Meningitis

The most frequent pathogens causing bacterial meningitis in Germany are Neisseria meningitidis, Streptococcus pneumoniae, Borrelia burgdorferi, Listeria monocytogenes and staphylococci. Since immunization against Haemophilus influenzae has become a routine vaccination procedure, this pathogen no longer plays a significant role in the etiology of bacterial meningitis. A number of pilot studies have indicated that selected PCR methods most probably represent the future etiological diagnosis of bacterial meningitis. The easiest and most rapid diagnostic method is, however, still a simple gram stain preparation. In fatal cases that ran a peracute course, especially in the Waterhouse-Friderichsen syndrome, only increased congestion of the surface of the brain is detectable at autopsy. In such cases, there is hardly any histological evidence of an inflammatory reaction of the leptomeninges. In cases of purulent meningitis, in addition to the typical infiltration of the subarachnoid space with abundant granulocytes, after some days of illness there is a wide-spread histomorphological picture of pathological alterations with fibrinoid vessel wall necroses, thromboses, ventriculitis, infarctions as well as venous and arterial vasculitis. The breakdown of the integrity of the blood-brain-barrier in bacterial meningitis is obviously due to a separation of intercellular tight junctions of the endothelium of the capillaries of the leptomeninges. The cause of death in meningitis, depending on the severity and duration of a concomitant sepsis, is an increase in intracranial pressure that leads to a circulus vitiosus (via a reduced central perfusion associated with metabolic acidosis) with cerebral vasodilatation. This is followed by an additional rise of intracranial pressure and finally a reduced cerebral blood supply and central dysregulation. The medico-legal expert is occasionally confronted with this topic against the background of a possible misjudgement of the disease due to insufficient diagnostics or delayed diagnosis and in the light of a posttraumatic or nosocomial origin of the illness.     

Linksventrikuläre Unterstützungssysteme

Because of the lack of organs for heart transplantations, left ventricular assist devices (LVADs) have become more and more important during the last few years. They are used for both bridging the time until transplantation as well as destination therapy for patients who are not able or willing to undergo a heart transplantation. Forensic and clinical pathologists will increasingly be confronted with fatalities of patients with LVADs. Beside natural causes of death and typical unavoidable complications, technical problems and user errors must be resolved. Under certain circumstances a suicidal or homicidal manner of death by manipulation of the device also has to be considered.     

C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria

The immunogenicity of recombinant protein or anti-viral DNA vaccines can be significantly improved by the addition of tandem copies of the complement fragment C3d. We sought to determine if the efficacy of a circumsporozoite protein (CSP)-based DNA vaccine delivered to mouse skin by gene gun was improved by using this strategy. Instead, we found that C3d suppressed the protective immunity against Plasmodium berghei malaria infection and deviated immunity, most notably by suppressing the induction of antibodies specific for the CSP C-terminal flanking sequence and by suppressing the induction of CSP-specific IL-4-producing spleen cells. We further showed that C3d bound to the C-terminal flanking sequence of the CSP, which may explain the immune deviation observed in CS/C3d chimeric antigen. We have thus identified C3d-mediated epitope masking and shifting of both the humoral and cellular immune responses as a potential novel escape mechanism, which plasmodia may use to divert the induction of protective immunity.     

Multiple sclerosis: II. Effects of prothymosin alpha on the autologous and allogeneic MLR in patients with multiple sclerosis.

We have recently demonstrated that peripheral blood monocytes from patients with multiple sclerosis (MS) have a defect in stimulating autologous and allogeneic T lymphocytes. This defect was found to correlate with disease activity. In this report we demonstrate that prothymosin alpha (ProT alpha), a rat thymus fraction 5 polypeptide, restores the MS monocyte stimulatory defect. The concentrations of ProT alpha which induced optimal enhancement of the mixed lymphocyte responses (MLR) were significantly higher when monocytes from patients with active disease were used as stimulators than when monocytes from patients with inactive disease were used. T4+ cells tested with autologous stimulatory monocytes harvested from an inactive stage of MS exhibited considerably higher proliferative responses than when stimulated with autologous monocytes obtained from an acute relapse. The decreased autologous proliferation of T4+ cells in MS patients was restored to normal levels after preincubation with ProT alpha in the environment of autologous monocytes. Our results demonstrate that ProT alpha is capable of fully restoring the deficient stimulatory function of MS monocytes and monocyte-associated functional defects of MS-derived T4+ cells.     

Malignant schwannoma with melanocytic and neuroepithelial differentiation in an infant with congenital giant melanocytic nevus: A complex neurocristopathy

We describe an infant girl, born with a pigmented giant nevus, who developed a malignant schwannoma in the retroperitoneum at 16 months of age. At birth the nevus covered over 50% of her body and histologically was a compound nevus with extension into the deep dermis surrounding dermal appendages. The malignant schwannoma was biphasic with areas composed of spindle and round cells. Ultrastructurally, the majority of the tumor cells exhibited a Schwann cell phenotype, but neuroepithelial and melanocytic cells were identified as well. We believe that this constellation of findings represents a form of neurocristopathy. Neurocristopathy, as defined by Bolande (Hum Pathol 5:409–429, 1974), is a disease that results from aberrations in the migration, growth, or cytodifferentiation of neural crest tissues. These diseases may be simple (a singular pathologic process, usually localized) or complex (multiple neuroectodermal lesions). We report this case because the occurrence of retroperitoneal malignant schwannoma arising in a 16-month-old infant born with a pigmented giant nevus is unique, and may represent a previously undescribed form of a complex neurocristopathy.     

Immunohistochemical study of alveolar and embryonal rhabdomyosarcoma

Paraffin-embedded sections of 11 alveolar and 12 embryonal rhabdomyosarcomas, 12 lymphomas, five neuroblastomas, five extraskeletal neoplasms resembling Ewing's sarcoma, and six epithelial tumors were tested for immunoreactivity against myosin, myoglobin, and isozymes BB and MM of creatine kinase with a peroxidase-antiperoxidase method. Of the 23 cases of rhabdomyosarcomas 17 were positive for at least three of the antigenic determinants. In contrast, the other investigated tumors were consistently negative for all markers, with the exception of breast and prostatic carcinomas. Our results establish that the presence of three or four of the above markers in a tumor is strongly suggestive of a rhabdomyosarcoma and helpful in the distinction of alveolar and embryonal rhabdomyosarcomas from lymphomas, neuroblastomas, and extraskeletal neoplasms resembling Ewing's sarcoma.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.