Fetal sulfated and nonsulfated bile acids in intrahepatic cholestasis of pregnancy. Nonsulfated the sulfated bile acids were determined in maternal and umbilical cord serum, amniotic fluid, and meconium samples in pregnancies complicated by maternal intrahepatic cholestasis, and the results were compared with those obtained in uncomplicated pregnancy. The serum levels of nonsulfated and sulfated bile acids were elevated in both maternal and fetal serum in cholestasis pregnancies, and there was a considerable maternal-to-fetal difference in their levels across the placenta, the lower values being in the fetal compartment. The proportion of sulfate conjugates of the total serum bile acids was similar in both compartments, about 10%. In amniotic fluid low levels of cholic and chenodeoxycholic acid were found in uncomplicated pregnancies. In the cholestasis pregnancies amniotic fluid bile acid levels were elevated, especially that of cholic acid. The swallowing of considerable amounts of bile salt by the fetus with the amniotic fluid leads to an increased accumulation of bile salt in the meconium in cholestasis. The proportion of sulfate-conjugated bile acids was large in the meconium samples in both uncomplicated and cholestasis pregnancies.


Cholesterol from serum and cholesterol-phospholipid dispersions by isolated rat hepatocytes in vitro. The rate of uptake of cholesterol by isolated rat hepatocytes from incubation medium containing rat serum was low and did not increase by the prolongation of incubation time up to 2 hr at 4 degree. However, the hepatocytes took up cholesterol very actively at 37.5 degree from serum as well as from a cholesterol-phospholipid dispersion. The cholesterol uptake by the cells from liposomes increased linearly with the increase of the cholesterol concentration of liposomes, but that from serum reached the maximum at about 1.5 mu mol/ml cholesterol and remained at a plateau level at higher concentrations. Cholesterol was transfered from every class of serum lipoprotein, although the uptake ratio was the highest from the LDL fraction. As the lipoprotein concentration was increased, the uptake ratio decreased in the same way as that observed in the incubation with whole serum. The concentration of labeled ester cholesterol in the medium decreased more rapidly than free cholesterol during incubation. Cholesterol in the hepatocytes, however, was found mainly as the free form, suggesting that ester cholesterol taken up by the cells was rapidly hydrolyzed. Cholesterol accumulation was not observed in hepatocytes incubated in medium containing serum, but their cholesterol content was increased after the incubation in medium with liposomes of high cholesterol concentration. Therefore the uptake of cholesterol by hepatocytes from serum lipoproteins is probably carried out by a process different from that of uptake from liposomes which is considered to be a physicochemical phenomenon.


Microtubule assembly in renal medullary slices: effects of vasopressin, vinblastine, and lithium. The effects of vasopressin and some of its inhibitors on the extent of MT polymerization (assembly) were studied in renal medullary slices by means of temperature-dependent polymerization-depolymerization procedure to determine the relative ratio of free (unpolymerized) tubulin to assembled MT's. Assembled MT's were stabilized in a medium containing high concentrations of glycerol and DMSO. Tubulin was assessed indirectly by the [3H]-CLC-binding assay. Incubation of slices at temperatures higher than 20 degree C promoted MT polymerization. Although vasopressin markedly increased the tissue levels of cAMP and activated in situ cAMP-dependent protein kinase, it did not change the extent of MT polymerization. On the other hand, VBL and to a lesser degree lithium chloride inhibited the rate of MT assembly. This finding suggests that VBL and lithium, which are known to inhibit the antidiuretic effect of vasopressin in vivo, may exert at least part of their inhibitory effect by interfering with MT assembly in the renal medulla. Present results thus are consistent with the view that vasopressin does not influence the extent of cytoplasmic MT polymerization in spite of the increase in tissue cAMP level and activation of protein kinase but that inact MT's are required for the cellular action of vasopressin.


The effect of experimental tobacco smoke inhalation on in vitro alveolar macrophage bactericidal function. The in vitro antibacterial activity of rat alveolar macrophages against a challenge of radiolabeled Staphylococcus epidermidis was studied following 30 and 60 consecutive days of in vivo tobacco smoke inhalation in a dose equivalent to approximately 1 1/2 packs of unfiltered cigarettes per day in man. Macrophages harvested by bronchopulmonary lavage, were cultured, infected, and assayed hourly for 3 hr to determine the relative percentage of surviving radiolabeled intracellular bacteria. Macrophages  harvested from smoke-treated rats for 30 days had an impaired capacity to kill bacteria when compared to macrophages from control and sham-smoked animals (63.5% +/- 3.3, 80.8% +/- 3.8, and 86.2% %/- 1.2 killed in 3 hr, respectively). Alveolar macrophages harvested from rats exposed to cigarette smoke for 60 days, however, did not have an impairment in their bactericidal activity relative to matched controls (73.3% +/- 3.9 vs 69.8% +/- 6.9 killed in 3 hr). These data imply that doses of cigarette smoke commonly consumed by man impair the in vitro bactericidal function of the rat alveolar macrophages following 30 consecutive days of experimental smoke treatment. The disappearance of this effect after 60 days of exposure to tobacco smoke suggests that an adaptation to the initial impairment has developed.


Comparison of screening methods for determination of N4-acetyltransferase capacity (acetylator phenotype) in outbred rabbit strains. The low incidence (10% to 35%) of slow acetylator phenotype requires development of efficient screening techniques for phenotyping rabbits. We report here the phenotyping of 166 rabbits by means of an IA calculated from the plasma determination of SDZ and NSDZ at 60 min after a dose of 20 mg/kg SDZ intravenously. The IA is compared to the elimination t 1/2 beta of SDZ as well as with other parameters. CITB and present of dose recovered in urine as NSDZ. The use of IA to screen for slow or fast acetylators when compared to t1/2 beta resulted in six rabbits being misclassified (13.3%); the use of CITB values from the same animals resulted in two misclassifications (4.4%); the use of percent of dose recovered in urine as NSDZ resulted in only one rabbit being misclassified (3.8%). We conclude that the IA provides an efficient screening procedure for acetylation phenotype in the rabbit with the further advantage that it can be performed as part of the definitive t1/2 beta determination, avoiding double handling of rabbits.


Dissociation of the neutrophill functions of exocytosis and chemotaxis. The peptide Gly-His-Gly is shown to be chemotactic for human neutrophils in vitro and for rabbit neutrophils in vivo but to be unable to induce lysosomal enzyme release from human neutrophils at sublytic concentrations. The failure of this chemotactic peptide to elicit lysosomal enzyme release provides evidence that interactions with a chemotactic receptor does not necessarily activate chemotaxis and exocytosis in the human neutrophil, thus suggesting that the presumed common pathway of exocytosis and chemotaxis may be divergent at the  cell receptor and/or postreceptor level.


Effect of protein deprivation on hematopoietic stem cells and on peripheral blood counts. Experiments were performed to determined the effect of protein deprivation on CFU-S in the spleen and femoral marrow, on the peripheral blood counts, and on the rate at which these parameters regenerate following radiation. Splenic CFU-S decrease in number after only 3 days on diets containing 5% protein or less. Marrow CFU-S, on the other hand, decrease only after mice are fed a protein-free diet for 4 weeks or more. The hematocrits, platelet counts, and WBC counts fall in the latter group. Marrow CFU-S regenerate more slowly in irradiated mice fed diets containing 5% protein or less. Also, the hemocrits, WBC counts, and platelet counts of irradiated mice fed diets containing 5% protein regenerate more slowly than do those of irradiated mice fed normal diets. The effect of protein deprivation on erythropoietin production, erythropoiesis, granulocyte function, and immunocompetence is well known. The studies reported here indicate, in addition, that protein deprivation also causes the numbers of CFU-S and the platelet counts to decline.


Variability in the interaction of beta-thalassemia with the alpha-chain variants Hb G-Philadelphia and Hb Rampa. Two unrelated families are reported in which beta-thalassemia trait occurred with a heterozygosity of Hb G-Philadelphia (alpha2 68(E17)Asn leads to Lys beta2) in one family and with Hb Rampa (alpha2 95(G2)Pro leads to Ser beta2) in the other. The percentage of Hb G-Philadelphia was not influenced by the simultaneous presence of a beta-thalassemai determinant, but that of Hb Rampa was descreased from 20% in the simple heterozygote to about 6% in persons with the Hb Rampa-beta-thalassemia combination. Data from  in vitro recombination experiments with isolated alpha X, alpha A, and beta A chains, with heme attached, indicated a preferential formation of Hb A over Hb Rampa but not over Hb G-Philadelphia in conditions of relative beta-chain deficiency. This suggests that the rate of assembly of monomers to form dimers or tetramers can be an important mechanism of controlling the quantity of certain hemoglobin variants with critical substitutions in heterozygotes.


An interactive data management and analysis system for clinical investigators. An interactive minicomputer-based system has been developed that enables the clinical research investigator to personally explore and analyze his research data and, as a consequence of these explorations, to acquire more information. This system, which does not require extensive training or computer programming, enables the investigator to describe his data interactively in his own terms, enter data values while having them checked for validity, store time-oriented patient data in a carefully controlled on-line data base, retrieve data by patient, variable, and time, create subsets of patients with common characteristics, perform statistical analyses, and produce tables and graphs. It also permits data to be transferred to and from other computers. The system is well accepted and is being used by a variety  of medical specialists at the three clinical research centers where it is operational. Reported benefits include less elapsed and nonproductive time, more thorough analysis of more data, greater and earlier insight into the meaning of research data, and increased publishable results.


Radioimmunoassay for human myoglobin: methods and results in patients with skeletal muscle or myocardial disorders. A sensitive and specific radioimmunoassay has been developed for the measurement of serum Mb. immunization of rabbit with human Mb yielded anti-Mb antibody which was purified by affinity chromatography. Human hemoglobin, CK, and the component of serum per se did not appear to cross-react with the antibody. Mb was radiolabeled by the chloramine T method. The radioimmunoassay method could detect as little as 0.3 ng of Mb and was not affected by hemolysis. Information is also given on precision, recovery, and specimen preservation. Mb levels could be detected in all of 120 normal adults, and the values ranged between 1 and 28 ng/ml (mean, 13.1 +/- 6.1). No sex difference was observed. Levels were markedly elevated in all the patients with progressive muscular dystrophy, especially in the Duchenne type at the level of 40 to 1700 ng/ml. It was also noticed that about 70% of female gene carriers of Duchenne type had a slightly increased Mb level. An elevated serum Mb was also noted in polymyositis. In every case of acute myocardial infarction, serum Mb levels were increased, peak values ranging from 175 to 4400 ng/ml and averaging 1162 +/- 287.9. Mb levels were elevated faster and peaked earlier (within 6 to 12 hr after the attack) than serum CK activity and returned to nearly normal range within 3 to 4 days. The increase in serum Mb was also noticed in shock and surgery. These data indicate that radioimmunoassay of Mb is a useful test for judging the myolytic state of myogenic myopathies and for early detection of myocardial infarction.


The anemia of chronic renal failure: studies of the effect of organic solvent extraction of serum. CRF serum contains a material(s) which is inhibitory to erythropoiesis in vitro. The chemical nature and mechanism of action of this material are unclear at the present time. To further study this problem, we extracted NL serum and CRF serum samples with two organic solvents, chloroform and petroleum ether. The serum samples were studied before and after extraction in a tissue culture system in which dog erythroblasts were stimulated by EP to synthesize heme. Before extraction, cells suspended in CRF serum synthesized less heme than cells cultured in NL serum. Extraction of CRF serum with chloroform, but not petroleum ether, resulted in an improvement in its ability to support heme synthesis. Studies of the material extracted by chloroform from CRF serum showed that it was inhibitory to erythropoiesis. We propose that the erythropoietic inhibitory substance in uremic serum in soluble in chloroform but not in petroleum ether, suggesting that it is a polar lipid.


The effect of serum from patients with chronic renal failure on erythroid colony growth in vitro. Considerable evidence suggests that insufficient EP production and the presence of a toxic factor inhibiting erythropoiesis are two major factors responsible for the production of anemia in patients with CRF. The toxic factor can be detected in a number of tissue culture systems. In order to evaluate its mechanism of action in a proliferation-dependent system, we studied the formation of erythroid colonies in plasma clots containing normal serum and CRF serum, using normal mouse marrow cells as the target organ. Fewer colonies were found in cultures containing uremic serum. This effect was greater as the concentration of serum was increased. No differences were found in the size or morphology of colonies formed. Addition of urea and creatinine to normal sera did not affect their ability to support colony growth. Uremic sera had no effect on white cell colony growth in the plasma clot system. We conclude that materials inhibitory to erythroid proliferation are present in CRF serum.


Catabolism of hemoglobin by human erythrocyte membranes. The role of the human erythrocyte membrane in degrading hemoglobin and hemoglobin subunits was investigated by determined the total radioactivity (cpm) of the nascent alpha and beta globin chains attached to the membrane after labeling of intact cells with 14C-leucine. In conditions characterized by balanced globin synthesis (normal and sickle cell anemia), the total radioactivity of membrane-attached alpha globin is always less than membrane-attached beta globin (alpha/beta = 0.60 +/- 0.10) despite the equal synthesis of alpha and beta chains in the hemolysate. In conditions characterized by unbalanced globin synthesis (alpha-thal and beta-thal traits) the cpm of membrane-attached alpha are also less than those of membrane-attached beta. Attachment of globin chains to the membrane is not related to the net ionic charge of individual chains, but the amount of attachment is related to the relative size of the free intracellular alpha chain pool. The alpha/beta ratio of less than 1 is not due to selective attachment of nascent beta chains or selective destruction of nascent alpha chains. The data indicate that part of the discrepancy between membrane and hemolysate alpha/beta radioactivities seen in the conditions studied is due to different rates of entry into the membrane and catabolism of newly labeled globin polypeptide chains by it.


A platelet procoagulant activity associated with platelet shape change. PCA was measured for human PRP by determining recalcification times assayed in a minimal-dilution, controlled PH/PCO2 system in a siliconized cuvette, with the use of light transmission measurements (aggregometry). Platelet shape, aggregation, and plasma clotting end points were assayed photometrically, with platelet morphology and aggregation studied in parallel by light microscopy. With varying concentrations of ADP preincubated with PRP initially containing essentially disc-shaped platelets, it was found that induced shape change in the absence of an aggregation is necessary and sufficient for the development of PCA. This was consistently measurable as a shortening of recalcification times by approximately 50% for suspensions of shape-changed platelets vs. disc-shaped platelets. The pharmacologic inhibition of the endoperoxide pathway-mediated platelet secondary aggregation and release by aspirin administered in vivo does not impair the ability of human platelets to develop this PCA. Inhibition of shape change with amounts of 5'-adenosine monophosphate insufficient to affect coagulation tests in the absence of platelets leads to 80% to 90% inhibition of the ADP-induced PCA. This PCA is shown to be fully reversible, with morphologic reversion of shape-changed platelets to the discoid form, and is shown to be distinct from other PCAs previously described for platelets activated in different ways, such as PF3 activity. It is suggested that the binding of coagulation factors to the platelet membrane may be regulated concomitantly with shape change.


Defective chemotaxis in uremia.

Defective chemotaxis in uremia. Of uremic patients, 37% demonstrated the presence of CFI in their sera. The serum factor acts directly on leukotatic factors, C5f, C3f, and BF to render them irreversibly inactive. Inhibitory activity was found in five of 16 patients: 37% to 61% for C5f, 25% to 36% for C3f, and 28% to 51% for BF. There is no correlation of this inhibitory activity with BUN or creatinine levels. The presence of this chemotactic inhibitor may be responsible for the increased incidence of infection in uremia.


Effect of nonsupressible insulin-like protein on glomerular protein synthesis. Partially purified preparations of NSILP were evaluated for effect on incorporation of labeled precursors into protein, collagen, and basement membrane by isolated rat renal glomeruli. Dowex-adsorbed NSILP (0.5 mU/mg) inhibited the secretion of protein and collagen and resulted in a significant diminution of incorporation of labeled lysine into glomerular basement membrane. Glomerular protein and collagen secretion were also inhibited in the presence of Sephadex G-200 NSILP (4.5 mU/mg), but an effect on incorporation of radiolabeled proline, hydroxyproline, lysine, and hydroxylysine into glomerular basement membrane was not observed. The in vitro response of renal glomeruli to NSILP constitutes another "insulin-like" effect of this substance.


The measurement of urinary prostaglandin E in normal subjects and in high-renin states. Antisera generated toward PGE was obtained from rabbits immunized with PGE2 conjugated to bovine thyroglobulin by the carbodiimide reaction. The specificity of the antibody is such that only PGE1 and PGE2 has significant cross-reactions. 13, 14-Dihydro and 15-keto PG's did not react. An RIA capable of measuring 6 pg of PGE2 was developed to measure PGE in human urine. Urine samples adjusted with buffer to pH-5 are extracted with 5% MeOH in CH2CI2 and chromatographed through Sephadex LH-20 columns. The second-antibody technique is used to separate bound from free. This urine method yields blank values of 2 +/- 2 pg per sample, with a between-assay precision determined by duplicate analysis of 14% and intra-assay precision of 8%. The mean urinary excretion rate is 500 +/- 74 (S.E.), +/- 209 (S.D.) ng/day (n = 8) in men and 300 +/- 70, +/- 242 (n = 12) in women. These values are in agreement with those reported by others using gas chromatography-mass spectrometry of receptor assay with hepatic plasma membranes. Patients in a high-renin state, whether normotensive or hypertensive, have elevated PGE in urine. These studies suggest a relationship between the renin-angiotensin system and renal PG's in man.


Interaction of plasma proteins with artificial surfaces: protein adsorption isotherms. A simple technique using a small disc which is dipped into a 125I-labeled protein solution has been devised to study the adsorption of human albumin, fibrinogen, and IgG onto Cuprophane or PVC. The purity of these human plasma proteins has been examined carefully with PAGE and immunochemical methods. The adsorption isotherms of albumin, fibrinogen, and IgG show a langmuir type adsorption. Delipidation of albumin did not alter the albumin affinity to Cuprophane and PVC. The surface saturation concentration (ng/cm2) for albumin, fibrinogen, or IgG were all found to be more on PVC (a hydrophobic surface) than on Cuprophane (a hydrophilic surface). The competitive adsorption of one protein species in a two- or three-protein mixture was also studied. Albumin and fibrinogen complete with each other for adsorption. The effects of IgG on the adsorption of albumin or fibrinogen were inconsistent and not predictable; the reason for this is unknown. The effect of laminar flow on albumin adsorption was studied with a specially designed Richardson flow chamber. In general caused an increase in albumin adsorption over that at static conditions. The increase of albumin adsorption was more pronounced also for PVC than for Cuprophane from 1 to 10 ml/min.


The surgery of congenital deafness.

The surgery of congenital deafness. This paper outlines the indications for surgery of congenital deafness in complete meatal aplasia, the methods of audiological and radiological assessment and an operative technique used in ten ears. It is felt that otologic surgery should be done before the pinna reconstruction as it is very important to try and introduce sound into these children at an early age. In addition, the position of the new auricle can be made more satisfactorily around an already established meatus. The value of tomography of the internal as well as the middle ear is stressed and the necessity for providing a stable and uninfected meatus emphasized with regard to the possible fitting of a hearing aid.


Sudden sensorineural hearing loss: electrocochleographic findings in 70 patients. The results of transtympanic ECochG in 70 patients with sudden sensorineural deafness are presented. ECochG was compared with traditional methods of audiometry as a means of deciding whether the deafness was mainly cochlear or retrocochlear. It was found to make a useful and sometimes unique contribution. ECochG gave a definite localization of the deafness in 22 out of 23 patients in whom conventional methods of audiometry had produced equivocal results and was also found to be extremely valuable in 17 patients with "dead" ears. Electrical stimulation of the cochlea may have a prognostic value in cases of sudden retrocochlear deafness. A rational approach to the treatment of sudden deafness depends on precise knowledge of the aetiology and pathology: accurate localization of the site of the lesion is a convenient first step.


Diploic dermoids.

Diploic dermoids. A diploic dermoid involving the orbital plate of the frontal bone is described in a 52-year-old man. It presented proptosis, downward displacement of the globe and limitation of its movement while looking up. Its extension into the anterior cranial fossa was detected by injecting a radio-opaque material into the cyst.


Idiopathic pleomorphic midfacial granuloma (Stewart's type). Idiopathic mid-facial granuloma is an unusual highly destructive disease which was virtually unknown prior to 1955. Great confusion exists, due in large part to the terminology applied to this entity as well as the clinical similarity of the process to other destructive mid-facial lesions. A classical case of idiopathic mid-facial granuloma of Stewart's type is presented, with characteristic lesions limited to the mid-face. Definitive histopathological features consist of pleomorphic inflammatory granulation tissue with patchy necrosis and no system lesions or neoplasia in the autopsy tissues.


Malignant lymphoma of the maxillary sinus. Extranodular lymphoma is not frequent and primary lymphoma of the paranasal sinuses is rare. An unusual case of malignant lymphoma of the maxillary sinus in a boy, involving the C.N.S. is reported.


Permanent closure of the nostrils in recurrent nasal myiasis. Four cases of recurrent nasal myiasis were treated successfully by permanent closure of the nostrils. In two patients unilateral, and in two patients bilateral, closures were performed without further recurrence of the disease.


A clicking larynx.

A clicking larynx. A case of a "clicking", painful act of deglutition is presented. Overriding of the hyoid bone and the thyroid lamina is thought to have been the mechanism. A partial thyroid laminectomy performed sub-mucoperichondrially effected an immediate and, at present, lasting cure. No similar case could be found in the literature after extensive searches.


Chondrosarcoma of the thyroid cartilage. A TUMOUR which had been present for nine years in the thyroid cartilage of a 45-year-old man, was shown on microscopy to be a chondrosarcoma. This tumour probably took its origin in a pre-existing benign tumour at this site. The literature on similar previously documented tumours is reviewed, and the classification, diagnosis and management of these rare tumours is briefly discussed. Primary cartilaginous laryngeal tumours are uncommon (Hyams and Rubuzzi, 1970; Zizmor et al., 1975). A tumour of the thyroid cartilage which had been present for about nine years was shown histologically to be a low-grade chondrosarcoma probably arising from a pre-existing chondroma at this site. The clinical and pathological features of this case are presented and discussed in the light of the available literature.


Surgery of the nasal septum.

Surgery of the nasal septum. A modification of the 'maxilla-premaxilla' approach for nasal septum surgery is described. With this modification the mucosal elevation in the area of the two inferior tunnels is performed from above along the crests of the vomer, maxillary and premaxillary bones, instead of from below through the undermined base of the nose as in the 'maxilla-premaxilla' approach. This mucosal elevation is performed under direct vision in the intraseptal area instead of by blind elevation as in the 'maxilla-premaxilla' approach where the progress of the elevator beneath the nasal mucosa is followed through the nasal chambers. It gives the surgeon the increased advantage of working under the perichondrium and periosteum and of overcoming any difficulty arising from malformations in the anterior (caudal) area of the septal cartilage, premaxillary wings and maxillary crest. With this modification, extensive undermining of the base of the nose is also avoided. Finally the septal framework is fully exposed as in the 'maxilla-premaxilla' approach but in a more easy and safe way while all the advantages of the 'maxilla-premaxilla' approach are preserved.


Changes of the nasal mucosa in altered airflow illustrated by blind quantitative histology. In 20 rabbits one nostril was closed surgically for 4, 10, 16, 20, 60 and 90 days, and thereafter the mucous membranes from the open and closed sides of the nose were investigated. Anteriorly on the open side a process of repair started as early as the 4th day after ciliary damage. This process consisted in hyperplasia of basal cells, displacement and gradual desquamation of ciliated cells and goblet cells, differentiation of basal cells into ciliated and goblet cells. On the 16th day the epithelium was again ciliated. As a result of a continued abnormally increased airflow new damage to the cilia occurred and a new cycle was initiated, so that on the 30th and 90th days the epithelium was again ciliated. Even though the epithelium is 'squamous-like' in some phases, there is no question of a transformation into squamous epithelium. On the closed side anteriorly there is increased secretory activity in the epithelium. Posteriorly blind quantitative histology showed no differences between the open and the closed side, or between 'treated' and control material.


Cancer of the naso-pharynx in Kuwait.

Cancer of the naso-pharynx in Kuwait. A clinico-pathological study of 143 cases of malignancy of the naso-pharynx diagnosed and treated at the E.N.T. and Radiotherapy Departments of Al-Sabah Hospital, Kuwait, between the years 1963 to 1974 inclusive is presented. The entire population of Kuwait is served and also a variable but small number of Nomads. During the years of the survey the population has been steadily increasing from about 500,000 in 1963 to about a million in 1974. It is composed of 45 per cent Kuwaitis of pure Arab stock and 55 per cent of immigrant workers, largely of Arabic origin. Cancer of naso-pharynx is the commonest of all head and neck cancers (18.3 per cent) and comprises 4.2 per cent of all malignancies. This is comparable with the 5.1 per cent in the Arab population of North Africa. The sex incidence is 2.2 Kuwaiti males and 0.8 females per 100,000; Non-Kuwaitis 2.0 male and 1.2 female per 100,000, giving an approximate ratio of 2.9 to 1 in both groups. The age distribution shows two peaks in male patients, Kuwaitis and Non-Kuwaitis in the 2nd decade (11.1 per cent) and fifth decade (28.8 per cent). In females, the graph shows a plateau pattern from the 3rd decade onwards. Cervical lymphadenopathy (83 per cent) was the commonest presenting symptom. The commonest histological finding was undifferentiated carcinoma and squamous cell carcinoma (28 per cent each). The hypotheses of the aetiology are reviewed.


Basal-cell carcinoma in maxillary osteomyelitis. A 40-year-old female with a basal-cell carcinoma in maxillary osteomyelitis is reported. Blood-stained discharge from a sinus associated with ulceration of the infra-orbital region and the onset of blindness wree the presenting features. It is suggested that biopsies from multiple sites of the lesion rather than reliance on the clinical picture would help in detecting early malignant change.


Bilateral post-intubation talc granulomata of the vocal cords. A clear histological picture of talcum powder within the vocal cord granulomata in one patient has been described. As talcum powder is not deliberately employed during the manufacture of surgical gloves or endotracheal tubes, accidental contamination of the endotracheal tube appears likely.


Rat myometrial activity in vivo: effects of oestradiol-17 beta and progesterone in relation to the concentrations of cytoplasmic progesterone receptors. The amplitude, frequency and rate of rise of intra-uterine pressure cycles in rats (postpartum, ovariectomized) were unaffected by treatment with progesterone. Amplitude was also unaffected by a combination of treatments with progesterone and oestradiol-17 beta, which was adequate to ensure the survival of 84% of foetuses in ovariectomized pregnant rats. The failure of progesterone to influence myometerial activity could not be attributed to a lack of "true" progesterone receptors since these were present in the myometria of the test animals in concentrations exceeding those of oestrous animals. Evidence was obtained which suggested that a high-affinity binding protein, different from the "true" receptor may predominate in the myometrium of the pregnant rat. Oestradiol-17 beta in single or repeated doses of from 0.25 to 5 microgram, however, was found to reduce the frequency of pressure cycles but to increase significantly their rate of rise of pressure. There was a latency of 6--8 h in these effects of oestradiol. The possibility that inhibition of the myometrium by oestrogen may play a part in the preparation for parturition is discussed.


Evidence that inhibition of myometrial activity by oestradiol in the rat is mediated by an RNA synthetic pathway. Within some 14 h of treatment with oestradiol benzoate (5 microgram), the intra-uterine pressure cycles in ovariectomized puerperal rats were almost abolished. However, treatment with 600 microgram actinomycin D 30 min before the administration of oestradiol benzoate interfered significantly with the inhibition of uterine mechanical activity during the following 14h. Treatment of rats with actinomycin D alone produced no significant fall in the frequency of pressure cycles. These results suggest that oestrogen inhibits myometrial activity in the rat through a mechanism which involves the synthesis of protein.


Prolonged oestrogenic and mitogenic activity of tamoxifen in the ovariectomized mouse. A dose of tamoxifen (ICI 46,474), which has been found to inhibit the vaginal smear response to oestrogens, exerted prolonged oestrogenic effects in mice and increased the rate of cell proliferation in both the vagina and uterus. The vaginal epithelium became multilayered with stratified or cornified surface layers and the uterus developed gross cystic glandular hyperplasia. This demonstrates that ICI 46,474 is simply a weak oestrogen in the mouse.


Separation of rat pituitary thyrotrophic cells. A method for the enrichment of live thyrotrophic pituitary cells is described. Pituitary glands of young male rats were removed into Earle's solution and dispersed in a 0.1% trypsin solution containing 0.5% bovine serum albumin, pH 7.2. Nylon fibres (25 microgram) were used for the separation of the thyrotrophic cells, by stringing them across a plastic frame which fitted a plastic Petri dish containing the cell suspension. The fibres were washed with light petroleum (b.p. 60--80 degree C) and carbon tetrachloride, hydrolysed with 3 M-HCL for 30 min at room temperature and washed with distilled water and phosphate-buffered saline (pH 7.2). The fibres were treated with thyrotrophin releasing hormone (TRH) alone or in the presence of soluble carbodiimide solution. After incubation for 1 h at room temperature, the fibres were transferred to a new Earle's medium and cells were released from the fibres by plucking them with a needle. The separated thyrotrophic cells were identified by radioimmunoassay and by electron microscopy. Using the above-mentioned methods, enrichment of thyrotrophic cells was obtained. Thus, the amounts of TSH, prolactin, LH and GH released, during 2 h of incubation, by 1.5 x 10(6) unseparated cells were 6.8 +/- 0.65, 4.1 +/- 0.47, 4.8 +/- 0.52 and 5.2 +/- 0.68 microgram respectively, while the same number of purified thyrotrophic cells released 76.1 +/- 0.42, 1.2 +/- 0.3, 0.6 +/- 0.35 and 1.6 +/- 0.22 microgram of the same hormones (means +/- S.E.M.).


Observations on the localization of labelled amino acid in mouse adrenal chromaffin cells after the injection of L-[4,5-3H] leucine. The intracellular localization of L-[4,5-3H] leucine in chromaffin cells has been observed using light and electron microscopic autoradiography and the association of the labelled amino acid with particular cell components confirmed by statistical analysis. By making observations at short intervals after a single intravenous pulse of [3H]leucine it has been possible to follow the movement of the isotope from the endoplasmic reticulum through the Golgi complex to the chromaffin granules. No evidence for movement of the label through the Golgi complex was observed in adjacent cortical cells. The time sequence of transport of the amino acid through the various cell organelles was very similar to that observed by previous workers in protein-secreting exocrine cells.


Purification of human parathyroid hormone: recent studies and further observations. During the isolation of human parathyroid hormone there is an extensive loss of immuno-assayble hormone over the successive extraction steps, due in part to the presence of fragments that are soluble in 4% trichloroacetic acid. These fragments are derived from both the amino- and carboxyl-terminal regions of the hormone. The hormonal fractions precipitated with trichloroacetic acid were further purified by gel filtration and ion-exchange chromatography. At the final ion-exchange purification step, some preparations of the hormone eluted in multiple fractions. When the various components were characterized separately by immunoassay, amino acid composition, enzymic cleavage and partial sequence analysis, they were found to be closely comparable, although the most acidic fraction contained a blocked terminal amino group. Extraction of a number of batches of tissue permitted revision of the amino acid composition of human parathyroid hormone. Biosynthetic studies with labelled amino acids confirmed the absence of tyrosine and the presence of phenylalanine and threonine and localized these residues to definite regions of the molecule.


Dose-related effects of non-steroidal antioestrogens nad oestrogens on the measurement of cytoplasmic oestrogen receptors in the rat and mouse uterus. The dose-related effects of non-steroidal antioestrogens and oestrogens on the measurement of cytoplasmic oestrogen receptors in the rat uterus have been determined. The simultaneous administration of tamoxifen or monohydroxytamoxifen and oestradiol on three consecutive days resulted in dose-dependent decreases in both the wet weight of the uterus and the number of available cytoplasmic oestrogen receptors. The oestrogenic triphenylethylenes ICI 47 699 and ICI 3188 both produced dose-dependent decreases in the number of available cytoplasmic oestrogen receptors. Increasing doses of ICI 47 699 resulted in increasing concentrations of oestrogen receptors within the nucleus. The effects of tamoxifen and oestradiol-17 beta were compared in the ovariectomized mouse; replenishment of uterine oestrogen receptors was less evident in tamoxifen-treated animals than in animals receiving oestradiol, although increases in uterine weight were similar. A single large dose of tamoxifen (50 microgram) produced a prolonged depletion of cytoplasmic oestrogen receptors whilst stimulating rises in uterine weight and DNA and protein content. The results demonstrate that the depletion of the uterine cytoplasmic oestrogen receptor pool is a function of the dose administered for any compound with the ability to translocate oestrogen receptors to the nucleus and as such is not an exclusive characteristic of non-steroidal antioestrogens.


A rapid simplified bioassay for somatomedin. A simplified, more rapid bioassay for the estimation of somatomedin activity, based on the porcine costal cartilage bioassay, is described. A micro-scale system based on the porcine costal cartilage assay is also described. These assay systems showed no decrease in sensitivity or precision, compared with other methods, as a result of the modifications. The assays have been used for routine hospital laboratory determinations, for the estimation of somatomedin activity in normal adolescent children of both sexes and in clinical studies of scoliotic, acromegalic and hypopituitary patients.


Three genes for lupus nephritis in NZB x NZW mice. The occurrence of early severe lupus nephritis in (NZB x NZW)F1 mice must depend on the action of at least two dominant or codominant genes (at least one gene from each parent) as neither of the inbred parental strains shows the disorder. Identifying affected animals by antemortem determinations of renal function, we have studied the incidence of the renal disease in 230 (NZB x NZW) x NZW backcross mice (an earlier study) and, in this study, in 150 (NZB x NZW) x NZB backcross mice. The data indicate that the NZB strain contributes only one gene and the NZW strain contributes two genes, or clusters of closely linked genes, to the renal disorder of the F1 hybrid. One of the NZW genes was found to be linked to the H-2 complex. All three genes must be dominant or codominant, as their effect is expressed in the heterozygous state.


Human immune responses to hapten-conjugated cells. I. Primary and secondary proliferative responses in vitro. An in vitro model was developed to study both primary and secondary proliferative responses of human lymphocytes to hapten-conjugated peripheral blood mononuclear cells. Coculture of human lymphocytes with autologous trinitrophenyl (TNP)-conjugated stimulator cells resulted in primary proliferative responses. Subjects segregated into high and low primary responders with mean stimulation indices of 11 and 2.1, respectively. Restimulation of primed cells from high responder subjects 3 wk after initial sensitization generated secondary proliferative responses. To investigate the antigenic requirements for secondary stimulation, autologous TNP-conjugate primed responders were restimulated with both autologous and allogeneic TNP-conjugated stimulators. In all experiments restimulation with autologous conjugated cells yielded substantially greater proliferative responses than with allogeneic conjugates. Experiments were then performed to ascertain whether HLA determinant homology between primed responder and stimulator cells influenced the level of secondary responsiveness. Homology for HLA-A and B locus serologic determinants was not associated with enhanced responsiveness. In contrast, D region determinant homology, detected by B-cell antigen typing, showed a highly significant positive correlation with the magnitude of secondary responses. The data thus strongly suggest that for secondary proliferative responses to TNP, human T cells recognize hapten in association with HLA-D region determinants.


Interaction of glucocorticoids with macrophages. Identification of glucocorticoid receptors in monocytes and macrophages. Glucocorticoid binding was measured in resident and thioglycollate-elicited mouse peritoneal macrophages, rabbit alveolar macrophages, and human monocytes. Two assays of binding were used--an assay with intact cells in suspension or monolayers, and an assay of cytosol and nuclear forms of glucocorticoid receptors. The mononuclear phagocytes contained approximately equal to 4--10 X 10(3) high affinity receptor sites per cell, with dissociation constants of approximately equal to 2--8 nM dexamethasone. The binding to the saturable sites was specific for steroids with glucocorticoid or antiglucocorticoid activity. Cortisol, corticosterone, and progesterone competed with dexamethasone for binding, whereas estradiol, dihydrotestosterone, and 11-epicortisol competed very little. Binding of dexamethasone to cytosol and nuclear forms of the receptor complex and temperature-sensitive translocation of cytosol forms to nuclear forms were shown. At 37 degrees C the predominant form of the hormone-receptor complex was nuclear. These results demonstrate that corticosteroids interact with macrophages at physiological concentrations.


The human complement system in thrombin-mediated platelet function. Thrombin-mediated platelet membrane-specific uptake of C3 and C5 was demonstrated by radiolabeled components and was visualized electron microscopically utilizing a ferritin marker conjugated to monospecific antibody to each component. The role of complement in thrombin-induced platelet function was determined. Though complement was not essential for thrombin-induced platelet aggregation and release of serotonin, these activities were significantly increased if complement was present. The release of serotonin was found to be a nonlytic process because under the conditions employed, no lactic dehydrogenase was released. The activation of complement was induced by a mechanism which has not been previously described. Thrombin associated with the platelet membrane presumably formed a C3 convertase that entered the known complement sequence at the C3 stage and proceeded to activate the terminal components through the known sequence to C9.


Secretory component of epithelial cells is a surface receptor for polymeric immunoglobulins. Epithelial cells of human fetal intestines and of a colonic carcinoma cell line (HT-29) exhibited intracellular and surface binding of polymeric immunoglobulins of IgA and IgM classes; monomeric IgA and IgG did not bind to these cells. Secretory component was identified as the receptor involved in the immunoglobulin binding. This conclusion was confirmed by the following experiments: trypsin abrogated the surface binding of polymeric immunoglobulin, reappearance of surface secretory component (SC) restored immunoglobulin binding; the appearance of SC in developing fetal tissues coincided with their potential to bind polymeric immunoglobulin; anti-SC reagents inhibited the binding of immunoglobulins to epithelial cells; and SC-containing secretory IgA did not bind to the surface of HT-29 cells.


The determination of total bilirubin with the Du Pont ACA with respect to neonatal sera. The interference of hemoglobin in the determination of total bilirubin with the Du Pont ACA was studied. The method seemed of limited value in our opinion especially with respect to neonatal sera. By changing the wave-length setting a rather broad plateau was found when the hemoglobin concentration was plotted against the actual bilirubin concentration. On the basis of these findings a new calibration graph was constructed and programmed into the ACA. The new method correlates well with two other micro bilirubin techniques.


[Laboratory findings in cerebrospinal fluid in relation to age: trivariate evaluation of albumin and immunoglobulin G concentrations (author's transl)]. In cerebrospinal fluid from controls ("non-diseased probands", n = 326) the following variables were determined: albumin and immunoglobulin G (by immunodiffusion) and total protein. Total protein rose parallel with the age of the subjects (r = 0.319); the albumin fractions (r = 0.126) and immunoglobulin G (r = 0.144) also correlated with age. The concentrations of albumin and immunoglobulin G were correlated even more closely (r = 0.589), leading to a particularly slender form of the elliptic bivariate normal range. The correlation of the variables albumin and immunoglobulin G with each other and with age was drawn upon as additional information, in order to discriminate between laboratory findings from diseased and from non-diseased subjects: a trivariate area of reference ("trivariate normal range") was calculated, which avoided errors of the second kind (diseased values not recognized) more powerfully than the usual one-dimensional ranges (x +/- 2s or percentile).


[A routine method for the investigation of the oxygen affinity of haemoglobin (author's transl)]. A method is described for the measurement of the half saturation pressure (p50) and the "standardised O2-saturation", as an index of the oxygen affinity of haemoglobin. In addition to the normal blood gas analysis, the only other parameter required is the O2-saturation after equilibration of the blood at pO2 = 31 mm Hg (4.72 kPa). The results are read from a specially prepared nomogram. Potential uses and limitations of the method are discussed.


A biomechanical invariant for gait perception. Viewers can determine the gender of a walker from sagitally projected, dynamic displays of point-lights attached to prominent joints. This article explores three interrelated approaches in search of a biomechanical invariant that viewers might use. The first, an index of torso structure, accounts for the data handsomely but seems inappropriate because it is not directly revealed in the dynamic stimuli. The second, a dynamic index of visible torsion in the trunk of a walker, also fits the data well but seems to have a logical problem and a difficulty in accounting for performance in certain conditions of several previous studies. The third has the strengths of the first two indices, and it can account for some other data as well. It is the center of moment and is a "deeper", more general description of the invariant. This center is a point around which all movement occurs. It can be thought of as one specification of the gestalt law of common fate and may be helpful for the study of movement perception in general.


Auditory streaming is cumulative.

Auditory streaming is cumulative. The auditory system appears to begin listening to an input with a basis toward hearing the input as a single stream, but it gradually accumulates evidence over a period of seconds which may lead to the input's being split into substreams. Several seconds of silence or of unpatterned noise slowly remove the bias of the mechanism in favor of these streams. The effects were demonstrated in experiments in which young adult listeners sped up sequences of tones until they split. The sequences varied in the number of tones packaged between recurrent "separators" (periods of silence or of white noise) and in the lengths of these separators.


Organizational factors in perceived dimensionality. The hypothesis that perceived dimensionality of projection drawings is influenced by perceived organization was tested in two experiments. Organization was biased by coloration: The drawings were (a) uncolored, (b) colored in ways that emphasized plausible three-dimensional parts of the represented objects, or (c) colored in ways that emphasized two-dimensional (2D) parts of the drawings themselves. In Experiment 1, subjective ratings of three-dimensionality (3D) were greater for the 3D-biased stimuli than for the unbiased stimuli, and ratings for the 2D-biased stimuli were lower than for the unbiased stimuli. Similar results were obtained in Experiment 2 in which latencies to perceive the drawings three-dimensionally were measured. The 3D-biased stimuli were seen in depth more quickly than the unbiased stimuli, and the 2D-biased stimuli were seen in depth more slowly than the unbiased stimuli. Additional results on the relation between ratings and latencies suggest that latencies are affected more strongly by object complexity than are ratings.


Quantification of three-dimensional structures. A mathematical model, based on additive subcomponents of grouping, subitizing and adding, was derived to account for quantification latencies of three-dimensional block arrangements. Subitizing is the process that people use to directly quantify a small number of objects without counting. It was found that most people consistently subitized up to four blocks. With more than four blocks, people resorted to grouping and adding, and the model was able to account for these data. The structural variables of compactness, symmetry, linearity, and planarity were shown to have small effects on quantification latencies relative to the large effect of number of blocks. Of these structural variables, compactness had the largest effect, and in terms of the model, it is suggested that visual structure had its effect on the perceptual grouping subcomponent.


Multidimensional same--different judgments: evidence against independent comparisons of dimensions. Commonly discussed models of performance in the multidimensional same-different task are based on the assumption that independent same-different decisions are reached for each of the stimulus dimensions used in an experiment. In these models, a higher level mechanism examines th outcome of these independent decisions in order to determine whether the stimuli are the same or different overall. Previous evidence indicating that these models are inconsistent with results from same trials is summarized, and a new test of the above assumption using data from different trials is proposed. Detailed analysis of reaction times from different trials is shown, at least for some pairs of dimensions, to be incompatible with the view that separate same-different decisions are reached for each dimension. The major finding is that there are more relatively fast responses in a condition with two dimensions different, compared with the two conditions with only one of the dimensions different, than any processing model treating the dimensions separately could predict. The results suggest that partial information may be combined across dimensions in order to reach a "different" judgment.


Reaction times and evoked potentials as indicators of hemispheric differences for laterally presented name and physical matches. Letter pairs, which could be name matches, physical matches, or mismatches, were presented at fixation or 2.5 degrees left or right of fixation. During different experimental sessions, the locations and the types of matches were fixed (and therefore known in advance by the subject) or were randomized. Right visual field superiority in reaction time occurred for name matches only when location was randomized, and then the extent of the superiority depended on whether the types of match called for were predictable. Evoked potentials to the letter pairs during this task revealed hemispheric and neural pathway differences that were independent of expectancy condition. Right hemisphere responses were larger than left. For some components, amplitudes were smaller and latencies were shorter for direct than for indirect projection of stimuli to each cerebral hemisphere. Indirect-direct differences in P300 amplitude varied for each cerebral hemisphere according to whether a physical or name match occurred. The P130 and N170 components manifested hemispheric differences that depended on whether the two letters of a pair were in the same or different cases.


Response bias in category and magnitude estimation of difference and similarity for loudness and pitch. Interval scales of sensory magnitude were derived from magnitude and category estimates of loudness differences, loudness similarities, pitch differences, and pitch similarities. In each of the four loudness experiments, a loudness scale was constructed from a nonmetric analysis of the rank order of the judgments. The four loudness scales so constructed were found to be equivalent to one another and indicated that loudness was a power function of sound pressure with an exponent of .29. A similar analysis for the four pitch experiments found the pitch scales derived in each case to be equivalent to one another and linear with the mel scale of pitch. Thus the same sensory and similarities for two distinct perceptual continua. For both pitch and loudness, these sensory scales were used to generate scales of sensory differences. A comparison of the category and magnitude estimates of sensory differences with the scale of sensory differences derived from the nonmetric analyses indicated the presence of significant response biases in both category and magnitude estimation procedures.


Peptic ulcer disease in children: report of a case and a problem-oriented review. The family physician who sees many children with vague abdominal pain must include peptic ulcer disease in the differential diagnosis. A case report is presented and the characteristics of primary and secondary ulcers in children are reviewed with respect to symptoms, signs, diagnosis, and treatment. Ulcers in children may be primary or secondary (stress) ulcers. Clinical and radiographic diagnosis is difficult. Medical therapy suffices in most cases, but there is a high recurrence rate in adolescence and adulthood. Peptic ulcer disease in children is a diagnostic dilemma, but the family physician may be in an excellent position to make the diagnosis since he/she is often the first physician to see the patient and is aware of altered family dynamics, which may play a role in this disease.


A case control survey and dysmenorrhea in a family practice population: a proposed disability index. Dysmenorrhea, though rarely coded as a diagnosis in the records of family physicians, is a common problem in their female patients. Responses to a questionnaire indicated that at least 50 percent of women experience menstrual pain at one time with a minimum of 29 percent experiencing pain in any two-month period. The average duration of pain was greater than one day. A disability index was developed which revealed that half the women were Grade 3, or severely disabled. This study suggests that menstrual pain is a common problem in family practice and clearly ranks as a major cause of temporary disability in women patients.


Depression in primary care: changes in pattern of patient visits and complaints during a developing depression. The purpose of this study was to characterize changes in patient behavior associated with a developing depression. The records of 154 depressed patients from a solo family practice were examined for type and number of complaints, number of visits, and amount of hospitalization during two periods of time. In addition, 154 patients were used as controls and matched to the depressive patients by age, sex, and season of year seen. Two similar time periods were examined in the controls. The depressed group in comparisons both with itself and with the control group showed, in the seven months prior to the diagnosis of depression, these changes: (1) increase in number of patient-initiated office and home visits; (2) increased incidence of hospitalization; and (3) increased number of presenting complaints of three types: ill-defined "functional" complaints; pain of undetermined etiology in a wide variety of sites: head, chest, abdomen, and extremities; and "nervous" complaints, mainly increased tension and feelings of anxiety. The study results indicate that increased number of office visits and "functional" somatic complaints or anxiety-tension feelings should suggest depression.


Group therapy in family medicine. Part 3: starting the group. This paper is the third in a four-part series and in it some issues and techniques pertaining to the pregroup screening interview are discussed as well as the initial meeting of a therapy group in a family practice setting. The screening interview enables patient and group therapists to decide whether or not the patient might benefit from group therapy. Topics covered in such an interview are discussed. Some ways of beginning and of ending the first session are described.


Ambulatory family practice experience as the primary and integrating clinical concept in a four-year undergraduate curriculum. The Upper Peninsula Medical Education Program seeks to graduate primary care physicians who will practice in rural, underserved areas. The program has a unique curriculum that involves four years away from Michigan State University's main campus and is based on ambulatory outpatient experience in a family practice model office. All basic and clinical sciences are learned in this setting. Novel ways of organizing faculty and student time help facilitate this plan. A thorough evaluation system helps monitor student progress. Preliminary results are promising indications that the program is meeting its goals.


Integrated residency training in family medicine and general practice dentistry. General practice dental training and family practice medical training can be combined into one effective integrated program. This combination benefits the patients in a family practice model unit, enhances family practice resident education, and will ultimately benefit patient care delivery. This paper describes the experience of such an integrated program which is now well established.


Determinants of physician recognition and follow-up of abnormal laboratory values. Potential determinants of physician recognition and follow-up of abnormal laboratory values were studied in the ambulatory primary care setting. Data support the hypothesis that a significant positive association exists between the clinical importance of a laboratory result and physician response. Clinical importance was indicated by degree of abnormality of the laboratory value, the type of test, and the indication for obtaining the test. Response was not significantly associated with type of laboratory report or resident's year of training, but a relationship was shown with resident's National Board scores. A model of 12 laboratory tests was found to be more appropriate for studying recognition and follow-up than one of 30 because of fewer repetitious tests and fewer results of doubtful clinical usefulness. With such a select model, recognition and follow-up of abnormals can be used as process measures of quality of medical care.


Hemoptysis.

Hemoptysis. Hemoptysis is an alarming symptom that should not be dismissed lightly. A thorough evaluation will lead to the correct diagnosis in 80 to 90 percent of cases. Surgery is occasionally necessary where life-threatening hemorrhage is present but, more commonly, appropriate therapy can only be determined when the etiology is discovered, thus mandating a careful, thorough diagnostic search.


Electron microscopic observation on sperm penetration and pronuclear formation in the fish egg. Unfertilized eggs of the medaka, Oryzias latipes were inseminated after being mechanically freed from the chorion. In the first step of penetration, as soon as it reached the vitelline surface, the whole spermatozoon was quickly enclosed by ooplasmic protrusions (fertilization cone) of the vitelline surface. In the second step, the egg plasma membrane fused with various regions of the plasma membrane of the enclosed spermatozoon; finally the sperm flagellum was also incorporated into the ooplasm. Initial disappearance of the nuclear envelope of the sperm with vesiculation at the apical region of the head is followed by dispersal of the sperm chromatin. The nuclear envelope is then reformed by fusion of elongated or flattened vesicles along the margin of dispersing nuclear chromatin. The mature male pronucleus has a large nucleolus within a wrinkled envelope. It seems that the fertilization process in this fish involves some features of that occurring in the marine invertebrate and the mammalian eggs.


The possible influence of temporal factors in androgenic responsiveness of urogenital tissue recombinants from wild-type and androgen-insensitive (Tfm) mice. Tissue recombinants of epithelium and stroma from embryonic and neonatal urogenital rudiments derived from wild-type and feminized (Tfm/Y) mice sere grown as grafts in intact male hosts and analyzed morphologically for androgenic response. When mesenchyme of embryonic wild-type urogenital sinus (UGS) was associated with epithelium from embryonic wild-type bladder (B), the epithelium developed into glandular structures resembling prostate. In the reciprocal recombinant (B mesenchyme + UGS epithelium) the response was mixed, half of the recombinants exhibited bladder morphology and half exhibited prostatic-like morphology. Vaginal-like histogenesis occurred in UGS recombinants of androgen-insensitive Tfm/Y mesenchyme and wild-type epithelium, while prostatic morphology developed in reciprocal recombinants of wild-type mesenchyme and Tfm/Y epithelium. These observations demonstrate (1) that the presence of wild-type mesenchyme appears essential for expression of androgen-dependent morphogenesis during embryonic periods; and (2) that Tfm/Y epithelium is capable of participating in an androgenic response. Conversely, in similar recombinants prepared with neonatal tissues, the presence of wild-type urogenital stroma may not be required for expression of certain androgen-dependent phenomena since maintenance of the height and cytodifferentiation of ductus deferens epithelium occurs even when this epithelium is associated with Tfm/Y urogenital stroma. It appears, therefore, that the requirement of urogenital epithelium for wild-type (androgen sensitive) stroma may vary temporally.


Atrophy of a breast muscle with a single fibre type (M. pectoralis) in fasting willow grouse, Lagopus lagopus (L.). The willow grouse (Lagopus lagopus) are arctic gallinaceous birds with small fat stores and large muscles. In winter, these birds may starve for periods of several days. It was important to know which energy reserves were utlized during periods of starvation. Body composition of female willow grouse and Bantam hens was studied before and after fasting. Grouse have much larger breast muscles than do Bantams, but reproductive organs are larger in hens. The relative amounts of adipose tissue are about equal in grouse and Bantams. When the birds had lost about 20% of their initial body weight due to fasting, Bantams had lost as much weight from their reproductive organs as from the adipose tissue, with little loss from the muscles. Grouse lost more weight from the pectoralis muscles alone than from the adipose tissue. Since the major component of muscle is protein, the grouse obtain a larger proportion of acloric needs during fasting from protein than do the Bantams. Grouse breast muscles are dark red, and the pectoralis consists homogeneously of type IIa (oxidative-glycolytic) fibres, assessed by ATPase and by Sudan Black staining. The supracoracoideus muscle has type II fibres, not resolvable in subtypes. The leg muscle biceps femoris contains the three fibre types I, IIa, and IIb. During fasting, the weight loss of the pectoralis muscle may be accounted for by all fibres losing some material.


Chimaera studies of the origin and formation of the pectoral musculature of the avian embryo. Cervical, brachial, and thoracic somites and brachial somatopleure were transplanted from quail into 2-day chick embryos to determine their contribution to the formation of the pectoralis major muscle. The results show that the musculature of the pectoralis major and pectoralis minor is derived entirely from brachial somites (16-20) while the brachial somatopleure provides much of the connective tissue of these muscles. Migration of somitic cells into the somatopleure appears to begin before the somites are fully formed. The primordium of the pectoralis muscle forms at the base of the wing bud and extends ventro-caudally into the thoracic area to attach to the sternum.


Enhanced identification of lethal yellow (Ay/Ay) mouse embryos by means of delayed development of four-cell stages. At present, experimental studies on the primary genetic lesion in Ay/Ay embryos are restricted by the absence of techniques designed to identify Ay homozygotes prior to the onset of secondary defects. This paper describes a methodology to enrich the yields of Ay homozygotes in experimental populations by taking advantage of an early homozygous Ay expression-lagging development in 4-cell embryos.


Differential activation of hepatitis B DNA polymerase by detergent and salt. Three patterns of activity were evident when the differential activation of the DNA polymerase associated with serum Dane particles by nonionic detergent and salt was investigated. The patterns were obtained by plotting the increase in enzyme activity mediated by the detergent Nonidet P-40 (NP-40) in increasing concentrations of KCl compared to the activity observed in the absence of detergent. The pattern of differential activity of hepatitis B (HB) DNA polymerase in detergent and salt was altered by subjecting the HBAg preparations to shearing forces. Hepatitis B DNA polymerase activity was stable even in NP-40 concentrations as high as 10%. In addition to hepatitis B DNA polymerase, DNA polymerase activated by calf thymus DNA was found in pellets containing Dane particles. The latter DNA polymerase activity was also activated by NP-40 and was not decreased by DNAse; this DNA polymerase coprecipitated with hepatitis B antigen (HBAg) upon addition of anti-HBs. However, the DNA polymerase activated by calf thymus DNA was inhibited by 0.4 M KCl. Electron microscopic observations of serum Dane particles in 0.4 M KCl showed no alterations of morphology of these particles when compared to particles in low-salt buffer. The data indicated that KCl activated HB DNA polymerase by a different mechanism from that of shear or NP-40, which removed the surface antigen coat from the Dane particles.


Coping and defense in relation to accommodation among a sample of blind men. The relation of 26  measures of ego functioning, as assessed by the responses of 101 blind men to the California Psychological Inventory, to employment status and travel freedom were examined. Previous research findings and methodology and the need to control for intervening variables were discussed. The accommodation of blindness was characterized by greater cognitive and intellectual articulation, the absence of intraceptive rigidity, and the flexible regulation of affect and impulse. While this pattern held true for those subjects born partially sighted and those acquiring total and partial blindness, no differences emerged for subject born totally or partially blind. Support was found for the construct validity of the ego measures, as well as Haan's proposition of complementary pairing of ego functions. On the basis of these results specific recommendations were made regarding the administration of the scales and counseling among the blind.


Alcoholic MMPI subtypes. Relationship to drinking styles, benefits, and consequences. The present study was designed, first, to attempt to replicate the previously derived Goldstein and Linden Minnesota Multiphasic Personality Inventory alcoholic personality subtypes, and second, to relate these personality patterns to a multidimensional measure of alcohol usage. Two of the previously obtained profile types were replicated through two independent cluster analytic procedures. These subtypes were defined as psychopathic and neurotic-depressive, respectively. Higher levels of drinking-related impairment were associated with anxiety and depression, while lower levels of impairment were related to psychopathic features among patients hospitalized primarily for alcoholism. However, relatively heterogeneous, distinctive configurations of reported drinking benefits, styles, and consequences were found across the Goldstein-Linden subtypes. Methodological factors potentially contributing to the failure to replicate two of the previously derived subtypes were discussed. The potential therapeutic utility of a multivariate classification of personality functioning and the use of a multidimensional assessment of alcohol usage within alcoholic populations was also discussed.


The frequency and persistence of depressive symptoms in the alcohol abuser. A survey of 61 outpatients admitted to a mental health center for the treatment of alcoholism determined that a majority of them (59 per cent) were clinically depressed. The depressive symptoms were rarely treated with anti-depressant agents and, at 1-year follow-up, were found to persist even though the patients had attended the standard treatment program for alcoholics. There is need for new treatment strategies that recognize the diagnostic heterogeneity of the alcoholic and that consider the use of appropriate psychopharmacological agents.


Toward a rationale for the seclusion process. The present paper summarizes three studies focusing on different aspects of seclusion room practices. The first study involved chart review to collect empirical data on reasons for seclusion, length of seclusion, and characteristics of secluded patients. The second study focused on staff attitudes toward seclusion; the third dealt with the attitudes of both secluded and nonsecluded patients. The average time of seclusion was approximately 4 hours and in most cases aggressive behaviors of various types were cited as the precipitating event. In addition, patient and staff attitudes implied that a major function of the seclusion process was to isolate patients from disturbing interactions and to maintain the smooth functioning of the ward minisociety. Two models of seclusion, an ethological model and a behavioristic "time out" model, were developed in order to integrate the results of these studies. Implications of the findings and models are presented for changes in seclusion room procedures.


Referral of patients from primary care physicians to a community mental health center. The referral process between primary care physicians and a community mental health center was examined in a community which lacks a geographically based psychiatrist. The method included inspection of referral completion rate and evaluation or patients' characteristics and attitudes concerning mental health care. The findings indicated that only 10 per cent of referred patients who have had no prior contact with the community mental health center completed the referral. Reasons for this low referral completion rate are discussed.


Catatonia associated with disulfiram therapy. This is the first report of a catatonic syndrome occurring in a patient receiving disulfiram treatment. A causal relationship is strongly suggested by the mode of onset, the absence of a previous history of catatonia, and the rapid resolution of the syndrome within 72 hours of discontinuance of the disulfiram therapy. Neurophysiological mechanisms which aid in elucidating the role of disulfiram in the etiology of catatonia are discussed. It is important that physicians be alerted to this serious, potentially lethal, complication, as it is readily reversible if the disulfiram is discontinued and appropriate supportive measures are taken. Also, it appears that these patients may be more susceptible to complications with future disulfiram usage and should be strongly counseled to seek alternative therapies for their alcohol problems in the future.


The influence of taipoxin on cholinergic synapses in the electric organ of Torpedo marmorata. The influences of the snake venom taipoxin on the cholinergic synapses of the electric organ of Torpedo mamorata were investigated. 1. In ultrathin sections presynaptic membrane indentations are noted under the influence of taipoxin/NaCl. 2. The presynaptic membranes often show small interruptions. 3. In taipoxin/horseradish peroxidase incubated organ pieces typical omega-shaped indentations are found, but on the postsynaptic side. 4. The vesicle density decreased under the influence of the taipoxin in contrast untreated cholinergic synapses. 5. In freeze etched preparations no membrane indentations and interruptions are observed, but only a small vesicle density was seen.


Location by paper chromatography of compensatory ovarian hypertrophy (COH) inhibiting activity in acetic acid extracts from bovine pineals. Acetic acid extracts of bovine pineals and cerebral cortex were separated on Sephadex G-25 columns. Subsequently two low molecular weight fractions, F2 and F3, were ultrafiltered through the membranes UM2 and UM05. The UM05 residues were gel filtered on Sephadex G-15 columns or chromatographed on Dowex W50-X4 columns. Fractions from these columns were tested and those which showed COH-inhibiting activity were separated by preparative paper chromatography in different solvents. The absorption spectra of those fractions were recorded and tested for COH-inhibiting activity were separated by preparative paper chromatography in different solvents. The absorption spectra of those fractions were recorded and tested for COH-inhibition. By these methods, a COH-inhibitor was localized in three different solvents. Some active paper chromatography fractions were studied in high pressure, reverse phase, liquid chromatography. This latter method showed that the active fractions obtained by paper chromatography contain several orthophthlaldehyde (OPT) positive compounds. Key words: acetic acid, bovine pineal extracts, compensatory ovarian hypertrophy (COH), paper chromatography, high pressure, reverse phase, liquid chromatography.


Hypothermic decrease in microtubule density and birefringence in unimyelinated axons. The density of microtubules, T.D. (number of tubules/unit area) is highest in small crab nerve axons. After cooling of the nerve at 0 degrees C, the tubule density tends to zero (T.D. 2% of the normothermic value). Once the cooled nerves are returned in normothermia, the reconstitution of the microtubules is evidenced (T.D. =  90% of the initial normothermic value). Therefore cooling "depolymerizes" the tubules, whereas rewarming leads to their "repolymerization." These results definitely improve the interpretation of the birefringence decrease by cooling: as tubules and filaments contribute to the positive fraction of the total positive birefringence, their depolymerization by cooling explains to a large extent the decrease in total birefringence.


Postsynaptic potentials in pacemaker cells: a correlation of behavior in command cells of an electric fish. Intracellular recordings were made from pacemaker-command cells of the electric organ discharge (EOD) of the weakly electric fish Eigenmannia virescens. The fish was immobilized with gallamine triethiodide (Flaxedil) which silenced the EOD. A simulated EOD of this fish (ca. 300 Hz) and a sine wave simulating a neighbor, a few Hz higher (+deltaF) or lower (-deltaF) were introduced into the bath to elicit the "jamming avoidance response" (JAR), monitored through the pacemaker potential. We observed that accompanying the JAR there is a minute hyperpolarizing postsynaptic potential (hpsp) superimposed on the pacemaker potential. A shift in the phase of the hpsp occurs with a change in the sign of deltaF, and therefore of the JAR. Assuming that the behaviorally correlated hpsp is inhibitory, it suggests that mutual inhibition may play a role in regulating the synchronous firing frequency of command neurons, which are electrically coupled with one-another. Scheich and Bullock (1974) proposed a neuronal scheme for the JAR in which they suggest that two systems (P and T) operate together in the nervous system. The T system affects the pacemaker cells at a precise, variable phase of the pacemaker cycle. Although the present results indeed reveal a shift in the hpsp with a change in the sign of deltaF, the actual significance of this shift remains to be evaluated. The unexpected direction of the shift suggests either that the hpsp is excitatory at the phases when it occurs, or that effectiveness of inhibition decreases at later phases in this case instead of increasing as in other cases, or that the hpsp opposes the JAR. The parallel P system is probably more important in explaining the JAR, acting by a DC level control rather than a phase control.


Feeding motor program in Limax. I. Neuromuscular correlates and control by chemosensory input. The feeding motor program(FMP) of the terrestrial slug Limax maximus was examined in vivo and in vitro. The feeding pattern of intact animals shows an initial increase in bite frequency followed by a plateau phase. Recordings obtained from semi-intact preparations of the lips, brain, and buccal mass established the correlation of activity in buccal ganglion nerve roots with the protraction-retraction bite cycle. A preparation of the lips, cerebral ganglia, and buccal ganglia was developed, such that, repetitive chemostimulation of the lips yields reproducible bouts of FMP. Sources of proprioceptive feedback from buccal muscles were demonstrated. The feasibility of computer scoring of the FMP is documented. The results demonstrate that aspects of in vivo feeding behavior are retained and identifiable in highly dissected, in vivo preparations.


Developmental abnormalities of identifiable neurons in the crayfish Procambarus simulans. We report anomalies of lateral giant neurons in field-caught animals. In one case, both lateral giant neurons arising from the fifth abdominal ganglion did not terminate in the next-most anterior ganglion, but rather continued to the third abdominal ganglion. In another case, an additional large neuron arising in the fifth abdominal ganglion coursed in a posterior direction. All othe CNS structures appeared normal in animals having either anomaly.


Serial synapses in Aplysia.

Serial synapses in Aplysia. Serial synapses occur between small profiles in the neuropil of Aplysia abdominal ganglion. Material was fixed in phosphate buffered OsO4, embedded in epon, and sections were stained with uranyl acetate and lead citrate. A class of synapses had the following characteristics: (1) synaptic vesicles clustered against the presynaptic membrane, (2) a widened extracellular space of about 20 nm containing electron-dense material, (3) straightening of the pre- and postsynaptic membranes, and (4) no postsynaptic membrane specialization. Some density between the presynaptic membrane and the adjacent synaptic vesicles was occasionally observed. Synapses occurred between small profiles in the neuropil (typical profile diameters were 1--3 micrometer). In this sample of approximately 100 synapses, four serial synapses were identified. The serial synaptic profiles were all small. In addition to the finding of serial synapses, 40% of the postsynaptic profiles contained vesicles similar to the synaptic vesicles seen in presynaptic profiles. Serial synapses may be the anatomical substrate of presynaptic inhibition and facilitation and of dishabituation.


Neurophysiological studies of autogenous sural nerve grafts. Sixteen autogenous sural nerve grafts used for ulnar and median injuries in the forearm have been studied neurophysiologically up to two and a half years after operation. Motor and sensory nerve conduction studies revealed a slow but sustained improvement during the follow-up period. By two years, motor conduction velocity across the graft itself reached in most cases 40 to 85% of the conduction velocity in the contralateral normal limb. Some reduction of motor conduction velocity was observed in the uninjured nerve proximal to the graft but this was less marked. Sensory nerve action potentials were obtained in 44% of nerves after 18 months although in all cases the amplitude of the potentials and in most cases their velocity, was greatly reduced.


Synaptic connections to individual tibialis anterior motoneurones in man. The characteristics of post-synaptic potentials in a single human motoneurone can be derived from the profiles of post-stimulus time histograms (PSTH) of that neurone when it is firing rhythmically. We have used this method to explore the synaptic connections to individual tibialis anterior motoneurones in man. Agonist group 1 volleys produced short latency excitation of 85% of tibialis anterior motoneurones probably representing the 1a EPSP. Excitation, at a latency of 70 ms, is attributed to a long loop reflex. Antagonist group 1 volleys produced short latency inhibition of 65% of tibialis anterior motoneurones probably representing the 1a IPSP. Excitation, at a latency of 97 ms, may represent spino-bulbo-spinal reflex. None of these effects are due to the excitation of cutaneous afferent nerve fibres.


Abnormalities of Bell's phenomenon in amyotrophic lateral sclerosis: a clinical and electrophysiological evaluation. A clinical and electromyographic study of oculomotor function was carried out in a series of 24 patients with amyotrophic lateral sclerosis (ALS). In 15 cases an alteration of Bell's phenomenon was found. In addition, three patients showed some impairment of conjugate ocular motility in the form of upward gaze paly. All cases had preserved oculocephalic reflexes in the vertical and horizontal planes. On clinical and electromyographic grounds, three degrees of altered Bell's phenomenon are suggested: attenuated (short and unsustained upward displacement of the eyeballs after forced closure of the eyelids), abolished (no upward displacement), and inverted (downward instead of upward displacement of the eyes). These oculomotor alterations were not directly related to the type of ALS at onset of the illness, nor with its duration. However they were correlated with the relative degree of the clinical bilateral pyramidal tract signs at the supraspinal level. The common involvement of the corticogeniculate tract in ALS could explain the unexpectedly high incidence of alteration of Bell's phenomenon found in this disease, but is is non-specific and similar lesions from different causes may also produce it.


Histocompatibility antigens (HLA) in multiple sclerosis in Iran. Thirty-five patients (19 male and 16 female) with clinically definite multiple sclerosis and 100 healthy control subjects were studied for the A and B locus of the HLA system. A significant increase of HLA A3 and A11 of the A locus and B7 of the B locus was observed in patients with multiple sclerosis compared with controls. An increase of antigen A3 was also observed in eight cases of probable multiple sclerosis. A significant increase of both A3 and B7 was observed in patients with multiple sclerosis.


Water intoxication in epileptic patients receiving carbamazepine. Plasma sodium and osmolality were determined in 80 adult epileptic patients receiving chronic treatment with carbamazepine and in 50 control patients treated with other anticonvulsant drugs. Mean plasma osmolality was significantly lower in the carbamazepine-treated patients but mean plasma sodium did not differ in the two groups. Hyponatraemia was found in five of the carbamazine-treated patients and hypo-osmolality in six. None of the control patients had hyponatraemia and only one had a borderline low osmolality. Three of the 13 patients receiving carbamazepine alone were hyponatraemic. Plasma sodium concentration correlated negatively with both daily carbamazepine dose and serum carbamazepine level. Free water clearance after an oral water load was determined in six patients on carbamazepine alone and in six normal subjects not receiving drug therapy. The capacity of some of the patients to excrete the water load was found to be grossly impaired.


Muscle hypertrophy after partial denervation: a human case. While undergoing long-term physiotherapy, a 41 year old woman with a chronic S1 radiculopathy developed progressive, painless enlargement of the weak calf. Gastrocnemius muscle biopsy disclosed changes of partial denervation and reinnervation, with small groups of type I and type II atrophic muscle fibres and abundant hypertrophic fibres of both types but mostly type II. It is postulated that, in addition to comprensatory work-induced type II muscle fibre hypertrophy, there was an element of (type I) stretched-induced hypertrophy of denervated fibres, a condition well recognised experimentally but not documented in man.


Intracranial venous thrombosis in the first trimester of pregnancy. We describe a fatal case of intracranial venous thrombosis occurring in early pregnancy. Such thrombosis usually occurs in late pregnancy or the puerperium but rarely during the first trimester of pregnancy. Computerized axial tomography suggested massive cerebral venous infarction. Necropsy findings showed not only cerebral venous thrombosis but also extensive pelvic and iliac vein thromboses. The relationship of cerebral venous thrombosis and pregnancy is discussed and the literature reviewed.


Thoracolumbar intraspinal tumours presenting features of raised intracranial pressure. Five patients are described in whom a benign or malignant thoracolumbar tumour, producing increased level of cerebrospinal fluid protein, was associated with hydrocephalus or papilloedema or both. A review of the clinical and laboratory features in these and 40 published cases underlines the difficulty in explaining the increased intracranial pressure in such patients. Slow absorption of cerebrospinal fluid as a result of the elevated protein levels or recurrent subarachnoid bleeding may play a part. When patients are discovered to have communicating hydrocephalus or a syndrome resemlbing benign intracranial hypertension, the finding of increased cerebrospinal fluid protein or any symptoms or signs relative to the spine should suggest the possibility of an intraspinal tumour.


Subdural haematoma and the malfunctioning shunt. Of 30 consecutive children with hydrocephalus treated by shunt implant, six developed subdural haematoma. Four of them presented with a malfunctioning shunt, and the diagnoses in all six cases were made by CT scan.


Properties of a spinal somatosensory evoked potential recorded in man. Somatosensory evoked potentials were recorded from the skin overlying the cervical and lumbar spinal cord of man after stimulation of median and tibial nerves respectively. The early negative component (N11) of the cervical potential and the negative lumbar potential (N14) were studied. The spatial properties of N11 and N14 indicate a spinal cord origin. Evidence partly from threshold studies, shows that the low threshold cutaneous afferent fibres were responsible for activating the generators of the potentials. A conditioning test stimulation procedure supports a postsynaptic generator. It is concluded that N11 and N14 have properties similar to the cord dorsum potentials recorded in animals and probably have the same generator, the neurones of the dorsal horn.


Pathogenetic profile of TIA before 55. A three-year investigation. Fifty-seven cases admitted to the Karolinska Hospital 1973-1976 with the diagnosis transient cerebral ischemia were reviewed. Seventeen cases were excluded as not fulfilling the strict TIA definition. An analysis of the records and the supplementary questionnaire of the remaining cases showed considerable sex differences in the stroke-prone profile. In the male group arteriosclerosis in the extracranial cerebral arteries was demonstrated in 90% of these examined by angiography. In the female group factors recognized as interfering with the coagulation system were obvious in more than 70% and two women had fibromuscular dysplasia. These differences may have therapeutic and prognostic implications. In the total material only 35% had hypertension. Diabetes was not present in any of the patients. Of the men 46.6% had abnormal blood lipids against 15.4% of the women. Seventy-five percent of the patients with verified arteriosclerosis were regular smokers. At a mean follow-up time of 18.7 months only one patient, in the untreated group, developed completed stroke.


Serum pyruvate-kinase (PK) and creatine-phosphokinase (CPK) in progressive muscular dystrophies. PK and CPK have been determined in the serum from 208 individuals including 70 normal controls (61 adults and 9 children) and 138 patients with a variety of neuromuscular disorders. In adult controls the mean activity (+/- SE) for PK is 1.2 +/- 0.05 mumol/ml/h. In normal children PK activity was about twice as high as in normal adults and decreases with increasing age. In 26 patients with Duchenne dystrophy the range of serum PK was 4.0-150.4 and in 17 individuals with the Becker type, 3.0 to 148.7. All had elevated PK and CPK levels. Eighteen of 20 patients with the facio-scapulo-humeral (FSH) from of muscular dystrophy had increased PK while only 9 had elevated CPK. Regression analyses have shown an inverse correlation between PK levels and age (or degree of disability in DMD). Kinetic and electrophoretic studies indicate that the PK isozyme found in the serum from affected patients and from heterozygotes for the DMD gene is mainly the M1 type PK, which is the only PK isozyme found in skeletal muscle and brain and the major component from myocardium.


An analysis of double discharges in the human electromyogram. Different characteristics of double discharges (doublets) of motor units in m. biceps brachii and tibialis anterior were examined. Doublets may occur physiologically at the beginning and termination of muscular effort and at the minimum rhythmic firing frequency, but doublets arising within a regular sequence of motor unit potentials can be regarded as abnormal. In neuromuscular diseases about 3% of motor units showed this firing pattern, but it was never found in intact limb muscles. Most of the abnormal doublets have the following characteristics: the interval between the first and the second component is 9 msec or less (longer intervals up to 22 msec occur very rarely); both components have nearly the same form; the amplitude of the second component is slightly smaller than that of the first; a stepwise or continuous jitter between doublet components is common; doublets recur randomly during a sequence of motor unit potentials; the interval between the doublet and the next MUP is usually about 50% longer than the mean MUP interval. A number of doublets differ, however, in one way or another from the above. The second component of the doublet may differ completely in amplitude and even in form from the first component; or they may fuse. It is thus hardly possible to define the lower limit of the interval between doublet components. Sometimes the post-doublet interval increase is absent. When applying all the criteria there is seldom any uncertainty about the identification of doublets.


Double discharges in neuromuscular diseases. Double discharges (doublets) of motor units were examined in routine EMG. The material consisted of 132 patients suffering from different neuromuscular diseases and 34 controls in whom the examined muscles were intact. Only m. tibialis anterior and biceps brachii were examined. Activity from at least 10 different motor units per muscle were recorded and analyzed off-line. Modified criteria were used in determining doubling units. Applying the modified criteria no doubling units were found in controls. In myopathies doublets occurred only in myotonic dystrophy and in one case of polymyositis in remission. In neuropathies, the occurrence of doublets was most common in proximal neuropathies. In polyneuropathies and root syndromes doubling units were relatively common, but none were found in exclusively distal neuropathies. It is concluded that doublets have a definite diagnostic value in routine EMG examination.


The effects of hydrocephalus upon the developing brain. Histological and quantitative studies of the ependyma and subependyma in hydrocephalic rats. A suspension of kaolin was injected into the cisterna magna of 44 rats at 2 weeks of age. Animals killed at intervals from 5--19 weeks of age showed varying degrees of hydrocephalus. Light microscopy, scanning and transmission electron microscopy revealed stretching and flattening of the ependymal cells but no significant loss of cilia. Histological evidence of periventricular tissue damage in these chronically hydrocephalic animals was only present when the ventricular dilatation was extensive. A quantitative assessment was made of the ependymal and subependymal cell reactions around the lateral ventricles of the hydrocephalic animals. Although the ependymal cells were clearly stretched around the ventricles, there was no apparent proliferation of these cells. An increase in the total number of subependymal cells was observed in hydrocephalic animals when compared with a series of 39 aged-matched controls. The greatest proliferation was in the dorsal and lateral walls of the ventricles which were the regions most severely stretched by the ventricular dilatation. There is evidence that subependymal cells differentiate into astrocytes and microglia so that proliferation of these cells may be interpreted as a response to continuing and progressive brain damage in chronic hydrocephalus. Such progressive tissue damage could adversely affect the developing brain.


Chemical control of cerebral circulation. Modification by a new vasodilator (YC-93). This study was undertaken to investigate influences of a new vasodilator, YC-93, a derivative of 1,4-dihydropyridine, on cerebral circulation and cerebrovascular CO2 reactivity. Cerebrocortical PO2, cerebrocortical PCO2, cerebrocortical blood flow and arterial blood pressure were continuously recorded by means of a PO2 electrode, a PCO2 electrode and a plate-type crossed thermocouple flowmeter placed on an exposed pial surface of the cat brain. The changes in each parameter induced by YC-93 were compared with those induced by papaverine hydrochloride. The effects of 5% CO2 inhalation were compared before and after the intravenous injection of YC-93. YC-93 (0.01 mg/kg) showed a more marked and longer-lasting hypotensive effect that papaverine (1 mg/kg) and yet produced a significant increase in cerebrocortical PO2. After the administration of YC-93, the degree of the increase in cerebrocortical PO2 during 5% CO2 inhalation was reduced significantly in comparison with that before the administration. The above data indicates that YC-93 has a vasodilating effect on cerebral blood vessels and that the drug causes a decrease in cerebrovascular CO2 reactivity.


Computerized tomography of brain and optic nerve in multiple sclerosis. Observations in 100 patients, including serial studies in 16. Computerized tomography (CT) of the brain was carried out in 100 patients with established or suspected multiple sclerosis (MS). The optic nerves were also examined in 53 of these patients. Areas compatible with demyelinating lesions were found in the cerebral hemisphere white matter and less frequently in the brain stem in 47% of cases. The hemisphere lesions were commonly multiple, typically situated in the deep white matter and periventricular regions, and were often asymptomatic. Small areas with unduly low attenuation coefficients were found in one or both optic nerves in 52% of patients in whom the optic nerves were examined. While these areas may represent demyelinating lesions their significance remains uncertain in view of poor correlation with clinical and electrophysiological parameters of optic nerve damage. Cerebral cortical atrophy and/or ventricular dilatation was found in 44% of cases, the frequency and severity of atrophy increasing with age and duration of disease. Serial studies after intervals of up to 21 months were performed in 16 patients, providing the opportunity to study the natural history of the cerebral lesions. While in some cases no significant change occurred, in others white matter lesions underwent an increase or a reduction in size, and in some cases new lesions appeared. In some patients minor degrees of atrophy became apparent over the period of the study. The value of CT in the investigation of patients with suspected MS and as a means of studying the natural history of the disease is discussed.