Megalencephaly in sudden infant death syndrome

The fresh brain weights of 79 infants with sudden infant death syndrome (SIDS) were tabulated and compared with expected "normal" brain weights. The series included 47 males and 32 females. Their ages ranged from 8 days to 16 months with a median of 2.5 months. The weights of all these brains were above the 50th percentile for age, and 64 of 79 brains (81%) were above the 95th percentile, including 15 (19%) at or above the 99.9th percentile. The ratio of the brain stem plus cerebellum weight to the whole brain weight of 93 formalin-fixed brains from victims of SIDS showed that the cerebrum was disproportionately heavier in most cases. No gross or microscopic evidence of cerebral edema was noted to account for the heavier weight. The significance of these findings is debatable. The increase in brain weight was less obvious in infants younger than 1 month of age but accelerated after that age. The brain weights of infants with SIDS may represent the really "normal" weights, since these patients were not known to be ill prior to death. If the brain weights of SIDS infants are really heavier than "normal," the possibility must be considered that disproportionately rapid growth of the brain during early infancy may be detrimental to the neural control of the cardiorespiratory system.     

Ensuring data quality in a multicenter clinical trial: remote site data entry, central coordination and feedback

In an ongoing multicenter clinical trial, "Treatment Strategies in Schizophrenia," the five participating sites have the capacity to perform a variety of tasks or study functions independently. These tasks include (a) verification of diagnostic eligibility through the use of computerized decision algorithms; (b) assignment of patients to treatment based on prognostic indicators using a computerized randomization algorithm; (c) entry of data into a microcomputer using a clinical trial data management system that performs simple range and missing data item checks; and (d) regular transfer of all data to the central coordinating team. The clinical trial data management system employed allows for both independent site functioning and assurance of consistency across sites. The integration of a variety of software outside the main data management system provides the central coordinators with the tools to monitor critical data as it is collected, as well as the capacity to assess the flow, quality, and uniformity of the ongoing trial.     

Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer

Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.     

Behavioural strategies used by the hookworms Necator americanus and Ancylostoma duodenale to find, recognize and invade the human host

The infective third-stage larvae of the hookworms Necator americanus and Ancylostoma duodenale infect their human hosts by active skin invasion, but A. duodenale is in addition capable of oral infection. The behaviour of the larvae when crawling on surfaces has already been described. Here we analyse in various in vitro systems the other behavioural invasion phases: activation, penetration, and orientation within the host. The larvae normally remained in a motionless, energy-saving, resting posture. An activation to sinusoidal locomotion was stimulated in both species by similar cues such as touch, vibration, water currents, heat, light, and chemicals. Human breath in addition stimulated searching and waving (nictating) behaviour, which facilitates a change-over to the host. Activating cues in air streams were warmth and moisture; CO₂ activated only in combination with warmth and/or moisture. Penetration behaviour in both species was stimulated by warmth and skin extracts. The stimulating components of skin extracts were fatty acids, but their stimulating characteristics differed from those inducing schistosome cercarial skin penetration. After penetration into agar substrates, both species showed thermo-orientation, but only A. duodenale followed gradients of serum. The directing serum cues were not amino acids and glucose (the supposed cues for schistosome blood vessel localization), but Ringers solution attracted the larvae. The host-finding and host-invasion behaviour of both hookworm species is well adapted to the invasion of the human skin, and there seems to be no particular adaptation of A. duodenale behaviour to the oral infection mode. Hookworm host-finding behaviour is not as complex as that of schistosome cercariae but seems well adapted to the ecological conditions in the transmission sites.     

Studies on the distribution of polioviruses in Surinam

Summary A study of the distribution of polioviruses in Surinam was undertaken by a regular virological examination of stool specimens from children of the 1–5 year age group for a period ranging from the beginning of 1964 to the middle of 1969. All three types of poliovirus were found to circulate continuously in the child population. A correlation was found between an increased level of poliovirus circulation and the appearance of clinical poliomyelitis. The application of trivalent oral vaccine at times that a clear increase of the level of poliovirus circulation was observed, had only a partial effect on this level since the acceptance rate for the vaccine was too low.Conducted with the support of the Surinam Government and the Netherlands Foundation for the Advancement of Tropical Research (WOTRO), and with technical assistance of Miss L. Kletter and Mrs. A. Arron.on temporary detachment at the Central Public Health Laboratory, Paramaribo, Surinam.     

Der Einfluss kondensierter Phosphate auf die Eisen-Resorption

Zusammenfassung Es sollte untersucht werden, ob die kondensierten Phosphate Tetranatriumpyrophosphat, Natriumtripolyphosphat, Hexametaphosphat, Kaliummetaphosphat und Plasmal die Eisenresorption beeinträchtigen. Als Maßstab für diesselbe galten die Hämoglobin- und Erythrocytenregeneration und die Gewichtszunahme anämischer Ratten. Die Anämie wurde durch Phenylhydrazinhydrochlorid-Injektionen bzw. eine eisenarme Ernährung (Milchdiät) hervorgerufen. Bei den herrschenden Versuchsbedingungen konnte ein nachteiliger Einfluß der getesteten Substanzen auf die Eisenresorption nicht nachgewiesen werden. Auf Grund dieser Versuche und allgemeiner Überlegungen wurde geschlossen, daß dies überhaupt unter physiologischen Bedingungen unwahrscheinlich ist.     

Public health impact of isoniazid-resistant Mycobacterium tuberculosis strains with a mutation at amino-acid position 315 of katG: a decade of experience in The Netherlands

A previous limited study demonstrated that Mycobacterium tuberculosis isolates with a mutation at amino-acid position 315 of katG (Delta315) exhibited high-level resistance to isoniazid and were more frequently resistant to streptomycin. In the present study, isoniazid-resistant M. tuberculosis isolates from 8,332 patients in The Netherlands (1993-2002) were screened for the Delta315 mutation. Isoniazid resistance was found in 592 (7%) isolates, of which 323 (55%) carried Delta315. IS6110 restriction fragment length polymorphism analysis showed that Delta315 isolates occurred in clusters, suggesting recent transmission, at the same frequency as isoniazid-susceptible isolates. In contrast, other isoniazid-resistant isolates clustered significantly less frequently. Delta315 isolates were high-level isoniazid-resistant, streptomycin-resistant and multidrug-resistant significantly more often, and may have a greater impact on public health, than other isoniazid-resistant isolates.     

Photoelectric recording of mechanical responses of cardiac myocytes

A method to monitor contraction of isolated myocytes by transmicroscopic photometry is illustrated. Two photodiodes are mounted inside an inverse microscope used for visual control of a cell. Illumination of one diode varies in proportion to changes in cell length. The contraction signal is amplified in a comparator circuit. Spatial resolution of the device is in the order of 1 m which corresponds to about 5% of cell shortening in the fully activated state of contraction. The method was tested on isolated myocytes from guinea-pig ventricle. Optical records of contraction in response to action potentials or during voltage clamp compare well with the contractile behaviour of multicellular preparations.