Biomedical subjects
Publications and source records attributed to G Jäger.
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BACKGROUND: Pruritus is the most frequent and distressing symptom associated with dermatoses and various internal and neurological diseases. OBJECTIVES: To investigate two different populations of patients with pruritus, one in Germany and one in Uganda, with a particular focus on clinical characteristics, aetiology and quality of life. METHODS: We investigated by questionnaire 132 patients (59 men, 73 women, mean age 54.5 years) who were referred to the Department of Dermatology at the University Hospital of Magdeburg, Germany, with the diagnosis of pruritus as a leading symptom. The questionnaire was also applied in 84 patients who consulted the Dermatology Clinic at Mbarara, Uganda for pruritus. The questions referred to personal data and disease history of the individual, history and present occurrence of concomitant diseases, present and past therapy, quality, frequency and triggers of itching and scratching, other disorders and complaints, quality of life and impact on work and disability. RESULTS: Seventy-five (57%) of the German patients had pruritus due to dermatoses, 47 patients (36%) had pruritus due to a systemic disease and in 10 patients (8%) pruritus was of unknown origin. Most had a history of pruritus of several months up to years. Pruritus associated with dermatoses mostly affected the whole body and was permanent with an undulatory character. Affective reactions such as aggression and depression occurred more frequently in dermatological patients compared with those with systemic pruritus. The former group felt that pruritus had a greater impact on their lives. Almost all Ugandan patients had pruritus due to dermatoses except for three patients with pruritus of unknown origin. Eczema and prurigo were the most frequently observed dermatoses in both German and Ugandan patients. Patients with pruritus in both populations showed an impaired quality of life. There was no pronounced difference between the populations with regard to feelings of depression and suicidal thoughts. CONCLUSIONS: A great deal of helpful information in this complex group of patients can be obtained using this questionnaire. Pruritus has a major impact on quality of life and especially impairs those patients with pruritus associated with dermatoses and pruritus of unknown origin.
BACKGROUND: Modern pathophysiological concepts indicate that the central nervous system is important for chronification of pain in cases of neuropathic pain. Taking these concepts into consideration, what significance then do those hemisensory disorders have that appear sporadically in cases of chronic nerve root irritation syndrome? RESULTS: The typical clinical findings are illustrated by two case reports. In addition to persistent neuropathic pain, both patients experienced hemisensory impairment of the entire side of the body ipsilateral to the radicular symptoms. Perception of sensitivity to touch, pain, and temperature was decreased on the entire side of the body in contrast to the contralateral side. CONCLUSION: Hemisensory impairment in patients with chronic nerve root irritation syndromes can indicate a functional disorder in dealing with noxious impulses in the ventral posterior nucleus of the thalamus. They represent a clinical correlative to subcortical neuroplasticity, which could explain the resistance to therapy in severe chronic pain syndromes.
Children with cancer or stem cell transplantation (SCT) are at considerable risk to develop life threatening viral infections. Due to both underlying disease and immunosuppressive therapy lymphocyte number and function are low and the cellular immunity against viral infections is restricted or missing. As immunosuppressive treatment regimens and mismatched or T-cell-depleted stem cell products are being used increasingly, viral infections will become an even greater problem in the future. PCR-based methods have become an indispensable tool for early recognition, preemptive therapy, and monitoring therapeutic responses by qualitative and quantitative approaches. Assays are now available that allow for parallel screening of the 16 most common viral agents. Responses to antiviral therapy are often limited in immunocompromised patients and mainly depend on the time of their initiation. Most antiviral agents have a toxicity profile that may become clinically relevant and curtail antiviral therapy. New options for treatment are therefore warranted. For the next future, these may include the transfer of specific T-cells and other immunotherapeutic approaches. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Hematology/Oncology (GPOH) and the German Society for Pediatric Infectious Diseases (DGPI) for diagnosis and treatment of viral infections in children with cancer or post HSCT. They are based on the results of clinical trials, case series and expert opinions using the evidence criteria set forth by the Infectious Diseases Society of America (IDSA).
We hypothesised that long-term tracheostomy in infants and children may perpetuate chronic airway inflammation and airway remodeling due to easier access to the lungs for microorganisms. Pulmonary surfactant represents an important part of the initial host defense, and in particular, the surfactant proteins (SP) A and D may directly interact with invading microorganisms and also modulate the activity of local immune cells. The goals of this study were to determine the presence and intensity of a peripheral airway inflammation and of potential deficiency states of surfactant proteins in nonsymptomatic children with tracheostomy. Bronchoalveolar lavage (BAL) cell pattern, bacteria and viruses recovered, and concentrations of SP-A, SP-B, SP-C, and SP-D were assessed in 46 children (4.3 years (1.6-6)) median (range) carrying a tracheostomy for 2.4 years (1.3-4.9), and were compared to 16 children with no lung disease. Children with tracheostomy had an increased total number of cells, increased neutrophils, and more frequently bacteria, but no viruses were recovered. SP-D concentration was reduced by 50% on average (P = 0.0002). SP-A, SP-B, and SP-C were not different between the two groups. SP-D was inversely correlated to neutrophils, and high numbers of bacteria were associated with lower SP-D concentrations. We suggest that bacteria and low SP-D support neutrophilic inflammation in the lower respiratory tract of nonsymptomatic with children with tracheostomy.
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Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis IV; four CMV reactivations III requiring i.v. ganciclovir; one pulmonary tuberculosis III; one herpes zoster III) were successfully treated and not associated with cumulative dose of alemtuzumab. In the observation arm, one herpes zoster infection II and one sinusitis I were documented. At 6 months after randomization, two patients in the alemtuzumab arm converted to CR, while three patients in the observation arm progressed. After alemtuzumab treatment, five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive (P=0.048). At 21.4 months median follow-up, patients receiving alemtuzumab showed a significant longer progression-free survival (no progression vs mean 24.7 months; P=0.036). In conclusion, a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL, but a safe treatment regimen needs to be determined.
Recent case-control studies reported an increased frequency of antibodies against Coxsackie virus (CV) antigens in patients with newly diagnosed type 1 diabetes and during pregnancy in mothers of diabetic offspring, suggesting a role for CV infections in the pathogenesis of type 1 diabetes (T1D). However, it is not known whether CV infections are causally related to the development of islet autoantibodies or merely represent secondary events in subjects already affected with established islet autoimmunity. Therefore we have prospectively evaluated CV infections from birth, prior to and in parallel with the appearance of islet autoantibodies in offspring of parents with T1D. Using indirect ELISAs, IgG-antibodies (abs) against a panel of CV, and IgG- and IgM-abs to CVB3, CVB4, and CVB5 were measured at 9 months, 2, 5, and 8 years in 28 offspring of mothers or fathers with T1D or of mothers with gestational diabetes who developed persistent islet antibodies (IAA, GADA, IA-2A), and compared to 51 islet autoantibody-negative offspring matched for place and date of birth. CV infections were also determined at delivery in 16 mothers whose offspring developed islet autoantibodies later in life and compared to 110 mothers (matched for HLA-DR, place and date of birth) whose offspring remained islet autoantibody-negative during early childhood. CV-antibodies were detected in only 2/28 (7.1%) offspring who developed islet autoantibodies during follow up and in 7/51 (13.7%) offspring without islet autoantibodies (median follow up time 3.0 years, range 2.0-8.7). CV-IgG abs were detected in one mother (6.3%), whose offspring developed islet autoantibodies during early childhood, compared to 15 mothers (13.6%) with islet autoantibody-negative offspring (P=0.5). Also, partum levels of CV-IgG and CVB3-, -4-, and -5-IgM abs were similar in both groups (median 35 U, 0.08 index (I), 0.08, 0.05 vs. 35 U, 0.06 I, 0.11, and 0.06, resp., P> 0.35 in each case). These data make it unlikely that CV infections during pregnancy or in early childhood play a major role in the induction of islet autoimmunity in offspring of mothers or fathers with T1D or of mothers with gestational diabetes.
UNLABELLED: Human herpes virus type 7 (HHV-7) has been associated with unspecific febrile syndrome, exanthem subitum (ES), viral rashes and Epstein-Barr virus (EBV) like syndrome. Neurological complications such as hemiplegia or seizures have been described in a few children with ES. Whether HHV-7 may also affect the CNS in the absence of ES is unknown. In this study, we investigated CSF samples from children with different neurological diseases for the presence of HHV-7 specific DNA. A HHV-7 specific nested polymerase chain reaction (PCR) was established amplifying a 478 bp DNA sequence of the glycoprotein U23 of HHV-7 strain SB. 68 children with CNS diseases with inflammatory CSF findings (n = 24), CNS diseases without inflammatory CSF findings (n = 18) and febrile seizures (n = 26) were examined. A total of 26 children with infectious diseases in the absence of neurological disease and 11 children without signs of a peripheral infection and without neurological disease served as controls. The CSF samples of six children from the study groups were HHV-7 PCR positive, but none from the controls. These children were diagnosed with aseptic meningitis (n = 1), viral encephalitis/meningoencephalitis (n = 2), facial palsy (n = 1), vestibular neuritis (n = 1) and febrile seizure (n = 1). CONCLUSION: These results indicate that human herpes virus type 7 infection is associated with central nervous system disease in children and should be considered in children whether inflammation in the cerebrospinal fluid is present or not.
Intestinal vasculitis caused by persistent measles virus infection of intestinal endothelial cells was described in Crohn's disease. Furthermore, endothelial cell autoantibodies have been demonstrated in inflammatory bowel disease (IBD). Autoantibodies against intestinal endothelial cells were visualized by indirect immunofluorescence in patients with IBD, in their healthy first-degree relatives, in patients with infectious enterocolitis, and in healthy, unrelated controls. In intestinal tissue specimens of 22 antibody-positive IBD patients a search for the measles virus genome was performed. Endothelial cell autoantibodies were significantly more frequent in patients with IBD, in both groups of first-degree relatives, and in patients with infectious enterocolitis than in the healthy controls (P = 0.0002 or less). The measles virus genome was found in none of the intestinal biopsies. Endothelial cell autoantibodies are not a genetic but rather an epigenetic (infectious) marker of disease susceptibility. The expression of these autoantibodies is unlikely to be triggered by a persistent measles virus infection.
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We report the effects of substitution with a virus-inactivated protein C (PC) concentrate in disseminated intravascular coagulation (DIC) in infants and children with meningococcal sepsis associated with purpura fulminans. It was a prospective open-label study. Eight pediatric and adolescent patients age 0.2 to 18.25 years with DIC associated with severe acquired PC deficiency (range 0.02 to 0.48 IU/mL; median, 0.22 IU/mL) in meningococcal septic shock and purpura fulminans were studied. Replacement therapy was initiated with a virus-inactivated PC concentrate with an initial intravenous bolus of 80 to 120 IU/kg followed by 50 IU/kg up to six times per day as an adjunctive therapeutic regimen to otherwise optimal intensive care treatment. After initial PC administration, plasma PC levels rose to normal ranges and were maintained under PC replacement therapy. Improving or even normalizing global hemostatic parameters were assessed in all patients. Markedly elevated plasminogen activator inhibitor type 1 (PAI-1) levels prior to treatment, reflecting a reduced fibrinolytic potential, decreased rapidly under PC substitution. Concomitantly improving signs of purpura fulminans reflected by decreasing size of skin lesions, demonstrated a restoring microcirculation. Six of the eight patients survived. One patient required limb amputation; two patients died because of multiorgan failure. Both presented with a severely low plasma PC activity of 0.02 IU/mL on admission to the hospital. No adverse effects were observed with the PC concentrate administration. It can be concluded that the administration of PC concentrate had a marked benefit on the deranged coagulation status of patients with purpura fulminans and meningococcal septicemia. Normalization or even partial correction of hemostasis as well as improvement of microcirculation accompanied by improving signs of purpura fulminans were demonstrated in all patients.
A previously healthy 10-year-old Greek boy born to nonconsanguineous healthy parents developed progressive liver disease after acute infectious mononucleosis. EBV-induced autoimmune hepatitis was suspected and treatment was started with high-dose prednisolone, acyclovir and intravenous immunoglobulins. Despite therapy, his liver function continuously deteriorated and the child died 9 months later in profound immune deficiency from candida septicemia. Flow cytometric analysis of his lymphocytes revealed a major subpopulation of atypical cells (20.3%) which were CD3+, fitted into the lymphocyte gate but showed a very low level of CD4 expression, comparable to that of monocytes. After short-time cell culture, the cells became adherent and developed granules and dendrites. We conclude that these cells may represent strongly activated CD4+ T lymphocytes with downregulated CD4 expression or a subtype of dendritic cells.
2-Chlorodeoxyadenosine (Cladribine) is a new purine analogue with high activity in pretreated low grade non-Hodgkin's lymphoma (NHL). To evaluate the efficacy of this drug in untreated patients with advanced NHL, we performed a prospective multicentre trial. Cladribine (0.12 mg/kg) was administered intravenously daily for 5 consecutive days in an out-patient setting. The treatment was repeated every 28 days for four cycles. Included were patients with a histological diagnosis of low grade NHL according to the Kiel classification and stage III or IV disease. Stage II patients were included when radiotherapy had failed. 55 patients were entered into the study. 50 patients were evaluable. The remission rate was 44/50 (88%; 95% confidence interval 82-100%), including complete remissions (CR) in 14 (28%) patients. Only 2 patients showed progression while on Cladribine treatment. The estimated overall survival, and time to treatment failure (TTF) were 85% and 51%, respectively, after a median observation time of 92 weeks. 11 (22%) patients showed grade 3 or 4 toxicity according to the WHO grading. Haematological toxicity was responsible for 86% of the overall toxicity and 100% of grade 3 and 4 toxicity. 7 patients (14%) had an infection, two of which were opportunistic. 12 (24%) patients did not experience any toxicity during the treatment. The results of this study clearly demonstrate the safety and considerable activity of this regimen. Cladribine is very effective even at lower doses than have been used so far.
We have evidence that the open reading frame previously denoted spoU is necessary for tRNA (Gm18) 2'-O-methyltransferase activity. The spoU gene is located in the gmk-rpoZ-spoT-spoU-recG operon at 82 minutes on the Escherichia coli chromosome. The deduced amino acid sequence of spoU shows strong similarities to previously characterized 2'-O-methyltransferases. Comparison of the nucleoside modification pattern of hydrolyzed tRNA, 16S rRNA and 23S rRNA from wild-type and spoU null mutants showed that the modified nucleoside 2'-O-methylguanosine (Gm), present in a subset of E. coli tRNAs at residue 18, is completely absent in the spoU mutant, suggesting that spoU encodes tRNA (Gm18) 2'-O-methyltransferase. Nucleoside modification of 16S and 23S rRNA was unaffected in the spoU mutant. Insertions in the downstream recG gene did not affect RNA modification. Absence of Gm18 in tRNA does not influence growth rate under the tested conditions and does not interfere with activity of the SupF amber suppressor, a suppressor tRNA that normally has the Gm18 modification. We suggest that the spoU gene be renamed trmH (tRNA methylation).
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