Multidrug-resistant Mycoplasma genitalium infections in Europe.

In Japan and Australia, multidrug-resistant Mycoplasma genitalium infections are reported with increasing frequency. Although macrolide-resistant M. genitalium strains are common in Europe and North America, fluoroquinolone-resistant strains are still exceptional. However, an increase of multidrug-resistant M. genitalium in Europe and America is to be expected. The aim of this paper is to increase awareness on the rising number of multidrug-resistant M. genitalium strains. Here, one of the first cases of infection with a genetically proven multidrug-resistant M. genitalium strain in Europe is described. The patient was a native Dutch 47-year-old male patient with urethritis. Mycoplasma genitalium was detected, but treatment failed with azithromycin, doxycycline and moxifloxacin. A urogenital sample was used to determine the sequence of the 23S rRNA, gyrA, gyrB and parC genes. The sample contained an A2059G single nucleotide polymorphism (SNP) in the 23S rRNA gene and an SNP in the parC gene, resulting in an amino acid change of Ser83 → Ile, explaining both azithromycin and moxifloxacin treatment failure. The SNPs associated with resistance were probably generated de novo, as a link with high-prevalence areas was not established. It is, thus, predictable that there is going to be an increase of multidrug-resistant M. genitalium strains in Europe. As treatment options for multidrug-resistant M. genitalium are limited, the treatment of M. genitalium infections needs to be carefully considered in order to limit the rapid increase of resistance to macrolides and fluoroquinolones.

Is psychotic disorder associated with increased levels of craving for cannabis? An Experience Sampling study.

OBJECTIVE: Although cannabis use among individuals with psychotic disorder is considerable, little is known about patterns of use and factors contributing to continuation of use. Therefore, we investigated craving in relation to cannabis use in patients with psychotic disorder and healthy controls. METHOD: The study included 58 patients with non-affective psychotic disorder and 63 healthy controls; all were frequent cannabis users. Craving was assessed with the Obsessive Compulsive Drug Use Scale (OCDUS) for cannabis, as well as in daily life using the Experience Sampling Method (ESM). RESULTS: Patients scored higher on the OCDUS (B = 1.18, P = 0.022), but did not differ from controls in ESM indices of craving (all P > 0.05). In daily life, ESM craving predicted cannabis use and this was stronger in controls (χ(2) = 4.5, P = 0.033; Bcontrols = 0.08, P < 0.001; Bpatients = 0.06, P < 0.001). In both groups ESM craving was predicted by negative affect, paranoia, and hallucinations (Bnegativeaffect = 0.12, P = 0.009; Bparanoia = 0.13, P = 0.013; Bhallucinations = 0.13, P = 0.028), and followed by an increase in negative affect at non-cannabis-using moments (B = 0.03, P = 0.002). CONCLUSION: The temporal dynamics of craving as well as craving intensity in daily life appear to be similar in patients and controls. Further research is needed to elucidate the inconsistencies between cross-sectional and daily-life measures of craving in psychosis.

[Cannabis use and the risk of psychotic disorders. An update]. / Cannabis als risicofactor voor psychose: een update.

BACKGROUND: The use of cannabis has been linked to an increased risk for psychosis, irrespective of confounding factors such as age, gender, use of other drugs and reverse causality. Over the last few years a great deal of research has been done to broaden our understanding of the underlying mechanisms of this link. AIM: To update studies that have examined the link between cannabis use and psychosis and that have investigated the possible mechanisms underlying this link. METHOD: This article discusses recent epidemiological and experimental research that sheds light on the nature of the link and the influence of interactions between genes and environment. RESULTS: The long-term effects of cannabis on the risk factors for psychosis and psychotic disorders are influenced to a large extent by genetic and environmental factors. Furthermore, patients with a psychotic disorder seem to be extremely vulnerable to the acute effects of cannabis. CONCLUSION: Studies show that cannabis use is an important risk factor for psychosis and psychotic disorders. So far, however, less research has been done into the effects of cannabis use on patients already suffering from a psychotic disorder.

Replication in two independent population-based samples that childhood maltreatment and cannabis use synergistically impact on psychosis risk.

BACKGROUND: There may be biological plausibility to the notion that cannabis use and childhood trauma or maltreatment synergistically increase the risk for later development of psychotic symptoms. To replicate and further investigate this issue, prospective data from two independent population-based studies, the Greek National Perinatal Study (n=1636) and The Netherlands Mental Health Survey and Incidence Study (NEMESIS) (n=4842), were analyzed. METHOD: Two different data sets on cannabis use and childhood maltreatment were used. In a large Greek population-based cohort study, data on cannabis use at age 19 years and childhood maltreatment at 7 years were assessed. In addition, psychotic symptoms were assessed using the Community Assessment of Psychic Experiences (CAPE). In NEMESIS, the Composite International Diagnostic Interview (CIDI) was used to assess psychotic symptoms at three different time points along with childhood maltreatment and lifetime cannabis use. RESULTS: A significant adjusted interaction between childhood maltreatment and later cannabis use was evident in both samples, indicating that the psychosis-inducing effects of cannabis were stronger in individuals exposed to earlier sexual or physical mistreatment [Greek National Perinatal Study: test for interaction F(2, 1627)=4.18, p=0.02; NEMESIS: test for interaction χ2(3)=8.08, p=0.04]. CONCLUSIONS: Cross-sensitivity between childhood maltreatment and cannabis use may exist in pathways that shape the risk for expression of positive psychotic symptoms.

Do cannabis and urbanicity co-participate in causing psychosis? Evidence from a 10-year follow-up cohort study.

BACKGROUND: Cannabis use is considered a component cause of psychotic illness, interacting with genetic and other environmental risk factors. Little is known, however, about these putative interactions. The present study investigated whether an urban environment plays a role in moderating the effects of adolescent cannabis use on psychosis risk. METHOD: Prospective data (n=1923, aged 14-24 years at baseline) from the longitudinal population-based German Early Developmental Stages of Psychopathology cohort study were analysed. Urbanicity was assessed at baseline and defined as living in the city of Munich (1562 persons per km2; 4061 individuals per square mile) or in the rural surroundings (213 persons per km2; 553 individuals per square mile). Cannabis use and psychotic symptoms were assessed three times over a 10-year follow-up period using the Munich version of the Composite International Diagnostic Interview. RESULTS: Analyses revealed a significant interaction between cannabis and urbanicity [10.9% adjusted difference in risk, 95% confidence interval (CI) 3.2-18.6, p=0.005]. The effect of cannabis use on follow-up incident psychotic symptoms was much stronger in individuals who grew up in an urban environment (adjusted risk difference 6.8%, 95% CI 1.0-12.5, p=0.021) compared with individuals from rural surroundings (adjusted risk difference -4.1%, 95% CI -9.8 to 1.6, p=0.159). The statistical interaction was compatible with substantial underlying biological synergism. CONCLUSIONS: Exposure to environmental influences associated with urban upbringing may increase vulnerability to the psychotomimetic effects of cannabis use later in life.

Anogenital malignancies and pre-malignancies.

Anogenital pre-malignancies and malignancies are frequently encountered. Aetiopathogenetically, human papillomavirus (HPV) infection plays a critical role. However, there is a variable degree of association of HPV infection with the development of anogenital malignancies. In this context, the high level of clinically unapparent HPV infection should be considered. Therefore, the question arises if the association with HPV is always causative. Besides HPV, pre-existent lichen sclerosus is also an important aetiopathologic factor in the development of anogenital malignancies. Common anogenital pre-malignancies comprise Bowen's disease (BD), Bowenoid papulosis (BP) and erythroplasia of Queyrat (EQ). From a clinical point of view, these are clearly different entities, but from a histopathological point of view, BD, BP and EQ are indistinguishable. They all represent forms of squamous intraepithelial neoplasia (IN). Intraepithelial neoplasia (IN) is not only restricted to squamous variants, but also includes non-squamous IN, Paget's disease (PD) and melanoma in situ. The risk of developing anogenital (pre)malignancies or other tumours is higher in immunocompromised and immunodeficient patients, in particular those suffering from human immunodeficiency virus (HIV) infection. Such risk factors will affect treatment and follow-up modalities. Regarding prophylactic measures, a relatively recent but very important development is the availability of HPV vaccination on a large scale. Momentarily, the effects of such vaccination, on a population-based scale, are not yet clear but will become apparent in the near future. Management of anogenital pre-malignancies and malignancies should be tailor-made and may be organized in a multidisciplinary fashion.

Arteriolosclerotic ulcer of Martorell.

In 1945, Martorell described ischaemic leg ulcers in patients with hypertension. He suggested that the ischaemic necrosis was secondary to a hypertensive arteriolar disease and referred to them as 'hypertensive ischaemic ulcers'. In recent years, the specific entity of these ulcers has been questioned. Others claim they have a much higher incidence, but presume the diagnosis is frequently missed. Almost 900 cases of Martorell's ulcers have been reported in literature since the first description. A systematic review and comprehensive search of literature (evidence-based) was needed to characterize this type of ulcer. Based on aetiology and histopathology, it seems to be justified to maintain the name 'arteriolosclerotic ulcer of Martorell'. We conclude that the arteriolosclerotic ulcer of Martorell is a specific entity with its own clinical and histological diagnostic keys, wound management and preventive measures. We introduce a set of criteria that may be used to facilitate diagnosing arteriolosclerotic ulcer of Martorell as well as a flowchart that includes diagnosis, treatment and prevention of this particular type of vascular leg ulcer.

COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life.

OBJECTIVE: A functional polymorphism in the catechol-o-methyltransferase gene (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted. METHOD: The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25). RESULTS: Carriers of the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability. CONCLUSION: The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.

Early exposure to cannabis and risk for psychosis in young adolescents in Trinidad.

OBJECTIVE: Cannabis use increases the risk for psychosis, but psychotogenic effects of cannabis may be restricted to exposure during early adolescence. METHOD: Four hundred and seventy-two participants (aged 12-23 years), randomly selected from the general population in Trinidad, completed questionnaires on past and current cannabis use and psychotic symptoms (using the Community Assessment of Psychic Experiences). RESULTS: Cannabis use increased the risk of experiencing psychotic symptoms and this effect was conditional on early exposure, defined around the mean age of onset of cannabis use. Thus, exposure before but not after the age of 14 years predicted psychotic symptoms (respectively beta: 0.71, 95% CI 0.22; 1.19, P = 0.004 and beta: -0.11, 95% CI -0.57; 0.36, P = 0.66). The developmental effect of cannabis use was independent of use of other drugs or current use of cannabis. CONCLUSION: Early adolescence may be a critical period with regard to the psychotogenic effect of cannabis across geographical settings and ethnic groups.

[A psychosis proneness-persistence-impairment model of psychotic disorders]. / De ontogenese van psychotische stoornis;een model van kwetsbaarheid voor psychose, persistentie en belemmering.

There is evidence that the normally transitory developmental expression of psychosis (psychosisproneness) may first of all become abnormally persistent (persistence) and later on become clinically relevant (impairment), depending on the amount of environmental risk to which the person is exposed. According to the psychosis-proneness-persistence impairment model, genetic background factors can impact on a transitory expression of psychosis. Whether or not this will lead to a poor prognosis in terms of persistence and clinical need will depend on the interaction between environmental exposure and genetic risk.

[A man with strange genital warts]. / Een man met rare genitale wratten.

A 36-year-old man came to the outpatient dermatology department with asymptomatic, skin-coloured to white/yellow, firm papules on his prepuce. Over the last 10 years he had received different treatments for condylomata accuminata, with no effect. After shave excision, the diagnosis of idiopathic calcinosis cutis was made.

Enhanced memory performance on an internal-internal source monitoring test following acute psychosocial stress.

Research on the effect of acute stress and high levels of glucocorticoids on memory has largely focused on memory tasks involving the medial temporal lobe (e.g., declarative memory). Less is known, however, about the effects of stress and glucocorticoids on more strategic memory processes regulated by the prefrontal cortex (e.g., source monitoring). In the current study, the authors investigated whether exposure to acute psychosocial stress would result in altered source monitoring performance relative to the performance of a nonstressed control group. To this end, the authors assigned nonsmoking, healthy, young men to either a stress (n = 22) or a control (n = 18) condition, after which the men were given an internal source monitoring test. Results show that relative to control participants, stressed participants made fewer source monitoring errors. This study suggests that stress may have differential effects on memory, depending on whether the memory test is regulated by the prefrontal cortex or the medial temporal lobe.

Epidermolysis bullosa simplex with mottled pigmentation: clinical aspects and confirmation of the P24L mutation in the KRT5 gene in further patients.

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare dermatologic disorder of autosomal dominant inheritance with intraepidermal blistering after minor trauma, reticular hyperpigmentation unrelated to the blistering, nail dystrophy, and mild palmoplantar keratosis. Keratin 5 and keratin 14 are known to be essential for the basal keratinocyte cytoskeleton and are defective in several forms of epidermolysis bullosa simplex. Recently, a 71C-->T transition in the keratin 5 gene (KRT5) causing a P24L substitution was identified in some patients with EBS-MP. We present a family with three affected members and a sporadic patient with EBS-MP. They exemplify clinically mild expression with intrafamilial variability and the possibility of improvement with time. In all of them, mutation analysis of the KRT5 gene showed the P24L mutation. So far, other mutations in the same or in other genes have not been reported in patients with EBS-MP.

Early adolescent cannabis exposure and positive and negative dimensions of psychosis.

AIMS: To investigate the effect of exposure to cannabis early in adolescence on subclinical positive and negative symptoms of psychosis. DESIGN: Cross-sectional survey in the context of an ongoing cohort study. SETTING: Government-supported general population cohort study. PARTICIPANTS: A total of 3500 representative 19-year olds in Greece. MEASUREMENTS: Subjects filled in the 40-item Community Assessment of Psychic Experiences, measuring subclinical positive (paranoia, hallucinations, grandiosity, first-rank symptoms) and negative psychosis dimensions and depression. Drug use was also reported on. FINDINGS: Use of cannabis was associated positively with both positive and negative dimensions of psychosis, independent of each other, and of depression. An association between cannabis and depression disappeared after adjustment for the negative psychosis dimensions. First use of cannabis below age 16 years was associated with a much stronger effect than first use after age 15 years, independent of life-time frequency of use. The association between cannabis and psychosis was not influenced by the distress associated with the experiences, indicating that self-medication may be an unlikely explanation for the entire association between cannabis and psychosis. CONCLUSIONS: These results add credence to the hypothesis that cannabis contributes to the population level of expression of psychosis. In particular, exposure early in adolescence may increase the risk for the subclinical positive and negative dimensions of psychosis, but not for depression.

Potential effect of patient-assisted teledermatology on outpatient referral rates.

We carried out a pilot study on the feasibility and accuracy of store-and-forward teledermatology based on patient-provided images and history as a triage tool for outpatient consultation. Patients referred by their general practitioner provided a history and images via the Internet. The information was reviewed by one of 12 teledermatologists and the patient then visited a different dermatologist in person within two days. Three independent dermatologists compared the remote and in-person diagnoses in random order to determine diagnostic agreement. Broader agreement was also measured, by comparing the main disease groups into which the two diagnoses fell. The teledermatologists indicated whether an in-person consultation or further investigations were necessary. There were 105 eligible patients, aged four months to 72 years, who were willing to participate. For the 96 cases included in the analysis, complete diagnostic agreement was found in 41% (n=39), partial diagnostic agreement in 10% (n=10) and no agreement in 49% (n=47). There was disease group agreement in 66% of cases (n=63). Nearly a quarter (23%) of participating patients could have safely been managed without an in-person visit to a dermatologist.

The reliability of diagnosis using store-and-forward teledermatology.

We compared diagnoses made by a teledermatologist from digital photographs and patient histories sent from general practitioners using a store-and-forward technique and those made by another dermatologist in a face-to-face consultation with the same patients. A total of 117 patients (mean age 47 years) were referred by 18 general practitioners for diagnosis of a skin condition. Between one and seven digital images were transmitted per case. In 31% of the cases, three images were transmitted. There was full concordance between store-and-forward and face-to-face diagnoses in 57 of 106 cases (54%); in 10 cases (9%) there was overlap between the differential diagnoses provided by the teledermatologist and the face-to-face consultant. Diagnostic categories with relatively high concordances were eczema and follicular eruptions. General practitioners need to be trained in the making of digital images and in giving a good patient history.

[The influence of HIV infections on the demand for assistance in an outpatient clinic for venereal diseases]. / De invloed van HIV-infecties op de hulpvraag in een polikliniek voor geslachtsziekten.

Educative campaigns on the danger of HIV infection have been quite successful. Within a decade the number of cases of gonorrhoea has sharply fallen. However, fear of AIDS does to some extent increase the demand for medical examination for sexually transmitted diseases. This explains why there is a discrepancy between the total number of consultations in the outpatient department and the actual number of cases of gonorrhoea diagnosed. From 1987 onward more time is being spent per consultation on counselling concerning HIV and prevention of HIV transmission by discouraging risk-bearing sexual practices. The numbers show that the target group has been reached successfully. In the University Hospital of Utrecht about half the patients with positive HIV serology were known before 1987 in the outpatient department for sexually transmitted diseases of that hospital. In the near future it will be mostly the venereal diseases clinics that will deal with the increasing demands concerning HIV.

[Sexually transmitted diseases in Limburg in 1997; prevalence according to a survey of family practitioners and specialists and according to reports from microbiological laboratories]. / Seksueel overdraagbare aandoeningen in Limburg in 1997; prevalentie volgens een enquête onder huisartsen en specialisten en volgens opgave van microbiologische laboratoria.

OBJECTIVE: To determine the incidence of sexually transmitted diseases (STDs) and to compare data reported by general practitioners (GPs) and specialists with those reported by microbiological laboratories. DESIGN: Retrospective. METHOD: All 593 GPs and gynaecologists, dermatologists and urologists in Limburg, the Netherlands, in 1998 were asked to fill in a questionnaire about the number of cases of Chlamydia trachomatis, condylomata acuminata, genital herpes and gonorrhoea in 1997, by sex, age and diagnostic test. Data were compared with information gathered from the six laboratories of medical microbiology. For gonorrhoea the results were compared with those from a study in 1985. RESULTS: The response to the enquiry amounted to 75%. A total of 2730 cases were reported (32 per 10,000 of the population. Infection with C. trachomatis was the most frequent sexually transmitted disease (46%), followed by condylomata acuminata (28%), genital herpes (17%) and gonorrhoea (8%). Of the diseases 84% occurred in persons younger than 35 years of age and 66% in women. The GPs saw 79% of the STDs, they diagnosed 'gonorrhoea' in 25% of the cases merely on the basis of the clinical picture. Compared to 1985 the number of gonorrhoea cases was decimated in Limburg in 1997. Of those who answered the questions about warning the partner (approximately 50% of those concerned), 87% reported that they had let the partner know. It appears from the data of the six laboratories that the incidence of C. trachomatis infection was 3.2 and that of gonorrhoea 0.6 per 10,000 of the population. For the diagnosis of infection with C. trachomatis the GPs and specialists use a culture in 50% of the cases, as against 2% of the laboratories, for the ligase chain reaction and polymerase chain reaction tests these proportions were 20 and 78%.

[HIV surveillance in an outpatient clinic for sexually transmissible diseases in Amsterdam, 1991-1994; low and stable prevalence among heterosexual clients]. / HIV-surveillance op een polikliniek voor seksueel overdraagbare aandoeningen in Amsterdam, 1991-1994; lage en stabiele prevalentie onder heteroseksuele bezoekers.

OBJECTIVE: To assess the HIV prevalence among heterosexual attenders of a clinic for sexually transmitted diseases (STD) and among subpopulations, including young gay men and ethnic minorities. SETTING: Outpatient clinic for sexually transmitted diseases (STD) of the Municipal Health Service of Amsterdam, the Netherlands. METHODS: Semi-annually in the period 1991-1994, blood samples given voluntarily and anonymously were tested for HIV antibodies and some characteristics were collected of approximately 1000 clinic attenders. RESULTS: Since 1991, 6766 clinic attenders were eligible for participation, of whom 6200 (92%) were actually tested. The overall HIV prevalence decreased from 3.9% in the first half of 1991 to 2.3% in the second half of 1994. Among heterosexual clinic attenders the prevalence remained stable below 1%, due mainly to visitors from abroad rather than to Dutch heterosexuals: 20 of the 23 HIV infected heterosexuals were not Dutch. None of these 23 seropositive persons knew of their HIV infection, mostly because they had not been tested previously. The HIV prevalence among gay men decreased over the years. In addition, the number of gay male attenders younger than 30 years decreased strongly over time. CONCLUSIONS: HIV infections among heterosexual STD clinic attenders are relatively few and are seen mainly among non-Dutch. We found no indications of an increase of the HIV prevalence among heterosexual clinic attenders. The results among young gay men are suggestive of a shift towards safer sexual behaviour in this group.

[Prevalence of HIV in clients of an outpatient clinic for sexually transmissible diseases and in a group of prostitutes and their clients]. / HIV-prevalentie bij bezoekers van een polikliniek voor seksueel overdraagbare aandoeningen en bij een groep prostituées en prostituanten.

In order to gain insight into the heterosexual spread of HIV infections in Amsterdam, a study was carried out in 1991 among persons attending an outpatient clinic for sexually transmitted diseases (STD) and among a group of prostitutes and prostitutes' clients. Out of 2362 persons attending the STD clinic, 2138 (90.5%) could ultimately be examined for presence of HIV antibodies. The HIV seroprevalence was 4.2% (90/2138); among homosexual males it was 22% (70/324), among heterosexual male intravenous drug users 12% (2/17) and among heterosexual males who never had used i.v. drugs 0.5% (5/997). The HIV seroprevalence among female intravenous drug users was 41% (12/29) and that among females who never had used i.v. drugs it was 0.1% (1/771). Among the heterosexually active subjects (active in the preceding six months, including the groups of bisexual males and intravenous drug users), the seroprevalence amounted to 1.5% (28/1884). HIV antibodies could be demonstrated in 1.5% (3/199) of the prostitutes and in 0.5% (1/213) of prostitutes' clients. However, the one positive male had had homosexual contacts in the past. Out of the total of nine heterosexually infected persons, two originated from the Netherlands, two from Ghana, two from Turkey, one from Nigeria, one from Pakistan and one from the Dominican Republic; six of them had commercial contacts. The heterosexual spread of HIV among the heterosexual population of Amsterdam can for the moment be classified as slight. However, further heterosexual transmission of HIV cannot be excluded, considering the frequency of unprotected sex.