Susceptibility of Baltic and East Atlantic salmon Salmo salar stocks to Gyrodactylus salaris (Monogenea).

The susceptibility of a Baltic salmon stock Salmo salar (Indalsälv, central Sweden) to Norwegian Gyrodactylus salaris (Figga strain, central Norway) was experimentally tested and compared with previously obtained results on East Atlantic salmon (Lierelva, SE Norway). Contrary to expectation, the Baltic salmon, which had no prior exposure to this parasite strain, appeared almost as susceptible as the Norwegian salmon parr that naturally experience G. salaris-induced mortality. Individually isolated salmon of both stocks sustained G. salaris infections with little evidence of innate resistance. A few individuals of the Indalsälv stock controlled their infection from the beginning, but overall there was considerable heterogeneity in the course of infection in both stocks. On individual hosts, G. salaris growth rates declined steadily throughout the infection, a trend which was particularly marked amongst the Lierelva stock. On shoaling Lierelva fish, there was some evidence of reduced parasite population growth towards the end of the infection; this was not apparent in Indalsälv fishes. These results reflect a growing awareness that not all Baltic salmon may be resistant to Norwegian G. salaris, and that Norwegian and Baltic G. salaris strains may differ in virulence. Consequently, management decisions concerning this parasite-host system should be based upon the actual, and tested, susceptibility of stocks under consideration and not upon identification of stocks as either Atlantic or Baltic.

Potential for cross-transmission of Dictyocaulus viviparus between cattle and white-tailed deer.

Development of an in vitro culture system for infectious Dictyocaulus viviparus larvae made it possible to study the potential cross-transmission of D. viviparus between white-tailed deer (Odocoileus virginianus) and cattle (Bos taurus). Between 26 September 1995-29 February 1996, six parasite-free bull calves were individually inoculated with 15 to 50 infective third stage larvae (L3)/kg of body weight cultured from adult D. viviparus collected from white-tailed deer. Three bull calves were simultaneously inoculated with 45 L3/kg of body weight recovered from cattle either by the Baermann technique or by in vitro culture as above. All three calves inoculated with the homologous cattle strain became patently infected while all six calves inoculated with the heterologous deer strain remained negative for the presence of D. viviparus in the feces and in the lungs upon necropsy.

An epizootic of hemorrhagic disease in white-tailed deer in Missouri.

As part of a white-tailed deer (Odocoileus virginianus) survival study in Missouri (USA) we were actively monitoring 97 radio-collared deer when 8 (8%) died. This mortality, which occurred from 20 August to 23 September 1996, consisted of five adult females, two yearling females and one yearling male. Based on the seasonality of this mortality and the isolation of epizootic hemorrhagic disease virus (EHDV) serotype 2 from one of these animals, we believe that these losses resulted from an epizootic of hemorrhagic disease. The remains of five unmarked deer that may have died from HD also were found on the study area during this same period. During the fall following this mortality, we tested serum from 96 deer taken by hunters in the immediate area. Fifteen (16%) were positive for EHDV or bluetongue virus (BTV) antibodies as determined by agar gel immunodiffusion tests. Serum neutralization test results indicated that previous infections were caused by EHDV virus serotype 2. Based on these data, and assuming that there was no prior exposure to EHDV serotype 2 in this population, the exposure rate for this epizootic was 24% of which 8% died. We noted hoof interruptions in only two of the 96 deer sampled. During this mortality event, the Missouri Department of Conservation received no reports of dead deer, and without the radio-monitored animals the event would have been undetected.

Environmental risk assessment of human pharmaceuticals in Denmark after normal therapeutic use.

An environmental risk assessment is presented for the 25 most used pharmaceuticals in the primary health sector in Denmark. Predicted environmental concentrations (PECs) for the aquatic environment were calculated using conservative assumptions and all PECs exceeded 1 ng/l. Measured concentrations were in general within a factor of 2-5 of PECs and ranged from approximately 0.5 ng/l to 3 micrograms/l for nine of the pharmaceuticals reported in literature. The calculation of predicted no-effect concentration (PNEC) based on aquatic ecotoxicity data was possible for six of the pharmaceuticals. PEC/PNEC ratio exceeded one for ibuprofen, acetylsalicylic acid, and paracetamol. For estrogens the PEC/PNEC ratio approached one when non-standard test was used. The ratio was below one for estrogens (standard test), diazepam and digoxin. For the terrestrial compartment, toxicity data were not available, and no assessment was carried out. Comparisons of predicted concentrations of furosemide, ibuprofen, oxytetracycline and ciprofloxacin in sludge based on either preliminary experimental sludge-water partition coefficients (Kd), octanol-water coefficients (Kow) or acid-base constants (pKa) revealed large variations.

[Acute water intoxication caused by intranasal desmopression--Minirin]. / Akut vandintoksikation forårsaget af intranasal desmopressin--Minirin.

Desmopressin is used for the treatment of nocturnal enuresis. Side effects reported with intranasal desmopressin are transient headache, nausea, abdominal cramps and water intoxication with hyponatremia and grand mal seizure. We report a case of water intoxication with low serum sodium and grand mal seizure in a healthy child treated for enuresis with desmopressin. The child experienced abdominal cramps and nausea prior to the convulsions. A computerised tomography scan of the brain gave the suspicion of increased intracranial pressure ICP. The child recovered fully. We therefore recommend that parents and child are fully informed about the administration and the risk of desmopressin. If a child on desmopressin treatment experiences abdominal cramps, nausea or headache the drug should be discontinued and a physician contacted for control of serum sodium. Temporary withdrawal of desmopressin should also be considered in cases of acute illness influencing water balance.

Incipient cardiomyopathy in young insulin-dependent diabetic patients: a seven-year prospective Doppler echocardiographic study.

Two echo-Doppler cardiographic investigations were performed 7 years apart in 17 insulin-dependent diabetic children without hypertension or nephropathy in order to detect early signs of cardiac abnormalities in this group without ischaemic heart disease. Relative to two matched control groups, the patients had reduced increase in left ventricular size (p < 0.01) and stroke volume (p < 0.05). An initially reduced end systolic wall stress and increased fractional shortening (p < 0.003) was normalized during the 7 years. Concomitant with early signs of autonomic neuropathy and aortic stiffening, left ventricular filling changed with increased velocity during atrial contraction (p < 0.01) correlating to the decreased stroke volumes (r = -0.57, p = 0.016). These early changes could suggest left ventricular restriction but could also reflect a changed sympathetic/parasympathetic balance in diabetic children. A reduced left ventricular cavity size and increased atrial ejection has thus been described in these insulin-dependent children without hypertension, nephropathy or evidence for ischaemic heart disease, suggesting the existence of a metabolically-induced cardiomyopathy.

Abnormal left ventricular diastolic function during cold pressor test in uncomplicated insulin-dependent diabetes mellitus.

1. Insulin-dependent diabetes mellitus is a known risk factor for congestive heart failure and an early diastolic dysfunction has been described. In order to see if diabetes itself and not complications like hypertension, nephropathy or ischaemic heart disease can be considered responsible for the abnormal diastolic function of the left ventricle, 17 young patients with uncomplicated insulin-dependent diabetes mellitus and 12 control subjects were exposed to a cold pressor test. 2. Blinded echo-Doppler examination was performed before and during the test. During basal conditions, left ventricular dimensions and volumes were smaller in diabetes and atrial contributions to left ventricular filling were increased. 3. During the cold pressor test, isovolumic relaxation time increased, peak early filling velocity (E) decreased, E deceleration time decreased and atrial contribution (A) increased significantly in diabetes, while only A increased in the control group. A marked increase in left atrial ejection force was seen in diabetes only (P < 0.002). This difference was seen in spite of comparable reductions in mitral area and atrioventricular compliance in the two groups. 4. The hyperfunction of the left atrium in diabetes is hypothesized to be due to reduce size of the left ventricle combined with incipient autonomic neuropathy.

An epizootic of hemorrhagic disease in white-tailed deer (Odocoileus virginianus) in Missouri: necropsy findings and population impact.

An epizootic occurred among white-tailed deer (Odocoileus virginianus) from July through October 1988 in Missouri (USA). From late July through September, nine necropsied deer had lesions of the peracute or acute forms of hemorrhagic disease (HD) or no apparent lesions, whereas two deer necropsied in October had lesions of the chronic form of HD. Epizootic hemorrhagic disease virus was isolated from two necropsied deer. Based on changes in population indices, there is evidence that deer populations declined in seven of Missouri's 57 deer management units from 1987 to 1990. Based on a deterministic model designed to simulate deer populations in management units, it appeared that summer and fall 1988 mortality ranging from 6% to 16% accounted for the population decreases in deer management units with population declines. Heavily hunted areas where high deer mortality was not reported in the summer and fall of 1988 did not have population declines. Based on these results, we believe that HD mortality was high and resulted in deer population declines in parts of Missouri when combined with hunting harvest.

Regulation of the HNF-1 homeodomain proteins by DCoH.

The pattern of expression of homeodomain proteins often exceeds their apparent domain of activity. Tissue-specific proteins that modulate the in vivo activity of homeodomain proteins have been proposed to account for this functional restriction. The first identified example of such an accessory protein is DCoH, which confers transcriptional activity to the hepatocyte nuclear factor 1 and provides a model of how other accessory factors might modulate the function of homeodomain proteins.

A G-->A substitution in an HNF I binding site in the human alpha-fetoprotein gene is associated with hereditary persistence of alpha-fetoprotein (HPAFP).

A family displaying hereditary persistence of alpha-fetoprotein (HPAFP) in adult life was detected in an antenatal screening programme for spina bifida. RFLP linkage analysis shows that the trait is linked with the albumin-AFP locus. The molecular mechanism responsible for the post-natal repression of the AFP gene is unknown. We wished to determine the molecular mechanism underlying HPAFP in this family. Sequence analysis of the 5'-flanking sequences of their gene revealed a GA substitution at position -119 associated with the trait. This substitution occurs in a potential HNF I binding site, and increases the similarity of the sequence to a consensus HNF I recognition site. In a competitive gel retardation assay the mutant sequence binds HNF I alpha more tightly than the wild type sequence. Furthermore, 5'-flanking sequences of the human AFP gene containing the G-->A substitution direct a higher level of CAT expression in transfected human hepatoma cells than the wild type sequences. We conclude that the G-->A substitution at position -119 of the AFP gene is the mutation causing HPAFP in this family. These results highlight the importance of this HNF I binding site in the developmental regulation of the AFP gene.

Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein.

Dimerization among transcription factors has become a recurrent theme in the regulation of eukaryotic gene expression. Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a homeodomain-containing protein that functions as a dimer. A dimerization cofactor of HNF-1 alpha (DCoH) was identified that displayed a restricted tissue distribution and did not bind to DNA, but, rather, selectively stabilized HNF-1 alpha dimers. The formation of a stable tetrameric DCoH-HNF-1 alpha complex, which required the dimerization domain of HNF-1 alpha, did not change the DNA binding characteristics of HNF-1 alpha, but enhanced its transcriptional activity. However, DCoH did not confer transcriptional activation to the GAL4 DNA binding domain. These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex.

Independent regulation of HNF-1 alpha and HNF-1 beta by retinoic acid in F9 teratocarcinoma cells.

Hepatocyte Nuclear Factor-1 alpha (HNF-1 alpha) and HNF-1 beta are homeodomain-containing transcription factors which interact with the GTTAATNATTAAC motif essential to the function of more than 15 promoters selectively expressed in the liver. These homeoproteins can form homo- and heterodimers in solution and share identical DNA-binding domains but have different transcriptional activation properties. During retinoic acid (RA) induced differentiation of F9 embryonal carcinoma (EC) cells, which stimulates aspects of pre-implantation embryogenesis, both HNF-1 beta mRNA and immunoreactive DNA-binding activity are strongly induced approximately 24 h post RA-treatment. In contrast, HNF-1 alpha mRNA increases approximately 4-fold after 5 days, concomitant with elevation of HNF-1 alpha DNA-binding activity and expression of the HNF-1 target gene alpha-fetoprotein. These results indicate that HNF-1 alpha and -1 beta expression can be controlled by regulatory hierarchies downstream of primary RA-response genes, and suggest that independent regulatory mechanisms for these factors can confer distinct and interactive developmental functions.

HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro.

HNF-1 alpha (previously referred to as HNF-1, LPB1, and APF) is a vertebrate transcription factor that contains a divergent homeo domain and plays a prominent role in regulating genes that have the common characteristic of being expressed in hepatocytes and a complex group of endodermally and mesodermally derived tissues. HNF-1 alpha is unique among the vertebrate homeo domain-containing proteins in that it dimerizes in the absence of its DNA recognition sequence, suggesting the possibility that the function of HNF-1 alpha may be diversified by forming heterodimers with other related proteins. We report the initial characterization of HNF-1 beta, which is closely related to HNF-1 alpha and is able to form heterodimers with HNF-1 alpha in vitro. Although HNF-1 alpha, but not HNF-1 beta, is expressed in the liver, HNF-1 alpha and HNF-1 beta are coexpressed in the murine Hepa1A cell line and in the mammalian kidney where a subset of hepatocyte genes are expressed. In contrast, exclusive expression of HNF-1 beta is associated with repression of a subset of hepatocyte-specific genes in the dedifferentiated hepatocyte cell line C2, differentiated F9 cells, in somatic hybrids between hepatocytes and fibroblasts, and in the lung. The extent of heterodimerization may be regulated in a tissue-specific way because freely exchangeable heterodimers are formed in Jurkat T cells transfected with HNF-1 alpha and HNF-1 beta, whereas in liver cells stable homodimers are present. These studies define a pair of homeo domain proteins that have the potential to interact to produce an embryologically complex pattern of gene expression.

Gastric emptying in adults treated for infantile hypertrophic pyloric stenosis.

The gastric emptying rate was scintigraphically determined in 6 women and 26 men who had undergone medical or surgical treatment for infantile hypertrophic pyloric stenosis a median of 29 years previously. Dyspeptic complaints were reported by four of the seven medically treated and nine of the 25 surgically treated group. No intergroup difference was demonstrated in the gastric emptying rate of liquid or solid food, and neither group differed significantly from the normal values. The gastric emptying rate, measured as in this study, thus was uninfluenced by treatment.

The epidemiology of infantile hypertrophic pyloric stenosis in a Danish population, 1950-84.

The epidemiology of Infantile Hypertrophic Pyloric stenosis (IHPS) was studied in a geographically well-delineated and demographically representative Danish region (The County of Funen), covering the period 1 January 1950 to 31 December 1984. Based upon 679 cases, the cumulative incidence from birth of IHPS was found to be virtually unchanged during the study period at a level of 4.8 per 1000 liveborn boys and 1.3 per 1000 liveborn girls. In an analysis of clinical and demographic variables, the development of IHPS was found to be associated with low parity status (regardless of maternal age). The preterm cases had a longer interval from birth to onset of symptoms, compared with those born at term. No statistically significant associations were found between IHPS and seasonal variations at onset of symptoms, ABO and Rhesus blood groups, and maternal age.

Infantile hypertrophic pyloric stenosis and subsequent ulcer dyspepsia. A follow-up study of medically and surgically treated patients.

Infantile hypertrophic pyloric stenosis was treated in 324 cases in 1950-1966. At follow-up 19-35 years later, 296 of the patients could be traced, and 284 replied to a questionnaire concerning ulcer dyspepsia. Among the 80 patients who had been medically treated for pyloric stenosis, the prevalence of ulcer dyspepsia was 13.8%, and in the 204 surgically treated patients it was 9.3%. The difference was not statistically significant.