Gastrointestinal and eating problems in SCN1A-related seizure disorders.

OBJECTIVE: Our study aimed to describe the prevalence and characteristics of gastrointestinal and eating problems in Dravet syndrome (DS) and other SCN1A-related seizure disorders and to determine the association between the occurrence of gastrointestinal and eating problems and core features of DS. METHODS: Gastrointestinal and eating problems were assessed with a questionnaire in a Dutch cohort of participants with an SCN1A-related seizure disorder. Associations between the number of gastrointestinal and eating problems and core features of DS, seizure severity, level of intellectual disability, impaired mobility, behavioral problems, and use of anti-seizure medication, were explored by multivariate ordinal regression analyses. Symptoms were divided into the categories dysphagia-related, behavioral, and gastrointestinal, and were assessed separately. RESULTS: One hundred sixty-nine participants with an SCN1A-related seizure disorder, of whom 118 (69.8%) with DS and 51 (30.2%) with Generalized Epilepsy with Febrile Seizures Plus / Febrile Seizures (GEFS+/FS), the non-DS phenotype, were evaluated. Gastrointestinal and eating problems were highly prevalent in DS participants, 50.8% had more than three symptoms compared to 3.9% of non-DS participants. Of participants with DS, 17.8% were fully or partly fed by a gastric tube. Within the three different symptom categories, the most prevalent dysphagia-related symptom was drooling (60.7%), distraction during mealtimes (61.4%) the most prevalent behavioral symptom, and constipation and loss of appetite (both 50.4%) the most prevalent gastrointestinal symptoms. DS participants who use a wheelchair (odds ratio (OR) 4.9 95%CI (1.9-12.8) compared to walking without aid), who use ≥3 anti-seizure medications (ASM) (OR 5.9 95%CI (1.9-18.2) compared to <3 ASM) and who have behavioral problems (OR 3.0 95%CI (1.1-8.1) compared to no behavioral problems) had more gastrointestinal and eating problems. CONCLUSION: Gastrointestinal and eating problems are frequently reported symptoms in DS. Distinguishing between symptom categories will lead to tailored management of patients at risk, will improve early detection, and enable a timely referral to a dietitian, behavioral expert, and/or speech therapist, ultimately aiming to improve the quality of life of both patients and caregivers.

[SLE (systemic lupus erythematosus)-related clinical features in dogs]. / SLE (systemische lupus erythematodes) gerelateerde ziektebeelden bij de hond.

Three dogs presented with lameness and/or vague clinical signs. The results of immunological tests were suggestive of a SLE-related syndrome. ANA (antinuclear antibodies) titres were very high, 1:40960 in one of the dogs, and antibodies against single-stranded DNA were detected. Complement levels were very low in two dogs. Antibodies against histones were detected in both the serum and the synovial fluid of one dog. In another dog there was evidence of high concentrations of PCNA antibodies, which in humans are specific for SLE. It is concluded that the three dogs showed signs of a syndrome possibly related to SLE. The description of the clinical signs and of the laboratory diagnostics serve as a clinical demonstration to draw colleagues' attention to this nosologically interesting clinical syndrome and to the need to request specific immunological tests when this syndrome is suspected.

[Extra-intestinal infections caused by Vibrio spp. in The Netherlands]. / Extra-intestinale infecties door Vibrio spp. in Nederland.

Six patients with serious cellulitis or ear infection due to Vibrio vulnificus, V. parahaemolyticus or V. alginolyticus are described. Four patients were infected during the summer in the Netherlands and two outside the Netherlands. Contact with seawater was the most probable source in four patients. In two patients the infection, caused by V. vulnificus, was transmitted by eel. This is a new way of transmission.

[Good Laboratory Practice (GPL) and quality control in Dutch laboratories]. / Good Laboratory Practice (GLP) en kwaliteitsbewaking in Nederlandse laboratoria.

A review of the origin of GLP (Good Laboratory Practice) and ISO (International Standard Organisation) directives is followed by a number of definitions of concepts such as quality, guarantees of quality, quality systems, etc. by laboratories (NEN 2653). These requirements are discussed in the paper. Certification is one of the guarantees of quality assessment by laboratories. Certification of laboratories is carried out by STERLAB (Laboratory Accreditation Board of The Netherlands) or the CCKL (National Coordination Committee for Quality Assurance for Health Care Laboratories in The Netherlands). In addition to certification, laboratories in the Netherlands are extremely active as regards external quality control (QC). QC is carried out by the various occupational groups. The paper finally closes with a discussion of future developments regarding quality control and certification in medical and veterinary diagnostic laboratories.

Corynebacterium haemolyticum septicemia in a girl with mononucleosis infectiosa.

Many isolates of Corynebacterium are dismissed as contaminants by technicians and microbiologists in the laboratory. We report the isolation of Corynebacterium haemolyticum from the blood of a 15-year-old girl with mononucleosis infectiosa and conclude that this species should be considered as a possible pathogen and not only be regarded as innocent bacteria, particularly in the immunocompromised host.

[Maternal immunity]. / Maternale immuniteit.

After a short introduction concerning immune system function, the physiological and pathophysiological aspects of the foeto maternal relationship are discussed. Ontogeny of the immune system, the foetus as an in utero 'foreign body', and maternal immune competence during pregnancy and lactation are all considered. The process of presentation of maternal antibodies to the foetus/neonate is then presented. The phenomenon of pinocytosis is also discussed. The article concludes with a discussion of the problem of neonatal infections.

[Host-parasite relations]. / Gastheer-parasiet relatie.

Our current knowledge of the host-parasite relationship is reviewed as part of a series entitled 'Papers of yesterday and today'. A retrospective view is taken of a paper written in 1898 by Professor H. J. Hamburger, entitled 'The Current Point of View of the Theory of Natural Immunity', which is also published in a slightly abridged version in this issue of Tijdschrift voor Diergeneeskunde. A review of the history of developments in research in the field of infectious diseases since 1898 is followed by a discussion of two phenomena, colonisation resistance and immune adherence. So-called non-specific as well as specific (= immunological) defense mechanisms are then discussed. Finally, our current knowledge of the 'Biological Response Modifiers' is considered particular attention being paid to possible uses of recombinant DNA interferons and interleukins in human and veterinary medicine.

The liver in the IgA secretory immune system. Dogs, but not rats and rabbits, are suitable models for human studies.

The liver transport of polymeric IgA (pIgA) from plasma into bile and the immunohistochemical distribution of secretory component (SC) in the liver were studied in dogs, and compared to those in humans, rats, and rabbits. Results were as follows: (i) according to bile and serum protein concentrations and specific activities, plasma pIgA in dogs, like in humans, is transported into bile approximately 10 times more efficiently than albumin, as compared to 320 and 1060 times in rabbits and rats, respectively. (ii) Only approximately 1% of an i.v. dose of [125I]pIgA is transported into bile over 8 hr in dogs, like in humans, as compared to approximately 50% over 3 hr in rats and rabbits. These results agree with much smaller daily fractional catabolic rates of intravascular pIgA in dogs (0.28) and humans (0.48) than in rats (24.0). (iii) Total bile IgA contributes daily about 1.5 mg per kg to intestinal pIgA in dogs, a figure similar in humans (0.8 mg per kg) but much smaller than in rats (38 mg per kg) and rabbits (35 mg per kg). (iv) Biliary obstruction in dogs, like in humans, results only in minor and late increases in serum pIgA levels, contrasting with greater than 8-fold increases within 24 hr in rats and rabbits. (v) Unlike in rats and rabbits, SC in dog liver as well as in human liver cannot be detected in hepatocytes although clearly present in bile duct cells. To conclude: (i) major species differences in plasma-to-bile transport of pIgA exist, most probably related to species differences in the ability of hepatocytes to synthetize SC.(ABSTRACT TRUNCATED AT 250 WORDS)

[Neonatology: immunological features]. / Neonatalogie: immunologische aspecten.

In the present paper which was inspired by a paper that was previously read, the title 'Neonatology: Immunological Features' is interpreted rather more widely to the extent that the entire field of perinatology including functioning of the mother during gestation and lactation will be reviewed. The following subjects are discussed in succession: (1) the mother - fetus relationship (maternal immunocompetence during gestation and lactation, fetal immunocompetence, the fetus as a 'semi-allograft'); (2) passive immunization produced by maternal antibodies (mode of transfer of antibodies and immunopathological features of this transfer, enteromammary link, feed-back due to maternal antibodies); (3) neonatal infection and (4) artificial rearing (differences with conventional rearing and consequences in the field). In the final conclusions, new insights into the problems of neonatal infection gained by immunological studies and their use in the prevention and control of these infections are evaluated.

Cerebrospinal fluid immunoglobulins in sheep with visna, a slow virus infection of the central nervous system.

Icelandic sheep were injected intracerebrally with visna virus, which produces a persistent infection of the CNS accompanied by encephalomyelitis and focal demyelinating lesions. Studies were conducted on two groups of sheep, with short-term infections (25 sheep sampled 1-3 months after infection) and long-term infections (14 sheep sampled 5-6 years after infection). Quantitative determination of CSF immunoglobulin levels 5 years after infection indicated that IgM concentration was usually elevated, IgG2 was occasionally elevated and IgG1 was rarely elevated. CSF oligoclonal bands were seen in about half the sheep examined 5 years after infection. There was a correlation between high titers of CSF antiviral antibody and both elevated CSF IgM concentration and CSF oligoclonal bands. Serum/CSF IgG1 ratios indicated that the blood-brain barrier was apparently intact in long-term visna infection, consistent with intrathecal synthesis of IgM and of antiviral antibody. The alterations in CSF immunoglobulins in visna resemble those found in other persistent CNS virus infections and in multiple sclerosis.

[Immunology and interferons (author's transl)]. / Immunologie en interferonen.

The general function of the immune system is discussed in the present review paper. In addition to the discussion of 'specific' and 'non-specific' defence mechanisms, particular attention is paid to the important role played by macrophages in the two systems. Macrophages are found to have a specific regulatory function both in the induction and the effector phase of the immune response. The part dealing with the effector phase of the immune response is concerned with the action of sensitized T lymphocytes on the one hand and provides a review of the present state of knowledge of (sub)classes of immunoglobulins in domestic animals on the other. In the section on interferon, efforts are made to answer a number of questions concerning the properties and chemical composition of interferons as well as the induction of interferons and the use of interferon inducers in veterinary practice. Moreover, a number of theories on the possible mechanism of action of interferons are discussed. The antitumour effect of interferons is examined more closely, the relationship with the antitumour activity of the immune system being a central feature. The part played by 'killer' and 'natural killer' cells is discussed. Finally, a look is taken into the future, and efforts are made to present an actual picture of the future possibilities of the use of interferons in therapy and prevention. A central question is whether it will be possible to produce interferons in sufficient amounts by particular bacteria (recombinant DNA studies) within a certain period.

[Immunology and joint disease (author's transl)]. / Immunologie en gewrichtsziekten.

The present view is concerned with a number of joint diseases occurring in man and pets, the pathogenesis of which is (partly) immunological. This review is preceded by the discussion of a relevant part of immunology. The diagnostic laboratory procedures dealt with in the paper consist in diagnostic routine tests performed in (medical) clinico-immunological laboratories. With a few exceptions, it appears to be possible to establish a diagnosis of similar diseases in animals using comparable methods. A reliable diagnosis of these joint diseases in pets is not only of importance from the point of view of comparative nosology, but may also revive interest in the animal as a model of these forms of disease. Finally, human so-called seronegative spondylo-arthropathy associated with the presence of particular tissue antigen, is briefly discussed. Similar associations in pets such as dogs should also be studied.

Quantitation of immunoglobulins in ovine sera and secretions by laser nephelometry. Comparison with the radial immunodiffusion (RID) technique.

In twenty-five ovine body fluids (serum, lung fluid and cerebrospinal fluid), the concentrations of IgG1I, IgG2, IgM and IgA were determined by laser nephelometry and radial immunodiffusion (RID). When nephelometric assays are carried out, antisera free from any turbidity are essential. Methods ensuring that goat and rabbit anti-sera will satisfy this requirement are described in the present paper. When sheep immunoglobulins were measured by laser nephelometry, adequate and reproducible results were obtained, comparable with those obtained by RID. Advantages of the nephelometric method include the speed of assay and its sensitivity, allowing precise determination of the very low concentrations of immunoglobulins in CSF.

A new era in veterinary immunology.

The importance of the creation of a new international journal of "Veterinary Immunology and Immunopathology" is apparent following the emergence of veterinary immunology as an identifiable discipline and the vital part played by investigations of animal models of immunological diseases of man. The journal will contain papers on basic immunology of domestic animals and on the many disease processes that result in domestic and laboratory animals from immunologic defects. It should thus have a wide appeal to workers in all immunologically related disciplines. Papers will be refereed by members of an international editorial advisory board.

Antibodies against purified pigeon IgA in pigeon breeders' disease.

It is demonstrated that previously described PDF1-A antigens from pigeon dropping extract contain pigeon IgA. The sera of patients with pigeon breeders' disease contain precipitating antibodies against pigeon IgA, in contrast to the sera of pigeon breeders suffering from unrelated forms of pulmonary dysfunction. The degree of complement consumption by PDF1A antigens, pigeon serum, and pigeon IgA turned out to be correlated. No correlation was found between precipitating anti-pigeon IgA antibodies and complement consumption by pigeon IgA in patients' sera.

Induction and effector phases of the immune response: physiological and pathophysiological features.

A review is given on the current state of knowledge about the induction and effector phases of the immune response. Physiological and pathophysiological features of the regulation of the immune response are discussed comparatively for both man and animals.