Detained adolescent females' multiple mental health and adjustment problem outcomes in young adulthood.

BACKGROUND: Although prior studies have shown that detained females are marked by significant adverse circumstances, little is known about their adult outcomes. METHOD: Prospective follow-up study of 184 (80.4% of original sample of 229) detained adolescent females who were reassessed 4.5 (SD=0.6) years later in young adulthood (mean age=20.0, SD=1.4) on mental health and adjustment outcomes. Associations between these outcomes and detained females' behavior problems and offense history were examined. RESULTS: In the total sample, 59.0% had one or more mental health problems at follow-up, whereas 96.2% were facing at least one adjustment problem. Subjects with a personality disorder (PD) reported more adjustment problems compared to subjects without PD. Mental health and adjustment problems in young adulthood were predicted by detained adolescent females' behavior problems and offense history. CONCLUSION: Detained adolescent females suffered from multiple mental health and adjustment problems in young adulthood. Females who developed PD were most impaired. Results of this study underline the compelling need for continued and gender-specific interventions. The identification of predictors during detention for poor adult outcomes can serve as targets for intervention.

Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy.

OBJECTIVE: To investigate coagulation inhibitors and abnormalities of the homocysteine metabolism, which are related to an increased thrombotic risk, as risk factors for placental vasculopathy. DESIGN: A case-control study comparing nonpregnant women with an obstetric history of placental vasculopathy (study group) with nonpregnant women (control group) matched for age and occupation. SETTING: Obstetric outpatient clinic in the University Hospital Nijmegen. SAMPLE: One hundred and one women in the study group and 92 women in a control group. METHODS: Determinations in blood samples of homocysteine concentrations; the occurrence of 677 C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene; protein C activities; activated protein C resistance ratios; concentrations of free protein S antigen; antithrombin III activities; and the occurrence of factor V Leiden mutation. RESULTS: Increased risk for placental vasculopathy was found in the study group with elevated homocysteine (odds ratio 2.28, 95% CI 1.18-4.39), MTHFR mutation (odds ratio 3.29, 95% CI 1.03-10.5), decreased activated protein C resistance ratio (odds ratio 2.46, 95% CI 1.06-5.72) and protein C (odds ratio 2.01, 95% CI 1.11-3.65). Any combination of two risk factors in the same individual resulted in a 3.40 (95% CI 1.80-6.42) higher relative risk for placental vasculopathy; combinations of three risk factors in a 6.83 (95% CI 1.52-30.7) higher risk. CONCLUSIONS: The thrombotic risk factors decreased levels of activated protein C resistance ratios and protein C, elevated homocysteine and the MTHFR 677 C-->T mutation are likely risk factors for placental vasculopathy. Combinations of these risk factors in one individual resulted in synergistic increase of risk.

A common mutation in the 5,10-methylenetetrahydrofolate reductase gene as a new risk factor for placental vasculopathy.

OBJECTIVE: This study was undertaken to investigate whether the cytosine-to-thymine substitution at nucleotide 677 (C677T) in the 5, 10-methylenetetrahydrofolate reductase gene is a risk factor for placental vasculopathy (abruptio placentae or placental infarction with fetal growth restriction). STUDY DESIGN: This case-control study enrolled 165 women with placental vasculopathy and 139 matched control women with normal pregnancy outcomes. Measurements included fasting total plasma homocysteine concentration, serum and red blood cell folate concentrations, serum vitamin B(12) concentration, whole-blood vitamin B(6) concentration, and analysis of the 5, 10-methylenetetrahydrofolate reductase gene C677T mutation. RESULTS: The median total plasma homocysteine concentration was significantly higher in the study group than in the control group (P <.01; odds ratio >97.5th percentile, 4.66; 95% confidence interval, 1.55-14.0). Homozygous genotype for the mutated 5,10-methylenetetrahydrofolate reductase gene was found in 12% of the study group and 5% of the control group (odds ratio, 2.45; 95% confidence interval, 1.00-6.02). CONCLUSIONS: Mild hyperhomocysteinemia was confirmed among women with placental vasculopathy, for which homozygosity for a mutated 5, 10-methylenetetrahydrofolate reductase gene was found to be a new risk factor. The risk of placental vasculopathy probably increases in conditions of low serum folate concentration.

Homocysteine metabolism in endothelial cells of a patient homozygous for cystathionine beta-synthase (CS) deficiency.

Homocystinuria due to cystathionine beta-synthase (CS) deficiency is the most common inborn error of methionine metabolism. Patients with CS-deficiency have an extremely high risk of vascular disease. The underlying mechanism is still unsolved. Dysfunction of endothelial cells could be the trigger in the formation of atherosclerosis and thrombosis. Therefore, differences in cell function were studied between normal and CS-deficient human umbilical endothelial cells (HUVECs). Total homocysteine (tHcy) concentrations in culture media as a measure of homocysteine export increased in all cell lines, including the cell line with CS-deficiency, with constant amounts of approximately 2.5 microM every 24 h. von Willebrand factor (vWF), tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in culture media were used as markers of endothelial function and increased also with progression of culture time. The effects of additions of folate, vitamin B6 and methionine to the culture medium were studied. The homocysteine export and the markers of endothelial function did not differ between the control and the CS-deficient HUVECs under various test conditions. These data show that CS-deficient endothelial cells have normal homocysteine export and normal endothelial cell function. In CS-deficient patients the very high blood levels of homocysteine, probably due to deficient CS function in liver and kidney, seems to be the hazardous factor to endothelial cells, thus promoting atherosclerosis and thrombosis in CS-deficient patients.

Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease.

Elevated homocysteine (Hcy) levels are observed in two apparently unrelated diseases: neural-tube defects (NTD) and premature vascular disease. Defective human methionine synthase (MS) could result in elevated Hcy levels. We sequenced the coding region of MS in 8 hyperhomocysteinaemic patients (4 NTD patients and 4 patients with pregnancies complicated by spiral arterial disease, SAD). We identified only one mutation resulting in an amino acid substitution: an A-->G transition at bp 2756, converting an aspartic acid (D919) into a glycine (G). We screened genomic DNA for the presence of this mutation in 56 NTD patients, 69 mothers of children with NTD, 108 SAD patients and 364 controls. There was no increased prevalence of the GG and AG genotypes in NTD patients, their mothers or SAD patients. The D919G mutation does not seem to be a risk factor for NTD or vascular disease. We then examined the mean Hcy levels for each MS genotype. There was no correlation between GG- or AG-genotype and Hcy levels. The D919G mutation is thus a fairly prevalent, and probably benign polymorphism. This study, though limited, provides no evidence for a major involvement of MS in the aetiology of homocysteine-related diseases such as NTD or vascular disease.

The effect of folic acid on the homocysteine metabolism in human umbilical vein endothelial cells (HUVECs).

Mild hyperhomocysteinaemia is associated with increased risk for vascular disease. We studied homocysteine export from human umbilical vein endothelial cells (HUVECs) by measuring total homocysteine (tHcy) concentrations in the culture medium. Under standard culture conditions tHcy concentrations in the HUVEC culture medium increased by constant amounts after 24, 48 and 72 h [mean = 2.5 (SD +/- 0.7) mumol L-1 homocysteine every 24 h]. As the cells are the only source of homocysteine increase in the culture medium, we designate this as homocysteine export from HUVEC. Folic acid supplementation to the culture medium lowered the homocysteine export in a dose-dependent manner. Methyl-tetrahydrofolate (MeTHF) and folinic acid (a stable precursor of MeTHF) were in this respect about 10 times more effective than folic acid. A 50% reduction in the homocysteine export was seen with 10-30 nmol L-1 MeTHF supplementation; reduction to almost zero was seen with 100-300 nmol L-1 MeTHF. Additions to the culture medium of the other vitamins involved in the homocysteine metabolism, such as vitamin B12, vitamin B6 and flavin adenine dinucleotide, did not show any effect on homocysteine export. Because homocysteine export reflects an imbalance in the homocysteine metabolism, our observations showed a susceptible dependency of this metabolism on folic acid in endothelial cells.

Villus height and crypt depth in weaned and unweaned pigs, reared under various circumstances in The Netherlands.

The height of the villi and depth of the crypts in the small intestine were studied after weaning in pigs reared under various circumstances in the Netherlands. Pigs taken from herds with a long history of postweaning diarrhoea had in general significantly shorter villi and deeper crypts than their counterparts from a specific pathogen-free herd. Weaning was associated with villus shortening, crypt deepening and subsequent villus lengthening in pigs from the specific pathogen-free herd. Giving supplementary feed during the sucking period was beneficial in preventing shortening of the villi and this villus shortening was less severe when the crypts were deep at weaning, a condition that perhaps lessens the severity of postweaning diarrhoea.

Clinical signs and performance of pigs treated with different doses of carbadox, cyadox and olaquindox.

An experiment was designed to study the clinical effects of different levels of carbadox, cyadox and olaquindox in the ration on health, weekly weight gain and feed conversion in pigs. Four different carbadox and olaquindox (25, 50, 100 and 200 ppm) levels and five different cyadox (25, 50, 100, 200 and 400 ppm) levels were tested in groups of 6 pigs during 6 weeks. The 13 groups were compared with a control group fed on the same diet with only vehicle. After one week the first clinical sign, a high faecal dry matter (FDM) content, was observed in the 200 ppm carbadox group, followed by the 100 and 50 ppm carbadox, the 400 and 100 ppm cyadox, and the 200 and 100 ppm olaquindox groups two weeks later. A second clinical sign, urine drinking from the floor or from pen-mates, was observed in the same pens, occurring in the same sequence. The third important clinical sign, a decreased abdominal volume, was also observed in almost the same sequence, however, in the 50 ppm olaquindox and cyadox groups this clinical sign was not observed. Average weekly weight gain was significantly decreased in the higher carbadox and olaquindox groups. Weight gain was significantly increased in the 200 ppm cyadox group. Hematocrit values were significantly increased in the 200 and 100 ppm carbadox groups only. From this study one may conclude that, within the dosages used, carbadox is more harmful than olaquindox for pigs, and it seems that cyadox is harmless for pigs in dosages up to 400 ppm.

Differences in virulence between two strains of Streptococcus suis type II after experimentally induced infection of newborn germ-free pigs.

Fifteen newborn germ-free pigs were inoculated with 2 strains, D-282 and T-15, of Streptococcus suis type II. Some pigs also were preinoculated with Bordetella bronchiseptica, which successfully predisposed them to S suis infection. The 2 streptococcal strains were differentiated by muramidase treatment, which released certain high molecular-weight proteins, termed muramidase-released proteins (MRP), from the cell wall of strain D-282, but not from the cell wall of strain T-15. Only strain D-282 (MRP-positive) induced clinical signs of disease and markedly increased neutrophil numbers in pigs. Streptococci were more frequently isolated from fecal swab specimens obtained from pigs inoculated with strain D-282 (MRP-positive) than from specimens obtained from pigs inoculated with strain T-15 (MRP-negative). Both strains were isolated from nasal swab specimens obtained from all infected pigs. Postmortem examination revealed fibrinopurulent meningitis, polyserositis, and polyarthritis in pigs inoculated with strain D-282; this strain was isolated from the CNS, serosae, visceral organs, heart, and joints. Whereas strains D-282 caused several pathologic changes, strain T-15, isolated from the lungs, caused only pneumonia. Both strains were isolated from the tonsils of all pigs. Virulence differed distinctly between the MRP-positive and the MRP-negative strains.

Comparative study of the effect of the effect of carbadox, olaquindox and cyadox on aldosterone, sodium and potassium plasma levels in weaned pigs.

To study the effects of olaquindox and cyadox on aldosterone, sodium and potassium in the blood in comparison with the effects of carbadox, weaned pigs were fed these compounds in different doses. Pigs treated with 100 and 200 ppm carbadox showed a significant decline of aldosterone after five and three weeks, respectively, compared with control values. In the 200 ppm group treatment was interrupted at week 4. With olaquindox a continuous, significant decline was found from 50 ppm and above after five weeks, and from 25 ppm and above (but excluding the 100 ppm group), after six weeks. In the cyadox groups a significant decline was measured after six weeks in the 50, 200 and 400 ppm groups. Only the 200 ppm group had an earlier response at three and five weeks. A decrease of sodium to hyponatraemic levels in the carbadox groups was seen after three weeks in the 200, and after five weeks in the 100 ppm group. In the olaquindox groups only the 200 ppm dosage showed a consistent decrease to hyponatraemic levels from four weeks treatment. In the cyadox groups the 200 ppm dosage reached a hyponatraemic level after six weeks. An increase of potassium to hyperkalaemic levels occurred at 100 and 200 ppm carbadox dosage after four and three weeks, respectively, and at 200 ppm olaquindox dosage after four weeks. No hyperkalaemic levels were seen in the cyadox groups. It is concluded that the toxic effect of olaquindox, despite minor differences, is comparable with that of carbadox but that cyadox is less toxic.

Changes in plasma renin activity and renal immunohistochemically demonstrated renin in carbadox treated pigs.

Carbadox is known to induce toxic effects on the adrenal cortex, resulting in hypoaldosteronism. To study the involvement of carbadox on the renin-angiotensin system, weaned piglets of five weeks old received feed supplemented with 0 (control group), 50, 100, 150 or 200 ppm carbadox. After four weeks the 100 and 150 ppm groups had significantly higher plasma renin activity levels than the control group and after nine weeks plasma renin activity levels of all treated groups were significantly higher than the control group. Five and 10 weeks after carbadox administration, three and two pigs, respectively, of all groups were necropsied and the kidneys were screened for immunohistochemically demonstrated renin. All dosed pigs demonstrated an increase of immunoreactive renin, which was dose- and time-related. From these results it is concluded that carbadox induces activation of the renin-angiotensin system, secondary to the suppressing effect on mineralocorticoid secretion and that these changes may be responsible for part of the clinical picture.

Persistence of carbadox-induced adrenal lesions in pigs following drug withdrawal and recovery of aldosterone plasma concentrations.

This study was performed to investigate the persistence of carbadox-induced adrenal lesions in pigs after withdrawal of the drug. Six groups (N = 13) received 0 (control group), 25, 50, 100 and 200 ppm carbadox. After 10 weeks, carbadox was withdrawn from the feed. Five and 11 weeks after withdrawal, two pigs per group were necropsied and the adrenals were examined histologically. Five weeks after withdrawal, recovery of lesions was seen in the 25 and 50 ppm groups. In the 100 and 150 ppm groups, adrenal changes were still present. After 11 weeks an incomplete recovery occurred in the 100 ppm group and in one of the pigs from the 150 ppm group; the second pig of this group still demonstrated moderate changes. Pigs from the 200 ppm group showed severe changes and absence of a clear zonal differentiation. Plasma aldosterone values started to recover 2 weeks after withdrawal of carbadox. Histological examination suggested stimulation of the aldosterone-producing glomerular zone, eventually resulting in regressive changes. The mechanisms that possibly induced this continuous stimulation are discussed.

Clinical signs and performance of pigs during the administration of different levels of carbadox and after withdrawal.

An experiment was designed to study the clinical effects of carbadox in pigs. Five different carbadox levels were tested namely 25, 50, 100, 150, and 200 ppm. They were compared with a control group fed on a diet without medication. After 10 weeks all pigs received a diet without carbadox till the end of the experiment, 21 weeks after the start. After two weeks of carbadox treatment the first clinical signs were observed in the 200 ppm group. The most obvious effects seen were production of dry faeces and drinking of urine from the floor or from pen-mates. Other signs were a decreased abdominal volume, a pale skin with long withered hair, perverted eating and a restless behaviour. The haematocrit values in pigs receiving 100 ppm and upwards were increased. There was a negative correlation between the dose of carbadox and the time after which the response occurred. Weight gain was significantly lowered and feed conversion essentially poorer in the 200 ppm, 150 ppm and 100 ppm groups during the treatment as compared to the controls. No growth promoting effect was seen in the 25 and 50 ppm groups. After withdrawal of carbadox, clinical signs persisted in the 150 and 200 ppm groups. The 100 ppm group produced normal faeces 5 weeks after withdrawal, whereas drinking of urine persisted. From this study it appears that only an oral dosage of 25 ppm or lower can be given to pigs without risks of toxic effects. The widely claimed growth promoting effect of carbadox could not be confirmed in this study. This might be due to the small number of animals per group.

[A case of selenium poisoning in piglets]. / Een geval van seleniumvergiftiging bij biggen.

Acute paralysis was observed in suckling piglets and weaner piglets on a pig breeding farm. Pathomorphological investigations revealed characteristic lesions in the central nervous system. These lesions were indicative of selenium poisoning. This was verified by chemical-toxicological analysis of organs and tissues of the affected pigs. Poisoning was shown to have been caused by the feed: one feed preparation contained an extremely large amount of selenium, which was due to human failure.

Incidence of indurative lymphocytic mastitis in a flock of sheep infected with maedi-visna virus.

Sheep in a flock in which 88 per cent of the ewes had antibodies to maedi-visna virus were clinically examined for udder induration during lactation and after drying off. On both occasions about half of the ewes had indurated udders. Histological examination revealed lymphocytic mastitis associated with maedi-visna virus infection, in the udders of six of 25 hoggs (24 per cent), 21 of 39 shearlings (53.8 per cent) and 42 of 67 ewes (62.7 per cent). Distinct lung lesions were found in 8 per cent of the hoggs, 12.5 per cent of the shearlings and 10 per cent of the ewes. The results of a clinical examination of dry udders were correlated with the histological findings.

Pathological effects of carbadox in pigs with special emphasis on the adrenal.

Weaned pigs, 4-weeks-old, were divided into 6 groups of 13 animals each, which received 0, 25, 50, 100, 150 and 200 ppm (mg per kg) of carbadox medicated feed, respectively. After 5 and 10 weeks of carbadox administration, three and two pigs, respectively, of each group were necropsied. After 5 weeks treatment, gross lesions were seen in pigs receiving 50 ppm or more. The main features were retarded growth, dehydration with dry contents in the intestine, especially in the colon and findings suggestive of pica. The severity of lesions increased with higher dosages. After 10 weeks, the same changes, though much more pronounced, were observed at 100 ppm or higher dosages. After 5 weeks histological changes in the adrenals were found at 50 ppm treatment and upwards. The common feature was a hydropic appearance of the glomerular zone. In the 50 ppm group one out of three and, in the higher dosed groups, all pigs showed these changes. There was a dose-response effect. At 100 ppm or more an enlargement of the glomerular zone was observed, resulting in narrowing of the fascicular layer. The adrenal capsule was slightly thickened and contained cells with PAS-positive granules. After 10 weeks, changes were found at 25 ppm dosage and higher. In the 25 and 50 ppm group half of the pigs had hydropic changes of the glomerular zone. In the higher dosed groups there were also chronic lesions. The outer part of the glomerular zone had become fibrotic. With 150 ppm or more the hydropic changes had extended into the fascicular layer, with development of hyperplastic nodules. This led to disappearance of zonal differentiation. From 100 ppm dosage, many richly granulated PAS-positive cells were present in the thickened capsule, more numerous and more granulated than after 5 weeks treatment. From this study, it can be concluded that carbadox may induce adverse effects on the adrenal in growing pigs at therapeutic (100 to 150 ppm) and feed-additive doses (50 ppm). Even at lower doses (25 ppm), mild lesions were found. The grade of lesions was positively correlated with the duration of exposure to this growth promoter.

[Initial cases of caprine arthritis-encephalitis in The Netherlands]. / Eerste gevallen van caprine arthritis-encephalitis in Nederland.

In a relatively large flock of dairy goats, a few goats suffered from arthritis. Serological investigation revealed the presence of antibodies to lentiviruses, which prompted pathological and virological investigation of two goats. The clinical and pathological picture showed strong resemblance with the descriptions of caprine arthritis-encephalitis (CAE). The virus that was subsequently isolated yielded a cytopathological effect characteristic of lentiviruses. Molecular analysis of the antibody response of both goats by means of the Western blotting technique revealed a close antigenic relationship with known CAE-virus isolates. On the basis of these results, the first diagnosis of CAE in the Netherlands was made.

Indurative lymphocytic mastitis in sheep after experimental infection with maedivisna virus.

In order to provide further evidence for the association of an indurative lymphocytic mastitis in sheep with MVV (maedi-visna virus) infection, an experimental study was performed. Fourteen MVV-free pregnant ewes, 2 years of age, were divided into two groups. Eight were intravenously inoculated with MVV (strain ZZV-1050); six ewes served as sham-inoculated controls. Post-mortem examinations were carried out at 8, 16 and 28 months. After 8 months, the 3 infected ewes had indurated udders with extensive lymphoid proliferation around lactiferous ducts and in the acinar tissue. The ducts were often partially obliterated. After 16 months, one of the two infected ewes suffered from indurative lymphocytic mastitis. The other was free of specific udder lesions. After 28 months only one of three infected ewes had mild lymphocytic infiltration in the udder. None of the controls, two in each post-mortem session, had lesions typical of this form of mastitis. The lesions were most severe 8 months after infection. At 16 and 28 months lesions were of a lesser degree or were absent. The lung lesions in the infected ewes 8 months after inoculation were similar to the changes in the udder regarding the lymphoid accumulation, although the proliferation around bronchial tree and blood vessels was less pronounced. After 16 and 28 months all infected ewes had peribronchial and perivascular lymphocytic infiltration though of a lesser degree than after 8 months. From these results it is concluded that in addition to the lung and brain lesions MVV infections may cause a specific indurative lymphocytic mastitis.