Familial clustering of infantile cirrhosis in Northern Germany: A clue to the etiology of idiopathic copper toxicosis.

Two cases of infantile liver cirrhosis of unknown origin occurred in a circumscribed rural area of Northern Germany. Both children had increased dietary copper exposure. The search for additional cases of what appeared to be idiopathic copper toxicosis (ICT) revealed a cluster of affected infants in this region, raising questions about the relative importance of genetic and environmental factors that are considered to be etiologic. We gathered clinical and pathologic data concerning the patients, analyzed the pedigrees of affected families, and searched for possible environmental factors contributing to the pathologic process. We encountered 8 cases of infantile liver cirrhosis in 5 families in Emsland, a circumscribed and predominantly rural area of Northern Germany; ICT was definitely proven in 2 cases. Clinical presentation and liver pathology in 6 additional cases were consistent with the diagnosis of ICT. Pedigrees of affected families revealed complex relationships with occasional consanguinity of parents, suggesting autosomal recessive inheritance. The households were served by private wells with water of low pH flowing through copper pipes, suggesting the possibility of increased alimentary copper exposure. These findings support earlier conclusions that ICT develops when an infant with a genetic predisposition is exposed to a copper-enriched diet.

Short communication: bovine paraplegic syndrome (Mal de Aquidabàn) in Paraguay caused by C. perfringens toxovar D.

In the vicinity of the river Aquidabán in Eastern Paraguay occurred in the last years an endemic disease within cattle herds which killed thousands of heads (Mal de Aquidabán [MdA]). The disease was seen in form of an afebrile, paralytic condition characterized by muscle tremors, swaying of the hind quarters, recumbence and sudden death of the animals. Therefore it was described as "Bovine Paraplegic Syndrome". Comparable symptoms in adult cattle have also being seen in Eastern and Central Venezuela. After we found in the peritoneal fluid of 2 animals, which died under typical symptoms, toxins of C. perfringens toxovar D, we started to investigate the occurrence of C. perfringens in the feces of clinical healthy animals on farms, where MdA was diagnosed before. There we found 73% of the isolated strains belonging to toxovar D. In herds with no case of the disease toxovar A was isolated up to 90%. The next step was the production of a vaccine (anaculture) with a high toxin producing strain of C. perfringens toxovar D. 2000 cattle were vaccinated for 3 years twice a year. None of the vaccinated animals diseased. In 2 control-herds some cases of MdA occurred. But we became quite sure that MdA was an infectious disease, when we started to vaccinate cattle of unvaccinated herds where MdA suddenly occurred. One or two animals died in the next 2 days and after this period the endemic disease was immediately stopped.

The effect of methotrexate and azathioprine on the serum levels of IgA-alpha 1-antitrypsin complex in juvenile chronic arthritis.

In the present study we investigated the influence of methotrexate (MTX) and azathioprine (AZA) on the serum levels of the IgA-alpha 1-antitrypsin (IgA-AT) complex in patients with the systemic form of juvenile chronic arthritis (JCA). Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immunosuppressive agent) were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg/kg-1 week-1, while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months) whereas AZA for 11 months (SD = 6 months). The average value of the complex was higher in JCA patients than in both control groups (0.74 +/- 0.73 U vs 0.37 +/- 0.13 U (control children), P < 0.001 and vs 0.23 +/- 0.12 U (control adults), P < 0.001). Values exceeding the normal range were found in twenty-two JCA patients (39.4%). Serum IgA-AT level was lowest in the MTX group compared to AZA and non-treated patients (0.56 +/- 0.24 U, 0.76 = 0.43 U, 0.95 +/- 0.52 U, respectively, P < 0.05). IgA values exceeding normal levels for age were found in 14% of the patients. A correlation between the levels of the IgA-AT complex and C-reactive protein (r = 0.43, P < 0.01), alpha 1-acid-glycoprotein (r = 0.45, P < 0.01), alpha 1-antichymotrypsin (r = 0.52, P < 0.01), alpha 1-antitrypsin (r = 0.40, P < 0.01) and IgA (r = 0.56, P < 0.01) was established.

The effect of methotrexate and azathioprine on the serum levels of IgA-alfa1-antitrypsin complex in juvenile chronic arthritis

In the present study we investigated the influence of methotrexate (MTX) and azathioprine (AZA) on the serum levels of the IgA-alpha1-antitypsin (IgA-AT) complex in patients with the systemic form of juvenile chronic arthritis (JCA). Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immuno-suppressive agent) were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg kg(-1) week(-1) while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months) whereas AZA for 11 months (SD = 6 months). The average value of the complex was higher in JCA patients than in both control groups (0.74 + 0.73 U vs 0.37 + 0.13 U (control children), P<0.001 and vs 0.23 + 0.12 U (control adults), P<0.001). Values exceeding the normal range were found in twenty-two JCA patients (39.4 percent). Serum IgA-AT level was lowest in the MTX group compared to AZA and non-treated patients (0.56 + 0.24 U, 0.76 + 0.43 U, 0.95 + 0.52 U, respectively, P<0.05). IgA values exceeding normal levels for age were found in 14 percent of the patients. A correlation between the levels of the IgA-AT complex and C-reactive protein (r = 0.43, P<0.01), alpha1-acid-glycoprotein (r = 0.45, P<0.01), alpha1-antichymotrypsin (r = 0.52, P<0.01), alpha1-antitrypsin (r = 0.40, P<0.01) and IgA (r = 0.56, P<0.01) was established.

On the monophyletic evolution of the metazoa.

1. The shift from unicellular life to multicellular, integrated organisms has been accompanied by the acquisition of adhesion proteins. Recently we succeeded in cloning some genes coding for such proteins from the lowest multicellular animals, the marine sponges (model: the siliceous sponge Geodia cydonium). 2. G. cydonium contains several lectins and cDNA for two of them (termed LECT-1 and LECT-2) was cloned. Both lectins have a framework sequence of 38 conserved amino acids which are characteristic for the carbohydrate-binding site of vertebrate S-type lectins. Next, we have isolated and characterized a cDNA coding for a receptor tyrosine kinase of class II (GCTK). The deduced amino acid sequence shows two characteristic domains: i) the tyrosine kinase domain and ii) an immunoglobulin-like domain. The latter part shows high homology to the vertebrate type immunoglobulin domain. This result, together with the lectin data, demonstrates that binding domains of such adhesion proteins are not recent achievements of higher animals but exist already in animals (sponges) which have diverged from other organisms about 800 million years ago. 3. Considering the fact that during embryogenesis of sponges a typical anteroposterior organization pattern is seen, a "homeotic" organ-like transformation has been postulated. The subsequent search for genes provided with the homeodomain sequence was successful. The deduced amino acid sequence of G. cydonium showed high homology to chicken and to the Antennapedia sequence from Drosophila melanogaster. 4. These data support the view that the kingdom Animalia is of monophyletic origin.

Cerebral aneurysms: assessment of 377 cases (1956-1982).

A review of 177 patients with cerebral aneurysms is made, out of whom 106 with ruptured aneurysms were examined, whose operational timing and prognostic chances were well documented (group B, 1979-1982) and in part updated to 1984. Furthermore, relevant data of a previous series of 200 cases of cerebral aneurysm, treated between 1956-1978 were used (group A). The patients were graded according to Hunt and Hess, assessing the risks involved. The percentages of recurrent bleeding were in group A 36.5% and 28% in group B. The incidence of vasospasm (as seen in angiography) was in group B 39.6% (42/106 patients). The highest rate of vasospasm in the spasm group division B was found to occur in the second and third week after subarachnoid haemorrhage and amounted to 64.7% and 62.5%. A pre-operatively present vasospasm had no negative effects on the mortality rate, but influenced the outcome for the survivors effectively. The total mortality in group A was 22.5% and in group B 11.7%. Timing of the operation among patients in Hunt and Hess-grades I and II needs to discussion. The surgical position of patients in grade V is also certain. What remains to be discussed and needs attention is grade III and patients in grade IVa. Here the time of operative intervention must be planned individually depending on the course of the neurological status.

Management of giant aneurysms.

Technical aspects and anatomical difficulties involved in the management of this entity and the risks associated give giant aneurysms a special place in the treatment of aneurysms as a whole. The direct attack needs careful planning and the right choice of instruments, especially clips. In spite of the progress in recent years, the rate of mortality is still very high. The indirect approach requires in many cases the occlusion of a major cerebral vessel, which in some cases could result in cerebral ischemia. However, by means of extra-intracranial by-pass operation this risk could be reduced. The method of balloon embolisation has progressed recently. This procedure brings the least discomfort to the patient. Results of this method of treatment must be observed critically for future assessment.

Cerebral aneurysms: assessment of 377 cases (1956-1982)

Os autores aprresentam revisäo de 177 pacientes com aneurisma observados durante o período de 1979 a 1982 (Grupo B) e dos quais 106 sofreram ruptura aneurismática. E feita comparaçäo com série prévia tratada de 1956 a 1978 (Grupo A), com 200 pacientes. Observou-se a classificaçäo de Hunt e Hess. No Grupo A, 36,5% sofreram ressangramento no Grupo B, 28%. Vasoespasmo foi observado (angiograficamente) em 42 de 106 pacientes do Grupo B (39,6%). Observou-se ainda que o vasoespasmo ocorreu preponderantemente na segunda e na terceira semanas após o sangramento inicial (64,7% - 62,5%). A presença de vasoespasmo pré-operatório näo mostrou efeito negativo quando relacionada ao índice de mortalidade, embora tenha influenciado no prognóstico e na recuperaçäo do paciente. A mortalidade do grupo A foi 22,5% e no grupo B, 11,7%. O cirúrgico para os pacientes classificados em grau I e grau II (Hunt e Hess) merece ainda discussäo. Pacientes em grau III e grau IV merecem atençäo especial: a indicaçäo cirúrgica deve ser planejada individualmente, dependendo da evoluçäo do quadro clínico-neurológico

Management of giant aneurysms

Os aneurismas gigantes merecem atençäo especial no que se refere a seus aspectos anatômicos, riscos e, principalmente, dificuldades técnicas ao seu manueio. A abordagem de tais aneurismas necessita de planejamento adequado e, sobremaneira, de material apropriado para sua clipagem. A mortalidade ainda permanece alta, apesar dos recentes progressos observados nos últimos anos. Por outro lado, a abordagem indireta requer, muitas vezes, oclusäo de um vaso cerebral importante, o que pode acarretar isquemia cerebral. Entretanto, por anastomose extra-intracraniana tais riscos podem ser diminuídos. O método de embolizaçäo por balöes tem-se mostrado eficaz. Este processo oferece menor incômodo ao paciente. Os resultados deste método devem ser observados criteriosamente para melhor avaliaçäo no futuro

Cow milk protein antigens and antibodies in serum of premature infants during the first 10 days of life.

Antigenic beta-lactoglobulin and alpha-casein were measured in the sera of 45 formula-fed infants of 31 to 41 weeks of gestation at 5 days and at 10 days of age. Quantitation was performed by a sensitive ELISA inhibition assay. On day 5 of life antigenic lactoglobulin was detected in 14 of 19 infants of less than 37 weeks gestation, but in only one of 10 infants of more than 36 weeks gestation. On day 10 of life the sera of all infants contained antigenic lactoglobulin. In contrast, on day 5 antigenic casein was present in four of 17 infants of less than 37 weeks gestation, but in 10 of 12 infants of the more mature group. On day 10 casein was detected in seven of 28 infants, with no difference between groups; anti-casein was found in eight of 12 infants. Infants of less than 37 weeks gestation have different absorption patterns than more mature infants do. "Gut closure" is an unlikely explanation for these findings.