Jan C. den Hollander

Resurgence of Lymphogranuloma Venereum in Western Europe: An Outbreak of Chlamydia trachomatis Serovar L2 Proctitis in The Netherlands among Men Who Have Sex with Men

BACKGROUND Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) and is rare in the Western world. Recently, 3 men who have sex with men presented with LGV proctitis at the Erasmus Medical Center, Rotterdam, The Netherlands. We investigated a possible outbreak in a sexual network of men who have sex with men (MSM). METHODS After active case finding, a total of 15 men presented and were investigated. Serum antibody titers to Chlamydia trachomatis were determined. Urine and rectum specimens were analyzed by polymerase chain reaction (PCR) for the presence of C. trachomatis. C. trachomatis-positive specimens were genotyped to detect the specific C. trachomatis serovars. All subjects underwent routine STD screening. Sociodemographic, clinical, and endoscopic characteristics were evaluated. RESULTS Thirteen subjects had high immunoglobulin (Ig) G and IgA titers to C. trachomatis, suggesting an invasive infection. Rectal specimens of 12 subjects were PCR-positive for C. trachomatis. All urine specimens were negative. Genotyping revealed serovars L(2) (n=8) and L(1) (n=1). An ulcerative proctitis was found in all subjects obtaining sigmoidoscopy (n=9). Eleven of 13 subjects with an LGV diagnosis were seropositive for human immunodeficiency virus (HIV), 6 had another concomitant STD, and 1 had recently acquired a hepatitis C virus infection. Further sexual contacts were reported from The Netherlands, Germany, Belgium, the United Kingdom, and France. CONCLUSIONS We revealed an outbreak of LGV proctitis among MSM in The Netherlands. The ulcerous character favors transmission of HIV, other STDs, and blood-borne diseases. From a public health perspective, it seems important to increase the awareness of possible LGV in MSM with symptomatic proctitis.

Discriminating basal cell carcinoma from perilesional skin using high wave-number Raman spectroscopy

An expanding body of literature suggests Raman spectroscopy is a promising tool for skin cancer diagnosis and in-vivo tumor border demarcation. The development of an in-vivo diagnostic tool is, however, hampered by the fact that construction of fiber optic probes suitable for Raman spectroscopy in the so-called fingerprint region is complicated. In contrast, the use of the high wave-number region allows for fiber optic probes with a very simple design. We investigate whether high wave-number Raman spectroscopy (2800 to 3125 cm(-1)) is able to provide sufficient information for noninvasive discrimination between basal cell carcinoma (BCC) and noninvolved skin. Using a simple fiber optic probe, Raman spectra are obtained from 19 BCC biopsy specimens and 9 biopsy specimens of perilesional skin. A linear discriminant analysis (LDA)-based tissue classification model is developed, which discriminates between BCC and noninvolved skin with high accuracy. This is a crucial step in the development of clinical dermatological applications based on fiber optic Raman spectroscopy.

Hepatocellular adenoma : findings at state-of-the-art magnetic resonance imaging, ultrasound, computed tomography and pathologic analysis

The purpose of this paper is to describe the most recent concepts and pertinent findings of hepatocellular adenomas, including clinical presentation, gross pathology and histology, pathogenesis and transformation into hepatocellular carcinoma (HCC), and imaging findings at ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging.

Heteronuclear 2D-correlations in a uniformly [13C, 15N] labeled membrane-protein complex at ultra-high magnetic fields.

One- and two-dimensional solid-state NMR experiments on a uniformly labeled intrinsic membrane-protein complex at ultra-high magnetic fields are presented. Two-dimensional backbone and side-chain correlations for a [U-13C,15N] labeled version of the LH2 light-harvesting complex indicate significant resolution at low temperatures and under Magic Angle Spinning. Tentative assignments of some of the observed correlations are presented and attributed to the α-helical segments of the protein, mostly found in the membrane interior.

Mastocytosis in children: a protocol for management.

Abstract:  Mastocytosis is characterized by an increased number of mast cells with an abnormal growth and accumulation in one or more organs. In most children mastocytosis is limited to the skin (cutaneous mastocytosis) and often transient as compared with that in adults in whom mastocytosis is usually progressive and systemic. Generally, we recognize three more common forms of cutaneous mastocytosis: maculopapulous mastocytosis (formerly urticaria pigmentosa), mastocytoma of skin, and diffuse cutaneous mastocytosis. Childhood mastocytosis can further be divided into cutaneous mastocytosis (nonpersisting and persisting) and systemic mastocytosis (extremely rare). An approach to management using a set protocol is described in table form. In most cases of mastocytosis, only yearly checkups are necessary and no treatment is required; preventive recommendations are warranted in those individuals with systemic disease and constitutional symptoms. Symptomatic therapy is advised in only a minority of cases. This article is meant as a guideline for physicians involved in the care of children with mastocytosis and their parents.

COL4A2 mutation associated with familial porencephaly and small-vessel disease

Familial porencephaly, leukoencephalopathy and small-vessel disease belong to the spectrum of disorders ascribed to dominant mutations in the gene encoding for type IV collagen alpha-1 (COL4A1). Mice harbouring mutations in either Col4a1 or Col4a2 suffer from porencephaly, hydrocephalus, cerebral and ocular bleeding and developmental defects. We observed porencephaly and white matter lesions in members from two families that lack COL4A1 mutations. We hypothesized that COL4A2 mutations confer genetic predisposition to porencephaly, therefore we sequenced COL4A2 in the family members and characterized clinical, neuroradiological and biochemical phenotypes. Genomic sequencing of COL4A2 identified the heterozygous missense G1389R in exon 44 in one family and the c.3206delC change in exon 34 leading to frame shift and premature stop, in the second family. Fragmentation and duplication of epidermal basement membranes were observed by electron microscopy in a c.3206delC patient skin biopsy, consistent with abnormal collagen IV network. Collagen chain accumulation and endoplasmic reticulum (ER) stress have been proposed as cellular mechanism in COL4A1 mutations. In COL4A2 3206delC fibroblasts we detected increased rates of apoptosis and no signs of ER stress. Mutation phenotypes varied, including porencephaly, white matter lesions, cerebellar and optic nerve hypoplasia and unruptured carotid aneurysm. In the second family however, we found evidence for additional factors contributing to the phenotype. We conclude that dominant COL4A2 mutations are a novel major risk factor for familial cerebrovascular disease, including porencephaly and small-vessel disease with reduced penetrance and variable phenotype, which might also be modified by other contributing factors.

Prenatal lethality of a homozygous null mutation in the human glucocerebrosidase gene

The complete spectrum of clinical phenotypes resulting from glucocerebrosidase deficiency continues to evolve. While most patients with Gaucher disease have residual glucocerebrosidase activity, we describe a fetus with severe prenatal lethal type 2 (acute neuronopathic) Gaucher disease lacking glucocerebrosidase activity. This 22-week fetus was the result of a first cousin marriage and had hydrops, external abnormalities, hepatosplenomegaly, and Gaucher cells in several organs. Fetal fibroblast DNA was screened for common Gaucher mutations, none of which was detected. Southern blot analysis using the restriction enzymes SstII and SspI ruled out a fusion gene, deletion, or duplication of either allele, and quantitative studies of SspI digested genomic DNA indicated that both alleles were present. Northern blot analysis of total RNA from fetal fibroblasts demonstrated no detectable transcription, although RT-PCR successfully amplified several exons, suggesting the presence of a very unstable mRNA. Direct PCR sequencing of all exons demonstrated a homozygous frameshift mutation (deletion of a C) on codon 139 in exon 5, thereby introducing a premature termination codon in exon 6. The absence of glucocerebrosidase protein was confirmed by Western analysis. This unique case confirms the essential role of glucocerebrosidase in human development and, like the null allele Gaucher mouse, demonstrates the lethality of a homozygous null mutation. The presence of this novel mutation and the resulting unstable mRNA accounts for the severity of the phenotype observed in this fetus, and contributes to the understanding of genotype/phenotype correlation in Gaucher disease.

Clinical Aspects of Diffuse Cutaneous Mastocytosis in Children: Two Variants

Objective: This paper describes two different clinical presentations of diffuse cutaneous mastocytosis (DCM), based on the largest series published to date. As far as we are aware, these two variants of clinical presentations have not yet been reported. Design: We undertook a case controlled analysis of 8 children with DCM. Results of laboratory testing including mast cell mediator levels, and clinical symptoms on presentation and during follow-up were analyzed. Results: The levels of relevant mast cell mediators were initially high in all cases but declined sharply later on. There was a reduction of 20% in 2 of the 7 cases, whereas there was a reduction of 80% in the remaining 5. No reduction occurred in 1 case. Clinical improvement followed the same pattern. Conclusions: DCM is a rare variant of cutaneous childhood onset mastocytosis. Various forms show the same or overlapping features at various times. It appears to follow a course similar to that in other types of childhood onset mastocytosis, taking into account the decreased symptoms and the levels of mast cell mediators during follow-up. Obtaining a bone marrow biopsy should be considered only in those cases where there is no improvement or even worsening of signs or symptoms and persistent elevated levels of mast cell mediators.

Unexpected life-threatening complications in Kabuki syndrome.

Kabuki syndrome is a rare multiple congenital anomalies/mental retardation syndrome comprising a distinct facial appearance and fetal fingertip pads. We observed two patients with Kabuki syndrome and describe unusual life-threatening complications, including stenosis of the central airways (not previously reported), extrahepatic biliary atresia, and congenital diaphragmatic hernia.

Inflammatory myofibroblastic tumour of the lung manifesting as progressive atelectasis.

Abstract A 6-year-old girl with an inflammatory myofibroblastic tumour of the lung is presented. The radiological features of this lesion are often atypical, as in this case, presenting as progressive atelectasis. The differential diagnosis is extensive and can be difficult, despite modern imaging techniques.