Optimizing VAP scars after childhood cancer treatment: a pilot study.

PURPOSE: Majority of pediatric cancer patients are treated with chemotherapy using Venous Access Ports (VAP). However, after surgical removal of the VAP prominent scars often remain and standard care is lacking. METHODS: Patients (N = 20) who were willing to participate were included prior to surgical removal of their VAP. All patients were off therapy at time of VAP removal. Patients had the option to either choose from Dermatix®, meridian color therapy (MCT), or no additional treatment (NAT). Assessment of scars was done prior to and 3, 6, and 12 months after surgical VAP removal using Patient and Observer Scar Assessment Scales (POSAS) questionnaires. To identify whether Dermatix® or MCT is associated with better scar healing than without additional treatment, Mann-Whitney U tests were used. RESULTS: After 12 months of follow-up, both patients and dermatologists noted VAP scars had healed better after MCT compared to those without treatment (P = 0.010 for both POSAS patient and POSAS observer). No significant differences were observed between VAP scars after Dermatix® use and those with no treatment. CONCLUSIONS: Scar healing after MCT significantly improved, whereas Dermatix® treatment showed no significant differences compared to NAT. To translate this to daily care, a larger prospective study is needed to validate these findings.

Vitamin E plasma kinetics in swine show low bioavailability and short half-life of -α-tocopheryl acetate.

Vitamin E is important for animal production because of its effects on health and product quality, but the amount and form required remains controversial. Our objective was to quantify the absolute bioavailability of oral -α-tocopheryl acetate (α-TAc) in swine (22 ± 1 kg and 8 wk old, fitted with jugular catheters) adapted to a diet supplemented with 75 mg/kg -α-TAc; 75 mg/kg was chosen because this level represents the nonweighted average inclusion level in piglet diets across Western key swine-producing countries. For this, a 350-g test meal (6% fat) was supplied at time 0 containing 75 mg deuterated (D9) -α-TAc to 9 animals, and 8 animals received an intravenous () dose containing deuterated (D6) RRR-α-tocopherol (α-T) at one-eighth the oral dose and a test meal without supplemental vitamin E. Plasma samples (12 to 13 per animal) were obtained at incremental intervals over 75 h for analysis of deuterated α-T using liquid chromatography-tandem mass spectrometry. Surprisingly, the i.v. dose rapidly disappeared from plasma and then reappeared. The half-life for this first peak was only 1.7 ± 0.3 min. The second peak had an appearance rate (Ka) of 0.10 ± 0.06 d and a half-life of 5.9 ± 1.2 h. Oral dosing resulted, after a lag of 56 min, in a Ka of 0.91 ± 0.21 d and a half-life of 2.6 ± 0.8 h. The bioavailability for oral α-TAc was 12.5%, whereas the area under the curve was only 5.4%. This low bioavailability, small area under the curve, and short half-life are likely because of various factors, that is, the use of only 6% fat in the diet, the use of the acetate ester and , and the high dose relative to requirements. In conclusion, i.v. dosed vitamin E shows both a rapid and a very slow pool, whereas orally dosed vitamin E shows a single slow pool. The oral material has a very short half-live (44% of i.v. or 2.6 h), low bioavailability (12.5%), and a very small area under the curve (5.4%), bringing into question the efficacy of typical doses of vitamin E in swine diets for alleviating oxidative stress.

Esophageal Dysfunction in Friesian Horses: Morphological Features.

Megaesophagus appears to be more common in Friesian horses than in other breeds. A prevalence of approximately 2% was observed among Friesian horses presented to the Wolvega Equine Clinic and the Utrecht University Equine Clinic. In this study, morphologic changes in the esophagi of Friesian horses with megaesophagus were compared with those of 6 control horses. Of 18 horses with clinically observed megaesophagus, only 12 animals had esophageal dilation at necropsy, usually involving the thoracic portion. Muscular hypertrophy of the distal esophagus was present in only one-third of the affected horses, indicating that this change is not the most relevant cause of megaesophagus in Friesians. Increased deposition of clumped and disorganized collagen was present in these clinically affected horses mainly in the non-dilated portion of the esophagus. At necropsy, a decrease in neural elements and elastin was present principally in horses with megaesophagus. Mild degeneration and necrosis of the tunica muscularis along the entire length of the esophagus were present in clinically affected horses and encountered only rarely in control animals. There were no significant differences among affected and control horses with respect to inflammation, mineralization, or the number of cells of Cajal. The increased occurrence of megaesophagus in the Friesian breed compared with other horse breeds, together with the presence of abnormal collagen in very young foals, supports the hypothesis that megaesophagus is hereditary in Friesians.

Aortic rupture and aorto-pulmonary fistulation in the Friesian horse: characterisation of the clinical and gross post mortem findings in 24 cases.

REASONS FOR PERFORMING STUDY: In horses, aortic sinus of Valsalva aneurysms or tears in the aortic root are well-recognised conditions in breeding stallions, often leading to sudden death. A more uncommon form of aortic rupture, located proximal to the ligamentum arteriosum has been reported in 3 Friesian horses. OBJECTIVES: The purpose of this study was to phenotypically characterise aortic rupture and aorto-pulmonary fistulation in Friesian horses in terms of clinical and post mortem data based on 24 cases. METHODS: Friesian horses that were diagnosed with aortic rupture and aorto-pulmonary fistulation over a period of 13 years (1997-2010) at the Department of Equine Sciences of Utrecht University (n = 15) and Wolvega Equine Hospital (n = 9), were included in this study. Case history, results of clinical examination and gross post mortem findings were screened and analysed. RESULTS: Some cases were found dead without prior symptoms, but in several cases signs such as recurrent colic, peripheral oedema and sustained tachycardia were present for several weeks prior to cardiac failure. Clinical examination during hospitalisation revealed increased rectal temperature, peripheral oedema and increased jugular pulse with a bounding arterial pulse. In the majority of horses an aortic rupture of the aortic arch near the ligamentum arteriosum, concurrent with a circumferential cuff of perivascular haemorrhage and aorto-pulmonary fistulation, was found at post mortem examination. CONCLUSIONS: Aorto-pulmonary fistulation in conjunction with aortic rupture is more common in Friesians than previously estimated. In some cases findings demonstrate a progressive pathology rather than acute cardiac failure and sudden death. An appropriate approach is necessary during post mortem examination of the heart in order not to overlook the diagnosis. POTENTIAL RELEVANCE: Equine practitioners should realise that in Friesian horses presented with a history of recurrent false colic, coughing, sustained tachycardia and/or peripheral oedema, aortic rupture and aorto-pulmonary fistulation should be included in the differential diagnosis.

[Eosinophilic colitis caused by clozapine]. / Eosinofiele colitis door clozapine.

BACKGROUND: Clozapine is an antipsychotic agent used when patients experience excessive extrapyramidal side effects from other antipsychotic agents or for therapy resistant schizophrenia. However, clozapine is also known for its serious adverse effects e.g. granulocytopenia and agranulocytosis. CASE DESCRIPTION: A 40-year-old male with known schizophrenia, presented with severe diarrhea and eosinophilia in the peripheral blood examination result, arising 2 weeks after starting clozapine. Histopathological examination demonstrated an eosinophilic colitis. After the patient discontinued clozapine, the symptoms disappeared completely. CONCLUSION: Eosinophilic colitis is a rare adverse effect of clozapine. It is only possible to diagnose this using endoscopy and biopsy, so that the complaint is often not recognised. The exact pathophysiology underlying this eosinophilic colitis is not known.

Subthreshold symptoms and obsessive-compulsive disorder: evaluating the diagnostic threshold.

BACKGROUND: In this study we compared subjects with obsessive and/or compulsive symptoms who did not meet all criteria for obsessive-compulsive disorder (OCD) (subthreshold subjects) to subjects with full-blown OCD and also to subjects without obsessions or compulsions. METHOD: The data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a large representative sample of the general Dutch population (n=7076). Using the Composite International Diagnostic Interview, Version 1.1 (CIDI 1.1), three groups were distinguished: subjects without lifetime obsessions or compulsions (94.2%), subthreshold subjects (4.9%) and subjects with full-blown OCD according to DSM-III-R (0.9%). These three groups were compared on various items, including psychological vulnerability, health and functional status, psychiatric co-morbidity and seeking treatment. RESULTS: Subthreshold and OCD subjects had similar scores on the majority of the items measured. Thus, there was little difference between subthreshold and OCD subjects in health, functional status, psychological vulnerability and psychiatric co-morbidity. However, OCD and subthreshold subjects scored worse on most of these items when compared to the controls without obsessions or compulsions. CONCLUSION: Having obsessions and compulsions is associated with substantial suffering and disability. Most subjects with obsessions and/or compulsions are not diagnosed with OCD according to the DSM-III-R criteria although these subjects generally display similar consequences to full-blown OCD subjects. We recommend that these subthreshold cases receive special attention in the development of DSM-V.

[Two horses with neurological symptoms: could this be equine botulism?]. / Twee paarden met neurologische verschijnselen: is botulisme in het spel?

Symptoms, diagnosis and therapy of equine botulism are discussed by the presentation of two detailed reports of horses with neurological symptoms and the results of laboratory investigations over the period 2003-2008 in the Netherlands. In addition a brief summary of the available literature is presented. Prevailing symptoms of botulism in horses include paralysis of the tongue, salvation, dysphagia and paresis and paralysis of the skeletal muscles, as well as signs of colic. Symptoms and prognosis vary with the amount of botulinum neurotoxin (BoNT) involved. For early clinical diagnosis of botulism thorough investigation of the facial nerves is important, for instance by the use of the 'Tongue Stress Test'. Laboratory results often remain negative, probably due to the sampling time, the high sensitivity of horses for botulinum neurotoxin or treatment with antitoxins. Most clinical cases in horses are caused by botulinum neurotoxin B (BoNT/B). For therapy to be successful antiserum needs to be administered in the earliest possible stage of the disease and this should be supported by symptomatic therapy. Botulism is a feed-related intoxication caused by either carcasses in the roughage or BoNT/B production after poor conservation of grass silage. This is the main source of botulism in horses due to the popularity of individually packed grass silage as feed for horses. As long as no vaccine is available in the Netherlands quality control of silage and haylage is strictly recommended in order to reduce the risk of botulism in horses.

Clinical, histopathological and immunophenotypical findings in five horses with cutaneous malignant lymphoma.

This study documents the clinical, histopathological, immunohistochemical and flow-cytometric findings in five horses with cutaneous non-epidermotropic malignant lymphoma (ML). The median survival time after discovery of the first subcutaneous nodules was 3.8 years (range 2-5 years: n=4). Histologically, the cutaneous ML had a pleiomorphic structure and contained a mixture of large reticulo-endothelial cells, medium-large sized lymphoid cells with a rounded nucleus and small nucleoli, many medium sized lymphoid cells with irregular nuclei, and some small lymphoid cells. Immunohistochemically (IHC) the lymphoid cells were positive for the pan-T-lymphocyte marker CD3 but negative for the B-lymphocyte markers CD21 and kappa and lambda immunoglobulin light chains. Although routine haematological examination revealed no abnormalities in the horses with cutaneous ML, changes in the peripheral blood lymphocyte population were apparent flow-cytometrically. Compared to clinically healthy horses, a decreased total percentage of cells was recorded in the lymphocyte gate. In three horses with cutaneous ML, an increase in CD4 positive cells was noticed in the monocyte gate. Flow-cytometric analysis of tumour cells collected by fine needle aspiration (FNA) suggested that the cutaneous MLs consisted primarily of CD4 and CD8 positive T-lymphocytes. The results were compared to those of a monomorphic multicentric T- and a monomorphic multicentric B-cell lymphoma. The results of immunohistochemistry and flow-cytometry were largely but not completely in accordance. In conclusion, the results of this study suggest that cutaneous non-epitheliotropic malignant lymphomas in the horse are of T-cell origin and that, after improvement of its accuracy, flow cytometric analysis of FNAs might become a useful aid to rapid tumour identification.

Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

BACKGROUND: The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome. METHODS: Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.

['Awakening': a confusing improvement during treatment with atypical antipsychotic agents]. / 'Awakening': een verwarrende verbetering tijdens behandeling met atypische antipsychotica.

Two schizophrenic women, aged 30 and 40 years, respectively, in whom the symptoms changed after a switch in medication from clozapine to aripiprazole and from olanzapine followed by quetiapine to risperidone, respectively, were initially thought to be experiencing a possible recurrence. After thoughtful consideration, the phenomena, such as disappearance of drowsiness and of loss of energy, in combination with cognitive improvement, could be understood as the result of a dramatic improvement, known as 'awakening'. This had significant consequences for the follow-up since the patients had to deal with new possibilities and emotions.

[The short- and long-term results of the "Intensive Care" of 160 sick neonatal foals]. / De korte- en lange-termijn-resultaten van 'Intensive Care' van 160 pasgeboren zieke veulens.

The short- and long-term results of admission to the 'Neonatal Intensive Care Unit' (ICU) at the Department of Equine Sciences of the Utrecht University were evaluated. The patients were categorized, based on specific criteria, into different groups: 'Sepsis', 'Pneumonia', 'Enteritis', 'Asphyxia', 'Premature', 'Isoerythrolysis', and 'Equine herpes virus (EHV)'. The survival rate and mean duration of hospitalization were determined for each group. The venous blood variables at admission were compared for 'surviving' and 'non-surviving' foals within groups, between groups, and for the overall group. From 1992 to 2001, 160 critically ill foals (younger than 7 days) were admitted to the ICU. Thirty-six percent of the foals survived. The mean duration of hospitalization was 6.6 days for the 'surviving' foals and 3.0 days for the 'non-surviving' foals. The pCO2 appeared to the the most important diagnostic and prognostic variable. The results of a telephone questionnaire (owner response of 81 %) revealed that in the long term 60% of the surviving foals lived up to the owner's expectations.

Combination of serum markers related to several mechanisms in Alzheimer's disease.

Alzheimer's disease (AD) probably involves several pathobiochemical mechanisms and this may be reflected by changes in different serum components. The present study investigated whether the combined analysis of serum molecules related to different mechanisms improves the discrimination of AD patients from healthy controls. Serum of patients with AD was analyzed for a broad spectrum of marker molecules, including 11 inflammatory proteins, 12 sterol intermediates and phytosterols, 2 brain-specific proteins and 4 constituents involved in homocysteine homeostasis. The serum molecule concentrations were combined in a logistic regression model, using a forward stepwise inclusion mode. The results showed that the combination of interleukin-6 (IL-6) receptor, protein alpha1 fraction, cysteine and cholesterol concentrations improved the discrimination between AD patients and healthy controls compared to the single markers. In conclusion, the results of this study have shown that the complex pathology in AD is reflected in a pattern of altered serum concentrations of several marker molecules related to several pathobiochemical mechanisms.

Homocysteine: a marker for cognitive performance? A longitudinal follow-up study.

The present prospective study investigated whether elevated total serum homocysteine concentration is a risk factor for cognitive decline. The outcomes were compared to the possible relation between cognition and vitamin B12 or folic acid. Cognitive performance of 144 normal aging individuals (aged 30-80 years) was tested at baseline and after six years of follow-up. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test) and verbal learning and memory (Word Learning Test Total; Delayed Recall). Serum concentrations of homocysteine, folic acid and vitamin B12 were determined. Serum concentrations of homocysteine correlated negatively with cognitive performance on the Word Learning tests at baseline, independent of age, sex, education level or folic acid concentration. Homocysteine concentration at baseline correlated negatively with cognitive performance on the Stroop and Word Learning tests during the whole six-year follow-up period. The folic acid concentration correlated to the Delayed Recall test at baseline only and no correlations were observed for vitamin B12. Thus, while a relation between vitamin B12 or folic acid and cognition was almost absent, elevated homocysteine concentrations were associated with prolonged lower cognitive performance in this normal aging population.

[Reliability of the glutaraldehyde test to measure gamma-globulin levels in foals and the use of this test to check colostrum intake of foals]. / Een onderzoek naar de betrouwbaarheid van de glutaaraldehydetest voor de bepaling van het gammaglobulinegehalte in het serum van veulens en naar de bruikbaarheid van deze test in de praktijk bij het controleren van de colostrumopname bij veulens.

The glutaraldehyde coagulation test is a semi-quantitative test used to determine the gammaglobulin concentration in serum. The purpose of this study was to examine the reliability of the different modifications of this test by determining the sensitivity, specificity, positive and negative predictive value, and the prevalence of hypogammaglobulinemia in foals. The results of the glutaraldehyde coagulation test were compared with the serum gammaglobulin concentration as a reference value, determined by measuring total serum protein and the serum protein spectrum. It was concluded that the glutaraldehyde coagulation test is a suitable test to use in the field for determining the serum gammaglobulin concentration in foals. The test has good sensitivity, specificity, positive and negative predictive value when using a 5% glutaraldehyde solution and when results are evaluated at 30 minutes for a serum concentration of 8 g/l and at 50 minutes for a serum concentration of 5.5 g/l, a concentration below which therapy is recommended.

[Serum markers in relation to cognitive functioning in an aging population: results of the Maastricht Aging Study (MAAS)]. / Serummarkers in relatie tot cognitieve functies bij ouderen. Resultaten van de Maastricht Aging Study (MAAS).

Little is known of the biochemical processes of cognitive decline during 'healthy' aging. Biological markers in body fluids, such as blood, could provide insight in those processes. In the present studies serum concentrations of different markers have been correlated to cognitive functioning of cognitively healthy aging individuals over a period of six years (mean age 57 years, SD 11, n = 93). Markers were related to mechanisms known to be involved in Alzheimer's disease, including inflammation, cholesterol homeostasis and homocysteine homeostasis. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test), and memory (Word Learning test: Total Words and Delayed Recall). Baseline concentrations of haptoglobine, homocysteine, lathosterol and lanosterol were negatively correlated with cognitive functioning on the Stroop test over the whole follow-up period of six years. Concentrations of all markers, i.e. haptoglobine, C-reactive protein, homocysteine, lathosterol and lanosterol, were also negatively correlated with functioning on the Word Learning test (Delayed Recall and for some markers also with the Total Words) over the whole six-years follow-up period. In conclusion, concentrations of serum markers related to inflammation, homocysteine and cholesterol homeostasis are not only associated with Alzheimer's disease, but also with cognitive functioning in the cognitively healthy aging population.

Inflammation markers in relation to cognition in a healthy aging population.

The relation between serum inflammatory protein levels and cognitive performance was investigated in a healthy population. Individuals were tested during 6 years of follow-up. Serum concentrations of 10 inflammatory proteins were correlated to cognitive speed (Letter-Digit Coding Test, LDCT), attention and information processing (Stroop) and memory (Word Learning). Haptoglobin levels at baseline correlated negatively with cognitive performance on the Stroop and Word Learning Recall test over the 6 years follow-up period. C-reactive protein (CRP) levels at baseline correlated negatively with performance on the Word Learning tests over the 6 years follow-up period. Thus, relatively high concentrations of haptoglobin and C-reactive protein may be indicative for impaired cognitive performance.

Serum cholesterol, precursors and metabolites and cognitive performance in an aging population.

The present study investigated if a causal relation exists between serum concentrations of precursors and metabolites of cholesterol and cognitive performance in a healthy aging population. Cognitive function addressing four domains of 144 individuals (30-80 years) was tested at baseline and after 6 years of follow-up. Serum concentrations of different sterols related to cholesterol were measured. Serum levels of lathosterol and lanosterol correlated negatively with cognitive performance on the Word Learning tests for verbal learning and memory. This was observed at baseline and follow-up and was independent of age, sex and educational level. Furthermore, the levels of lathosterol and lanosterol at baseline correlated with performance on the Stroop test and Word Learning tests over the 6-year follow-up period. Serum levels of 27-hydroxycholesterol and 24S-hydroxycholesterol showed inconsistent correlations, while cholesterol, desmosterol, sitosterol and campesterol were not related to cognitive performance.Thus, relative high serum ratios of the cholesterol precursors lanosterol and lathosterol, indicative for a high rate of endogenous cholesterol synthesis, are associated with relatively low memory performance in this aging population.