Antibody-dependent cell-mediated cytotoxicity of sera from cancer patients against cultured cervical cancer cell lines.

Cytotoxicity of sera from cervical cancer patients mediated by peripheral blood lymphocytes against cervical cancer cell lines was studied. Percentages of reduction of target QG-K by sera from healthy controls and cervical cancer patients were 4.7% and 32.0%, respectively. Sera from patients with pulmonary tuberculosis also exhibited antibody-dependent cell-mediated cytotoxicity (ADCC) against the cells. Especially, high degree of activity was observed in the sera from patients with stage IV and the activity decreased to the control level in recurrent cases. The titer of the sera varied against different target cell lines, and the activity was found even at 1:10(4) dilution of the sera. These activities remained after absorption of the serum with other tumor cells. Complement-dependent cytotoxic activity of the sera was not observed. The meaning of the cytotoxic activity of the sera from cervical cancer patients was discussed.


Changing form and function in one ventricle hearts.

Postnatal changes in morphology of hearts with one functioning ventricle influence physiology, natural history and physical signs. The most important and early changes relate to the acquiring of subpulmonary or subaortic stenosis. For this to occur, the basic anatomy has to be of particular arrangement; investigators should be aware of the problems and search for gradients both at rest and on Isuprel stimulation when the anatomy is appropriately disturbed. Atrio-ventricular valve regurgitation and calcification may also develop. Many changes are predictable from study of the basic pathology and knowledge of them helps to plan management at the correct time in the living patient.


Clinical use of metoclopramide test in the diagnosis of women with hyperprolactinemia.

14 women with elevated prolactin (PRL) serum levels (greater than 25 ng/ml) were given 2.5 mg of metoclopramide, by bolus intravenous injection, to evaluate its diagnosic potential as a stimulus for PRL release. Following metoclopramide injection there was a prompt increase in serum PRL in normal subjects and in patients with moderate PRL elevations associated with galactorrhea-oligomenorrhea. The women with amenorrhea-galactorrhea regardless of the presence of absence of a pituitary tumor, showed a blunted response. Metoclopramide failed to induce TSH secretion in all cases. the use of the metoclopramide test provides no additional clinical information to that furnished by the basal serum PRL concentration for the hyperprolactinemic patient.


The transsphenoidal surgical approach to the pituitary.

The operating microscope and intraoperative fluoroscopic monitoring have converted this approach from a blind procedure into a precise operation that permits selective (as well as nonselective) resection of pituitary tumors, often restoring function to normal or near-normal levels. Experience with the technique has also shed new light on the pathophysiology of acromegaly, Cushing's disease, and hyperprolactinemia.


Fc receptors for human, rabbit and pig antibodies on human eosinophils from normal persons and patients with atopic dermatitis.

The presence of Fc receptors on eosinophils from normal persons and atopic patients was investigated using a rosetting technique. Normal eosinophils were found to react with pig antibody (32.5% rosettes), rabbit antibody (46,6% rosettes) and human antibody (29.3% rosettes). Eosinophils from atopic dermatitis patients also formed rosettes with these antibodies, but the percentage of rosettes with pig antibody was significantly higher (63,5%; p less than 0.001) than that given by normal eosinophils. A similar result was found with eosinophils from patients with other atopic diseases (asthma and hay fever) suggesting a similar pattern of eosinophil alteration in all atopic patients. On the other hand, eosinophils from patients with non-atopic eczemas did not differ from those of normals.


Lymphocyte migratory pathways in adjuvant disease. II. Distribution of thoracic duct lymph-borne immunoblasts.

Evidence for enhanced extravasation of thoracic duct lymph-borne immuno-blasts within joints of rats during the onset of adjuvant disease was sought by adoptive transfer of cells radiolabeled with (125I)-iodo-2-deoxyuridine. Migratory behavior of cells from normal or adjuvant disease donors, during both inductive and overt stages of the disease process, was contrasted in normal and adjuvant disease recipients. The results provided no evidence to indicate enhanced joint-seeking properties of lymph-borne immuno-blasts obtained from adjuvant disease donors, either during the period preceding overt joint involvement or during the phase of chronic inflammation. The ability of lymph-borne cells to passively transfer the disease thus appears more likely due to systemic actions of these cells, mediators produced by them, or concomitantly passaged antigen upon patterns of inflammatory cell mobilization and/or vascular endothelial cell activation.


C142 complement activity and conglutinogen in bovine milk.

Bovine milk, derived from uninflamed glands in mid-lactation, is shown to contain the complement components of the classical pathway up to C3. Using functional tests, C142 activity and conglutinogenic activity can be demonstrated in undiluted whey. Conglutinin is rarely found in normal milk.


Immune-mediated inflammation in the lumen of the bovine mammary gland.

Two groups of cows were sensitized to ovalbumin (OA) during lactation by a subcutaneous injection of OA either in Freund's complete or incomplet adjuvant; two groups of animals injected with the respective adjuvants only served as controls. Intraluminal infusion of microgram quantities of OA in uninflamed mammary glands elicited inflammation, i.e., release of leukocytes into the milk, only in the animals previously sensitized to OA. This indicates that an antigen-specific inflammatory pathway can be established in the mammary gland by parenteral sensitization. Immune-mediated release of leukocytes into the milk could not be reproduced by infusing complement fixing. OA-anti-OA complexes into the lumen of uninflamed glands of unsensitized cows.


Immune deficit in patients with lepromatous leprosy: its nature and relation to genetic factors, spectrum, and duration of the illness.

Cell-mediated immunity or hypersensitivity to M. leprae and other unrelated antigens, such as tuberculin and dinitrochlorobenzene, was studied in 73 leprosy patients of different histopathologic types. It was found that specific as well as nonspecific anergy intensified as the disease spectrum shifted from the tuberculoid toward the lepromatous immunologic pole. Within the lepromatous group, the impairment of cellular immunity became more pronounced as the bacillary load increased. It was found that the impairment of the cell-mediated immunity towards antigens other than M. leprae became more severe as the duration of the illness increased. Late lepromin responsiveness, which is the hallmark of resistance of an individual to M. leprae, may be absent even before the onset of clinical illness. Its deficit seems to be primary and has a genetic predisposition.


Immunologic shin titration in leprosy patients and contacts.

A method of studying delayed-type hypersensitivity was developed with specific antigen in leprosy patients and contacts, measuring the dose-response curve at different lepromin concentrations. This "immunologictitration" is highly efficient for discriminating the degree of hypersensitivity reactions among the groups tested. With respect to the Fernandez reaction, the results obtained showed that there was a similar behavior in all groups studied, except in the tuberculoid group which had a more intense response, four times higher than that yielded by contacts of lepromatous patients. In the Mitsuda reaction, a similar behavior was also found among the different groups, except with respect to the reactivity intensity of contacts of lepromatous patients. Here it was demonstrated that this group had a significant depression in response to M. leprae antigen when compared with that from the other groups, independent of the degree of consanguinity or closeness to bacilliferous cases. In order to explain this immunosuppression in contacts of lepromatous patients, a hypothesis is proposed. It is suggested that changes could occur in M. leprae derived from lepromatous patients, diminishing their capacity to produce an adequate immune response.


The cellular basis for extremity bone loss in leprosy.

Osteoclasts and osteolytic osteocytes have been observed in the majority of 60 samples of bone taken from five patients with lepromatous or tuberculoid leprosy. These results are interpreted to mean that bone loss in patients with leprosy is an acceleration of a normal cellular process and not the result of avascular necrosis. The acceleration of bone resorption could be due to local release of products from M. leprae or host cells, a hypothesis testable by organ culture methods. The presence of lymphocytes and mononuclear cells in bone samples in this and previous studies is discussed with respect to recent evidence of a role for lymphoid cells in bone resorption.


Pathologic changes in testis and epididymis of infertile leprotic males.

Thirty-two cases of male infertility in patients having leprosy were studied. One case was oligospermic and the remaining 31 cases were azoospermic. Pathologic changes in the testis and epididymis are described and illustrated. An important observation was the presence of obstruction in the tail of the epididymis in five cases and this obstruction was undoubtedly the cause of sterility in these five cases as the head of the epididymis was full of sperm and testicular biopsy was more or less normal. In the remaining 27 cases, the cause of sterility was testicular affection with fibrosis and hyalinization of the seminiferous tubules in most of the cases.


Reversal reaction: the prevention of permanent nerve damage. Comparison of short and long-term steroid treatment.

Borderline leprosy patients with a reversal reaction were studied and short-term steroid treatment compared with prolonged steroid treatment using voluntary muscle testing (VMT) to assess the results. Prolonged steroid treatment was shown to be superior to short-term treatment and free of harmful effects. It is concluded that with the described antireaction treatment, permanent nerve damage can be prevented, provided that the reversal reaction is detected in time (within 3-4 months).


Actin filaments in cells of human trabecular meshwork and Schlemm's canal.

With subfragment-one of myosin used as the histochemical marker, actin filament distribution was mapped in cells of the aqueous outflow pathway. In uveal, corneal-scleral and juxtacanalicular meshwork cells, bundles of actin filaments were present along the basal cytoplasm. Some of these bundles terminated at adhesion plaques. Juxtacanalicular meshwork cells contained, in addition to bundles, randomly oriented actin filaments at the end of cell extensions. Giant vacuoles in the inner wall of Schlemm's canal did not have actin filaments associated with their membranes; there were, however, intermediate filaments present along the membrane. Bundles of actin filaments were also found within the cells of both inner and external walls of Schlemm's canal. Cells of both the meshwork and inner wall of Schlemm's canal had actin filaments extending out into the cytoplasm from cell junctions. In all areas of the meshwork and especially in the area external to Schlemm's canal, cells were observed which had a cytoplasm, very rich in actin filaments. These cells had characteristics common to smooth muscle cells. The actin filaments of cells of the aqueous outflow pathway could have any or all of several functions. Bundles of filaments in the meshwork could contract to lift and separate trabecular sheets and/or, through their association with adhesion plaques, they could stabilize cells on their collagen substrate, thus acting as cytoskeletal struts. Randomly oriented actin filaments, noted particularly in cells of the juxtacanalicular meshwork, may play a role in phagocytosis. Actin filaments found in association with junctions may be important structures for maintaining cell-to-cell contacts. Lack of actin filaments around giant vacuoles in Schlemm's canal indicates that they do not play a role in shuttling aqueous across the endothelium of the canal. The significance of "actin-rich" cells in the meshwork and those external to Schlemm's canal is unknown.


Morphologic classification of inflammatory, nonspecific, and proliferative lesions of the urinary bladder of mice.

A morphologic classification of inflammatory, nonspecific, and proliferative lesions of the urinary bladder of mice has been developed. The system was developed over a period of several years in order to tabulate and summarize the lesions for review. The classification has successfully met the needs of the National Center for Toxicological Research and has also provided useful information in understanding the biologic significance of urothelial lesions in mice.


Serum sex hormone binding globulin and testosterone binding after estradiol administration, castration, and their combination in men with prostatic carcinoma.

We measured serum sex hormone binding globulin (SHBG) binding capacity, the index of testosterone binding to SHRG, and the serum concentrations of testosterone, 5 alpha-dihydrotestosterone, and estradiol in 16 patients treated for advanced prostatic carcinoma in order to evaluate the effectiveness of various therapeutic regimes in reducing total and biologically active androgen in blood. Polyestradiol phosphate (Estradurin, 80 mg im as a monthly injection) treatment alone is not as efficient as castration in reducing serum testosterone and 5 alpha-dihydrotestosterone. There was no clear difference between the castration and combination treatment (castration followed by polyestradiol phosphate administration) groups in this respect. It is apparent that Estradurin treatment alone and in combination with castration results in small but significant increases in SHBG binding capacity, whereas this parameter did not alter after castration alone. All three forms of treatment resulted in relatively similar significant increases in the index of testosterone binding to SHBG. The rather mild effect of Estradurin on the parameters measured may be attributable to the binding of the exogenous estradiol to SHBG, which thus greatly reduces its biologic activity. We concluded that castration is clearly more effective in reducing the amount of biologically active testosterone than Estradurin and the combination of these treatments has little influence on further reducing total or biologically active circulating testosterone.


Coexistence of hypertrophic obstructive cardiomyopathy and mitral annular calcification: proposed etiologic relationship.

A case of combined hypertrophic obstructive cardiomyopathy and mitral annular calcification is reported. The characteristic features of both entities were clearly demonstrated by thorough noninvasive examinations. It is proposed that the association of the two conditions is not coincidental but that mitral annular calcification, by narrowing of the left ventricular outflow tract, can result in the development of hypertrophic obstructive cardiomyopathy. Mitral annular calcification should possibly be added to the other causes of pressure overload of the left ventricle--such as hypertension and valvular or discrete subvalvular aortic stenosis--as a potential etiology of secondary hypertrophic obstructive cardiomyopathy.


The role of allergy in chronic pulmonary disease of horses.

Twenty-five horses with chronic pulmonary disease were skin tested with allergenic extracts of 24 molds, 4 thermophilic actinomyces, barn dust, hay dust, soya-bean mill dust, and grain mill dust. The results were compared with those obtained on 25 normal horses. Between the 2 groups of horses, there was a highly significant difference in positive skin test results at 30 minutes and 4 hours.


Formaldehyde dehydrogenase from Pseudomonas putida. Purification and some properties.

Formaldehyde dehydrogenase was isolated and purified in an overall yield of 12% from cell-free extract of Pseudomonas putida C-83 by chromatographies on columns of DEAE-cellulose, DEAE-Sephadex A-50, and hydroxyapatite. The purified enzyme was homogeneous as judged by disc gel electrophoresis and was most active at pH 7.8 using formaldehyde as a substrate. The enzyme was also active toward acetaldehyde, propionaldehyde, glyoxal, and pyruvaldehyde, though the reaction rates were low. The enzyme was NAD+-linked but did not require the external addition of glutathione, in contrast with the usual formaldehyde dehydrogenase from liver mitochondria, baker's yeast, and some bacteria. The enzyme was markedly inhibited by Ni2+, Pd2+, Hg2+, p-chloromercuribenzoate, and phenylmethanesulfonyl fluoride. The molecular weight of the enzyme was estimated to be 150,000 by the gel filtration method, and analysis by SDS-polyacrylamide gel electrophoresis indicated that the enzyme was composed of two subunit monomers. Kinetic analysis gave Km values of 67 microM for formaldehyde and 56 microM for NAD+, and suggested that the reaction proceeds by a "Ping-pong" mechanism. The enzyme catalyzed the oxidation of formaldehyde accompanied by the stoichiometric reduction of NAD+, but no reverse reaction was observed.


Number of anti-troponin striations along the thin filament of chick embryonic breast muscle.

Anti-troponin formed 25 to 29 striations with a period of 38 nm along the whole length of thin filaments in chick embryonic breast muscle, in contrast with the uniform formation of 24 striations in adult muscle. This indicates that the thin filament in embryonic breast muscle is longer than that in the adult muscle.


Nerve growth factor receptors. Characterization of two distinct classes of binding sites on chick embryo sensory ganglia cells.

Steady state and kinetic studies on the binding of 125I-beta nerve growth factor (NGF) to single cells from sensory ganglia of 8-day-old chick embryos show two distinct, saturable binding sites with dissociation constants of Kd(I) = 2.3 X 10(-11) M and Kd(II) = 1.7 X 10(-9) M. The difference in the affinities is due to different rate constants of dissociation (k-1(I) = 10(-3) s-1, k-1(II) = 2 X 10(-1 s-1). The association to both sites is apparently diffusion controlled (k+1(I) = 4.8 X 10(7) M-1s-1, k+2(II) = 10(7) to 10(8) M-1s-1). The binding of betaNGF to both sites is specific, since none of a number of hormones or proteins tested compete for the binding of 125I-betaNGF to either of those two sites. The heterogeneity of the binding of 125I-betaNGF is not due to heterogeneity of the 125I-betaNGF preparation nor to a negatively cooperative binding. In experiments where the dissociation of 125I-betaNGF is induced by the addition of saturating amounts of unlabeled betaNGF, the ratio of the 125I-betaNGF released with either of the two dissociation rate constants is solely dependent on the occupancy of the two sites before dissociation is started and is independent of the total occupancy of the sites during dissociation. The rate of dissociation of 125I-betaNGF from the higher affinity binding site I is accelerated by unlabeled betaNGF under conditions where the occupancy is both increased and decreased. Although the dissociation characteristics of 125I-beta NGF change with increasing times of exposure of the cells to the ligand, and 125I-beta NGF is degraded after it binds to the cells, these secondary processes do not interfere with the analysis of the binding data. At the lowest concentration of 125I-beta NGF used for the analysis less than 10% of the 125I-beta NGF is degraded. Both kinetic and steady state binding data reveal the two NGF binding sites at 2 degrees C as well as at 37 degrees C.


Cytoplasmic and nuclear progestin receptors in human myometrium during the menstrual cycle and in pregnancy at term.

Exchange assays have been developed for the determination of the total progestin in receptor sites (unoccupied and occupied with endogenous hormone) in the cytosol and nuclei of human myometrium using radiolabeled R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. These assays have been applied to the measurement of cytosol and nuclear progestin receptor sites in the myometrium during the menstrual cycle and in pregnancy at term. Both the cytosol receptor levels as well as the sum of cytosol and nuclear receptor levels were highest during the proliferative phase of the cycle, dropped moderately but significantly in the secretory phase, and decreased markedly in pregnancy at term. Despite the marked drop in cytosol receptor levels, nuclear receptor levels in pregnancy at term were similar to those observed in the proliferative or secretory phase. In addition, the fraction of the total cellular receptor that was associated with the nucleus increased from 5.5% in the proliferative phase to 60% in pregnancy at term. The decrease in cytosol progestin receptor concentration as well as the relative increase in nuclear localization of the receptor in human myometrium in pregnancy at term may be related to the high circulating progesterone levels.


Association of HLA-DRw2 with autoimmune thrombocytopenic purpura.

Peripheral blood lymphocytes from 38 patients with autoimmune thrombocytopenic purpura (AITP) were tested for HLA-A, -B, and -C alloantigens. Isolated B lymphocytes from 20 of these patients were tested for HLA-DRw (Ia) alloantigens. The profile of HLA alloantigens in the patients with AITP was significantly different from that of a matched control population. The most significant finding was the presence of the HLA-DRw2 alloantigen in 75% of patients as compared with 23% in the control population, P less than 0.001, relative risk 10.0 (A relative risk of 1 would indicate no association between the presence of the antigen and the disease.) The co-occurrence of either A3 and B7 (known to be in linkage disequilibrium with DRw2) or A26 and Bw38 was significantly increased as compared with the control population (P less than 0.001). Of the patients positive for DRw2, 47% had the association A26 and Bw38 as compared with the control population association incidence of 21% (P less than 0.1). Thus, in the patient population, A26-Bw38 appears to be a haplotype that is in linkage disequilibrium with DRw2 (as presumably is the case with A3-B7). These data indicate that a predisposition to AITP is inherited with a DRw2 gene of the major histocompatibility system.


Bovine antigens and the formation of circulating immune complexes in selective immunoglobulin A deficiency.

We have shown that levels of circulating immune complexes are closely associated with the presence of precipitating antibodies to bovine milk proteins in individuals with selective immunoglobin (Ig)A deficiency. To test whether milk proteins are involved in immune complex formation, sera of seven IgA-deficient individuals were studied for the appearance of complexes after milk ingestion. In three of the seven, an initial fall in the level of complexes was followed by an increasing value, which peaked at 120-150 min. In another three, there was a tendency toward the formation of two peaks of complexes, the first at 30-60 min and the second at 120-150 min after drinking milk. One subject, who had had recent treatment for two separate neoplasms, had a steady level of complexes that did not change during the course of this test. After drinking milk, the molecular weight of the complexes found in the sera of one individual at the start of the milk test fell from >19S to 7-11S, and in vitro additions of progressively increasing amounts of a mixture of milk proteins or bovine gamma globulin, to sera that contained complexes produced a progressive reduction in the level of complexes detectable. We conclude that the circulating immune complexes found in some patients who lack IgA contain bovine milk proteins and that periodic fluctuation of the molecular weight of such complexes, depending upon antigen ingestion, appears likely. It remains uncertain what effect the chronic circulation of complexes has upon the clinical state of this group of patients.


Effects of differential interference with postnatal cerebellar neurogenesis on motor performance, activity level, and maze learning of rats: a developmental study.

The region of the cerebellum was X-irradiated in infant rats with selected exposure schedules designed to produce animals in which the cerebellar cortex was (a) essentially normal except for agenesis of late forming granule cells with axons situated in the uppermost molecular layer (12--15X), (b) lacking in stellate cells, with a severe reduction in granule cells with axons in the upper molecular layer (8--15X), (c) morphologically disorganized but had only intermediate cell agenesis (4--5X), or (d) disorganized and devoid of practically all postnatally forming interneurons (4--15X). In the first two experiments young adults had to traverse rotating rods that differed in texture and types of obstacles. The 8--15X animals showed no deficits on any of the rods tested. The third study dealt with spontaneous motor performance in the open field at three ages. The 4--5X and 4--15X animals were hypoactive as infants and young adults; this was attributed to their motor deficits. The 8--15X and 12--15X animals were hyperactive in the open field as young adults. The fourth experiment examined intra- and/or intersession habituation. No group differences were found in habituation patterns. In the fifth experiment, using activity wheels, the 4--15X group was hypoactive, and the 8--15X and 12--15X groups were hyperactive as young adults. In the sixth experiment young adults were tested for learning performance in a multiple-unit water maze. The 4--15X group was deficient on single alternation; the 4--5X and 12--15X groups on double alternation. The seventh experiment shed some light on the single alternation deficit of the 4--15X group; only these animals failed to alternate spontaneously in a nonaversive situation. In conclusion, these behavioral results, combined with those of recent morphological investigations, suggest that the cerebellar cortex is hierarchically organized: The basal domain of Purkinje cells and the lower molecular layer are implicated in the coordination of movements; the apical domain of Purkinje cells and the upper molecular layer, in the coordination of actions.


Effect of reconstitution on vitamins A and C content of whey-soy drink mix.

The nutritive quality of a whey-soy drink mix was determined by measuring the retention of added vitamins A and C after the product was reconstituted in boiling water. In one study the mix was mixed in boiling water for up to 5 min and analyzed for vitamin content after each 1 min heating interval. The reconstituted product lost approximately 50% of the original vitamin content after being boiled for 1 min. Little further decrease in vitamin content was observed after several additional minutes of boiling until the 5-min interval when both vitamins dropped to about 35% of original amounts. In another study the mix was reconstituted by mixing the powder in boiling water for 20 s, then allowing the mix to stand at room temperature with no additional heating. This mixture decreased slightly in vitamin content when analyzed at 5 min intervals for up to 25 nin. For maximum vitamin retention whey-soy drink mix should be reconstituted by blending it in boiling water for about .5 min, then allowing the mixture to stand at room temperature before serving.


Microwave cookery of beef patties: browning methods.

Four microwave cooking/browning methods were studied to determine their effects on energy consumption, cooking time, cooking losses, and sensory quality. Ground beef patties were cooked by the following methods: Microwave and browning element, microwave with browning grill, microwave and broiler, combination range oven, microwave only, and conventional range oven. Browning plus microwave cooking increased cooking time by 51 to 71 per cent and energy consumption by 53 to 87 per cent, depending on the method. The microwave-with-browning-grill method showed an over-all advantage over other browning methods. The combination range oven was the least efficient.


Hospital cook/chill foodservices systems. Effect of end temperature of initial cooking on yield and moisture of beef loaf during processing.

Hospital cook/chill foodservice systems are characterized by two heat processes: Intial cooking and microwave heating for service. End temperature (ET) of initial cooking for beef loaf in actual and in simulated cook/chill systems has been reported to vary from 123 degrees F. (51 degrees C.) to 170 degrees F. (77 degrees C.). After preparation, beef loaf (5 kg.) was initially uncooked or initially cooked to ETs of 113 degrees, 140 degrees, 167 degrees, or 194 degrees F. (45 degrees, 60 degrees, 75 degrees, or 90 degrees C.), stored chilled (24 hr. at 42 degrees F. [6 degrees C]), and portions (100 gm.) were microwave heated to 165 degrees F. (74 degrees C.) or above. Multiple comparison t-test on data for yield and for moisture content of beef loaf indicated that increasing the ET of initial cooking significantly (P of less than or equal to 0.01) decreased yield and moisture content of beef loaf after initial cooking and after microwave heating for service.


Changes in corneal curvature associated with contact lens wear.

Brief answers are given to 5 complex questions about the corneal curvature of contact lens wearers. Short-term (circadian) and long-term (withdrawal) changes are significant time variables which are often overlooked.


The effect of federal drug law on the incidence of drug abuse.

The Controlled Substances Act (CSA) is the prevailing "drug abuse" control statute in the United States. Its manifest objective is to prevent or reduce drug use's "substantial and detrimental effect on the health and general welfare of the American people." Evaluating CSA's effectiveness in 1975, a Domestic Council Task Force reported in a White Paper to President Gerald Ford that its control measures do "reduce abuse of dangerous drugs." The Task Force's evidence was based upon a before-and-after analysis of the frequency of "drug abuse episodes" reported to the nation's Drug Abuse Warning Network (DAWN). This research note challenges the conclusion of the Domestic Council Task Force, subjecting the DAWN evidence to more rigorous scrutiny, and concluding that we do not presently have adequate materials to assess whether CSA meets its health objectives. The context of this conclusion is that of drug control, but its implications apply to health policy and health policy evaluation in general.


Effect of gamma-irradiation on the survival and development of the infective larvae of the hookworm, Gaigeria pachyscelis.

Irradiation of the infective larvae of Gaigeria pachyscelis Railliet and Henry, 1910 with gamma rays upto 160 Kr had no significant effect on the in vitro survival of these larvae for a period of 49 days, maintained either at room temperature (32.2--39.4 degrees C) or at 4 degrees C. However, the behaviour of the irradiated larvae in the lamb host was much changed, as shown by a marked reduction in the worm establishment and the development of stunted and sterile worms from these larvae. As the level of irradiation increased, there was a corresponding decrease in the subsequent worm establishment. It was found that male larvae are more sensitive to the effects of irradiation than female ones, particularly at higher levels.


The use of gamma-radiation-attenuated larvae of Gaigeria pachyscelis Railliet and Henry, 1910, for vaccination in lambs.

The results of vaccination trial in lambs with gamma-irradiated infective larvae of Gaigeria pachyscelis are described. A single percutaneous (P/C) vaccination of lambs with 2000 infective larvae irradiated at 40 Kr induced the development of resistance. The vaccinated lambs successfully resisted a lethal challenge infection of 5000 non-irradiated larvae 3 months later. In the vaccinated lambs, the manifestations of resistance were shown by marked reduction in the worm establishment, development of retarded and functionally sterile worms and absence of clinical signs of hookworm disease after the challenge infection.


Partial purification and characterization of Schistosoma mansoni soluble egg antigen with Con A-Sepharose chromatography.

A crude preparation of Schistosoma mansoni soluble egg antigen (SEA) was subjected to affinity chromatography with concanavalin A (Con A) bound to Sepharose 4B. The resulting Con A fractions (bound and unbound) were characterized with sodium dodecyl sulfate (SDS) gel electrophoresis, immunoelectrophoresis, immunodiffusion, and lymphocyte blastogenesis techniques. In the fraction that did not bind to Con A there were at least two distinct antigens, and there were also at least two distinct antigens in the fractions that did bind to Con A. With SDS polyacrylamide gel electrophoresis, at least 20 distinct protein bands (Coomassie blue staining) and three glycoprotein bands (PAS reactive) were present in the unbound fractions from Con A chromatography. The bound fractions separated into at least six distinct glycoproteins with SDS electrophoresis. Although both the bound and unbound fractions contained precipitating antigens, only the bound fractions were capable of eliciting lymphocyte blastogenic responses.


Immunoaffinity purification of Schistosoma mansoni soluble egg antigens.

Schistosoma mansoni egg antigens were purified from a heterogeneous mixture of soluble egg antigens (crude SEA) with an immunoaffinity column that consisted of the specific anti-SEA antibodies contained in 16-week S. mansoni-infected mouse serum bound to Sepharose 4B. On sodium dodecyl sulfate (SDS) gel electrophoresis, the purified antigen fraction yielded at least eight bands staining with Coomassie blue and at least five bands staining with Coomaisse blue and at least five bands reacting with periodic acid-Schiff (PAS). All of the proteins in the antigenic fraction appear to contain carbohydrate residues. Upon immunoelectrophoresis the antigen yielded four precipitin arcs. The antigenic fraction isolated by means of the immunoaffinity column was then compared to various fractions obtained from concanavalin A (Con A) chromatography of SEA. The results of Ouchterlony immunodiffusion and immunoelectrophoresis indicate that the antigenic fraction isolated by immunoaffinity purification of SEA contains the major antigens found in the fractions obtained from Con A chromatography of SEA. The results of SDS gel electrophoresis indicate that the major PAS-reacting bands of the antigenic fraction isolated by immunoaffinity purification are found in the 3rd peak (bound fraction) resulting from Con A chromatography of SEA, whereas the major Coomaisse blue-staining band in the isolated antigenic fraction is found in the 2nd peak (unbound fraction) from Con A chromatography of SEA.


Immunoregulation in experimental schistosomiasis: in vitro induction and assay of spleen cell suppressor activity.

Spleen cells from normal CBA/J mice or mice infected with Schistosoma mansoni were exposed for 48 to 72 hr to either concanavalin A (Con A), soluble egg antigen (SEA), or soluble worm antigenic preparation (SWAP), treated with mitomycin C to prevent further DNA synthesis, and admixed with either normal or sensitized syngeneic spleen cells exposed to a concentration gradient of phytohemagglutinin (PHA) or SEA, respectively. Both nonspecific (by Con A) and "antigen-specific" (by SEA and SWAP in infected mice only) induction of suppression was observed when using PHA-induced blastogenesis as the final assay. The number of mice with inducible splenic suppressive activity and the degree of PHA suppression induced by exposure to SEA appeared to decline between 8 and 20 weeks of infection. In contrast, when the response of spleen cells from mice infected for 8 weeks to SEA served as the final assay, strong suppressive activity was induced from the spleen cells of all chronically infected mice (20 weeks of infection). This model permits parallel analysis of the induction of suppressor activity by nonspecific and schistosome antigen-specific signals during the course of this chronic, immunoregulated condition, schistosomiasis mansoni.


Antibody-dependent cell-mediated cytotoxicity against cells infected with respiratory syncytial virus: characterization of in vitro and in vivo properties.

An in vitro 51Cr release assay for human antibody-dependent cell-mediated cytotoxicity (ADCC) against HeLa cells infected with respiratory syncytial virus (RSV) has been characterized by using leukophoresed and adherent cell-depleted adult lymphocytes. Lymphoytes from RSV seronegative children were also competent as effector cells. Sera from children with :1) primary and recurrent natural RSV infections, or 2) live attenuated RSV vaccine infection were examined to characterize the behavior of ADCC antibody in vivo. After natural RSV infection ADCC antibody rose and fell more rapidly than neutralizing antibody. In two children undergoing primary RSV infection with attenuated vaccine, neutralizing antibody was formed in the absence of detectable ADCC antibody. The nonparallel behavior of ADCC and neutralizing antibodies suggests the heterogeneity of either the antigen involved or the mechanism of antibody production in the two antibody systems.


Relation between decreased mental efficiency in mice and the presence of cerebral lesions after experimental encephalitis caused by yellow fever virus.

The behavior of 1,072 mice that had recovered from encephalitic infection with intracerebrally injected yellow fever virus 17D and of 216 normal mice was tested in a maze and on a horizontal rod rotating around its axle. Infected animals needed more time (average, 8.90 min) to find their food in a maze than did normal animals (average, 4.37 min). Infected mice were able to stay on the rotating rod for a shorter time (average, 6.4 seconds) than were normal animals (average, 9.0 seconds). The correlation between the concentration of virus injected and the performance of the mice was confirmed by the extent of lesions found by histologic study: animals that had anatomic lesions after surviving encephalitic infection showed abnormal behavior.


Oxygen consumption in the lizard genus Lacerta in relation to diel variation, maximum activity and body weight.

1. Diel recordings of VO2 under a 12 h Light/12 h Dark regime, constant light or constant dark reveal a strong endogenous diurnal rhythm in L. sicula. L. vivipara show an exogeneous rhythm with activity occurring only in the light whilst L. viridis have a weak endogeneous rhythm that is modified by behavioural factors and inhibited by dark. 2. Standard (or basal) VO2 can only be attained after several hours in an 'indifferent' environment, shielded from extraneous stimuli. Measurements must be at night (light or dark) for unrestrained L. sicula and in the dark (day or night, restrained or unrestrained) for L. vivipara and L. viridis. Intrageneric std VO2 (ml h-1 STPD) = 0.328 W0.76 or 0.216 W0.77 for 1- or 3-days starvation at 30 degrees C for 0.2 to 34 g Lacerta. 3. Intrageneric maximum VO2 (determined for 30 to 60 s of provoked activity during the day) = 2.66 W0.747 at 30 degrees C for 1-days starvation. 4. Respiratory exchange ratio, R = 0.75 or 0.85 for std VO2 after 1 or 3 days starvation and 0.95 and 1.45 for mean daily and max VO2. High R values are considered a result of anaerobic metabolism and hyperventilation during activity.


Further evidence in support of a role for hamster sperm hydrolytic enzymes in the acrosome reaction.

The effects of trypsin inhibitors and phospholipase inhibitors on the acrosome reaction of washed cauda epididymal sperm of golden hamsters were studied using two different incubation systems. One incubation system, a non-synchronous acrosome reaction inducing system, included the use of a highly purified BSA and a protein-free motility factor preparation from hamster adrenal gland. The other system was a relatively synchronous acrosome reaction-inducing-system utilizing the calcium ionophore A23187. Acrosome reactions were inhibited by three low molecular weight synthetic trypsin inhibitors, benzamidine, NPGB and TLCK, when they were added five minutes prior to the initial occurrence of acrosome reactions in the non-synchronous system or five minutes prior to induction of acrosome reactions by A23187 in the synchronous system. Two phospholipase A inhibitors, p-bromophenacyl bromide and mepacrine, were also effective in inhibiting hamster sperm acrosome reactions in both incubation systems. TPCK, an inhibitor of several non-trypsin-like proteases, indomethacin, a prostaglandin synthetase inhibitor, and soybean trypsin inhibitor, a large molecular weight polypeptide, did not inhibit acrosome reactions. The inhibition of those acrosome reactions induced by A23187 provides further indirect evidence that the effective inhibitors were functioning at a site within the sperm. The overall results provide: (1) further support for our earlier work suggesting the involvement of an internal trypsin-like enzyme (presumably acrosin) rather than an exogenous trypsin-like enzyme in the hamster sperm acrosome reaction and (2) the first evidence suggesting the possibility that a sperm phospholipase may also be involved in the mammalian acrosome reaction.


Human megakaryocytes. I. Characterization of the membrane and cytoplasmic components of isolated marrow megakaryocytes.

Human marrow megakaryocytes have been isolated with high purity and yield by processing marrow cells sequentially through density centrifugation and velocity sedimentation. Analysis of the isolated cells for various platelet-associated components by immunofluorescence demonstrated that fibrinogen, plasma factor VIII antigen (factor VIII:AGN) platelet myosin, platelet glycoproteins I and III are present on the membrane and in the cytoplasm of over 90% of marrow megakaryocytes. Parallel studies of human and mouse megakaryocytes and platelets for IgG receptor (FcR), complement receptor type one (CR1) (C3b receptor), complement receptor type two (CR2) (C3d receptor), and Ia antigen by fluorescence and (or) rosette formation methods were performed. FcR were present on most human megakaryocytes and platelets. The Ia antigen was detected on a proportion (10-15%) of human megakaryocytes but it was undetectable on human platelets. CR1 was found on 20-40% of mouse megakaryocytes and also on a proportion of mouse platelets. These differentiation markers may be of use in monitoring megakaryocyte maturation.


Ionic mechanism of the fertilization potential of the marine worm, Urechis caupo (Echiura).

Microelectrode and tracer flux studies of the Urechis egg during fertilization have shown: (a) insemination causes a fertilization potential; the membrane potential rises from an initial level of -33 +/- 6 mV to a peak at +51 +/- 6 mV (n = 16), falls to a plateau of about +30 mV, then returns to the original resting potential 9 +/- 1 min (n - 10) later; (b) the fertilization potential results from an increase in Na+ permeability, which is amplified during the first 15 s by a Ca++ action potential; (c) the maximum amplitude of the fertilization potential, excluding the first 15 s, changes by 51 mV for a 10-fold change in external [Na+]; (d) in the 10 min period after insemination, both Na+ and Ca++ influxes increase relative to unfertilized egg values by factors of 17 +/- 7 (n = 6) and 34 +/- 14 (n = 4), respectively; the absolute magnitude of the Na+ influx is 16 +/- 6 times larger than that of Ca++; (e) in the absence of sperm these same electrical and ionic events are elicited by trypsin; thus, the ion channels responsible must preexist in the  unfertilized egg membrane; (f) increased Na+ influx under conditions of experimentally induced polyspermy indicates that during normal monospermic fertilization, only a fraction of available Na+ channels are opened; we conclude that these channels are sperm-gated; (g) Ca++ influx at fertilization is primarily via the membrane potential-gated channel, because kinetics are appropriate, and influx depends on potential in solutions of varying [Na+], but is independent of number of sperm incorporations in normal sea water.


Familial Y/22 translocation in a woman.

A phenotypically normal 35-year-old woman who had a malformed fetus was found to have a Y/22 translocation. One brother as well as a sister and her three children also have the Y/22 chromosome while another sister lacks it. The problem raised by the presence of this translocated chromosome for genetic counseling, especially for prenatal diagnosis, is emphasized.


Endocrine function and diagnostic problems in a prepubertal case of 48,XXYY.

A five-year-old 48,XXYY boy with normal external genitalia, slight bone anomalies and mild mental retardation is described. An endocrine examination revealed normal values with the possible exception of a slight increase of the LH values and the LH response to LH-RH stimulation.


Primary biochemical defect in copper metabolism in mice with a recessive X-linked mutation analogous to Menkes' disease in man.

The defect in Menkes' disease in man is identical to that in Brindled mice. The defect manifests itself in a accumulation of copper in some tissues, such as renal, intestinal (mucosa and muscle), pancreatic, osseous, muscular, and dermal. Hence a fatal copper deficiency results in other tissues (e.g., hepatic). The copper transport through the intestine is impaired and copper, which circumvents the block in the copper resorption, is irreversibly trapped in the above-mentioned, copper accumulating tissues where it is bound to a cytoplasmatic protein with molecular weight 10,000 daltons, probably the primary cytoplasmatic copper transporting protein. This protein shows a Cu-S absorption band at 250 nm, and the copper:protein ratio is increased. Such copper rich protein was found neither in the kidneys of the unaffected mice nor in the liver of the mice that do have the defect. Three models of the primary defect in Menkes disease are proposed.


Blood-brain barrier dysfunction to peroxidase after air embolism, aggravated by acute ethanol intoxication.

Ethanol-intoxicated and non-intoxicated rats were injected with horseradish peroxidase and Evan's blue-labelled albumin and given a small air embolus in the right common carotid artery after ligation of the external carotid branch. In both ethanol-intoxicated and non-intoxicated rats, some endothelial cells, mainly in arteries and arterioles, showed a diffuse distribution of peroxidase in the cytoplasm. In some arterioles with a diffuse endothelial distribution of peroxidase there was a detachment of endothelial cells from the vessel wall, with an exposure of the adluminal basement membrane to blood elements. This endothelial detachment was mainly observed in ethanol-intoxicated rats. The vascular basement membranes underlying detached endothelial cells contained peroxidase, both in ethanol-intoxicated and in non-intoxicated rats. There was a considerable leakage of peroxidase via endothelial pinocytotic vesicles into the vascular basement membranes, mainly in arterioles, but also in capillaries and venules of the embolised hemisphere. This transendothelial pinocytotic transport of peroxidase was more prominent in ethanol-intoxicated than in non-intoxicated rats.


Occlusion of cerebral artery due to metastasis of chorioepithelioma. Case report.

A case of cerebral metastasis of chorioepithelioma with an occlusion of the angular artery is presented. The occlusion was verified angiographically, surgically, and microscopically.


Methylmalonic acid metabolism of germfree and conventional vitamin B-12 deprived rats fed precursors of methylmalonate.

Experiments using germfree (GF), ex-germfree (XGF) and conventional (CONV) rats were conducted to study the relationship of intestinal microorganisms to vitamin B-12 (B-12) status and to methylmalonic acid (MMA) excretion of the host animal, since B-12 depleted GF rats have been found to excrete less than expected level of urinary MMA. The possibility that the GF rat lacks sufficient precursor of MMA was tested by feeding GF, XGF and CONY rats diets low or high in MMA precursors and examining urinary excretion of MMA and formiminoglutamic acid at intervals. The possibility that the GF rat may metabolize propionate and MMA differently from the CONV rat was examined by a MMA loading-recovery study and a CO2 collection study after [14C]propionate injection. Plasma and tissue B-12 levels were determined at the beginning and the end of the study. Results indicate that 1) lack of sufficient precursor of MMA is partly responsible for the failure of GF, B-12 deficient rat to excrete MMA, 2) GF and CONV rats metabolize propionate and MMA by the same pathways and 3) the presence of intestinal microorganism depletes the body B-12 store of the rat.


Demonstration of a novel molecular species in chick embryo brain: cellular retinol-binding protein, F-type.

By sucrose density gradient sedimentation analysis, a cytosol component of small molecular size which bound 3H-retinoic acid was detected in the chick embryo brain, exhibiting a peak on day 14 (7 days before hatching). In general, cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) have been distinguished by showing binding specificity for retinol or retinoic acid, respectively. However, the component found in embryo brain cytosol exhibited binding affinity for both retinol and retinoic acid, being similar in less ligand-specificity to CRBP (F) which was originally recognized in fish eye cytosol. Moreover, the component also showed a lack of binding affinity for prealbumin (PA), excluding the possibility that chicken plasma RBP was contaminated in the cytosol. These findings strongly suggest that a distinct molecular species of cellular binding protein for vitamin A exists in the brain cytosol of a developing chick embryo.


Hyperlysinemia with saccharopinuria due to combined lysine-ketoglutarate reductase and saccharopine dehydrogenase deficiencies presenting as cystinuria.

A 7-year-old boy with speech delay, hyperactive behavior, and minor neurologic abnormalities had been found in the past to have "intermittent cystinuria." A more detailed investigation revealed hyperlysinemia and hyperlysinuria, with lesser increases in urinary excretion of arginine and cystine. The plasma and urine abnormalities increased on a diet of 3 gm of protein/kg body weight/day. Saccharopine, a normal metabolite of lysine not found in the body fluids of normal people, was present in plasma, cerebrospinal fluid, and urine of the patient. Lysine-ketoglutarate reductase and saccharopine dehydrogenase activities were not detectable in extracts of cultured skin fibroblasts. Re-examination of the urine of previously studied cases of this double enzyme deficiency suggests that saccharopinuria of variable degree is the rule and not the exception.


Comparative utilization of pyruvate by Brugia pahangi, Dipetalonema viteae, and Litomosoides carinii.

The metabolism of pyruvate by the adult filarial parasites Brugia pahangi, Dipetalonema viteae, and Litomosoides carinii has been compared. Istopic carbon-balance studies indicate the presence of significant pyruvate dehydrogenase activity in L. carinii but little or no activity in either B. pahangi or D. viteae. In all 3 helminths, the quantities of pyruvate that were completely oxidized to CO2 and water were very small. The activities of some of the tricarboxylic acid cycle enzymes of B. pahangi also were determined. In particular, a relatively low level of isocitrate dehydrogenase was noted in the mitochondria of B. pahangi. It is suggested that the tricarboxylic acid energy generating pathway is of doubtful importance as an energy yielding pathway in any of these parasites.


Development of Dipetalonema gracile and D. caudispina to the infective stage in Culicoides hollensis.

The microfilariae of 2 species of Dipetalonema (i.e., D. gracile and D. caudispina), common parasites of South American monkeys, develop to the third (infective) stage in the biting midge, Culicoides hollensis. Development of both species occurs in the abdominal fat body; D. gracile requires 13 days and D. caudispina 9 days. Despite similarities in the patterns of development of both species, the third-stage larvae of each is morphologically distinct.


Histopathology of hepatic and pulmonary granulomata experimentally induced with eggs of Schistosoma mansoni.

Hepatic granulomata were experimentally induced in previously unexposed white mice, albino rats and golden hamsters by injecting viable exogenous eggs of Schistosoma mansoni via the mesenterico-portal system. Histopathologic studies of livers of these animals showed that the lesions were similar to those in infections resulting form exposure to cercariae as occurs naturally in Mansonian schistosomiasis. Comparable observations made of the lungs of animals that had received egg injections via their tail veins, showed striking differences with respect to timing of the occurrence of various histopathologic stages, mean size of granulomata, cellular composition and pathologic manifestations.


Additive physical dependence: evidence for a common mechanism in alcohol dependence.

In previous studies we demonstrated that mice could be made physically dependent with 3 or 6 days inhalation of t-butanol or ethanol vapor. In the present experiments the mice were treated with 3 days of t-butanol followed immediately by 3 days of ethanol at equipotent concentrations, for a total of 6 days continuous exposure. Other mice were given these alcohols in the reverse order. Withdrawal reactions, quantitated by scoring convulsions elicited by handling, were equivalent to those resulting from 6 days exposure to either alcohol alone. One alcohol not only substituted for the other in the maintenance of dependence, but also augmented the abstinence syndrome produced by the first 3 days exposure. An additive effect of ethanol and t-butanol in producing a withdrawal reaction is consistent with the hypothesis of a single underlying mechanism for producing physical dependence on alcohols. This experimental model may be useful for studying cross-dependence.


Bilateral mycotic myositis, osteomyelitis and nephritis in a dog caused by a cephalosporium-like hyphomycete.

A mycetoma like syndrome in a dog caused by a hyphomycete reminiscent of Acremonium hyalinum (Sacc.) W. Gams, is described. The organism was seen in smears of pus and sections from the kidneys and myocardium and was isolated in pure culture from the lesions.


Mapping the dopamine receptor. 1. Features derived from modifications in ring E of the neuroleptic butaclamol.

Several analogues of the neuroleptic agent butaclamol, having modifications in the ring E region of the molecule, have been synthesized. Pharmacological evaluation identified two of the analogues as being equipotent to butaclamol, namely, anhydrobutaclamol (8) and deoxybutaclamol (9a). The molecular structures of both the active and inactive analogues were analyzed and the results have been used for mapping the central dopamine receptor. The existence of a previously proposed lipophilic accessory binding site on the receptor macromolecule has been confirmed. Its minimum dimensions, as well as its locus with respect to the primary binding sites, have been defined. A receptor model incorporating the above features is proposed.


Mapping the dopamine receptor. 2. Features derived from modifications in the rings A/B region of the neuroleptic butaclamol.

Several analogues of the neuroleptic agent butaclamol having modifications in the rings A/B region of the molecule have been synthesized. Pharmacological evaluation identified the benzo[5,6]cyclohepta analogue 2b, isobutaclamol, as being equipotent to butaclamol. The molecular structure of this compound has been analyzed, and the results have been used for mapping the central dopamine receptor. A planar catechol primary binding site, composed of alpha and beta regions, has been identified and its minimal dimensions deduced. Its locus with respect to the nitrogen location site and its complementary hydrogen bond donor site has been specified. Using a Cartesian coordinate system, a receptor model is proposed which incorporates the above-mentioned features. The receptor model has been used to rationalize the observed chirality of the central dopamine receptor.


Biochemical assessment of the nutritional state of gravida of different socio-economic classes at the Wesley Guild Hospital, Ilesha, Nigeria.

Non-pregnant women from the low socio-economic class were found to have significantly lower haemoglobin, plasma transferrin and retinol-binding protein concentrations than those from the upper classes. Pregnancy in these poor women resulted in a further significant lowering of these constituents. Children born to such mothers had significantly lower birthweights and plasma transferrin concentrations. A highly significant positive correlation was found between maternal serum transferrin concentration and birthweight, suggesting that this protein is a sensitive index of nutritional state in pregnancy.


Gluconeogenic response during glucose infusions in patients following skeletal trauma or during sepsis.

In order to quantitate the effect of sepsis and skeletal trauma on gluconeogenesis, four septic and five skeletal trauma patients were evaluated for their ability to convert 14C-L-alanine to 14C-glucose while receiving 5% dextrose by peripheral vein. In the septic group, the mean glucose pool size increased by 35% and the glucose turnover rate increased by 85% over normal. The alanine conversion averaged 11.1% of the dose. The skeletal trauma group showed a glucose pool size increase of 61%, a 100% increase in glucose turnover rate and a 11.7% conversion of the alanine dose to glucose. The increased conversion of 14C-alanine to 14C-glucose in both sepsis and skeletal trauma in the face of an exogenous glucose infusion indicates an abnormal unsuppressible response. Each of the above parameters when compared to normal values was found to be significant at levels greater than 97.5%. The percentages of the dose expired as 14CO2 in three hours were not significantly different from the normals.


The comparative oxidation of glucose, fructose, sorbitol and xylitol in normal man.

The aim of the study was to compare the effects of fructose, sorbitol and xylitol with those of glucose on blood glucose and insulin levels and carbohydrate utilization in man. The experiment was performed by means of continuous indirect calorimetry in five groups of five to six normal volunteers during infusion of either glucose, fructose, sorbitol, xylitol or a mixture of fructose, glucose and xylitol in the proportion of 2:1:1. Glucose and insulin did not present any important variations during the fructose, sorbitol and xylitol infusiosns. However, carbohydrate oxidation rose significantly during administration of these substrates. Carbohydrate oxidation rose 80 mg/min for fructose, 27 mg/min for sorbitol, 39 mg/min for xylitol and 75 mg/min for the carbohydrate mixture, in comparison to 101 mg/min for glucose. It is concluded that fructose, sorbitol and xylitol provoke an increase in carbohydrate utilization without a corresponding rise in glycemia and insulinemia.


Echocardiographic and angiocardiographic features of supravalvular aortic stenosis in children.

Fourteen patients with SVAS served as subjects of echocardiographical and angiocardiographical studies and the data obtained were compared. There were significant decreases in aortic diameter at the level of ascending aorta compared to those of the aortic leaflets and significant differences of the percentage change of the aorta between the patients with SVAS and the normals. Echocardiography is, therefore, a useful noninvasive method for evaluating SVAS. If the values of percentage change of the aortic diameter obtained by echocardiogram are below -30%, the values of peak systolic pressure gradients across the supravalvular stenotic region should be higher than 20 mmHg. The value of LV M/V under 1.0 suggests that the pressure gradient is lower than 20 mmHg.


Effect of graded coronary constriction on the flow reserve in regional myocardium in dog.

Effects of coronary constriction on the flow reserve of regional myocardium were studied in the anesthetized open-chest dogs. Regional myocardial blood flow (RMBF) was continuously measured using heated crossthermocouple method. Left circumflex coronary artery (LCX) was constricted gradually with a screw type constrictor. The coronary constriction decreased subendocardial myocardial blood flow, while subepicardial myocardial blood flow was not affected until reactive hyperemia in LCX nearly disappeared. Recovery and arrival to peak flow rate of RMBF following the release of 15-second's occlusion of LCX were progressively delayed with an increase in the constriction, especially in the subendocardial myocardium. Repayment of flow debt, however, was remained relatively well since the duration of reactive hyperemia in RMBF was prolonged by an increment of the constriction. From these findings, it might be concluded that in the heart with coronary stenosis recovery from ischemia was caused by prolonged duration of reactive hyperemia, and is suggested that the time required for recovery from ischemia or ischemic abnormalities after the cessation of stress might be an important marker for the severity of coronary insufficiency.


Excitatory and inhibitory electrodermal reflexes evoked by cutaneous stimulation in acute spinal cats.

The electrodermal reflex (EDR) was recorded from the paws of acute spinal cats by a DC potential recording method. The EDR was produced either by pinching the skin in various areas of the trunk, or by electrical stimulation of cutaneous afferents of various spinal segments. It was found that not only excitatory but also inhibitory EDRs were produced and that occurrence of the excitatory and inhibitory EDRs depended on both the segmental position and the laterality of the stimulated area. Cutaneous stimulation generally produced excitatory EDRs more frequently than inhibitory ones, except when afferent inputs entered the spinal cord at or close to the segments of sudomotor outflow; in the latter case inhibitory EDRs were comparatively frequent and strong. Maximal inhibitory EDRs were elicited by stimulation of the group II afferent fibers of the cutaneous nerves only, whereas maximal excitatory EDRs were elicited after stimulation of the group II, III and IV afferent fibers of cutaneous origin.


[Connatal leukaemia and pseudoleukaemia--two cases with cytochemical findings (author's transl)].

Two newborn infants with hyperleukocytosis and blast cells in the peripheral blood are compared. Case 1 represents a connatal leukemia, which could be characterized as monocytic by the naphthol-ASesterase reaction, which was inhibited by NaF. The child died after a few hours. Case 2 must be diagnosed as "pseudoleukemia" in mongolism. The blast cells were classified as lymphoblastic on the basis of a strong granular beta-glucuronidase reaction. The patient achieved spontaneous remission.


[Encephalopathy due to vincristine sulfate (author's transl)].

A cytotoxic effect by vincristine sulfate on the cerebral cortex is claimed in literature. In 188 children treated with vincristine we saw no so called "Vincristine-induced Encephalopathy". The proportional risk of vincristin-induced cerebral complications amount to 1%, as demonstrated by various authors. In 67 children investigated 5 weeks up to 2 years after last vincristine-injection we found no EEG-tracing, which could be discussed as a vincristine-induced finding.


[Analysis of normal and methylated urinary nucleobases: a new criterion for diagnosis and follow-up of malignancies (author's transl)].

The qualitative and quantitative analysis by high performance liquid chromatography of the normal and modified nucleobases excreted in urine represents a new and versatile tool. Its use for the diagnosis of malignancies, deliminating infectious diseases, and for the follow-up of the effects of a cytostatic therapy is shown. This method offers a chance to introduce the analysis of a series of fragments of primary gene products into the routine of clinical biochemistry.


[Grading procedures for neuroblastoma (author's transl)].

Various procedures of practical significance for grading neuroblastoma are described. The comparability of the grading procedures was studied on the basis of a series of 75 cases of neuroblastoma. When the grading procedure of Hughes et al. was applied to the material collected at the Childhood Tumor Registry in Kiel, the proportions of the various grades of malignancy agreed with the data on the collection in Manchester. More than 50% of the cases of neuroblastoma were undifferentiated, corresponding to grade III. An anaplastic type of neuroblastoma is also described. When applying grading procedures, one has to take the possible variations in the histologic picture of neuroblastoma into consideration.


[Resection of a primarily inoperable Ewing's sarcoma of the pelvis (author's transl)].

A primarily inoperable Ewing's sarcoma in a 10 yrs. old boy arising from the pelvis was totally resected following preoperative T-6 chemotherapy and radiotherapy. A new approach to the treatment of Ewing's sarcoma is discussed.


Alcoholism and cancer. I. Effects of long-term exposure to alcohol on spontaneous mammary adenocarcinoma and prolactin levels in C3H/St mice.

Serum prolactin levels were significantly lower in mice exposed to alcohol for 28 days than they were in controls, and the latency period for adenocarcinoma development was significantly shorter in the alcohol-exposed animals.


Increased susceptibility to kindled seizures in rats following a single injection of alcohol.

After 2 or 2.5 g of alcohol, rats previously subjected to low-intensity electrical stimulation of the amygdala showed first a suppression followed by a potentiation of motor seizures and afterdischarges.


Cardiac valve replacement in children: comparison of tissue with mechanical prostheses.

Replacement of cardiac valves in children has been associated with high rates of mortality and morbidity in the past. We have compared 24 children from 2 to 18 years of age who have received mechanical valves with 24 children who have received porcine valves. The groups were similar except that (1) there were more mitral operations in the mechanical valve group and more aortic operations in the porcine valve group; (2) more porcine than mechanical valves were implanted in recent years; and (3) the porcine valve group comprised more young patients under 8 years and required more complex operations. Early and late mortality rates were higher in the mechanical than in the porcine valve group. Major late complications were seen in 50 percent of the mechanical valve group and 13 percent of the porcine group. Implantation of an adult-sized aortic valve was made possible in all patients by the use of aortic augmentation annuloplasty. Higher operative mortality rates in the mechanical valve group may have been related more to technique of myocardial preservation during operation than to type of valve. Although differing rates of late morbidity and mortality may also have been related to myocardial preservation and other technical factors, the type of valve used seemed to be an important determinant of the better results in the porcine group. Despite unknown durability of the porcine valve, our data suggest that the safest prosthetic valve to use in children at this time is the glutaraldehyde-fixed porcine prosthesis.


[Injured tongue due to bite of fer-de-lance (author's transl)].

A nine-year-old boy was bitten in the tongue by an Asiatic fer-de-lance, a Trimenesurus wagleri. No generalized toxic reaction developed; there was only locally a massive edema of the tongue leading to a severe dyspnea. The child was intubated and administered antiphlogistics, antibiotics, cortison, a tetanus booster shot as well as parenteral nutrition. After three days the local status was unchanged. Because of the danger of the development of necrosis in the laryngeal region as a result of the toxic effect and the sustained intubation, a tracheotomy inferior was carried out. The status localis improved considerably after surgery, so that a week after the bite the tracheostoma could be closed. Four weeks later no pathological findings were made any more, the tracheostoma had healed up well.


Factors affecting plasma amino acid concentrations in control subjects.

Plasma amino acid concentrations were determined in groups of normal control subjects under fasting and postprandial conditions. Differences were observed that were found to be, to a considerable extent, sex-related. Fasting females had lower concentrations than fasting males of several amino acids, although postprandial differences in concentrations between the sexes were not significant. Under the dietary conditions normal for a British population, no significant diurnal variation of plasma amino acid concentrations was found. Reducing the dietary protein by 30% failed to affect plasma amino acid concentrations; however, increasing the dietary protein by 50% resulted in a significant increase in the plasma concentrations of several amino acids, and induced a significant degree of variation throughout the day in six, proline, half-cystine, methionine, valine, leucine, and isoleucine. The importance of these results with regard to the interpretation of population mean values and disease diagnosis is discussed.


[Use of the reaction product of beta-alanine and formaldehyde in the kinetic method of determining defects in secondary structure].

It is shown that the kinetics of DNA despiralization in the presence of beta-alanine--formaldehyde reaction product (beta-ALA-FORM) can be described in terms of theory of DNA despiralisation by "slowly reacting agents". Conditions are determined in which beta-ALA-FORM product can be used to establish the concentration of defects in DNA secondary structure. Possible advantages are discussed of using the new agent in the kinetic method of determining DNA defects as compared to formaldehyde, in particular in analysis of DNA complexes with proteins. The data obtained throw some light on the nature of the interaction between beta-alanine and formaldehyde in slightly acidic solutions and with the excess of aminoacid.


Autosomal dominant "spheroid body myopathy".

A slowly progressive autosomal dominant neuromuscular disease--termed spheroid body myopathy--is described in four successive generations and documented by muscle biopsies in five patients of two generations. With an onset in adolescence, the disease proceeds to some motor incapacitation, but life span is apparently not shortened. The salient morphologic feature is the presence of spheroid bodies, chiefly occurring in type 1 myofibers. Ultrastructurally, these spheroid bodies are composed of tiny filaments but are devoid of organelles; in some cases they resemble cytoplasmic bodies. "Smearing in the 1-band" is a frequent and early finding. At a later age, signs of denervation are also present, both clinically and in muscle biopsies. The clinical and morphologic features justify the designation of this neuromuscular condition as a distinct entity.


Black grain mycetoma: the ultrastructure of Madurella mycetomi.

Madurella mycetomi, the fungus pathogen of black grain mycetoma, shows an elaborate development of mesosomes as its most striking ultrastructural feature. These occur in addition to mitochondria and endoplasmic reticulum. Condensations of hyphal cytoplasm and recurring intrahyphal growth of new hyphal cells are features of the pigment-producing and pathogenic phases of the organism. The abundant pigment which histochemically resembled melanin was not traceable to any ultrastructural granule, nor was it built from a tyrosine precursor. The ultrastructural changes occurring in collagen through a sclerotizing action by the fungus are briefly noted.


Biosynthesis of the major human red cell sialoglycoprotein, glycophorin A, in a continuous cell line.

During biosynthesis of glycophorin A in K562 cells a precursor is rapidly transferred through the endoplasmic reticulum membrane with the COOH-terminal remaining in the cytoplasm. This is glycosylated within the cell and appears at the cell surface after about 30 min. The biosynthetic pathway resembles that described for viral membrane glycoproteins.


Substantia nigra as an out-put station for striatal dopaminergic responses: role of a GABA-mediated inhibition of pars reticulata neurons.

Intranigral administration of kainic acid results in loss of pars reticulata neurons without damage to axons traversing or terminating within the nigra. Unilateral nigral lesions with kainic acid result in an ipsilateral turning upon administration of apomorphine, a dopamine (DA)-receptor agonist and in contralateral turning upon administration of haloperidol, a DA-receptor blocker. Destruction of post-synaptic structures in the striatum of the side contralateral to that injected with kainic acid results in a drastic reduction, abolition or even reversal of the turning effects elicited by apomorphine and haloperidol. Unilateral intranigral microinjection of nanogram amounts of the GABA-receptor antagonists picrotoxin and bicuculline elicits ipsilateral circling upon apomorphine administration. Kainic-induced lesion or microinjection of picrotoxin or bicuculline in the nigra ipsilateral to a 6-OHDA-lesion of nigro-striatal DA-neurons results in reduction, abolition or reversal of the contralateral circling produced by apomorphine. The results indicate that the nigra pars reticulata is a station for dopaminergic impulses originating from the striatum and suggest that the turning behavior in response to striatal DA-receptor stimulation is due to a GABA-mediated inhibition of ipsiversive pars reticulata neurons.


[Middle cerebral arterial occlusion secondary to brain tumor -- case report (author's transl)].

A thirty-year-old man who had sudden onsets of unconsciousness, right hemiparesis and conjugate deviation to the left side, was admitted to our clinic. The clinical symptoms were similar to an apoplexic attack. The neurologic examination showed right hyperactive knee and ankle reflexes, and left inferior temporal retinal arterial occlusion. The serial left carotid angiography, performed immediately after admission, showed the occlusion of left middle cerebral artery at the location of trifurcation. We diagnosed this case as a cerebral vascular disease, and then the large amount of Urokinase and Heparin were injected immediately after the diagnosis. The clinical symptoms were improved tremendously after the injection. Three days later, the second left carotid angiography showed the complete recanalization of the occlusion, and further did a tumor stain at the distal portion of the occlusion. The brain scintigram revealed an increased up-take of 99mTc in the left parieto-temporal region. We finally diagnosed brain tumor, and the tumor was subtotally removed by the left parieto-temporal craniotomy. The histological findings of the tumor showed angioblastic meningioma. The cerebral arterial occlusion secondary to the brain tumor should be caused by the compression of the vessels and the hemorrhage of the tumor. This case is rarely reported.


The complementary nature of computed tomography and angiography in the diagnosis of cerebellar hemangioblastoma.

Cerebellar hemangioblastomas were seen in seven persons, five being members of the same family. All were studied with constrast enhanced CT scans and vertebral angiograms. The CT scans were superior for demonstrating the cystic component of the tumors and associated hydrocephalus, features not usually evident on the angiograms. The angiograms were superior for revealing the vascular nature, supply and drainage of the tumors. In several patients the angiograms revealed more tumors than could be seen by CT. Both CT and angiography contribute important information in the diagnosis of these neoplasms.


Cellular immunity to acetylcholine receptor in myasthenia gravis: relationship to histocompatibility type and antigenic site.

To determine the nature of the cellular immune response directed against acetylcholine receptor in myasthenia gravis, we compared lymphocyte stimulation by eel receptor with clinical factors. The mean (+/- SEM) stimulation index was 4.5 +/- 0.9 for 39 myasthenic patients and 0.97 +/- 0.18 for 48 controls (p less than 0.001). Positive response in patients was associated with disease onset after 50 years (10 of 13 patients) and presence of thymoma (seven of eight patients), but not with HLA type. Stimulation index correlated with disease activity (rs = 0.63, p less than 0.01). Blocking the active portion of the receptor molecule with naja toxin resulted in 68 percent diminution of the response, suggesting that this site plays a significant role in the cellular immune response in myasthenia gravis.


The risk of epilepsy following febrile convulsions.

A cohort of 666 children who had convulsions with fever were followed to determine the risks of subsequent epilepsy. High risks were found in children with preexisting cerebral palsy or mental retardation. Other major risk factors were atypical features of the febrile convulsions (such as focal seizures) and duration of febrile seizures for 10 minuts or more. The risk of developing epilepsy by age 20 was about 6 percent for all children who had experienced febrile convulsions. However, this risk figure consisted of a combination of 2.5 percent of children without prior neurologic disorder or atypical or prolonged seizures, and 17 percent of those with such complications.


CT scans in Menkes disease.

The clinical courses and serial computerized tomography (CT) scans of four patients with Menkes disease are described. Although the initial clinical presentations were similar, head growth and serial CT scans showed striking individual differences. The CT scans varied from showing no abnormalities early in the disease to showing diffuse cortical atrophy, subdural accumulation of fluid, or multifocal areas of ischemic infarction. The pathologic findings in one patient showed only cerebral and cerebellar atrophy, whereas the findings in another patient showed areas of ischemic infarction, probably secondary to abnormal vessels. Menkes disease should be suspected in male infants with psychomotor deterioration and seizures, or when trauma is suspected from subdural hematoma and multiple fractures.


Microangiopathy of the brain and retina.

Two women (26 and 40 years old) developed an unusual microangiopathy that affected the brain and retina. Psychiatric symptoms initially overshadowed the subacute features of the progressive neurologic disorder. Ophthalmoscopic findings of multifocal branch retinal artery occlusions provided clinical evidence of vasculopathy. Laboratory data did not reveal evidence of the known vasculitides, including systemic lupus erythematosus (SLE) and syphilis. Cerebral angiography suggested vasculitis in the younger patient. Brain biopsy in the older patient (after 3 months of steroid therapy) revealed a sclerosis of the small pial and cortical vessels that was consistent with a "healed" angitis. Both patients seemed to respond to steroid therapy.


Cerebral infarction and migraine: clinical and radiologic correlations.

Cerebral infarction was documented by arteriography and serial computed cranial tomography (CT) in four young adults (ages 16 to 32 years) with migraine. In one case, posterior cerebral artery occlusion produced a deep parietotemporal infarct. The other three cases all had frontotemporal infarcts (one hemorrhagic) in the territory of the middle cerebral artery, without major arterial occlusion. Two infarcts produced lasting neurologic deficits; one was associated with mild, transitory symptoms, and one was asymtomatic. Laboratory investigations in two cases revealed no hematologic or cardiovascular predisposition to cerebrovascular disease. Cerebral infarction, as revealed by CT, may be more prevalent in "complicated" migraine than is generally appreciated. Such lesions may or may not develop in chronologic and anatomic relationship to the headache, and may involve either large or small arteries. The prognosis for functional recovery, based on this limited sample, seems favorable.


Behr syndrome: a clinicopathologic report.

Two sisters had Behr syndrome; autopsy was performed on one. The autopsy revealed central atrophy of the optic nerves and total disarray of the normal laminar pattern of the lateral geniculate nucleus, dropout of neurons, and gliosis. There were numerous axonal spheroids in the neuropil. Similar spheroids with cell loss and gliosis were also observed in other thalamic nuclei and, rarely, in the pallida. We raise the possibility that Behr syndrome is a manifestation of a heterogeneous group of disorders, and suggest relationship of this particular disease to infantile neuroaxonal dystrophy.


Calcification of the basal ganglia: computerized tomography and clinical correlation.

During a 1-year period, 4219 consecutive computerized tomograms (CT) were reviewed for basal ganglia calcification; 14 patients with such calcification were identified. Calcifications on CT scan were bilateral in 12 of these cases and unilateral in 2. All bilateral calcifications were symmetric. The globus pallidus was the site of calcification in 13 of the 14 patients. Bilateral dentate nucleus calcification was seen in one patient. Skull radiograms were normal in all but one. Patients had diverse symptoms that were often explained by other findings, suggesting that calcifications may be coincidental and that basal ganglia calcification may not be a nosologic entity. Disturbances of calcium metabolism were not found in these patients, minimizing the pathophysiologic significance of altered calcium metabolism and the need for extensive endocrinologic evaluation. The finding of basal ganglia calcification alone does not justify invasive diagnostic procedures. Extrapyramidal signs may be associated with basal ganglia calcification; parkinsonism associated with basal ganglia calcification differs from idiopathic parkinsonism in being resistant to levodopa therapy.


Capgras syndrome: a reduplicative phenomenon.

A patient recovering from a severe head injury developed a prolonged Capgras syndrome in which he believed his wife and five children had been replaced by nearly identical substitutes. Although this phenomenon is considered a functional disorder in the psychiatric literature, recent reports postulate an organic basis. Recent studies of the comparable neurologic disorder, reduplicative paramnesia, have stressed the importance of bilateral frontal and right hemisphere pathology. Neuropsychologic and neuroradiologic data in our patient revealed this combination, suggesting that the Capgras syndrome may be a form of reduplicative paramnesia with the same pathologic substrate.


Influenza and myoglobinuria in brothers.

Two adult brothers became ill within 48 hours of each other, and both had severe myoglobinuria. One brother died of oliguric renal failure. The other did not have renal failure and survived. Acute influenza A infection was documented serologically and from throat washings in the surviving brother, and by isolation of the influenza A virus from throat cultures and lung tissue of the brother who died. It is not certain whether a genetic myopathy made these brothers susceptible to viral-induced myoglobinuria, but a normal response of venous lactate to ischemic work excluded lack of phosphorylase or phosphofructokinase as a cause of the myoglobinuria in the surviving brother. Neither brother had a history of recurrent episodes of myoglobinuria precipitated by exercise, cold, or fasting, thus making carnitine palmityl transferase deficiency unlikely.


Bromocriptine in Parkinson disease: further studies.

Bromocriptine was administered to 66 patients with advanced Parkinson disease (PD) and increasing disability despite optimal treatment with levodopa/carbidopa (Sinemet). Forty-five patients tolerated at least 25 mg per day of bromocriptine (the "adequately treated" group) in addition to Sinemet and had significantly decreased rigidity, tremor, bradykinesia, gait disturbance, and total score, but increased involuntary movements. Twenty-five of these 45 patients improved by at least one stage. Among the 45 patients, 27 had "on-off" effects, and in 19 the "on-off" effects decreased on bromocriptine. The mean dose of bromocriptine in adequately treated patients las 47 mg, permitting a 10 percent reduction in the dose of levodopa. Twelve adequately treated patients received bromocriptine for at least 1 year, and 8 continued for longer than this. Bromocriptine was discontinued in 29 of 66 patients because of adverse effects, including mental changes (14 patients) and involuntary movements (9 patients). All adverse effects were reversible. Despite adverse effects, expense, and scarcity, bromocriptine, when added to levodopa, is useful in patients with advanced disease who no longer respond satisfactorily to levodopa, and for whom no other treatment is available.


Spinocerebellar degeneration: hexosaminidase A and B deficiency in two adult sisters.

Two adult sisters had spinocerebellar degeneration. Biochemical studies revealed a very low activity of both fraction A and fraction B of the lysosomal enzyme, hexosaminidase, in serum and leukocytes. A skin biopsy showed lesions suggestive of neuronal storage disease. The disorder seems to be an adult form of GM2 gangliosidosis.


Computed tomography in a verified case of tuberculous meningitis.

In a verified case of tuberculous meningitis, postcontrast computed tomograms demonstrated enhancement of the area corresponding to the cistern surrounding the brainstem. This enhancement disappeared after successful drug treatment of the meningitis.


Alexia without agraphia: lateral and medial infarction of left occipital lobe.

Four cases of alexia without agraphia were studied by 99m-technetium pertechnetate brain scan. Two types of increased uptake were seen. One was of the triangular type near the midline in the posterior view, said to characterize an infarction in the distribution area of the posterior cerebral artery. This was associated with the well-known clinical picture of alexia without agraphia accompanied by hemianopia and color-naming defect, and was confirmed by postmortem examination. The other type of pathologic isotope uptake, observed in three patients, was more laterally placed, in the basal part of the left occipital lobe, and did not reach the midline. In these cases the alexia was transient and not associated with color-naming defects.


Idiopathic hypoparathyroidism presenting as dementia.

Subacute dementia was the sole neurologic symptom in a 32-year-old man with idiopathic hypoparathyroidism. This condition resolved with medical therapy, in parallel with the return of serum calcium content to normal.


Ruptured aneurysm of the spinal artery of Adamkiewicz during pregnancy.

Solitary aneurysms of the extramedullary arteries of the spinal cord, not associated with arteriovenous malformations from which they are clinically indistinguishable, are rarely reported; only four cases have appeared in the recent literature. An aneurysm of the great anterior radicular artery of Adamkiewicz was found at autopsy in a 34-year-old pregnant woman. The aneurysm had ruptured into the subarachnoid space.


Bedside evaluation of large motor units in childhood spinal muscular atrophy.

One hundred patients with motor unit disease were examined to determine the diagnostc reliability of several clinical signs of large motor units. These signs were high-intensity, low-pitched rumbling on skeletal muscle auscultation, voluntary contraction fasciculations, contraction fasciculation trembling, and palpable contraction fasciculations. Among 22 cases of spinal muscular atrophy, contration fasciculation trembling was noted in 86 percent, abnormal muscle auscultation in 68 percent, palpable contraction fasciculations in 64 percent, and voluntary contraction fasciculations in 50 percent.


Quantitative ultrastructural study of muscle satellite cells in Duchenne dystrophy.

Quantitative ultrastructural studies of satellite cell populations, and nuclear chromatin analysis of satellite cell nuclei and true subsarcolemmal nuclei were carried out in normal and Duchenne muscular dystrophy (DMD) muscles. There was a remarkable increase in the number of satellite cells in muscles of patients with mild to moderate stages of DMD, as compared to preclinical or very early and probably advanced stages of DMD, and a significant increase in euchromatin content was found in the satellite cell nuclei in DMD. Since it is generally accepted that satellite cells participate actively in muscle fiber regeneration, this study suggests that muscle fiber regeneration is ineffective in DMD.


Reversibility of Parinaud syndrome in thalamic hemorrhage.

Parinaud syndrome, associated with a left thalamic hemorrhage, disappeared completely in a 57-year-old woman after ventriculoperitoneal shunt. The syndrome may be attributed to increased intracranial pressure owing to mass effect on the pretectal region and tectum, or to tightness in the incisura causing hydrocephalus secondary to aqueduct compression. The lesions responsible for the syndrome may not be irreversible.


Acute hydrocephalus in cerebellar infarct and hemorrhage.

Although cerebellar infarction was known at the turn of the century, not until 1956 was it realized that large cerebellar infarctions could cause acute obstructive hydrocephalus. There are many more reports of cerebellar hemorrhages. The clinical differentiation between hemorrhage and infarction was difficult prior to computerized tomography (CT). Cerebellar hemorrhage is a neurosurgical emergency, as are some cerebellar infarctions. We present three patients with acute hydrocephalus resulting from these vascular syndromes; they are first cases to be successfully treated by ventricular drainage and shunting. Four other cerebellar infarcts demonstrate the efficacy of CT.


Diazepam and dialysis encephalopathy.

A patient with the clinical and electroencephalographic features of dialysis encephalopathy exhibited dramatic improvement with the initiation of diazepam therapy. Although improvement was sustained for a period of several weeks, her clinical condition eventually deteriorated despite continued treatment with diazepam and dialysis. Dialysis encephalopathy in this patient is compared with other cases recently reported in the medical literature as having a similar dramatic response to diazepam. It is concluded that diazepam transiently reverses a component of the dialysis encephalopathy syndrome, but it does not appear to change the ultimate prognosis for patients with this condition.


Hepatic ketogenesis and muscle carnitine deficiency.

The levels of plasma free carnitine and ketone bodies have been found to fluctuate inversely in fasting individuals without muscle disease. Circulating short-chain acyl-carnitines paralleled beta-hydroxybutyrate levels. A patient with lipid storage myopathy and muscle carnitine deficiency, and his two daughters, developed exaggerated ketogenesis on fasting. The content of total carnitines in the patient's liver was normal, but free carnitine was reduced to 50 percent, and total esterified carnitines were four times greater than the mean value for the controls. The decreased muscle carnitine content in this case may have resulted from chronic hepatic ketogenesis, draining muscle carnitine. Alternatively, decreased muscle carnitine content may have initiated hepatic ketogenesis.


The pathology of drop attacks: a case report.

A 65-year-old man had four drop attacks in several days and then a fixed stroke with quadriplegia. At autopsy infarction in the lower pons and upper medulla affected principally the corticospinal tracts. Tegmental destruction included reticular formation nuclei with rostral projections, but spared the lateral reticular formation nuclei, from which arise the descending reticulospinal tracts. This case is the first detailed autopsy report of a patient with drop attacks, and supports the view that at least some drop attacks are caused by transient ischemia of the corticospinal tracts.


Computed tomography in aneurysmal subarachnoid hemorrhage.

Among 50 patients with subarachnoid hemorrhage (SAH) from aneurysm, computed tomography (CT) demonstrated evidence of bleeding in 28. In 12 cases, the location and configuration of the high-density blood cast visualized by CT was characteristic and predicted the site of the ruptured aneurysm. CT was reliable in identifying infarction, edema, localized hematoma, hydrocephalus, or rebleeding in patients with SAH and neurologic abnormalities. In four cases, the plain and contrast CT suggested a large intracranial aneurysm. These findings did not permit definitive diagnosis or precise anatomic detail of angiographically defined aneurysms less than 2.0 cm in size.


Brain aluminum in aging and Alzheimer disease.

Aluminum was assayed by atomic absorption spectroscopy in 274 brain samples, and assayed in neurons isolated in bulk from the frontal cortex of patients with Alzheimer dementia and from age-matched patients with no neurologic disease. Brain aluminum concentration increased with age, from late middle age to old age. There were no statistically significant differences in brain aluminum concentration between the 10 patients with Alzheimer disease (mean, 2.7 microgram per gram dry weight of tissue; mean age, 81 years), and the 9 nonneurologic controls (mean, 2.5 microgram per gram; mean age, 73 years). In both groups, the hippocampus had the highest concentration of aluminum (5.6 microgram per gram), and the corpus callosum the lowest (1.5 microgram per gram).


Chronic ECHO type 5 virus meningoencephalitis in X-linked hypogammaglobulinemia: treatment with immune plasma.

A patient with X-linked hypogammaglobulinemia developed chronic meningoencephalitis. ECHO virus type 5 was repeatedly cultured from cerebrospinal fluid (CSF). Infusions of high-titer, specific plasma resulted in clinical improvement, but failed to eradicate the virus. After more intensive plasma infusions, the virus could not be cultured from the CSF. The patient died 8 months after institution of intensive therapy. The cause of death was unknown. Autopsy showed persistence of perivascular and meningeal inflammation. Specific anti-ECHO-virus-5 plasma was shown to be more effective in lowering CSF ECHO-virus titers than was plasma without anti-ECHO-virus antibody.


Short-latency somatosensory responses in multiple sclerosis.

Cervical and cortical somatosensory evoked potentials were measured in 80 patients with suspected or established multiple sclerosis (MS). The cervical response was a more sensitive diagnostic indicator than the cortical response, and was abnormal in 86.7 percent of patients with definite MS and in 40.9 percent of MS suspects. The complementary value of measuring both responses was greatest (89.3 percent) in early probable or latent MS. Comparing the responses obtained from stimulation of the left and right extremities increased the overall diagnostic yield by 25 percent. Abnormal responses were frequently obtained from clinically normal limbs.


Enzyme replacement in Tay-Sachs disease.

Enzyme replacement therapy was attempted with two Tay-Sachs-diseased individuals--a 14-month-old child and a 7-week-old infant. Treatment consisted of repeated weekly intrathecal injections of pure hexosaminidase A. Injection of this enzyme resulted in almost complete disappearance of GM2 from the serum, but did not bring about dissolution of the GM2 membranous cytoplasmic bodies in the brain, as detected by electronmicroscopy. Both patients tolerated the treatment without apparent clinical complications, but no clear-cut improvement was noted as a result of prolonged injections of hexosaminidase A. Since this treatment was initiated in both an advanced stage and a very early stage of the disease, we conclude that enzyme replacement treatment by this route is not beneficial for patients with Tay-Sachs disease.


Disordered growth hormone and prolactin secretion in primary disorders of sleep.

Growth hormone (GH) and prolactin (PR) secretion were evaluated in 28 patients who had sleep apnea or narcolepsy but no other primary neurologic or endocrine disorders. Eighty-one percent of subjects with impaired alertness failed to demonstrate serum GH concentrations in excess of 5 ng per milliliter following oral administration of L-DOPA, 500 mg. Diminished GH responses to sleep and intravenous arginine were observed in 57 percent and 44 percent, respectively, of patients tested. Sleep-related PRL release was less than normal in women with narcolepsy, with or without sleep apnea. All patients had at least one abnormality in GH or PRL secretion.


Computerized cranial tomography in Wilson disease.

Hepatolenticular degeneration (Wilson disease) is suspected by the clinical picture and confirmed by characteristic laboratory demonstration of impaired copper metabolism. Three patients with Wilson disease involving the basal ganglia were shown to have abnormalities on computerized tomography (CT) scan, whereas four other patients without signs of cerebral involvement had normal brain scans. Wilson disease may be added to the long list of diseases to which the EMI scan may make a useful diagnostic contribution.


Transient global amnesia: clinical and electroencephalographic findings in 10 cases.

We studied 10 patients with transient global amnesia (TGA). Routine electroencephalograms (EEGs) were normal in six; two showed mild temporal lobe abnormalities, one had bitemporal delta activity with rare sharp waves, and one showed bioccipital rhythmic theta activity. Nasopharyngeal (NP) recordings were obtained in seven patients; five showed independent mesial temporal spike discharges during drug-induced sleep. The discharges are probably due to transient ischemia in deep temporal structures.