SS disease. More information is needed before a logical policy can be evolved for surgical intervention in cholelithiasis in SS disease.


Dyskeratosis congenita: hematologic evaluation of a sibship and review of the literature. Dyskeratosis congenita is a rare genodermatosis whose hematologic complications include pancytopenia of variable time of onset, a propensity for opportunistic infections, and neoplasia. A family in which the disorder segregated in 3 generations and involved 9 members is reported, and the hematologic data of the 46 previously reported cases are reviewed.


Inappropriate erythropoietin secretion in polycythemia vera. A patient with classical polycythemia vera (PV) was found to have an inappropriately elevated serum erythropoietin (Ep) level. Investigations did not reveal any lesion or blood abnormality known to be associated with excessive Ep production and erythrocytosis. Sudden withdrawal of blood to reduce the Hb and Hct from 18.5 gm% and 56% to 13.6 gm% and 41.5%, respectively, resulted in an increment of serum Ep to abnormal level. With iron treatment there was a brisk return of Hb and Hct to prebleeding levels which was associated with reduction in the serum Ep. The inverse relationship between the Ep and Hb or Hct is inconsistent with the presence of excessive Ep-producing lesion. These results suggested that the threshold for Ep secretion from normal Ep-secreting tissue to Hb and Hct levels is set at an abnormal level. This patient's marrow cells when cultured in vitro in the absence of Ep, unlike other PV patients' (except one) marrow cells, did not grow erythroid colonies. In the presence of Ep, however, the colonies comparable to those formed from normal marrow cultures were obtained. These results suggested that his marrow erythropoietic cells were neither Ep independent nor Ep-hyperresponsive, as has been suggested by some investigators for erythropoiesis in PV. This patient presents phenomena that hitherto have not been reported.


Chronic lymphocytic leukemia--well-differentiated lymphocytic lymphoma with monoclonal IgA:IgA production by circulating lymphocytes. A patient is described in whom morphologic features of well-differentiated lymphocytic lymphoma (WDL) or chronic lymphocytic leukemia (CLL) and immunologic features of multiple myeloma were present. Studies of isolated peripheral blood lymphocytes demonstrated de novo synthesis of IgA K, the same paraprotein that was identified in the serum. Predominant IgA synthesis by peripheral lymphocytes has not been previously shown in either WDL or CLL.


Absence of VIII AHF response to adrenalin in hemophilia A. Proportionate twofold or greater increases in both Factor VIII procoagulant activity (VIII AHF) and Factor VIII-like antigen (VIII AGN) have been observed to follow the administration of adrenalin in normal individuals. Levels of factor VIII procoagulant or clot-promoting activity (VIII AHF) and VIII AGN were measured immediately before and one hour after the subcutaneous injection of adrenalin (0.35 ml) in ten adults with hemophilia A documented by low VIII AHF levels (ranging from 0.01-0.25 units/ml, normal VIII AGN levels, and normal VIII VWF levels as measured by the washed-platelet ristocetin assay). Eighteen normal adults served as controls. Results were analyzed by the paired test. It was shown that VIII AGN increased significantly, while VIII AHF did not change, in hemophiliacs after adrenalin stimulation, regardless of the base line level. This fixed rate of VII AHF production, release, or activation may help to explain the constancy of VII AHF levels in individual hemophiliacs and their affected family members.


Coagulopathy in amyloidosis: combined deficiency of factors IX and X. Combined severe deficiencies of blood clotting factors IX and X were observed in 2 patients who suffered from systemic amyloidosis. This unique deficiency state was marked by refractoriness to Vitamin K as well as to transfusion therapy. Increased antithrombin activity was present in both individuals and corresponded in time to the emergence of a monoclonal IgG kappa light chain paraprotein in 1. Both patients demonstrated profound bleeding disorders. It is hypothesized that the Vitamin K dependent factors have special affinity for amyloid deposits due to an unusual amino acid (gamma-carboxyglutamic acid) present in these factors.


The use of filtration techniques for the lysis and study of red blood cells. A filtration technique for the gentle lysis of erythrocytes has been developed using cellulose triacetate membranes. When cell suspensions are filtered under nitrogen pressure, lysis occurs at the surface of the filter in such a way that the cell ghosts are retained on the filter. The contents of the cell are extruded through the pores of the filter without mixing with the cell suspension. Cell ghosts and intact erythrocytes have been collected on membranes and examined by electron microscopy. These preparations have the advantage of being free of the structural artifacts that result from centrifugation. In addition, the filter facilitates preparation for electron microscopy by providing a support for the sample during fixation and then dissolving during the dehydration of the sample.


Chemotaxis radioassays: a simplified, quantitative method using technetium-99m radiocolloid labeled granulocytes. Selective labeling of phagocytes in human blood can be achieved by incubation of unseparated, heparinized blood with 99mTc-sulfur colloid. We have developed a method for quantitation of granulocyte chemotaxis using granulocytes labeled by this technique. The method was found to be more accurate and less tedious to perform than the conventional Boyden chamber chemotaxis assay. The assay was also less time-consuming and as quantitative as a previously described granulocyte chemotaxis radioassay in which 51Cr-labeled leukocytes were used. The simplicity and reliability of this technique and the ready availability of 99mTc-sulfur colloid may provide one standardized method for granulocyte chemotaxis quantitation in clinical and experimental medicine.


Levels of erythropoietin in patients with the anemias of chronic diseases and liver failure. Two mechanisms are felt to be responsible for the production of anemia in patients with chronic diseases. The first is failure to produce adequate amounts of erythropoietin (EP), and the second is failure to deliver iron to the bone marrow in amounts sufficient to support normal erythropoiesis. In order to evaluate these hypotheses we studied urine and serum EP levels and levels of 2,3-diphosphoglycerate in normal subjects, in patients with the anemia of chronic diseases, in patients with chronic liver disease, and in patients with a variety of other anemias. Based on the results, we propose first that insufficient production of EP is one of the major mechanisms responsible for anemia in patients with chronic diseases. Second, insufficient production of EP is, in part, responsible for anemia seen in patients with chronic liver disease. Third, serum and urine EP levels decrease with aging, and this correlates with the fall of hemoglobin levels seen in older normal subjects.


The effect of serum from uremic patients on erythropoietin. Serum from patients with chronic renal failure (CRF serum) contains a substance inhibitory to erythropoiesis in vitro. This paper explores the mechanism of the inhibition. Four experiments were performed to evaluate the effects of CRF serum on erythropoietin (EP). In the first 2 experiments, the effect of exposure of EP solutions to CRF serum was evaluated using the plethoric mouse EP assay system and a tissue culture system containing normal dog marrow cells. In the third study, dog marrow cells were preincubated with CRF serum before being stimulated with EP. Finally, EP-dose response curves were constructed in the dog marrow tissue culture system and analyzed using an enzyme kinetic model. The results show no evidence of inhibition or inactivation of EP by CRF serum, although in vitro heme synthesis is clearly depressed in the presence of CRF serum. We conclude that CRF serum inhibits erythropoiesis by directly, although reversibly, impairing the ability of erythroblasts to synthesize heme.


Amphotericin inhibition of hematopoiesis in vitro. The effect of amphotericin B on human and murine hematopoiesis was studied in vitro using assays for erythroid and myeloid colony-forming cells. Amphotericin consistently inhibited colony formation by erythroid and granulocyte-monocyte progenitor cells. Clear effects were observable at amphotericin concentrations of 1.0 microgram/ml, and concentrations of 2.0 microgram/ml caused approximately 50-60% inhibition of cloning of both murine and normal human bone marrow. These data suggest that amphotericin, in concentrations achieved in therapy, can impair hematopoiesis by a direct effect on precursor cells.


Changes in distribution of platelet membrane glycoproteins in patients with myeloproliferative disorders. Glycoproteins have been discovered to be important to platelet function both in normal and pathological states. We have studied membrane glycoprotein patterns in 16 patients with various myeloproliferative disorders. There was an abnormal ratio of glycoprotein I:glycoprotein IV in patients with myeloproliferative disease compared with controls. There was no discernible correlation between glycoprotein pattern and aggregation response or platelet count, but patients with megathrombocytes had higher values for glycoprotein IV than those without megathrombocytes. These experiments suggest that patients with myeloproliferative disorders may have alterations in membrane glycoproteins that could alter platelet function.


A study of the relationships between perceived organizational stratification, and individual job satisfaction and adaptiveness in hospital laboratories. Most studies of organizational stratification have remained largely at the narrative or inferential level. Few attempts have been made to empirically assess the consequences of a status system. This paper sought to examine the proposition that stratification is inversely related to job satisfaction and adaptiveness. Although not overwhelmingly demonstrated, there is presumptive evidence that stratification does have an impact upon the organization. It was concluded that medical technologists prefer a supportive, well-structured environment that provides an opportunity for them, through participation, to maintain a degree of control over their work setting. Practical implications of the findings and recommendations were made.


Lecithin/spingomyelin ratio procedure by thin-layer chromatography. We assessed several modifications of thin-layer chromatography for evaluation of amniotic fluid lecithin/sphingomyelin ratios. For a procedure which is reliable, economical, and easy to perform, we preferred laboratory-prepared plates using SI-LICAR TLC-7GF. For spot detection, we preferred the iodine vapor method.


The anticoagulant dilemma--a prescription for its resolution. Despite the fact that heparin and the coumarins are effective drugs in the prevention of venous thromboembolism and of systemic embolism and have been in use for more than one quarter of this century, there has been no recognized decrease in overall deaths attributable to these agents. Several factors contribute to this paradox: (1) the disparity between the high prevalence of thromboembolic events and the low incidence of associated mortality or disability has rendered the required size of trial populations exceedingly large, cumbersome, and costly; (2) the major use of anticoagulants has occurred after a thromboembolic event rather than as an instrument of primary prophylaxis; (3) the difficulties in regulating drug dosage persist and serious hemorrhage remains in infrequent but real complication of therapy; and (4) the physician is invariably apprised of clinical failure (further thrombosis or hemorrhage) but rarely of success (no thrombosis). Recent advances in our understanding of the mechanism of intravascular coagulation, of the pathophysiology of thromboembolism, and of the molecular basis of anticoagulant action have begun to permit more effective use of the classical drugs and to suggest the potential value of other agents and modalities for the prevention of the thromboembolism in different segments of the vasculature.


The effects of proprandolol and histamine on the ventilation response to carbon dioxide inhalation in normal subjects. A method was developed to measure the oxygen cost of ventilation during CO2 rebreathing. In 20 healthy normal subjects SGaw, MMEF, and FEV1 were measured prior to and following the infusion of propranolol. In five of the same subjects airway constriction was induced by inhalation of histamine. The use of both agents was followed by a significant decrease in the ventilation response to carbon dioxide inhalation. Even more significantly, the oxygen cost of the increase in ventilation measured during CO2 rebreathing rose significantly following either propranolol or histamine.


Acute renal failure due to intravascular hemolysis in the North Indian patients. Acute renal failure due to intravascular hemolysis is a common clinical problem in North Indian patients. It constituted 21.5 percent of 325 patients dialyzed for acute renal failure over an 11-year period at Chandigarh. Thirty patients had developed acute intravascular hemolysis in association with erythrocyte glucose-6 phosphate dehydrogenase (G-6PD) deficiency, 17 due to copper sulphate intoxication and 8 due to envenomation by snakes. Less frequent causes were insect stings, incompatible blood transfusion, intake of anti-leprosy drug--dapsone in non-G-6PD-deficient patients, and mercuric chloride toxicity in two patients each; naphthalene poisoning in one; and uncertain causes in six patients. Renal histology was available in 55 patients. Acute tubular necrosis was seen in 54 and bilateral diffuse cortical necrosis in one patient. Fifty patients (71.43 percent) survived and 20(28.6 percent) diet. G-6PD erythrocyte deficiency, which is present in 4.5 percent of the North Indian population, was the most frequent cause of acute renal failure in this group.


Exaggerated natriuretic response to volume expansion in patients with primary biliary cirrhosis. Fluid retention and ascites are rarely seen in patients with primary biliary cirrhosis (PBC). This contrasts with the conspicuous tendency of patients with Laennec's cirrhosis to retain salt and water. In an attempt to clarify this clinical observation, renal handling of sodium was studied during extracellular volume expansion (ECVE) and maximal suppression of antidiuretic hormone in five patients with PBC. These PBC patients were compared with two control populations: five edema-free patients with Laennec's cirrhosis and nine healthy volunteers. The natriuretic and diuretic response to ECVE was significantly greater in the patients with PBC as compared with the two control groups. CH2O for given rates of urine flow were similar in PBC patients as compared with normal subjects. The data suggest that a supranormal rejection of sodium at the proximal tubule in response to ECVE underlies the exaggerated natriuresis of PBC. The augmented elimination of salt during ECVE in patients with PBC may explain the rarity of ascites and edema in this variety of cirrhosis.