[Male-female ratio in Dutch academic psychiatry]. / Man-vrouwverhouding in de Nederlandse academische psychiatrie.

Background   Psychiatry is at the forefront of the emancipation of women as medical specialists. The share of women in the training of psychiatrists is high. In the labor market of the academia, however, there are indications of structural inequality. At university medical centers in the Netherlands 28% of the professors are female. How are women represented in the higher positions in academia in psychiatry? Aim   To explore how women are represented in the higher positions in psychiatric academia and what interventions can lead to a more equal labor market. Method   Information was obtained through universities and educational institutions on the current proportion of women in various positions in academic psychiatry. By searching the literature, interventions that can lead to a more equal labor market were investigated. Results   In psychiatry departments in the Netherlands 24% of the professors and 33% of the directors of psychiatric residency are female. Women are with 22% also a minority on editorial boards of scientific journals. Conclusion   In the higher academic positions in psychiatry, there is an unequal gender distribution. Culture change in combinations with policy changes can lead to a more equal labor market.

[CYP2D6 and CYP2C19 genotyping: effectivity in psychiatric practice] / CYP2D6- en CYP2C19-genotypering: effectiviteit in de psychiatrische praktijk.

BACKGROUND: International guidelines recommend in patients with an in- or decreased CYP2D6 and CYP2C19 metabolism to adjust the dose of medication metabolized by these enzymes. This is in purpose to increase effectiveness and to lower the risk of side-effects of this medication. However, it is still unclear if dose adjustment based on genotype results in better clinical outcomes. AIM: To provide an update regarding CYP2D6 and CYP2C19 genotyping in psychiatry in relation to ethnic diversity.To provide an update regarding CYP2D6 and CYP2C19 genotyping in psychiatry in relation to ethnic diversity. METHOD: We conducted a comprehensive meta-analysis to the prevalence of non-normal metabolizers as the equivalent of the sum-prevalence of poor, intermediate and ultrarapid metabolizer CYP2D6 and CYP2C19 predicted phenotypes. For the prevalence and effectiveness study, a total of 166 Antilleans living in the Netherlands and 269 psychiatric patients (on the island Curaçao) were genotyped for CYP2D6 and CYP2C19. Of the psychiatric patients, 45 non-normal CYP2D6 metabolizers using medication metabolized by CYP2D6, were included for dose adjustment and were matched with 41 normal metabolizers. All 45 patients were using antipsychotic medication for a minimum of two years. Four months after dose adjustment they were reassessed. RESULTS: The mean total probability estimates of having a non-normal predicted phenotype worldwide were 36% and 62% for CYP2D6 and CYP2C19, respectively. There was a large interethnic variability (min-max 2.7-61.2% (CYP2D6) and minmax 31.7-80.1% (CYP2C19)). No significant difference was found in the phenotypes of psychiatric patients, Dutch Caribbean subjects from the general population, and European populations. There were no beneficial effects of dose adjustments to phenotype in the non-normal CYP2D6 metabolizers. CONCLUSION: More than 75% of the world population has a non-normal CYP2D6 and/or CYP2C19 phenotype. Dose adjustment to the CYP2D6 phenotype according to international guidelines in patients on long-term antipsychotic treatment showed no beneficial effect. Further research to CYP genotyping in psychiatry is warranted.

Distinct blood and milk 18-carbon fatty acid proportions and buccal bacterial populations in dairy cows differing in reticulorumen pH response to dietary supplementation of rapidly fermentable carbohydrates.

Nine Holstein dairy cows were fed diets with increasing proportions of rapidly fermentable carbohydrates (RFCH) to investigate the effect on reticular pH, milk fat content (MFC), 18-carbon fatty acid proportions in blood plasma and milk, and bacterial community in buccal swab samples. Inter-animal variation was expected in terms of reticular pH response upon higher RFCH proportions, which would be reflected in the occurrence or not of milk fat depression (MFD). Moreover, this variation in occurrence of MFD was hypothesized to be related to differences in blood and milk fatty acid proportions and in the bacterial community in buccal samples. Cows were fed a total mixed ration throughout the experiment, which consisted of 4 periods: adaptation (d 0-4) and low (d 5-18), increasing (d 19-24), and high RFCH (d 25-28). During the increasing RFCH period, the standard concentrate (211 g of starch/kg of dry matter) was gradually and partly replaced by a concentrate high in RFCH (486 g of starch/kg of dry matter). The reticular pH was measured using a bolus and the time below pH 6.00 was calculated on a daily basis. On d 13, 14, 25, 27, and 28, plasma and milk samples were collected and analyzed for 18-carbon fatty acid proportions, and buccal swabs were collected for bacterial community analysis based on 16S rRNA gene amplicon sequencing. Inter-animal variation was observed in terms of reticular pH, which allowed us to divide the cows into 2 groups: tolerant (time below pH 6.00 ≤ 0.1 h/d) and susceptible cows (time below pH 6.00 ≥ 1.26 h/d). The lower reticular pH of susceptible cows was accompanied by lower MFC. Both groups already differed in reticular pH and MFC during the low-RFCH period. Furthermore, higher RFCH amounts did not decrease the reticular pH in either of the 2 groups. Nevertheless, MFD was observed in both groups during the high-RFCH period compared with the low-RFCH period. Lower MFC in animals with lower reticular pH or during the high-RFCH period was associated with a shift in 18-carbon fatty acids toward trans-10 at the expense of trans-11 intermediates, which was observed in plasma as well as in milk samples. Moreover, lower MFC was accompanied by shifts in the relative abundance of specific bacteria in buccal samples. Genera Dialister, Sharpea, Carnobacterium, Acidaminococcus, and uncultured genera belonging to the Betaproteobacteria were more abundant in situations with greater trans-10 proportions.

Susceptibility of dairy cows to subacute ruminal acidosis is reflected in milk fatty acid proportions, with C18:1 trans-10 as primary and C15:0 and C18:1 trans-11 as secondary indicators.

The current study was carried out to assess 2 hypotheses: (1) cows differ in susceptibility to a subacute ruminal acidosis (SARA) challenge, and (2) the milk fatty acid (FA) pattern can be used to differentiate susceptible from nonsusceptible cows. For this, 2 consecutive experiments were performed. During experiment 1, the milk FA pattern was determined on 125 cows fed an increasing amount of concentrate during the first 4 wk in milk (WIM). The coefficient of variation of several SARA indicative milk FA (i.e., C15:0, C18:1 trans-10, C18:2 cis-9,trans-11, and C18:1 trans-10 to C18:1 trans-11 ratio) increased, indicating that cows reacted differently upon the concentrate build-up. A first grouping was based on the milk fat C18:1 trans-10 proportion in the third WIM. Fifteen cows with the highest proportion of the latter FA (HT10) and their counterparts with low C18:1 trans-10 and equal parity distribution (LT10) were compared, which revealed that milk fat content and milk fat to protein ratio were lower for the HT10 group. From each of the HT10 and LT10 groups, 5 animals were selected for experiment 2. The subselection of the HT10 group, referred to as HT10s, showed a high proportion of C18:1 trans-10 at 3 WIM (>0.31 g/100 g of FA), a high level of C15:0 (on average ≥1.18 g/100 g of FA over the 4 WIM), and a sharp decrease of C18:1 trans-11 (Δ ≥ 0.25 g/100 g of FA during the 4 WIM). Their counterparts (LT10s) had a low milk fat C18:1 trans-10 proportion at 3 WIM (<0.23 g/100 g of FA), an average C15:0 proportion of 0.99 g/100 g of FA or lower, and a rather stable C18:1 trans-11 proportion. The HT10s group was hypothesized to be more susceptible to a SARA challenge, achieved by increasing amounts of rapidly fermentable carbohydrates in experiment 2. The HT10s cows had a lower nadir, mean, and maximum reticulo-ruminal pH; longer period of reticulo-ruminal pH below 6.0; and higher daily reticulo-ruminal pH variation compared with LT10s cows. Throughout experiment 2, HT10s and LT10s cows differed in levels of SARA indicative milk FA. Five animals, including one LT10s and 4 HT10s cows, experienced SARA, defined as reticulo-ruminal pH <6.0 for more than 360 min/d. These results indicate that it is possible to distinguish cows with different susceptibility to a SARA challenge within a herd by monitoring the milk FA composition when cows receive the same diet.

Patient survival in uveal melanoma is not affected by oncogenic mutations in GNAQ and GNA11.

BACKGROUND: Mutations in GNAQ and GNA11, encoding the oncogenic G-protein alpha subunit q and 11, respectively, occur frequently in the majority of uveal melanomas. METHODS: Exons 4 and 5 from GNAQ and GNA11 were amplified and sequenced from 92 ciliary body and choroidal melanomas. The mutation status was correlated with disease-free survival (DFS) and other parameters. RESULTS: None of the tumours harboured a GNAQ exon 4 mutation. A GNAQ mutation in exon 5 codon 209 was found in 46 out of 92 (50.0%) of the tumours. Only 1 out of 92 (1.1%) melanomas showed a mutation in GNA11 exon 4 codon 183, whereas 39 out of 92 (42.4%) harboured a mutation in exon 5 of GNA11 codon 209. Six tumours did not show any mutations in exons 4 and 5 of these genes. Univariate analyses showed no correlation between DFS and the mutation status. CONCLUSION: GNAQ and GNA11 mutations are, in equal matter, not associated with patient outcome.

Birt-Hogg-Dubé syndrome: clinical and genetic studies of 20 families.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal-dominant genodermatosis characterized by skin fibrofolliculomas and an increased risk of spontaneous pneumothorax, renal and possibly other tumors. A causative gene (FLCN) on chromosome 17p has recently been identified. We here report clinical and genetic studies of 20 BHD families ascertained by the presence of multiple fibrofolliculomas or trichodiscomas in the proband. Pathogenic FLCN germline mutations were found in 11 (69%) of 16 probands tested and in 14 family members. Six different FLCN germline mutations were detected, four of which have not been reported previously. The clinical features were variable. None and less than 10 skin lesions were observed in two mutation carriers at the age of 67 and 29 years, respectively. Spontaneous pneumothorax was reported in four and renal carcinoma of mixed histological types in two of 36 BHD-affected individuals and/or FLCN mutation carriers. Both the prevalence of spontaneous pneumothorax and renal tumors appeared to be relatively low compared with previously reported data. Various other extracutaneous tumors were observed in 11 of 36 BHD-affected individuals and/or FLCN mutation carriers. This study of the second largest cohort to date contributes to the expanding data on the variable phenotype and underlying gene defects in BHD.

[Restrictive dermopathy: a rare, lethal genodermatosis]. / Restrictieve dermopathie: een zeldzame, letale genodermatose.

In a premature male infant born of consanguineous parents, restrictive dermopathy was diagnosed. This is a rarely described, lethal, congenital skin disease. The diagnosis was based on the clinical and histopathological findings: a fixed facial expression (so-called 'porcelain face') with palpebral fissures inclined laterally downwards, microstomia with the mouth in the 'O'-position, micrognathia and low-set ears inclined toward the rear, prominent blood vessels in the skin and contracture of all the joints; histopathological examination of a skin biopsy revealed a smooth epidermis and a relatively thin dermis with an abnormal structure of the dermal connective tissue in which the collagen fibres were arranged more or less horizontally, parallel to the epidermis, and the number of elastin fibres was sharply decreased. Various adnexal structures were present but the hair follicles had an abortive appearance. Thanks in part to the finding of a homozygous mutation in the so-called ZMPSTE24-gene, it could be concluded that restrictive dermopathy is probably an autosomal recessive laminopathy, related to progeria. Increasing the clinical awareness of this disease may contribute to reducing the presumed under-reporting, so that future research will become possible.

Is PPD a useful screening agent?

In this study, the usefulness was assessed of para-phenylenediamine (PPD) base as a marker for contact allergy to para-compounds and disperse dyes. 59 patients with a positive reaction to PPD were patch tested with a series of para compounds and disperse dyes. This dyes series was also tested in patients with a suspect medical history of contact allergy to hair, fabric or leather dyes. In total 610 patients were tested. As 24 patients became positive over the weekend, late readings, day 6 or 7, are important. These reactions were most probably relevant in 17/24 patients. Positive reactions to PPD correlated well with reactions to para compounds like p-aminoazobenzene and p-toluenediamine sulphate but not with disperse dyes. Reactions to Disperse Blue (106, 124) and Orange (1 and 3) were seen most frequently. PPD is a good screening agent for hair dye, but not for disperse dye, sensitivity.

[Simulation of pigmented mucosa in complete dentures: development of an oral pigment index]. / Simulatie van de gepigmenteerde mucosa in gebitsprothesen: ontwikkeling van een classificatie.

In the non-Caucasian population the skin and oral tissues show pigmentation to a variable degree, but much more than in Caucasian. When a person becomes edentulous, the tissues containing oral pigmentation disappear. The patient's ethnic background gives no information to predict the characteristics of individual oral pigmentation; other sources have to be found. The mucosal pigmentation of 106 non-Caucasian, dentate people in Amsterdam and Los Angeles was investigated; a classification-chart of oral pigmentation with six types was designed. This tool makes it possible to help patient, dentist and dental technician to choose an accurate simulation of the contour of oral pigmentation in a denture. It is recommended to document the individual pigmentation before extractions are performed.

[Tumor of the omentum in 2 patients with a large, mobile mass in the upper abdomen]. / Omentumtumor bij 2 patiënten met een grote, mobiele zwelling in de bovenbuik.

A mobile mass in the right upper abdomen was felt in an 81-year-old woman with nausea and a 45-year-old man with exertional dyspnoea. Radiological investigations did not reveal sufficient information, whereupon laparotomies were carried out. In both cases, a tumour was found at the exit of the greater omentum. Following resection, the tumour recurred in the woman five months later, and she died as a result; the man made a rapid recovery and remained tumour-free two years later. Tumours originating in the omentum majus are rare. The presentation of these tumours is late, due to late presentation of complaints. These tumours are usually only detected once they reach a diameter of more than 10 centimetres. In general, it is difficult to establish whether the tumour is benign or malignant either pre- or peri-operatively. Surgery is the only curative option. A wide resection is preferable, with resection of any (parts of) organs which may be involved.

Histological and bacteriological evaluation of digital dermatitis in cattle, with special reference to spirochaetes and Campylobacter faecalis.

Tissue samples from the feet of slaughtered cattle exhibiting different stages of digital dermatitis were sectioned and stained with haematoxylin and eosin and silver staining techniques. Three morphological variations of spirochaetes were observed, whereas control samples from feet which were macroscopically negative for digital dermatitis were also negative for spirochaetes. In an immunofluorescence test, Campylobacter faecalis was found to be abundant on superficial wound smears from the classical ulceration of digital dermatitis.

Acquired ichthyosiform erythroderma and sarcoidosis.

We describe a patient with ichthyosiform erythroderma as a manifestation of sarcoidosis. This is the first report of the simultaneous occurrence of erythroderma and ichthyosis in sarcoidosis.

Toxic pustuloderma associated with clemastine therapy.

Toxic pustuloderma is an acute pustular eruption of the skin occurring a few days after the initiation of treatment with the responsible drug. A case of toxic pustuloderma following treatment with the antihistamine clemastine is now reported.

Bacterial involvement in denture-induced stomatitis.

Denture and mucosal plaque samples were collected from eight full-denture wearers of whom four suffered from denture-induced stomatitis (DIS). Cultures were made, and a proportional identification to species level was carried out of bacteria and yeasts. An inventory was made of the predominant flora. Results showed that the predominant microflora of both groups, both on dentures and the denture-bearing mucosa, consisted mainly of Gram-positive bacteria. Differences in the proportions of cocci were found between the predominant bacterial flora on the dentures. In the control group, 69% of the denture flora consisted of cocci, while on the dentures of the DIS group a mean of 33% cocci was found. Neither group of palates revealed any differences in the proportions of cocci. On these locations a mean of 69% was found. The plaque of dentures and the palates of the healthy group showed means of 35% and 31%, respectively, of obligate anaerobic bacteria, while in the DIS group these percentages were 56% and 43%, respectively. No obligately aerobic bacteria were found. Candida species was detected in both groups, both on dentures and palates in very low numbers (DIS group, median palates 0.02%, median dentures 0.25%). The predominant organisms were Streptococcus species, of which S. salivarius was mostly present on the palates of both groups. Other species which were regularly found at different locations were Veillonella parvula and species of Lactobacillus, Bacteroides, and Actinomyces.

Efficacy of 2.5% Pimafucin suspension in the treatment of denture stomatitis.

This double-blind clinical trial was carried out in 38 patients to compare the efficacy of 2.5% Pimafucin suspension with a placebo in the treatment of denture stomatitis. The diagnosis of Candida infection was confirmed by the making of cultures and microscopic examination. Data were analyzed from 32 patients, of whom 18 received Pimafucin suspension and 14 a placebo suspension. Pimafucin suspension-treated patients showed a significant reduction of Candida infection in terms of culture, culture growth, and number of colonies within the first week of therapy. There was no statistical evidence of relapse during the 4-week period after therapy was stopped. The group receiving a placebo failed to show any statistically significant improvement with respect to the mentioned parameters. Erythema of oral mucosa showed significant improvement in both groups. No side effects were found.