Influence of age and sun exposure on the biophysical properties of the human skin: an in vivo study. The physical properties of the skin were measured by using noninvasive methods on 72 people displaying various levels of solar elastosis on the neck. The physical parameters measured were the skin extensibility, the elastic recovery, the skin colour, the skin thickness and the electrical conductance. The correlation between the above parameters, the clinical grades of elastosis and the chronological age of each subject were studied using two different statistical approaches. They both showed that elastotic skin is less elastic, dryer, darker, more erythematous and less yellowish than the nonexposed skin. The similarities and differences between the properties of elastotic skin and purely chronologically aged skin are discussed.


Gallyas-Schiff stain for senile plaques. Gallyas technique was modified by a direct application of Schiff's reagent after physical development, resulting in distinctive staining of amyloid deposits in argyrophilic structures. With this modified method, senile plaques in Alzheimer's disease are clearer. This method is easy to perform and suitable for routine neuropathological examination.


Development of fern sporangia: a fluorescence microscopy study. The utility of fluorescence microscopy for studying development of fern spores is investigated. Changes in the fluorescence characteristics during the developmental stages of fern sporangia can be attributed to the changes in the chemical composition of the cell wall. Bright blue autofluorescence of the spores indicated the presence of sporopollenin. The sporangial walls and the spores autofluoresced yellow under blue light excitation. Fluorescence microscopy is a useful addition to light, scanning, and transmission electron microscopy because living specimens can be studied owing to their fluorescence properties.


In situ hybridization of plant meiotic and mitotic chromosomes: differences in signal detection. The technique of in situ hybridization to both meiotic and mitotic chromosomes of Rumex acetosa is described. Differences in the efficiency of signal detection were observed between the two types of material. The implications of these results for in situ hybridization to other plant species are explored.


Short fixation-shock freezing and freeze-drying versus chemical fixation and dehydration: computer assisted image analysis of morphological variables and immunogold labeling density on pituitary secretory granules. We have performed a computer assisted image analysis evaluation of the effects of two preparation protocols on morphological variables and immunolabeling density of secretory granules using rat adenohypophysis as a model. Glutaraldehyde (GA) fixation for 2 hr and chemical dehydration was compared with short GA fixation (15 min) followed by cryofixation and freeze-drying (CF-FD). The 2 hr GA fixed specimens showed spherical nuclei and secretory granules regardless of their size, contrasting with the more irregularly shaped nuclei and secretory granules after short GA-CF-FD. In the latter group of specimens a correlation could be found between smaller nuclear areas and more irregular shapes. The differences in morphological variables between the two preparation protocols might be due to a better protein stabilization and a reduced collapse of macromolecules after the 2 hr GA fixation, strengthened by the chemical dehydration. The specific immunolabeling with antiserum to growth hormone was much greater but more varied after short time GA-CF-FD than after long GA fixation. Epon surface topography over the granule area also differed: smooth after short time GA-CF-FD and furrowed after long GA fixation. Our results, demonstrating important differences in morphological parameters and immunolabeling density between two common preparation protocols, seem critical for more reliable interpretation in quantitative immunoelectron microscopy. We also emphasize the need for computer assisted image analysis and measurements in immunoelectron microscopy to ensure objective evaluations.


Bromodeoxyuridine immunohistochemistry for evaluating age-related changes in the rat mandibular condyle decalcified by intravenous infusion. Age-related changes in cell proliferation kinetics of the mandibular condyle were studied in Sprague-Dawley rats using bromodeoxyuridine (BrdUrd) immunohistochemistry in decalcified, paraffin-embedded tissues. Intraperitoneal injection of 40 mg/kg BrdUrd was given 1 hr before animal sacrifice. Continuous perfusion of EDTA solution via the left ventricle shortened the decalcification time. Immunohistochemical staining was performed with monoclonal anti-BrdUrd antibody. BrdUrd labeled cells, i.e., the S-phase cells, were clearly visible with well-preserved cytological detail. Their nuclei exhibited homogeneously stained granules. The labeling index in the intermediate zone of the condyle decreased with increasing age of the animals. This method is useful for evaluating physiological and pathological changes of the rat mandibular condyle as well as other bones and joints.


Calibration of quantitative histochemical methods: estimation of glycogen content of muscle fibers using the PAS reaction. A fairly simple method for calibrating microdensitometric histochemical assays is described. The method is based on paired biochemical and histochemical assays on single freeze-dried skeletal muscle fibers which differ widely in their properties. As an example, the method is applied to investigate the validity of the periodic acid-Schiff (PAS) reaction for the microdensitometric estimation of glycogen content. Some problems that may interfere with the calibration are discussed.


A method for thin sectioning heavily sclerotized cuticle of Odontotaenius disjunctus. Elytra of the bessbeetle, Odontotaenius disjunctus were thin sectioned after embedding in epoxy resin. Sections were cut with a diamond saw, ground to the desired thickness on a rotary grinder and polished. Tearing and distortion were reduced when compared to knifecut sections of heavily sclerotized cuticle.


A simple method for handling grids.

A simple method for handling grids. A simple method for handling electron microscope grids is described here. While assuring their identification and safety, this method provides improved handling, temporary storage, and identification of grids bearing ultra-thin sections, and in addition, provides a novel method for preparing bulk samples. Grids are attached at their edges to the weakly adhesive surface of a "Post-it" note pad which sits in a petri dish. The grids are safely immobilized on the pad, classified based on their location, and identified by convenient pad notation. Grid manipulation and identification are simplified using this device, which is easily assembled from readily available and inexpensive materials.


Capillarity in rat skeletal muscle: effects of rapid freezing versus perfusion fixation. We determined the effects of rapid freezing and perfusion fixation on fiber geometry and capillarity in rat skeletal muscle. Fiber areas were significantly decreased, and capillary densities significantly increased, in perfusion-fixed versus quick-frozen muscle. Significant differences in capillary-to-fiber ratios were not observed, suggesting that differences in fiber geometry, not the methods of quantifying capillaries, accounted for the differences in capillary density. We conclude that estimates of fiber geometry, capillarity, and diffusive gas conductances obtained from perfusion-fixed muscles are subject to significant error due to shrinkage.


[Effects of stress on relative leukocyte frequency and serum sodium and potassium concentrations in bovines]. The leucocyte and mineral profile changes were studied in bovines with different waiting time at the slaughterhouse. The stress induced by the waiting time at the slaughterhouse brought changes in relative leukocyte frequency, with inverted neutrophil:lymphocyte relation in animals with 24 hours of waiting time (1.45). However the sodium:potassium relation in the animals with 48 hours of waiting time was significantly lower (23.6, p < 0.001) than that almost normal in animals with 24 hours of waiting time (33.1). Also the high correlations between the parameters studied show an unique physiological or pathological situation. The found values point out hormonal changes similar to those in stress situations.


Effects of post-training beta-endorphin and Met-enkephalin administration on two-way active avoidance task in well-nourished and protein malnourished rats. Protein malnutrition during suckling period or throughout the life affects the hypothalamic beta-endorphinergic system of adult rats. In the present study, rats were undernourished during suckling by feeding their dams an 8% casein diet whereas well-nourished dams received a 25% casein diet from birth until weaning (21 day of postnatal life). After weaning, the offsprings were maintained with the same diet as their dams. When rats were 3 month-old, they were subjected to two-way active avoidance task. Protein malnutrition did not affect the performance in the two-way active avoidance task. Post-training beta-endorphin or Met-enkephalin administration impaired the retention of shuttle avoidance task in both well-nourished and undernourished rats. However, the amnesic effect of the peptides was only achieved in undernourished rats with higher doses of opioids when compared to the well-nourished rats. These data suggest that undernourished rats present alterations in opioid sensitivity which may be related to changes in the levels of beta-endorphin previously observed both in brain and hypothalamus of early undernourished adult rats.


Developmental changes in blood glucose and tissue carbohydrates in the fetal rat: effects of insulin and adrenaline. The ontogeny of glucose regulation was studied in the rat by measuring the levels of plasma glucose, tissue glucose and tissue glycogen from fetal day 15 (E15) to adulthood. Since insulin and adrenaline are important glucose regulators in the adult, we also tested the effects of these hormones on above variables. The main findings are the following: 1) Umbilical blood glucose was very low (25 mg/100 ml) from E15 to E19, increasing to 66 mg/100 ml by E21 but still below maternal levels (110 mg/100 ml). 2) Umbilical venous-arterial (VEN-ART) glucose differences were very small (1 mg/100 ml) from E15 to E17, increased to 6 mg/100 ml by E19, but dropped again becoming negative (-15 mg/100 ml) just before birth when umbilical arterial blood glucose rose above venous blood glucose. 3) Glucose and glycogen concentrations rose drastically in liver towards the end of gestation. 4) Tissue glycogen and, to a much lesser degree, glucose, fell after birth to rise again in adulthood. 5) Insulin injection caused an increase in liver glycogen from E17 onwards, and also increased glycogen in brain and placenta on E19. However, insulin decreased glycogen in brain and kidney by E21. 6) Adrenaline caused an increase in the umbilical venous-arterial glucose difference at E15 and E17 with a concomitant increase in liver, brain and heart glycogen at E15. By E21 the response of liver glycogen to adrenaline was drastically reversed. Our data suggest that the mechanism regulating glucose homeostasis changes half way through fetal development. Tissue self-regulation is replaced with a centralized mechanism similar to that of the adult.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of lipoxygenase and cyclo-oxygenase inhibition on oleic acid-induced lung oedema. The contribution of cyclo-oxygenase and 5-lipoxygenase metabolites on hemodynamics and oedema formation was investigated in 21 isolated rabbit lungs after a 10 min Oleic Acid (OA) infusion, by recording the changes on Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP). Lungs (n = 7) were pre-treated with indomethacin (cyclo-oxygenase inhibitor) 50 min prior to OA or with Diethylcarbamazine (5-lipoxygenase inhibitor) (n = 7) or not pre-treated at all (control group, n = 7). The FFR in the indomethacin group was significantly greater than in the control and Diethylcarbamazine (DEC) groups 12 min after OA (7.6 +/- 2.3 mg.min-1 vs. 2.3 +/- 0.8 mg.min-1 and 0.96 +/- 0.8 mg.min-1 respectively) (P < 0.01). The FFR in the control lungs 20 min after OA was significantly greater than the corresponding DEC value (4.2 +/- 0.5 mg.min-1 vs. 1.6 +/- 1.0 mg.min-1) (P < 0.01). Mean Pulmonary Artery Pressure (MPAP) increased both in control and indomethacin groups (16.0 +/- 2.0 Torr to 24.3 +/- 3.7 Torr after 20 min OA and 14.4 +/- 2.5 Torr to 24.6 +/- 3.6 Torr at 10 min after OA, respectively), but MPAP value in DEC group did not significantly change 30 min after OA (14.7 +/- 1.5 Torr to 16.0 +/- 2.3 Torr) (P > 0.05). So we conclude that the selective inhibition of the 5-lipoxygenase metabolites (leukotriene-5hete) may play a protective role in OA induced oedema, whereas the selective inhibition of the cyclo-oxygenase pathway may have a deleterious effect on the hemodynamics and endothelial permeability in our experimental condition.


[The posterior interosseous artery. Descriptive anatomy. Possibilities of clinical and orthopedic applications]. Study of 25 forearms of fresh cadavers, whose the arteries have been injected with colored latex. The posterior interosseous artery is known for its superficial branches, which allow to autonomise cutaneous dorsal flaps. Its way, along the ulna allows to imagine other possibilities by use of the constant branches of this artery, which supplies the proximal and the distal extremities of the bone. The proximal branch is the posterior recurrent radial artery, which supplies the posterolateral face of the proximal pars of the diaphysis, in touch of the insertions of the supinator muscle, and the lateral edge of the olecranon. The distal arteries shape 2 or 3 fascicles, which disperse on the extremity of the diaphysis and the cervical pars of the ulna. To realize a vascular pedicle with the posterior interosseous artery, two cases can be envisaged: use of the distal ulnar epiphysis and creating of a direct pedicle. use of the proximal ulnar epiphysis and creating of a recurrent pedicle.


[The intermetatarsal transverse ligaments and their connections with the tarsometatarsal articulations]. The authors have performed 20 systematical dissections of the distal part of the foot, conserved in the Toulon's liquor and 3 dissections of fresh cadavers. The last ones have been submitted at different puttings in charge before and after the resection of the intermetatarsal transverse ligament. The intermetatarsal transverse ligament is supple, extensible, but very strong. It constitutes the area of convergence of all the neighbouring fibrous structures and of several tendons of the foot. It connects together the heads of the metatarsus. It renders them jointly liable and its action is reflected above. By its modulating of the convergence of the metatarsus and their necessary associated palmar inclination, by its limitation of their divergence in relation with their dorsal inclination, it modulates and it limits the amplitude of the tarsometatarsal joints. It is helped for that by the little intermetatarsal transverse ligaments, whose the presence has been always confirmed. The metatarsus varus, very frequently associated with the hall valgus, means the escape of the first ray from the effect of the transverse intermetatarsal ligament.


[Extension of the fingers. III. Morphologic and structural study]. The volar fascicles of the interosseous muscles possess two separate components: the proximal and glenoidal one, the distal and aponeurotic other. The armature of the dorsal aponeurosis is constituted the deep, the central and the collateral expansions of the extensor digitorum muscles, and the interosseous muscles, whom are added the lumbrical muscles. The deep expansions are constant and are fixed respectively at the basis of the first phalanx. The central and the collateral expansions constitute equally the central and the collateral, then terminal tendons, which are respectively fixed at the basis of the second and at the third phalanx. The unitive structures: dossiere, triangular and retinacular ligaments are intricate with this of the armature and render jointly the whole. All the concerned fascicles have the mechanical and histological characteristics of the tendon.


[Extension of the fingers. IV. Morphologic and structural study]. The putting in tension of the dorsal aponeurosis of the digits induces its retraction and the nearness of its insertions on the basis of the 3 phalanges. It depends on the extensor digitorum, interosseous and lumbrical muscles. The aponeurosis is not a single driving belt, but set off in itself 3 types of reaction: 1) The gliding on the sides of the pyramid, which constitute the proximal epiphyses of the phalanges. It suppresses the central dorsal-ward tensions. 2) The displacement of the axes of insertion and rotation of retinacular ligaments inducing collateral volar-ward tractions. 3) The modifications of the way of the structures of transmission: at one time the lengthening of the way is induced by the interactions of the fibers; at other times a shortening is suppressed by the extension of the close proximal joint. Analysis of the different fibrous and fascicular interactions and translations.


[Extension of the fingers. V. Anatomic approach to lesions of the extensor apparatus]. The physiopathology of the main deformities of the fingers, induced by the injury of the dorsal aponeurosis of the fingers, is caused by an imbalance of forces: proximally between extrinsic and intrinsic muscles; distally between central and collateral structures. The ulna Claw, caused by the whole paralysis of the intrinsic muscles, can be corrected by an interosseous tenodesis on the basis of the finger. The boutoniere is induced by the exaggeration of the action of the collateral structures with respect to this of the central structures. The swan neck is induced by the exaggeration of action of the central structures with respect to this of the collateral structures. The surgical treatment consist to give back those structures their normal lengthening and way, or else to create new detours or shortenings, allowing to give back the balance. So, any structures, spared by the traumatism, will not injure by the surgeon.


[The bronchial arteries and their anastomoses with the coronary arteries]. We studied bronchial arteries (BA) and their anastomoses with coronary arteries in 53 adult subjects (30 female and 23 male, mean age 82) and one 2 month old child. Each subject had 1 to 4 BAs, born from an area on the anterior side of the descending aorta measuring less than 2 cm in diameter in 62 percent of the cases and never exceeding 4 cm in the other cases. In 6 cases BAs vascularize the left auricle; more than half of all cases had an anastomose with the coronary arteries: 11 with the right coronary artery and 9 with the left one. These anastomoses preserve the vascularization of the carina after a cardio-pulmonary transplantation. The may have a function of vascular supply in some coronarian patients and the study of associated coronary pathology gives confirmation of it in one fourth of the cases.


[Aspects of facial morphogenesis in the rat]. The facial morphogenesis of the rat has been observed by scanning microscopy on embryos taken every day from the 10th post-coitum day to term. Three points should be noted. Firstly the muzzle has at the beginning of the development an individuality which tends to diminish later. Secondly the vibrissae, whose primary elements are grouped in plates, are of great importance in the development of the muzzle. Finally, the opening between the internal parts of the nasal ridges is elevated with at the top a sharp angle, contrary to that of man which is little elevated and is arched. This could express the difference relating in each of the two cases the mesenchymatous naso-dorsal center, to which divergence between the two types of face, one with muzzle and the other without, would be linked. The primates presenting these two types, the tendency at the moment is to classify them using this discrimination. The study of the two corresponding aspects would supply a precious addition to these observations.


[Lymphatic drainage of the heart].

[Lymphatic drainage of the heart]. The study was carried out on 91 adult cadavers to point out clearly the lymphatic drainages of the heart into the blood circulation. 45 right and 63 left ventricles and 9 right and 5 left atria were injected by means of a green modified gerota medium. A right collecting trunk received its afferents from 29 right and 5 left ventricles, ran upwards in front of the ascending aorta, involved the left brachiocephalic nodes and opened into the left subclavicular veins but also in 1 case in 5 into thoracic duct. A left collecting trunk received its afferents from 59 left and 23 right ventricles, ascended along the pulmonary trunk, involved the right paratracheal nodes and opened into the right subclavicular veins. From the right paratracheal nodes were also injected the left tracheobronchial nodes in 14 cases, and then the left brachiocephalic nodes twice, the left paratracheal nodes in 3 cases until the thoracic duct once and directly the thoracic duct in the mediastinum in one case. Afferents from the right atria ran upwards the superior vena cava and involved the right brachiocephalic nodes but connected also with the right paratracheal nodes as did the afferents of the left atria too. The connections with the thoracic duct must be emphasized.


Type I familial amyloidotic polyneuropathy in Japan. We studied 107 cases and 64 carriers of type I familial amyloidotic polyneuropathy (FAP) residing in 16 districts in Japan. The age of onset of illness ranged from 20 to 71 years old, with a mean of 40.1 +/- 12.8 years (SD). One quarter of the cases were late-onset patients who developed the disorder after age 50. Asymptomatic carriers older than age 50 accounted for 20% of total carriers, with the oldest carrier being a 94-year-old woman. All the patients had a variant transthyretin with a methionine-for-valine substitution at position 30 with a mean serum level of 9.78 +/- 3.27 (SD) mg/dl. The serum level did not significantly differ by gender in either patients or carriers, nor between patients and carriers. Incomplete penetrance of clinical expression was shown in eight cases. This study indicates that there is a considerable variety in age of onset, progression and geographic distribution of type I FAP in Japan.


Paraneoplastic cerebellar degeneration: successful early detection and treatment of cancer through characterization of the anti-Purkinje cell antibody. Paraneoplastic cerebellar degeneration (PCD) is thought to be caused by an autoantibody against both tumor and neuronal tissue. Such autoantibodies are most frequently detected in patients with gynecological or breast cancer, and are designated as anti-Yo. We report here a patient with PCD whose underlying cancer could not be detected despite extensive tumor survey. IgG in her serum and cerebrospinal fluid reacted with the cytoplasm of cerebellar Purkinje cells immunohistochemically. On immunoelectron microscopy, the endoplasmic reticulum and Golgi complex were stained. Her IgG bound to the 58 kD band on immunoblots of cerebellar proteins. A reaction was also observed with the recombinant proteins deduced from the complementary DNA clone encoding a neuronal cell antigen reported by Sakai et al (Ann Neurol 28: 692, 1990). Based on these results, successful early resection of fallopian tube adenocarcinoma was performed. It is crucially important to characterize these PCD related autoantibodies for the early treatment of underlying malignant tumors.


Effect of interferon (IFN) on refractory idiopathic thrombocytopenic purpura: administration of 6 million units of recombinant IFN alpha-2b. Five patients (six courses) with refractory idiopathic thrombocytopenic purpura (ITP) were given 6 million units of recombinant interferon (IFN) alpha-2b in 12 doses to achieve an improved response rate compared to previous studies using 3 million units. From the initial IFN administration, the platelet count increased from a pre-treatment level of 20.7 +/- 17.7 x 10(3)/microliters (mean +/- SD) and reached its first peak in weeks 2 or 3 of therapy (p < 0.05). In week 5, the platelet count made its second and maximum peak (66.5 +/- 57.9 x 10(3)/microliters; p < 0.05). A relatively good response of the platelet count (an increase to > 50 x 10(3)/microliters) was observed in three patients (four courses) out of five. These responses were not much faster or more improved than in previous reports, and a dose of 6 million units may be too large to treat some ITP patients. The platelet-associated IgG level showed a tendency to be reduced with IFN therapy. The mechanism for the increase of the platelet count may be the modification of platelet autoantibody production.


A 72-year-old female with adult Still's disease. We treated a 72-year-old woman with adult Still's disease. The diagnosis was made on the basis of a prolonged, high grade, quotidian fever, polyarthritis, maculopapular skin rashes and exclusion of other possible diseases. A high serum ferritin value was a key factor both in making the diagnosis and in the follow-up. The patient responded to the administration of oral prednisolone at 30 mg/day, which was tapered to 10 mg/day, with no recurrence of symptoms. This disorder can be an important cause of prolonged fever in the elderly as well as in the younger population.


Mixed connective tissue disease associated with protein losing enteropathy: successful treatment with intravenous cyclophosphamide therapy. A patient with mixed connective tissue disease who developed protein losing enteropathy (PLE) is described. The PLE and other symptoms improved dramatically after monthly intravenous administration of 700 mg/day cyclophosphamide three times combined with oral prednisolone, while they were ineffective to the treatment with intravenous methyl-prednisolone 500 mg per day for 3 days. The serum level of CA125 antigen paralleled the severity of symptoms, signs and laboratory data associated with PLE. Thus, pleural effusion, ascites, edema and hypoalbuminemia improved along with the decrease in the level of CA125, suggesting that CA125 might be a marker of the activity of PLE.


A rare case of extramedullary plasmacytoma in the mediastinum. A rare case of extramedullary plasmacytoma in the mediastinum is reported. An 80-year-old man was admitted for further examination of a mediastinal tumor. Chest computed tomography (CT) revealed a large mediastinal mass and right interlobar pleural effusion. Needle biopsy under CT guidance established a diagnosis of plasmacytoma. Immunohistochemical staining revealed that the tumor cells were producing monoclonal IgA kappa. Serum immunoelectrophoresis revealed an IgA kappa monoclonal component with a serum concentration of 5,040 mg/ml. The bone marrow aspiration was normal. Bone roentgenogram and bone scintigram showed osteoporosis but no neoplastic lesion.


Chondroid chordoma presenting with hypopituitarism. A 28-year-old man with chondroid chordoma, an uncommon variant of chordoma, is reported. The patient presented with visual disturbance and hypopituitarism. The latter is a rare complication of intracranial chordoma. The preoperative diagnosis of chondroid chordoma of the skull base was based on unique findings on computed tomography and magnetic resonance imaging studies. The development of the tumor over six years suggests that the prognosis of chondroid chordoma may be poor in younger patients, as recently reported. Although chondroid chordoma is very rare, it should be included in the differential diagnosis of hypopituitarism.


Mesenchymal hamartoma of the liver: report of an adult case and review of the literature. A case of mesenchymal hamartoma of the liver incidentally found to be a hyperechoic mass by abdominal ultrasonography in a 62-year-old male is described. Computed tomography and magnetic resonance imaging of the liver confirmed the presence of a well-demarcated inhomogeneous mass in the left medial segment. Hepatic arteriography revealed the mass to be generally hypovascular. Histopathologic diagnosis of the resected specimen was a solid form of benign mesenchymal hamartoma, a rather rare lesion for the patient's age. Fifteen adult cases of hepatic mesenchymal hamartoma in the literature including the present case are reviewed.


Disseminated intravascular coagulation in lupus erythematosus with acute liver damage. A case of disseminated intravascular coagulation (DIC) in a patient with systemic lupus erythematosus (SLE) with acute liver dysfunction is described. A 37-year-old man with SLE developed acute DIC and marked liver damage after fracture of the right clavicle and pharyngitis. Treatment with high-dose steroids, heparin, antithrombin III, gabexate mesilate, and antibiotics resulted in prompt improvement. The recovery of an SLE patient after acute DIC and marked liver damage is considered very rare. We report here such a case and discuss the previous reports.


Primary extramedullary plasmacytoma of the lung. A case with primary plasmacytoma of the lung is described. The patient, a 55-year-old Japanese female, who simultaneously had a pulmonary plasmacytoma and bladder carcinoma. The bladder tumor was treated with transurethral resection. Pathologically, the bladder tumor was a non-invasive, papillary transitional cell carcinoma, grade II. The lung tumor was located in the right upper lobe and upper lobectomy was performed. The tumor measured 2.8 x 2.7 x 2.0 cm and had a white-yellowish cut surface. Histologic, electron microscopic and immunohistochemical examinations of the lung tumor revealed monoclonal proliferation of plasma cells (IgA, lambda light chain). There was no evidence of multiple myeloma.


Disseminated cryptococcosis presenting with adrenal insufficiency and meningitis: resistant to prolonged antifungal therapy but responding to bilateral adrenalectomy. A case of disseminated cryptococcosis with features of primary adrenal insufficiency and meningitis in an immunocompetent host is presented. Despite antifungal chemotherapy, neither meningitis nor bilateral adrenal gland enlargement was improved. Aspiration biopsy of the adrenal gland revealed necrotic tissue with numerous fungi, suggesting that the adrenal glands were the focus of the persistent fungemia. Removal of bilateral adrenal glands led to improvement by making the patient more sensitive to antifungal chemotherapy.


Locally invasive pulmonary aspergillosis in a healthy man successfully treated with oral fluconazole. A 74-year-old healthy man with locally invasive form of pulmonary aspergillosis (PA) is reported. Chest X-ray film showed a segmental infiltration of right upper lobe (RUL) without cavitation, and the transbronchial lung biopsy specimen contained numerous hyphae of aspergillus species. Complication of bronchial asthma, or bronchiectasis were absent, and hyphae of aspergillus were present at only one segment of RUL. After 5 months of therapy with oral fluconazole, the PA had dramatically improved. Fluconazole was found to be effective for the locally invasive form of PA in a healthy man.


Mosaic expression of dystrophin in the cerebellum of heterozygote dystrophic (mdx) mice. The monoclonal NCLDys1 revealed the presence of dystrophin in the Purkinje cells of normal mice but not of mdx mice and a mosaic staining in Purkinje cells of heterozygote mdx mice. Dystrophin was present in the soma and the dendrites of the dystrophin positive Purkinje cells and was absent in both regions of the dystrophin negative Purkinje cells. However, the polyclonal antibody d10 produced a uniform labeling of all Purkinje cells not only in the normal mice but also in mdx and heterozygote mdx mice. This staining was attributed to a reaction of this antibody not only with dystrophin but also with a different isoform of dystrophin or with a dystrophin related protein present even in mdx mice.


Analysis of the tissue distribution and inheritance of heteroplasmic mitochondrial DNA point mutation by denaturing gradient gel electrophoresis in MERRF syndrome. MERRF (Myoclonic Epilepsy and Ragged-Red Fibres) syndrome is one of the maternally inherited diseases for which a mitochondrial DNA (mtDNA) point mutation has recently been identified. The mutation is always heteroplasmic, that is normal and mutant mtDNA coexist within the same individual. We studied mtDNA heteroplasmy in two families with MERRF syndrome, using a denaturing gradient gel electrophoresis technique that avoids the errors in the evaluation of wild/mutant mtDNA ratios caused by restriction enzyme cutting in the situation of amplification of a heteroplasmic DNA. In two patients, the proportion of muscle mutant mtDNA was in agreement with the severity of muscle mitochondrial proliferation, energy defect and fibre type I predominance. In nine patients from three generations of one family, mutant mtDNA proportion in leukocytes was in relative agreement with the clinical severity of the disease. Transmission of mutant mtDNA through these three generations did not show any tendency toward homoplasmy. Homogeneity of the mutant mtDNA proportion among different tissues from one patient was demonstrated in brain, liver, muscle and heart but a possibility of divergence of the mutant mtDNA proportion during mitosis was documented in cultured skin fibroblasts.


Experimental regeneration in canine muscular dystrophy--1. Immunocytochemical evaluation of dystrophin and beta-spectrin expression. The expression of dystrophin and beta-spectrin was examined from 1 to 56 days in regenerating muscle fibres in normal and dystrophic dogs, following necrosis induced by the venom of Notechis scutatis. Normal and dystrophic dog muscle regenerated at an equal rate and new myotubes were present in both at the periphery of necrotic fibres by 3 days. In normal dogs dystrophin was detected in the sarcoplasm of the regenerating fibres by 3 days and was localized to the plasma membrane by 4 days. The localization of dystrophin is independent of beta-spectrin and was detected before beta-spectrin, which was not observed until 5-6 days. Normal peripheral labelling of both was restored by 14 days in normal dogs. Normal beta-spectrin labelling of regenerating dystrophic fibres was also restored by 14 days and is not dependent on the presence of dystrophin in dystrophic dogs. A proportion of regenerating fibres in normal and dystrophic dogs showed weak immunolabelling of beta-spectrin prior to 14 days. This is a feature of immature muscle fibres. Antibodies to different domains of dystrophin bound to the periphery and sarcoplasm of regenerating fibres in dystrophic dogs, particularly during the first 7 days of regeneration, but the fluorescence was less intense than in normal dogs. Weak labelling with antibodies corresponding to the C-terminus of the rod domain of dystrophin persisted on dystrophic regenerating fibres up to 21 days. This may relate to developmental isoforms of dystrophin.


Terminal intramuscular motor innervation and motor end-plates in thyrotoxic myopathy. Thyrotoxic myopathy was induced in 64 mice. Examination of their muscles revealed excessive axonal branching and degenerative changes of preterminal axons. Moreover, the mean diameter of their end-plates decreased and the levels of end-plate cholinesterase appeared to be reduced. In 43 patients with thyrotoxic myopathy, increased axonal branching and degenerative changes of preterminal axons, similar to those in the experimental mice, were also seen. The possibility that excess thyroid hormone may interfere with axonal transport or neuromuscular interactions is discussed.


Age-dependent axonal loss in nerve biopsy of patients with xeroderma pigmentosum. We describe the histomorphometric changes in the superficial peroneal nerve biopsy from 13 patients with xeroderma pigmentosum (XP). The mean age at time of biopsy was 15 yr (range 2.5-24 yr). The clinical examination was normal in the two youngest patients and showed absence of the deep tendon reflexes, with choreo-athetosis in ten patients. In addition, in the three oldest patients there were cerebellar signs, ataxia and Babinski signs. The nerve biopsy showed an age-dependent decrease of myelinated fibres, which was mild in the youngest and severe in the oldest patients. This was associated with rare acute axonal degeneration, sparse axonal regeneration, rare axonal atrophy and few onion bulb formations. These findings suggest a neuropathic process. This neuronal degeneration seems to be a progressive and stereotyped phenomenon in XP.


Cognitive functions in Duchenne muscular dystrophy: a reappraisal and comparison with spinal muscular atrophy. In order to clarify cognitive functions in Duchenne muscular dystrophy (DMD), we performed a new controlled neuropsychological study. IQ (WISC-R), verbal skills (fluency, confrontation naming and syntax comprehension) and memory abilities (BEM) were studied in two matched groups; 24 DMD children and 17 spinal muscular atrophy (SMA) children aged 12-16 yr. A significant difference appeared between the DMD and SMA patients: only in the DMD group were there significant disabilities in certain specific functions and normal scores in others. Despite similar education, the DMD children more often had significantly greater learning disabilities. There were more DMD left-handers. Verbal IQ was significantly low whereas performance IQ was at a normal level. DMD children also performed poorly in reading tasks and in some memory functions such as story recall and verbal recognition. Specific cognitive disabilities in certain DMD children, not seen in SMA children, suggest a relationship with a DMD genetic disorder.


A randomized controlled trial of early surgery in Duchenne muscular dystrophy. We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.


Chronic myopathy in a patient suspected of carrying two malignant hyperthermia susceptibility (MHS) mutations. Malignant hyperthermia (MH) is a pharmacogenetic myopathy triggered by a variety of anaesthetic agents and muscle relaxants. In humans, susceptibility to MH is inherited as an autosomal dominant trait, and susceptible patients do not show a clinically relevant myopathy unless having suffered from a MH crisis. Homozygosity for the MHS trait is thought to be an uncommon finding, and so far only a few cases of patients suggested to be homozygous for MH on the basis of pedigree information were reported and described as having a more severe form of this condition resulting in clinical symptoms also in the absence of triggering agents. We report clinical findings in a patient with chronic myopathy beginning at the age of 2 yr and associated with a number of unique features, the most important being a family history of MHS present in both parents. She became symptomatic with marked muscular weakness and elevated serum CK levels. A muscle biopsy showed a distinct enlargement and increase of muscle mitochondria. In the in vitro contracture test the patient's muscle responded with unusually high contractures already at basal levels of triggering agents indicating a particularly severe MHS condition. DNA markers for the MHS1 locus, described previously on chromosome 19q12-13.2 in Irish and Canadian pedigrees, could not be used to confirm her homozygous state because our molecular genetic studies had previously excluded the MHS trait in this pedigree from this locus.(ABSTRACT TRUNCATED AT 250 WORDS)


Variability of the expression of muscle mitochondrial damage in ocular mitochondrial myopathy. In this study we comparatively analysed deltoid histochemistry, biochemistry and mitochondrial DNA (mtDNA) in two groups of ten sporadic ocular mitochondrial myopathies (OMM), respectively with and without ragged red fibres (RRF). (1) All but one RRF--patients presented the mild form of OMM with blepharoptosis but without ophthalmoplegia; (2) the occurrence of cytochrome c oxidase deficient (COX-) fibres was significantly higher in the RRF+ group, but four RRF- cases also showed COX- fibres; (3) no difference was observed in biochemical findings between the groups; (4) two RRF- patients without COX- fibres showed mtDNA heteroplasmy; (5) in two RRF- patients without deltoid mtDNA deletion, biopsy of an eyelid muscle showed significant mitochondrial alterations. These results suggest that the expression of a mitochondrial defect can vary and that the absence of RRF in a skeletal muscle biopsy does not necessarily rule out the diagnosis of OMM, if other data support that.


Unusual course of nemaline myopathy.

Unusual course of nemaline myopathy. A boy with onset features common for a moderate form of congenital nemaline myopathy, after some years developed scapulo-humeral syndrome. Extra- and intrafusal muscle fibers overloaded with rods and indicating focal degenerative changes were seen in the first biopsy. The biopsy was later repeated and revealed an improvement in muscle architecture with a dramatically decreased number of rods. This transformation suggests that rods, as well as Z-line streaming, might be a reversible anomaly of Z-discs.


Polyglucosan body myopathy: a new case.

Polyglucosan body myopathy: a new case. We report a 51-yr-old woman with late-onset progressive weakness affecting proximal limb muscles. Muscle biopsy revealed a vacuolar myopathy with accumulation of amylopectin-like polysaccharide resembling the polyglucosan found in type IV glycogenosis and adult-onset polyglucosan body disease. A biochemical study ruled out specific enzymatic defects known to cause storage of this abnormal material. Our case confirms the existence of a 'polyglucosan body myopathy' as a distinct clinicopathological entity in which the biochemical defect is unknown.


Synthesis and secretion of lipids by long-term cultures of female rat hepatocytes. The objective of this work was to characterize lipid metabolism in long-term cultures of adult rat hepatocytes from female rats and explore the potential use of this culture system to study the effect of hormones, drugs and toxic chemicals on it. Hepatocytes, seeded on a feeder layer of 3T3 cells, maintained for 2 weeks their typical morphology. The cultures were able to take up [14C]acetic and [14C]oleic acid from the culture medium and incorporate them into lipids. The synthesis and secretion of lipids by [14C]acetic acid-labeled cultures had a maximum value after 11 and 13 days in culture. Triacylglycerols were the main lipidic species synthesized and secreted by hepatocytes (up to 67% of the total lipids); they also synthesized and secreted phospholipids, cholesterol and cholesterol esters from [14C]acetic acid. Similarly, [14C]oleic acid-labeled cultures synthesized and secreted mostly triacylglycerols (up to 60-70% of the total lipids), but they were also able to incorporate the labeled precursor into both cellular and secreted phospholipids and cholesterol esters. The activity of glycerol-phosphate-dehydrogenase, marker enzyme of glycerolipid synthesis, decreased slightly during the culture time whereas the activity of malic enzyme, marker of fatty acid synthesis, increased. Our results show that long-term cultures of female rat hepatocytes are able to synthesize and secrete several lipids, specially triacylglycerols, from both [14C]acetic and [14C]oleic acid for at least 2 weeks and that they maintain enzyme activities related with the synthetic pathways of glycerolipids and fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)


Segregation of viral double-stranded and single-stranded DNA molecules in nuclei of adenovirus infected cells as revealed by electron microscope in situ hybridization. Formation of progeny viruses in the nuclei of HeLa cells infected with adenovirus type 5 was studied at the ultrastructural level by in situ hybridization techniques allowing specific detection of either viral double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA). Prior to the initiation of replication of viral genomes, infective DNA molecules which entered the nucleus of the target cell were randomly distributed among host chromatin fibers including nucleolus-associated chromatin. They were double-stranded, that is, without single-strand breaks. Such association of viral DNA with host condensed chromatin also occurred in mitosis. The initiation of viral genome replication occurred simultaneously with the appearance in the nucleoplasm of small fibrillar regions containing intermingled viral dsDNA and ssDNA. Later, at the intermediate stage of nuclear transformation, viral dsDNA and ssDNA molecules were almost entirely separated into two contiguous substructures. At this stage, viruses were observed occasionally in the vicinity of viral ssDNA accumulation sites. Still later, an additional substructure developed in the centre of the nucleus which consisted of large quantities of viral dsDNA, traces of viral ssDNA and abundant viruses. Portions of viral ssDNA were attached to some viruses even at late stage of nuclear transformation, an association which strongly suggests the occurrence of encapsidation of at least some of the viral genomes while they are still engaged in replication.


Drosophila C virus cycle during the development of two Drosophila melanogaster strains (Charolles and Champetières) after larval contamination by food. Drosophila C virus (DCV) cycle during Drosophila melanogaster development was studied after feeding contamination at the first, most sensitive, instar (L1). Two Drosophila strains were examined and compared. Presence of DCVC in apparently healthy animals (L3 larvae bred on a contaminated rearing medium and adults coming from larvae which were grown on medium containing DCVC) was demonstrated by biological tests. Using the immunofluorescence technique, DCV was exhibited in the diseased Charolles larvae, in the lumen of the digestive tract and in the basal part of gut cells which is in contact with the haemolymph. On the contrary, in Charolles larvae which seemed 'healthy', DCV was exhibited only in the lumen of the digestive tract at the apical boundary of the gut cells. But DCV typical protein capsid was not shown in the tissues of Drosophila L3 and adults. However, C virus remained in Drosophila tissues even after host metamorphosis and would seem to interact with Drosophila cells. Hypotheses are proposed concerning the intracellular state of Drosophila C virus in this case.


Properties of chicken cardiac dystrophin. We investigated the presence of dystrophin by immunoblot and immunofluorescence analyses, negative staining, rotatory shadowing and immunogold electron microscopy in chicken cardiac muscle. Saponin was found to be better than Triton X-100 for providing a new 'dystrophin-enriched' solution for use in biochemical studies of the molecule. By Western blot analysis, only a 400-kDa band was revealed with polyclonal antibodies directed against a central region (residues 1178-1723) of the dystrophin molecule and no cross-reactions with other proteins or degraded products were observed. Specific cleavage of the dystrophin molecule showed that the central rod-shaped domain corresponded to a resistant 'core'. This structure might rigidify the protein. By immunofluorescence, dystrophin was localized at the periphery of cardiac ventricular cells. The molecule was examined by electron microscopy and found to have variable lengths (140-160 nm for the monomeric from and about 260 +/- 10 nm or more for oligomeric forms). These oligomeric structures are considered to be associated molecules which are only partially overlapped lengthwise. The precise distribution of dystrophin within the cardiac muscle was determined by visualisation of gold particles in immuno-electron microscopy. Gold particles were found on the sarcolemma with no evidence of any association with cytoplasmic structures. The present data provide further details on the cardiac dystrophin molecule and suggest that its capacity of self-association may elasticize the dystrophin dimer.


Immunodetection and localization of protein(s) related to retinal S-antigen (arrestin) in kidney. S-antigen (arrestin) is a cytosolic protein which regulates phototransduction in retinal rods. A protein immunologically related to S-antigen was identified in fractions from soluble extract of bovine kidney enriched by gel filtration or by immunoaffinity chromatography using a polyclonal antibody to retinal S-antigen. On immunoblots, this protein was recognized by a panel of monoclonal antibodies (mAbs S2D2, S1A3 and S9E2) directed against different S-antigen epitopes and displayed the same apparent molecular mass (48 kDa) as retinal S-antigen. All three mAbs revealed a specific immunoreactivity by indirect immunocytochemical technique on rat kidney sections. The three mAbs recognized some but not all glomerular cells, identified as epithelial cells by immunoelectron microscopy using the mAb S9E2. Both mAbs S2D2 and S1A3 gave a diffuse cytoplasmic staining in all tubule cells. Proximal tubule cells exhibited a weak immunoreactivity, whereas distal and collecting tubule cells were strongly labeled. In contrast, the mAb S9E2 immunoreaction was restricted to a cell subpopulation from distal and collecting tubules corresponding to intercalated cells identified by immunoelectron microscopy. With the mAb S9E2, the labeling of proximal tubule cells was localized in the apical region of the cytoplasm. These results suggest that two or more 48-kDa proteins immunologically cross-reactive with retinal S-antigen are present in kidney. The observed pattern of distribution is in keeping with the hypothesis that such proteins could play a role in the regulation of G-protein-related receptors present in renal glomerulus and tubule epithelial cells.


Developmental changes in the heterocellular epidermis of Pelobates syriacus integument. Changes in characteristic components of the skin epidermis of the large tadpole of Pelobates syriacus were studied throughout its development. The fate of two specific cells in the skin epidermis was followed, from the young tadpole to the adult was studied. It was found that flask-shaped type cells in the tadpole epidermis which are PAS-positive, stain with peanut lectin (PNA). There is no detectable band 3 in the premetamorphosed stages, and mitochondria-rich cells are very rare. This pattern of staining changes completely upon metamorphosis: the PAS-positive cells, specific to the tadpole epidermis disappear, and the mitochondria-rich (MR) cells in the adult skin epithelium react with polyclonal anti-band 3 antibody. Western blot analysis showed the presence of a band 3-like protein of about 95 kDa, only in the adult epithelial extract, corroborating the immunocytochemical observations. The finding of the presence of band 3-like protein in the MR cells of Pelobates, is similar to the observations made in the skin of other amphibian species. On the other hand, the binding of peanut lectin to MR cells is species-specific, since it does not react with the MR cells in the skin epithelium of Pelobates syriacus.


Sample size for a dose-response study.

Sample size for a dose-response study. This paper deals with a method of sample size allocation for a dose-response study assuming a logistic model for the dose-response curve. The method is based on the precision with which one wishes to estimate the dose that would produce the efficacy resulting in a clinically important difference from a placebo. An example is given to illustrate the methodology. The main development of the paper is for a binary response and is suitably modified for a continuous variable.


A statistical test to assess changes in spontaneous behavior of rats observed with a computer pattern recognition system. A computer pattern recognition system, RAPID, has been used to study the spontaneous motor activity of Sprague-Dawley rats. This system produces a large number of measures of the activity of control and experimental groups in any given study. The large number of measures involved presents a problem when one attempts to decide whether the behavioral activity of the exposed group differs from that of the control group. Extensive Monte Carlo studies have been performed in an attempt to develop and validate a simple statistic to be used in such decisions.


Exploratory data analytic techniques to evaluate anticancer agents screened in a cell culture panel. Information theory is used to provide a measure of selectivity, i.e., the degree to which a drug has preferential toxicity or growth inhibition for one or a few cell lines from a large panel. The selectivity measure is intended to complement a measure of differential growth inhibition in evaluating the drug development potential of a new compound. Also, a similarity measure obtained from information theory is used to classify drugs according to their pattern of responses on the panel. Some structure-activity relations emerge. This work is applied to 176 agents selected to be tested by the National Cancer Institute in about 50 cell lines.


The analysis of a multiple-dose, combination-drug clinical trial using response surface methodology. We consider the situation where a multiple-dose, combination-drug clinical trial is conducted to identify one or more combinations that satisfy regulatory requirements. Generally, these requirements involve a compound hypothesis with multiple comparisons. The min test has been shown to be an optimal alpha-level test for testing a single combination drug. Analysis procedures in a multiple-dose, combination-drug study have typically involved classical ANOVA models or multiple regression models in a response surface methodology (RSM) framework. An inferential procedure based on an ANOVA model uses a screening test to address multiple comparison issues and multiple min tests to explicitly identify combinations satisfying regulatory requirements. An exploratory procedure based on RSM modeling is used to build a segmented linear model and a stairstep linear model to describe dose-response relationships. The two procedures are mutually supportive of one another in providing a broader assurance in the identification of effective combinations.


A comparison of expiration dating period estimation methods. Two methods of estimating expiration date have been compared. For a drug whose potency is expected to decrease with time, method 1 fits a linear regression line to the stability data, calculates a 95% lower confidence limit of the true degradation line, and estimates the expiration date by comparing the confidence limit with the lower specification limit. Method 2 calculates a 95% lower confidence limit b1 of the slope of the true degradation line, constructs a new line y" using b1 as its slope, and finally estimates the expiration date by comparing y" with the lower specification limit. In this work we show that in most practical situations, method 1 estimates greater expiration date than method 2.


A comparison of linear and exponential models for drug expiry estimation. While a large portion of pharmaceutical stability data is known to follow an exponential model decay, linear modeling of this data for expiry estimation is the norm. Expiry predictions based on linear and exponential fits to stability data were made to estimate the bias due to the linear fitting. It was found that within the usual expiry limits on drug potency, the difference between the model fits is relatively trivial. In cases of loss of potency greater than 15%, small assay variability, or great disparity between the length of the study and the time of expiry prediction, however, there is a nontrivial difference in the predictions and the exponential model is preferable.


False alarm rates of statistical methods used in determining increased frequency of reports on adverse drug reaction. Several statistical methods have been proposed or used in the determination of an increase in frequency of reports of adverse drug reactions. Some of the methods are based on large sample approximation or equal sample sizes assumption. The actual type I error may differ significantly from the predetermined nominal level of 5% when the methods are applied to rare adverse events. Simulated false alarm rates of the methods were compared under the assumption of 10 or less expected reports in the reference period.


Statistical comparison of stability study designs. Studies are routinely conducted during development of a new drug to investigate the effect of strength, package, batch, storage condition, and storage time on stability of the dosage form. A typical study will have three batches, several strengths, several packages, and several storage conditions. Thus, if every batch by strength by package combination is tested for every storage condition, i.e., if a complete factorial design is used, a substantial expense is involved. To reduce expense, a matrix design is commonly used; e.g., only the smallest and largest bottles are tested. Fractional factorial-type designs for stability studies are proposed, and the statistical powers of various designs are compared.


Alternative approaches to the analysis of binary and categorical repeated measurements. The purpose of this paper is to describe, illustrate, and compare a number of different approaches to the analysis of repeated binary and categorical data. These approaches include empirical generalized least squares and generalized estimating equations, as well as traditional log-linear modeling methods. It is shown that the interpretation of the parameters in the various models depends critically on the type of model fitted. In particular, we contrast the population-averaged and subject-specific models. Two example data sets are used to illustrate the approaches, and throughout we concentrate on methods that can be easily implemented.


General estimation of relative potency using prior information. A general point and interval estimator of the log relative potency is exhibited in closed form, which incorporates prior information on the log relative potency for symmetrical as well as asymmetrical parallel line bioassay. The point estimator turns out to be a weighted average of the usual estimator and the prior mean where the weights are determined by the prior variance.


Expanded confidence intervals, one-sided tests, and equivalence testing. An argument, based on expanded confidence intervals, is given for always performing one-sided tests. However, if goals are not one-sided and "follow-up" inferences are required, then the usual two-sided confidence intervals (corresponding to two-sided tests) are generally appropriate. When equivalence testing is required (the goal being to show that treatments are "not too different"), expanded confidence intervals are more efficient than Westlake's symmetrical confidence intervals.


Directional baseline differences and type I error probabilities in randomized clinical trials. Adequate correction for baseline differences that occur in the same or opposite direction from inferred treatment effects in a simple randomized experimental design is addressed by Monte Carlo simulation. Results confirm that the analysis of covariance (ANOVA) can provide appropriate correction whether baseline means differ significantly by chance in the same or opposite direction from the inferred treatment effect. The results from analysis of simple pre-post difference scores are highly dependent on the direction of chance baseline deviations in relation to the directional treatment effect that would be inferred from rejection of the null hypothesis. The attempt to correct for baseline differences by expressing outcome as percentage of baseline entails directional bias that depends on the location of the zero point, the direction of change, and the level of correlation between baseline and follow-up measurements.


Baseline correction in a two-way randomized blocks design. Randomized blocks designs are used in clinical psychopharmacology research to test the hypothesis that relative effectiveness of different drug treatments depends on the type of patient being treated. Monte Carlo methods were used to evaluate the adequacies of different approaches to statistical control over baseline differences in such a design with special concern for the treatments x blocks interaction effect. Given the usual assumptions, analysis of covariance (ANCOVA) was shown to provide adequate baseline correction with consequent unbiased tests for the treatments x blocks interaction, as well as the main effect for the randomized treatments. Tests relying on simple pre-post difference scores and percentage change scores evidenced seriously conservative or nonconservative bias in the test for treatments x blocks interaction effect, a bias that depended on the direction of the corresponding interaction effect observed in the baseline measurements alone. This is discussed as a serious matter because the interaction effect in a randomized blocks design is a common basis for the claim of specific indications of drug treatments for particular types of patients.


Demonstration of the reproducibility of treatment efficacy from a single multicenter trial. According to the Food and Drug Administration's Guidelines for the Format and Content of the Clinical and Statistical Sections of New Drug Applications, approval of a new drug "should be supported by more than one well-controlled trial and carried out by independent investigators. This interpretation is consistent with the general scientific demand for replicability." Nevius has described a four-point proposal for assessing statistical evidence in a single multicenter trial. Briefly, these four points are: (1) combined analysis shows significant results, (2) consistency over centers in terms of direction, (3) consistency over centers in terms of producing nominally significant results in centers with sufficient power, and (4) evidence of efficacy after adjustment for multiple comparisons. What is not clear from Nevius' proposal is how to quantify whether the amount of evidence in a single multicenter trial is equivalent to that from two separate trials. It is proposed that the post hoc subdivision of a multicenter trial may address this issue if the inherent multiple testing problem is accommodated. A minimax statistic is developed to test the hypothesis that the effect of the drug has been reproduced in a single multicenter trial. Monte Carlo simulation is used to generate the distribution of the minimax statistic under the null and several alternative hypotheses. Data from a multicenter trial are used to demonstrate the technique. Bootstrapping is used to determine the null distribution of the minimax statistic.


On assessment of bioequivalence under a higher-order crossover design. In bioavailability studies of two formulations of a drug, the standard two-sequence, two-period crossover design is usually considered to assess bioequivalence. The standard two-sequence, two-period crossover design, however, may not be useful when differential carryover effects are present. In addition, it does not provide independent estimates of intrasubject variabilities for the two formulations. To overcome these problems, alternatively, a higher-order crossover design may be considered. In this paper, we derive statistical methods based on Schuirmann's two one-sided tests procedure for assessing bioequivalence for some commonly used higher-order crossover designs. Four designs, including Balaam's design, the two-sequence dual design, and two four-period designs (with two and four sequences), are considered. The relative merits of these designs as compared to the standard two-sequence, two-period design are discussed. Two examples concerning bioequivalence are used to illustrate the use of these methods.


QCIS: a SAS-based relational database/query system for the Current Index to Statistics. A portable, menu-driven software system for the Current Index to Statistics (CIS) cumulative database is described. The SAS-based system converts the CIS datafiles into a relational SAS database and provides windows for users to easily define their queries. Query execution may occur in batch or interactive mode.


Computerized assessment in neuropsychology: a review of tests and test batteries. This article contains detailed reviews of 13 computerized neuropsychological and performance test batteries and six stand-alone computer tests. Tasks found on these instruments are described and tables illustrate which batteries employ which measures. In addition to issues of reliability and validity, special considerations apply to computerized assessment. These issues are discussed and readers are provided information to help them assess computerized tests in relation to their particular clinical and research needs. Since many computerized tests were developed as performance assessment tools, the relationship between performance and neuropsychological assessment is examined.


Memory deficits in Alzheimer's patients: a comprehensive review. Despite considerable experimental work on Alzheimer's disease (AD), the underlying cognitive mechanisms as well as the precise localization of neuropathological changes critical for memory loss remains undefined. A review of the neuropsychological literature on long-term memory deficits in AD patients suggests that AD patients display (a) a pervasive deficit of explicit memory, (b) a partial deficiency of implicit memory for verbal and visuoperceptual material (as measured by repetition priming procedures), and (c) a substantial sparing of implicit memory for visuomotor skills. The explicit memory loss is likely a result of encoding as well as consolidation difficulties. A faulty lexical-semantic knowledge structure appears responsible for deficient repetition priming effects. Since neuropathological changes diffusely affect the brain of AD patients, establishing a clear relationship between localization of cerebral lesions and memory deficits is particularly difficult. Nevertheless, data suggest that extensive involvement of the hippocampal-amygdala complex plays a major role in explicit memory loss. Damage to associative cortical areas likely is involved in repetition priming deficits. The relative integrity of primary motor and sensory cortical areas and of the basal ganglia likely subsume, by contrast, the normal learning of visuomotor skills.


[Novel possibilities for treatment of parkinsonian tremor and other abnormal movements by stimulation of the nucleus ventralis intermedius thalami]. Chronic thalamic stereotactic stimulation has been performed in 22 patients with disabling tremor and poor response to drug therapy: 17 parkinsonian tremors and 5 essential tremors. Our first results are presented with a mean follow-up of 26 months. Parkinsonian tremors 17 = complete disappearance: 12, clear improvement: 5. Essential tremors 5 = complete disappearance: 3, clear improvement: 1, failure 1 cured by thalamotomy. Choreic or ballistic dyskinesias 7 = complete disappearance: 5, clear improvements: 2. Dystonic dyskinesias 3 = complete disappearance: 2, failure: 1. This new stereotactic procedure permits to control easily not only tremor but also L-Dopa induced dyskinesias: choreic or ballistic dyskinesias and biphasic dystonic dyskinesias. The place of this surgical treatment among the other therapeutic possibilities is discussed.


[Pseudomonas aeruginosa infection in cystic fibrosis: predominance of a single strain and the influence of antibiotic therapy and the environment]. We analysed the implantation pattern and persistence of Pseudomonas aeruginosa in the tracheobronchial tracts of patients with cystic fibrosis, and investigated the relation of this bacterium with the environment and antibiotic therapy. We used four different techniques to ensure the precise and detailed identification of isolates. In particular, chromosomal differences were assessed by pulsed field electrophoresis (pulsotype determination). Sputum samples were collected from 8 patients, from 6 to 22 years-old, over a period of 19 to 24 months. Only a single strain was isolated from samples from each five patients taken at different times, and there was a predominant strain in the samples from two others. Patient 8, aged 14, was free of infection throughout the study. None of the infections was eradicated by antibiotic therapy (an association of two antibiotics for 15 days at one or two months interval). The strains isolated from two patients became resistant to imipenem: 3 out of the 4 resistant strains were the result of mutation in the resident, susceptible strain. Swabs were taken from the environments of infected patients and were tested for P. aeruginosa: this bacteria was found in three sites, and two of these contained an isolate with the same pulsotype as the strain responsible for the infection, whereas no P. aeruginosa was detected in the environment of an uninfected patient. The detailed and accurate identification of the isolates (by pulsotyping) enabled us--to show that each infected patient was infected by a single or predominant strain,--to investigate the relationship of these strains with those in the environment and the effects of antibiotic therapy.


Is anorexia nervosa a neuropsychological disease? Evidence for central nervous system, and more particularly cortical, etiology of anorexia nervosa is reviewed. Topics covered are neuropsychiatric comorbidity, inheritance patterns, the neurobiology of body-image disturbance and of the eating function, perinatal and alcoholic insult to the brain, neurochemical and neuroelectric disturbance, anatomic and metabolic brain imaging, and neuropsychological impairment. It is concluded that there is indeed an important neuropsychological etiological dimension to anorexia nervosa. The profile most frequently associated with anorexia nervosa is right posterior hypometabolism, followed by right anterior hypermetabolism, both associated with right-sided abnormal electroencephalogram spiking. It is also proposed that bulimia consists of a "positive" neurological subtype and that restricting anorexia represents a "negative" neurological subtype. Priorities for further research into anorexia nervosa are specified to include twin adoption studies, brain electrical topography studies, postmortem histological studies, and experimentally inspired neuropsychological studies.


[Health education at school].

[Health education at school]. The major health problems of our time cannot be solved only by the physicians. Despite important scientific advances, the number of cancers, cardiovascular diseases, bronchopathies and drug addictions increases. Prevention is a way of improving this alarming situation. Actually, the health of our contemporaries largely depends on themselves. For example, in a world without tobacco, one third of cancers and ninety per cent of lung and larynx tumors would not occur. Thus, the protections of human being's and nature's health are equally essential. Both are the State responsibility. Including hygiene in school education is a critical necessity in view of teaching young French students good health practices by which they will be impressed all their life. School has not only to teach but also to educate. This wish is in agreement with the Declaration of Child Rights voted by the General Assembly of United Nations on November 20, 1959. Unfortunately, the signatory nations do not put in practice this resolution which states that children must be protected against social risks. Descartes believed that "if the human species can be improved the means must be searched in medicine". This essential mission belong today to the educative system from home to school. At the dawn of the third millennium this "children institution", as Montaigne said, may provide health to future generations.


[Secondary auditory risks from listening to portable digital compact disc players]. The recent availability of portable high-performance digital disc-players in addition to cassette players, and with an increased dynamical range, has enhanced the risk to hearing for their users. The present study aimed at attempting to evaluate this hazard. After selection of a digital player, 12 normally-hearing voluntary subjects were exposed to listening to two records (classical music and hard-rock) at an acoustic level complying with safety regulations. Their temporary threshold shifts (TTS) were determined at 4 and 6 kHz just after exposure. The 0.5 kHz auditory thresholds were also measured as a control. At 4 and 6 kHz, the average value of TTS was 5 dB (standard deviation 3.1 to 5.9 dB). There was no statistically significant difference neither between the TTS at 4 and 6 kHz (p > > 0.05), not between TTS for the two types of music. A voluntary subject, suffering from a mild high-frequency hearing loss, was also tested. His TTSs were higher than average and may have corresponded to slower recovery (may be non monotonous). Therefore special caution should be recommended in such cases. The measurements have pointed out that very high acoustic levels could be reached (125 to 127 dBA) with a Leq (1 hour) od 110 dBAi.e. much higher than tolerable levels. Thus there is a serious risk to hearing, possibly increased by high level transients. Moreover, better headphones are likely to provoke TTS also above 8 kHz, which might be evaluated by high-frequency audiometry.(ABSTRACT TRUNCATED AT 250 WORDS)


[Humanitarian surgical missions].

[Humanitarian surgical missions]. Humanitarian surgical missions are one of the most promoted aspects of french humanitarian action in the third world through the media. This action, previously limited, is now well-organised and its actors have become real professionals. The working conditions of this kind of surgery, are characterised by its lack of means and insecurity. Logistic, technical and ethic constraints have led to propose specific training suitable for these special conditions.


[Human transmissible dementia: prion diseases?]. Subacute transmissible spongiform encephalopathies (STSE) represent a cause of presenile dementias, found in man (Creutzfeldt-Jakob disease, Gerstmann-Straussler syndrome, Kuru), in sheep and goats (scrapie), in cattle (bovine spongiform encephalopathy) and in various mammals. It seems that the frequency of the human spongiform encephalopathy (HSE) is more frequent than thought up to now and an alimentary origin is not to be discarded. Many discussions are held concerning the nature of the transmissible agent: virus, virino, prion? Isolation of an abnormal protein, the isoform PrPSc resulting from an unknown alteration of a protein PrPc encoded in man by the chromosome 20 is presently the basis for seeking the cause of transmissible dementias. Molecular genetic studies of the gene PrP have demonstrated the existence of many mutations: are they the actual cause of the STSE or only a favouring factor? The existence of familial sporadic or infectious forms of HSE might be explained by alterations of the conformation of PrPc into PrPSc, able to induce this structure modification to last when thereafter the synthesis of the normal protein is achieved. The "chaperone" protein model can be questioned in this respect. For the moment the research work is developed into characterization of humoral or genetic markers able to detect the predisposed subjects in high-risk families. HSE are also an interesting model for other types of dementias, especially the Alzheimer disease which is still the preferred target of research in this field.


[Genetic engineering in plants].

[Genetic engineering in plants]. Until recent years, plant genetic was involved in heredity studies through the analysis of segregations in progenies after crossing. New potentiality arose as genetic tools with the use of dissociated plant elements, transforming and cultivating them in vitro. When plants are regenerated from manipulated tissues, new structures of varieties (clones) new genotypes (transgenic plants) and new regulations of genes expression (vitrovariants) open new ways for plant genetic engineering. Progressively these technological tools are integrated in the methods of plant breeding. Yet all possible consequences of these new types of heredity and of these new genetic structures must be evaluated. As first priority the analysis of possible incidences in the field of food, nutrition and health gives the basis for diagnostics and organisations aiming to avoid the release of genotypes which could have unwanted effects.


[Current trends in the field of animal husbandry]. The progress achieved over the past 30 years in the areas of nutrition, physiology, genetics and prophylaxis has lead to the intensification of animal production. Feed additives have been one of the factors involved in this evolution often wrongly accused of being at the origin of a so-say degradation of the quality of the products. Where nutritional quality is concerned, it must be observed that the genetic determinism and the homeostasis of the organisms maintain practically constant the proportions of the elementary constituents (amino acids, fatty acids) and the composition of the basic components (proteins, phospholipids) of the living matter. However, the relative proportions of these components (proteins/lipids) can be modified by genetic and nutritional factors. If the quantitative modifications of composition are easily balanced by the diversity of the human diet, they can heavily influence the technological and organoleptic properties of the individual animal products. The on-going evolution, namely the incidence of the new biotechnologies, should not modify this situation, if only to lead to the production of animals whose tissue and product composition would be adapted to the technological and dietetics demand. The nutritional balance should then be assumed by a better educated and informed consumer.


[Biotechnology using modified microorganisms]. Few microorganisms, as compare to their high diversity, are used for human needs. They can produce molecules of interest, process fermentation, protect crops, treat wastes or clean environment. Molecular technics and genetic engineering are new tools offer to geneticists which breed microorganisms for years. Using them, it is now possible, theoretically, to introduce any gene in any organism. Some examples are given concerning genetic modifications in yeasts and lactic acid bacteria to optimize agrofood processes and to improve nutritive and flavour characteristics of fermented products like bread, beer, wine, cheese, meat, vegetable juices... In spite of scientific and industrial interest of the new technologies, limiting factors can explain that genetically modified microorganisms are not routinely used in agrofood yet. First, risks assessment on human health and environment are still in debate, but their is a consensus, within the scientific community, to consider that new characteristics of improved microorganisms are more important than the technics used for their construction. Second, regulations turn out to impose constraints susceptible to discourage technological innovations. At least, the public perception about the new technologies appears, actually, as the major factor to limit their development.


[Ionization].

[Ionization]. Having demonstrated the wholesomeness of irradiated food, then scientists had to prove that nutritional impact of food irradiation was minor. Animal testing, vitamin and amino acid measurements in irradiated food, and no longer in solutions, have demonstrated that recorded changes, at commercial doses i.e. 1 to 10 kGy did not present any hazard. It must be noted that sensory qualities of radiosensitive food products like milk, are altered well before nutriments.


[Novel technologies in the food and agriculture industry]. Product innovation obtained by means of new processes or novel raw materials or ingredients is not a recent event. The consumer today has access to a large array of products from which he may compose a nutritionally balanced diet with no inherent questions regarding food safety or wholesomeness. The controversial opinions of the consumer with regard to certain new technologies applied to food should not be confounded with the possible existence of a related unacceptable risk of the corresponding products. Scientific knowledge, from which such technologies are the result, provides a solid basis for the establishment of food safety. The principle of risk assessment should be applied by the manufacturer whenever innovative technologies are introduced in the creation of new food products.


[The control of foodstuffs at the beginning of 1993]. The 1st January 1993 the frontiers between the Member States of the European Community and the customs controls will disappear. The abolition of this type of control won't affect the food security. The french administration has strong legal rules to ensure the protection of consumer's health. The regulations prepared by European Community in order to allow the free circulation of goods also ensure a high level of consumer's protection. In case of harmonization, each Member state keeps some rights when there are risks for consumer's health. In absence of community regulations the principal of mutual acknowledgement aiming to avoid the barriers to trade can then not be applied for health and security necessities. The authorities controls are now resolutely inserted in an european context: priority to controls during production, harmonized methods of intervention to promote the required acknowledgement of controls enforced in each Member state, involvement in an european alert system, and development of the cooperation between the national administrative authorities of inspection. Regarding the matter of food security the authorities need the assistance of the scientific community and of its national and international representative organisations. They take an essential part in diagnosing, emergency and advice during the elaboration of regulations. Their power should be even greater with the implementation of the european scientific cooperation.


Stable triple helices are formed upon binding of RNA oligonucleotides and their 2'-O-methyl derivatives to double-helical DNA. Pyrimidine oligoribonucleotides bind to the major groove of double-helical DNA at homopurine.homopyrimidine sequences. They recognize Watson-Crick base pairs by forming T.A x U and C.G x C base triplets via Hoogsteen hydrogen bonding. The stability of these triple helices is much higher than that of triple helices formed by oligodeoxyribonucleotides as shown by an increase of the temperature at which half-dissociation of the third strand occurs. When the 2'-hydroxyl group of ribose moieties is replaced by 2'-O-methyl substituent, triple helix stability is further increased.


[Is the centrosome a dynamic structure?]. Ca++ effects on the organization of human centrosomes isolated according to Bornens et al., were followed by double immunofluorescence technique. Ca++, at millimolar range, is able to modify the distribution of the pericentriolar material (PCM) and to decrease the intercentriolar distance. In the light of these results, we have slightly modified the centrosome isolation method and shown that centrosomes isolated in the absence of EDTA have several structural differences from the previously described structure. In particular, centriole diameter is decreased by a transverse sliding of microtubule triplets with respect to each other, suggesting the possibility of movements within centrioles themselves.


TAP1 and TAP2 transporter genes and predisposition to insulin dependent diabetes mellitus. Genetic control of insulin dependent diabetes mellitus (IDDM) is mainly dependent on HLA genes in the major histocompatibility complex (MHC). The participation of TAP1 and TAP2 genes, located in the MHC region and coding for antigenic peptide transporters, was investigated in 116 IDDM patients and 98 normal controls using oligotyping after DNA amplification. The TAP2-B allele had a dominant protective effect, additive to that of the DR2 haplotype but antagonist to the susceptibility associated with the DR3 and/or DR4 haplotypes. The TAP2-A allele, in the homozygous state, had a predisposing effect. TAP1 allelic distribution did not differ among IDDM patients and controls. These data argue in favour of the role of peptide transporter gene in diabetogenesis.


[Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies]. Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.


[Hospital costs: results of empirical studies]. The DRG hospital payment system will be introduced in France in 1993-94 under the name of GHM ("groupes homogènes de malades"). However the method for evaluating costs is mainly based on past trends and, as a matter of fact, they exclude innovative care behavior from the doctors. Three new methods are therefore experimented: (i) standardized operation protocols; (ii) observation of consumed products and time of health personnel; (iii) observation of the costs resulting from the tariffs of the Social Security administration. The empirical studies were carried out in Montpellier and Nantes, two middle size cities of France.


[Application of Bayes discriminatory analysis to malaria stratification in Hainan province]. The present study was conducted to explore a new method for stratification of malaria endemicity. Several socioeconomic and geographic factors deemed appropriate to be employed in association with malaria epidemic potential were deal with Bayes discriminatory analysis.55 local villages in 12 counties of Hainan province were selected for socioeconomic survey, among which 33 villages were taken as the modelling sample and 22 villages were the non-modelling sample. The questionnaire contained a total of 12 relevant items. After socioeconomic inquiry was performed, the data were analysed through Bayes discriminatory theorem. Six important factors ware selected, i.e. topography (X1), proportion of labour forces (X4), income per person (X5), house structure (X8), knowledge of malaria control (X10), frequency of over-night stay in mountain forest (X12). Three discriminatory function formulas referring respectively to hyper-, meso-, and hypo-endemicity were set up. These 3 discriminatory function formulas were further applied to fit the endemicity of 33 model-sampling villages and 22 non-model-sampling villages. The agreement rate were 91.0% and 77.3% respectively.


[Road violence among young people aged 15-24 years]. During the last decade, the annual number of deaths by road accident in France was approximatively 10,000 whose 3,000 aged 15-24. Road accidents were, and remain, the first cause of death among youngsters and young adults, preceding suicide. Since the early 70's, public authorities were aware of the problem and laws and regulations were implemented, aimed at curbing the disastrous trend. Some results were obtained, but the situation is far from satisfactory. Social, economic, psychological conditions of modern society are favouring road violence, which is today among the most acute public health issues, as far as the young are concerned. Road accidents vary according to the age of the young. Moreover, its rate varies according to the region within the country.


[Management or strategy within hospitals]. A study was conducted on certain number of hospital departments to identify the kind of variables which determine decision-making and decision-implementation as concerns innovations, both in medical process and hospital organization. Among the internal variables, one can quote the size of the hospital, its ownership type, its main field of activity, its situation in the local health structure, its resources ... Among the external variables one can quote the supply of care at the local level, the local health networking, the state of technological development, interrelationship of the health sector, the manufacturing sector and the research sector, the presence of managerial tools and skills...


[An epidemiological investigation of outbreak of measles among temporarily living people in Shenyang]. This paper reported an outbreak of measles occurred in a factory of Heping District in Shenyang in March 1989. All of the six diagnosed cases were temporarily workers, which represented 15 percent (6/40) of total workers. No secondary cases were detected. The results of epidemiological and laboratory analysis showed that this outbreak was caused by an imported case, and only spread in temporarily workers. Furthermore, we discussed that under the condition that measles incidence was limited under control level, even imported cases could not cause epidemic of measles. So, it is indicated that the flowing people can easily cause accumulation of susceptible people in cities, which may result in outbreak of some infectious diseases.


[Econometric and ethical validation of regression logistics. Reducing of the number of patients in the evaluation of mortality]. In general, a large number of patients is needed to conclude whether the results of a therapeutic strategy are significant or not. One can lower this number with a logit. The method has been proposed in an article published recently (Cost-utility analysis of early thrombolytic therapy, Pharmaco Economics, 1992). The present article is an essay aimed at validating the method, both from the econometric and ethical points of view.


[Survey on tick vectors of Lyme disease spirochetes in China]. Since 1987 we have been studying on Lyme disease in China. There were 71 isolates of Borrelia burgdorferi recovered from six species of ticks including Ixodes persulcatus, Ixodes granulatus, ixodes rangtangensis, Haemaphysalis concinna. Haemaphysalis bispinosa and Haemaphysalis longicornis, and 55 isolates from Ixodes persulcatus collected from Heilongjiang, Jilin, Liaoning, Nei-Monggol, Hebei and Xinjiang region (province). Ixodes persulcarus is the dominant species accounted for more than 80% of the total number of collected ticks, 20 or 45 per cent adult Ixodes persulcatus contained spirochetes as determined by direct immunofluorescence in the northeast and northwest. The seasonal change of adult Ixodes persulcatus is coincident with that of the patient with Erythema migrant. These studies proved that Ixodes persulcatus play the leading role in transmission of Borrelia burgdorferi to human in north region of China. It is not clear what species of tick is the principle vector in the south region of China, though the spirochetal isolates were cultivated from Haemaphysalis bispinosa, Ixodes granulatus and Ixodes rangtangensis. Comparison between Chinese strains of spirochetes from ticks and American strain B31 in Ultrastructure, monoclonal antibodies reaction and outer surface protein profile revealed certain differences.


[A case-control study on the transmission factor of hepatitis A outbreak of Wenzhou in 1988]. This investigation described a pair-matched case-control study on transmission factors of hepatitis A outbreak in Wenzhou City in earlier 1988. The results during early stage of the epidemic showed that, for the people having had meal in eating houses OR was 9.08, whereas for those having eaten clams OR was 3.63. The results during middle and later stages showed that, for the contactor of hepatitis A patients OR was 5.02, while for those having eaten clams OR was 4.29. The result of this investigation showed that this outbreak was related to eating in eating houses during the early stage of the epidemic, but related to both contact with HA patients and eating clams during middle and later stages of the epidemic.


[Immune response to hepatitis B revaccination in children]. In this report, we investigated the efficacy of revaccination with hepatitis B vaccine in thirty-eight children after primary immunization. The results showed that anti-HBs immune response developed in 37 children after revaccination. with a response rate of 97.4% (37/38). The geometric mean titres (GMTs) of anti-HBs at 3rd weeks, 3rd and 6th month after the booster dose reached 824.1, 407.7 and 193.6IU/L, which were 24.5, 12.1 and 5.8 times higher than those before the booster dose (33.6IU/L), respectively. The peak levels reached at 3rd week after revaccination. However anti-HBs levels declined rapidly, the percentage of antibody decrease were 50.5%, 76.5% at 3rd and 6th month after booster dose respectively. The immune response to revaccination gave a strong correlation to the primary immunization. In conclusion, our findings indicated that a good response to revaccination with a dose of 10 micrograms of hepatitis B vaccine in children were observed.


[Detection of Toxoplasma antibody among pregnant women and newborns in Jingmen]. 748 sera from lying-in women and newborns were tested for anti-toxoplasma antibody with the method of IHA. The positive rate was 13.1% in lying-in women, and 4.01% in newborns. The occurrence of spontaneous abortions in anti-toxoplasma antibody positive women was 36.7%, which was higher than that in normal lying-in women. The occurrence of Fetal Distress and Asphyxia Neonatorum were 33.3% and 40% respectively, both of which were higher that those in normal newborns.


[Surveillance of infectious diseases among the persons going abroad through Harbin Port]. This paper reported the results of the health examination of 7447 persons going abroad and 70 persons returning home. The results showed that 349 cases carried HBsAg (with the positive rate 4.7%), and 41 cases with pulmonary tuberculosis (with the positive rate 0.6%), 4 cases with venereal disease (with the positive rate 0.05%). No AIDS and syphilis cases were detected. Suitable measures were taken for the these cases to meet the goal of surveillance.


[Surveillance on ViII phage typing and antimicrobial susceptibilities of S. typhi strains in Guangdong Province]. 72 S. typhi strains collected in Guangdong were tested for their Vi II phage types and their antimicrobial susceptibilities. The result of Vi II phage typing showed that 62 strains could be divided into definite types. The result of antimicrobial susceptibilities showed that, as national standard reference strains, all the 72 local strains were susceptible to choloramphenical, gentamycin, neomycin and polymycin B and were of different resistance to other 14 antimicrobial agents. The resistant profiles of strains isolated in different ages shared no significant difference. Choloramphenical remains Commonally selectable to treat Typhoid.


[A carboxylated latex agglutination test for the serological diagnosis of human and animal brucellosis]. A carboxylated latex agglutination test was developed for detecting antibodies in sera of human and animals with Brucellosis. The latex was chemico-linked with B. melitensis 16M extracted with 5% NaCl. Comparing with physico-sorbent latex antigens in detecting antibodies in sera of human and animals with Brucellosis, the chemico-linked latex is more stable, more specific and more sensitive. In addition, preparation of chemico-linked latex and some factors affecting the result of the test were also described in the paper.


[A case-control study on the relationship between neonatal hyperbilirubaemia and usage of oxytocin during labour]. Analytical method for multiple exposure level data of matching (1:1) case-control study was employed in the study on the relationship between neonatal hyperbilirubinemia and usage of oxytocin (during) in labour. The result showed that there was significant association between them (chi 2 = 15.538, df = 3, P = 0.0014). The odds ratios for various exposure level were 1-5.9 (u): OR = 1.085; 6-8.9 (u): OR = 5.5; 9 + (u): OR = 3.687 and the log linear trend among them was significant (chi 2 = 11.991, df = 1, P = 0.0005).


[Study on the immunization effect of measles vaccine by capture-EIA]. Capture-EIA was applied to detect specific IgM antibody (SIgM) to measles virus in paired sera from 72 children before and after primary vaccination and HI antibody was also tested simultaneously. The SIgM and HI antibodies were not detected in 72 prevaccinated and 7 post-inoculated sera by both the capture-EIA and HI test. Among the 65 sera-conversion samples by HI test in the 15 days after immunization, comparing with the results obtained by the capture-EIA, the comformability were 83-100%. The results showed that there was a certain relationship between the level of SIgM produced and the vaccine dose inoculated. So, the results indicated that for investigation of the effect of immunization with measles vaccine. Capture-EIA is as good as HI test.