[Tularemia lymphadenitis. An emerging differential diagnosis of necrotizing granulomatous cervical lymphadenitis]. / Tularämie-Lymphadenitis. Eine wichtige Differenzialdiagnose granulomatös-nekrotisierender zervikaler Lymphadenitiden.

Tularemia is emerging as an important differential diagnosis of necrotizing granulomatous lymphadenitis, particularly in the head and neck region. The causal organism, Francisella tularensis is a Gram-negative coccoid bacterium. Tularemia usually presents with necrotizing granulomatous purulent lymphadenitis featuring multiple mostly small granulomas with geographic necrosis bordered by palisades of histiocytes. Diagnosis is mainly based on these characteristic but non-pathognomonic histological features in conjunction with negative tests for mycobacterial infections and serological confirmation of tularemia-specific antibodies or detection by polymerase chain reaction (PCR). This article describes our experiences with five patients with tularemia lymphadenitis and gives an overview of the diverse histopathological features and the differential diagnosis of this uncommon but possibly underrecognized disease.

Chronic vasculitis and polyneuropathy due to infection with Bartonella henselae.

Bartonella henselae, the causative agent of cat scratch disease and bacillary angiomatosis, is associated with an expanding spectrum of diseases. Here, we report on a 40-year-old patient suffering from chronic recurrent painful ulcers of the toes, distal axonal sensomotor polyneuropathy and Raynaud's phenomenon. Biopsy of the sural nerve demonstrated an axonal neuropathy with a neurogenic muscular atrophy. Treatment with high dose corticosteroids had no beneficial effect. A biopsy taken from a recurring ulcer 7 years after the beginning of the disease revealed superficial ulcerated hyperkeratosis with subepithelial proliferation of small vessels compatible with a diagnosis of verruca peruana, however, without detection of microorganism. Serologic analysis revealed an elevated IFT titer of 1:1,024 against B. henselae. Treatment with erythromycin induced healing of the ulcer, remission of the vasculitis and the polyneuropathy, and a decline of the IFT titer. This case illustrates that B. henselae infection should be considered in patients with vasculitis and polyneuropathic syndromes.

Seronegative Lyme neuroborreliosis in a patient on treatment for chronic lymphatic leukemia.

We report on a patient who developed seronegative Lyme neuroborreliosis complicating chemotherapy for chronic lymphatic leukemia. After the fifth cycle of chemotherapy (FCR: fludarabine, cyclophosphamide, rituximab and prednisone) the 63-year-old patient developed night sweat, arthralgia in elbows, wrists, proximal interphalangeal joints (PIPs) and strong neuropathic pain in both legs, followed by paresthesia and hypesthesia in the feet, arms and face. Laboratory analysis revealed an elevated C-reactive protein (CRP), a slight elevation of liver enzymes and decreased IgG levels. Cerebrospinal fluid (CSF) analysis showed a lymphomononuclear pleocytosis and an elevation of protein. A broad diagnostic work-up was negative including a negative Borrelia IgG and IgM ELISA. The patient did not remember recent tick bites, but after specific questioning he recollected a transient erythema on his leg developing just before the start of the last cycle of chemotherapy. As the combination of neuropathic pain and arthralgia, the transient erythema and the lymphomononuclear pleocytosis raised the suspicion of Lyme neuroborreliosis, the patient was treated for 3 weeks with ceftriaxone. On therapy all symptoms resolved and CRP normalized. Retrospective PCR analysis of a CSF sample confirmed the clinical diagnosis by detecting Borrelia garinii DNA. This case demonstrates that in immunosuppressed patients borrelial serology may be negative and that additional diagnostic approaches (including tests for direct Borrelia detection) may be needed to demonstrate borrelial infection.

[Occupationally acquired tuberculosis in an administrative assistant: aspects of an expert report]. / Beruflich erworbene Tuberkuloseerkrankung bei einer Verwaltungsangestellten. Gutachterliche Aspekte.

HISTORY: Since the age of 48 years an administrative assistant had been treated with immunosuppressive drugs for a mixed connective tissue disease. She was in direct personal contact with newly arrived Africans while working at an admittance centre for refugees. At the age of 53 years the symptoms changed with increasing joint pains and loss of weight. The immunosuppressive therapy with corticoids was increased. A total hip arthroplasty followed. An infection of the wound occurred and many revisions of the scar tissue followed. After a total knee arthroplasty an epileptic seizure occurred. A tuberculous meningoencephalitis was diagnosed. Mycobacterium tuberculosis was detected in urine, sputum and in secretions of different joints. A detailed analysis revealed Mycobacterium tuberculosis var. africanum. At the age of 59 years the patient died during a period of rehabilitation, the clinical signs indicating pulmonary embolism. CONCLUSIONS: The haematogenous spread of Mycobacterium tuberculosis was undoubtedly exacerbated by the immunosuppressive therapy. As a preventive measure a competent occupational consultation could have stopped the occupational exposure to Mycobacteria by transferring the patient during immunosuppressive therapy. The change of symptoms had been misclassified as worsening of the mixed connective tissue disease. Considering legal aspects of the German social insurance system the criteria of an occupational disease would have been fulfilled.

Mononeuritis multiplex caused by Coxiella burnetii infection (Q fever).

After 1 week of flu-like illness, a 64-year-old man developed rapidly progressive mononeuritis multiplex involving the right arm and both legs. Serologic studies identified Coxiella burnetii as the cause of the febrile disease (Q fever). Fourteen days doxycycline treatment (200 mg daily) induced rapid and complete recovery. After 6 months, flu-like symptoms, weakness and hypalgesia of the right leg reappeared. Antibody titers again identified Q fever. Doxycycline was re-established and induced prompt recovery. Q fever has been associated with various neurologic complications such as meningoencephalitis, cerebellitis, optic neuritis or polyneuroradiculitis. This is the first report on Q fever related mononeuritis multiplex. Prolonged antibiotic treatment may be required to prevent relapsing infection from the resistant bacterium.

[Increased incidence of immunoglobulin G antibodies against Helicobacter pylori among trainee nurses]. / Erhöhte Inzidenz serologisch nachweisbarer Infektionen mit Helicobacter pylori während der Ausbildung in der Krankenpflege.

BACKGROUND AND OBJECTIVE: It is unclear whether persons in the nursing profession are at special risk of infection with Helicobacter pylori. If faecal-oral, oral-oral or gastro-oral transmission occurs, infections with H. pylori should be observed after the start of nursing. We studied the incidence of serologically proved infections in a collective of trainee nurses. METHODS: The presence of immunoglobulin G antibodies against Helicobacter pylori in nurses (128 women, 37 men, mean age at the beginning of training: 22.2 +/- 5.6 years) was tested at the beginning and end of training. RESULTS: At the beginning of training a prevalence of 12.5% was found among German nurses (n=152) and of 46.2% among foreign nurses (n=13). In the follow up test after a mean of 30 months, eight German nurses had new positive results, indicating recent infection. The annual incidence was calculated to be 2.3 % and exceeded the expected value for adults not occupationally exposed to infectious material. RESULTS: In view of the calculated increased incidence, nursing must be considered to be a risk factor for infection with Helicobacter pylori.

The AMOR study: a randomized, double-blinded trial of omeprazole versus ranitidine together with amoxycillin and metronidazole for eradication of Helicobacter pylori.

BACKGROUND: Besides antibiotics, additionally effective acid inhibition is necessary for the eradication of Helicobacter pylori. OBJECTIVE: To assess the significance of acid suppression and, in particular, treatment with proton pump inhibitors (PPIs) compared with H2 receptor antagonists (H2 RAs). The primary target parameter for the study was H. pylori eradication. In addition, the ulcer healing rate, speed of pain reduction, score for gastritis in the antrum and gastric body, and rate of side effects were recorded. DESIGN: Randomized, double-blinded, multicentre study. PARTICIPANTS: A total of 456 patients between the ages of 18 and 80 years with H. pylori-positive duodenal ulcers were included in the study. METHODS: Using a randomization list, patients were assigned either to a treatment group receiving omeprazole 40 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (OAM), or to a group receiving ranitidine 300 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (RAM). The treatment period was 7 days in both groups. Long-term acid-suppressant treatment was not given. RESULTS: The eradication rate was 87.1% (169/194, intention to treat [ITT]) in the OAM group and 77% (137/ 178, ITT) in the RAM group. The difference of 10.1% (95% CI 2.5-18%) is statistically significant (P= 0.0104). The ulcer healing rate was 93.3% in the OAM group (181/194, ITT) and 92.1% in the RAM group (164/178, ITT, NS). With regard to the speed and intensity of pain reduction, the OAM group was superior to the RAM group. In patients in whom H. pylori eradication was successful, the reduction in the antral and gastric body gastritis score was significantly greater than in patients without eradication. In the OAM group, 39.1% of the patients (n = 90) reported one or more side effects, compared with 44.7% (n = 101) in the RAM group (P= 1.5449, NS). CONCLUSION: Omeprazole (40 mg once daily in the morning) is significantly more effective than ranitidine (300 mg once daily in the morning) with respect to H. pylori eradication when used together with amoxycillin (750 mg three times a day) and metronidazole (500 mg three times a day) for a 7-day treatment period.

A case of aortic valve disease associated with Tropheryma whippelii infection in the absence of other signs of Whipple's disease.

A case of endocarditis caused by Tropheryma whippelii is reported. The 69-year-old patient was diagnosed as suffering from severe aortic regurgitation requiring aortic valve replacement, but showed no other symptoms of Whipple's disease. T. whippelii was detected in the explanted aortic valve by broad-range PCR amplification of the 16S rDNA and subsequent sequence analysis of the product. The etiologic agent was classified as a type 2A sequence variant based on the 16S-23S intergenic spacer and the 23S rDNA (domain III) sequences. The histological examination of the aortic valve was compatible with Whipple's disease. A duodenal biopsy revealed an infection with Giardia lamblia, but T. whippelii and histological signs of Whipple's disease were not detectable.

[Nosocomial pneumonias in a neurology intensive care unit]. / Nosokomiale Pneumonien auf einer neurologischen Intensivstation.

BACKGROUND AND OBJECTIVE: Nosocomial pneumonia in patients in an intensive care unit (ICU) are a great problem as a cause of increased morbidity and mortality as well as the resulting high cost of treatment. This study was aimed at determining the incidence of nosocomial pneumonia and the risk factors for its occurrence in patients with severe neurological disease. PATIENTS AND METHODS: Between 1.1. and 31.12.1997, 217 patients (125 men, 92 women; average age 63.4 years) were prospectively included if they were treated for more than 48 hours in the ICU of the Neurology Department of Erlangen University. The occurrence of nosocomial pneumonia (NP) was noted, using the criteria of the Center of Disease Control and Prevention (CDC). Incidence of the diseases was related to age, sex, initial state of consciousness, type of ventilation, duration of stay in the ICU and any associated medical condition. RESULTS: NP was diagnosed in 68 patients (31.4%). Statistically significant relative risks were male sex (2.4 fold, P < 0.01), clouded consciousness with a Glasgow coma score < 8 (6.2 fold, P < 0.001), mechanical ventilation (8.4 fold, P < 0.001), time in ICU > or = 8 days (9.3 fold, P < 0.001) and associated medical condition (3.3 fold, P < 0.005). In 17.7% of cases no relevant pathogen was identified microbiologically. A mixed infection was present in 36.8% of cases. The most common Gram-positive organism was Staph, aureus (35.3%), the most common Gram-negative ones were Ps. aeruginosa (25%), Kl. pneumoniae and Kl. oxytoca (11.8%), E. Coli (10.3%) and Acinetobacter species (7.4%). There was also a high rate of infection or infestation with Candida albicans or glabrata (41.2%). NP played a clinically decisive role in the fatal course of 13 of the 47 patients who died. CONCLUSION: These data (incidence, relative risk) can, by taking into consideration various aspects of specialist and hospital hygienic practices, contribute to a continuing optimization of the prevention and treatment of disease.

Silver catheter study: methods and results of microbiological investigations.

Within the framework of the clinical study of the Erlangen silver catheter 104 silver catheters and 105 control catheters were tested by microbiological culture. This was done by rolling the catheter on a blood agar plate, washing the lumen through with tryptic soy broth (TSB) and, after ultrasound treatment, incubating the catheter tip in TSB as an enrichment culture for detecting very low bacterial counts. There was good agreement in the numbers of colony-forming units (CFU) detected by the roll plate and luminal washout cultures in 92% of the silver and 89% of the control catheters tested. Seventy-six (73%) of the 104 silver catheters showed no bacterial growth and 16 (15%) showed very low bacteria counts (< 15 CFU), or growth only after enrichment, which were attributed in both instances to catheter contamination. Twelve catheter tips (12%) showed significant bacterial counts greater than 15 CFU which were indicative of colonization or catheter-related infection. Corresponding results in the control catheters were 59 (56%), 28 (27%) and 18 (17%), respectively, a higher rate of infection or contamination which was statistically significant (chi-square test: P = 0.04).

Optimal tobramycin dosage in patients with cystic fibrosis--evidence for predictability based on previous drug monitoring.

A retrospective analysis of files of patients with cystic fibrosis and pulmonary exacerbations was performed to investigate whether an individual dosage of tobramycin once established by serum level determination allows a reliable prediction of the adequate dosage in a consecutive exacerbation. All patients hospitalized > or = 2 times between May 1997 and September 1998 with pulmonary exacerbation due to Pseudomonas aeruginosa infection susceptible to tobramycin were included. The initial dosage to tobramycin was 5 mg/kg body weight every 12 h followed by drug level determinations to establish the optimal dose. In a consecutive exacerbation the same dosage per kg body weight was used again and drug level determinations were repeated. Sixteen patients (six female = 38%) with a mean age of 24 years (median: 26 years, range: 9-33) were hospitalized for 49 pulmonary exacerbations (2-6 per patient, mean: 3, median: 2.5). During the first episode of tobramycin treatment in the study period all trough levels were < 2 microg/ml (median: 0.6) and the peak levels were 7.1-16.9 microg/ml (median: 11.9). In four patients the peak level was > 12 microg/ml. In 28 consecutive episodes the dosage of tobra myci n was chosen based on optimal results of previous drug level monitoring and in 27 instances (96%) the previously established optimal dose was confirmed. In five consecutive episodes the tobramycin dosage had been increased erroneously and this resulted in abnormally high peak levels in three cases. These findings suggest that a safe and therapeutic tobramycin dosage in an individual patient with cystic fibrosis is predictable based on a previously established optimal dosage.

[Tick bite and Lyme borreliosis. An epidemiologic study in the Erlangen area]. / Zeckenstich und Lyme-Borreliose. Eine epidemiologische Untersuchung im Raum Erlangen.

BACKGROUND: Lyme borreliosis is transmitted by tick bites. Approximately every fifth local tick (Ixodes ricinus) is infected. Transmission, therefore does not occur with every bite, and disease doesn't always follow infection. The goal of the study was to investigate the risks of infection and disease after tick bites in the area of Erlangen/Germany. METHODS: Between April 1989 and October 1991 seventy-one of our out-patients (30 females, 41 males) aged 6 months to 29 years had a tick bite and were enrolled into the study. After the ticks had been removed, a blood specimen for a specific Borrelia burgdorferi antibody assay (IFT) was collected. An interview by phone was performed 4 weeks later and an appointment for a second blood collection was arranged. RESULTS: In 69 patients the initial titer was negative, in two patients it was 1:32. Sixty patients could be reached by phone, and in 43 a second blood sample was available. There was seroconversion detectable in 4 instances, two of whom were asymptomatic, one had unspecific symptoms and one developed lymphocytoma. There were no manifestations of late stage disease in the study population. CONCLUSION: These results confirm the current recommendation of the Bundesgesundheitsamt (German Federal Health Institute) that generally antibiotic treatment after a tick bite is not necessary.

Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis.

OBJECTIVE: To document the persistence of Borrelia burgdorferi in ligamentous tissue samples obtained from a woman with chronic Lyme borreliosis. METHODS: Spirochetes were isolated from samples of ligamentous tissue, and the spirochetes were characterized antigenetically and by molecular biology techniques. The ligamentous tissue was examined by electron microscopy. Humoral and cellular immune responses were analyzed. RESULTS: Choroiditis was the first recognized manifestation of Lyme disease in this patient. Despite antibiotic therapy, there was progression to a chronic stage, with multisystem manifestations. The initially significant immune system activation was followed by a loss of the specific humoral immune response and a decrease in the cellular immune response to B burgdorferi over the course of the disease. "Trigger finger" developed, and a portion of the flexor retinaculum obtained at surgery was cultured. Viable spirochetes were identified. Ultramorphologically, the spirochetes were situated between collagen fibers and along fibroblasts, some of which were deeply invaginated by these organisms. The cultured bacteria were identified as B burgdorferi by reactions with specific immune sera and monoclonal antibodies, and by polymerase chain reaction amplification and Southern blot hybridization techniques. CONCLUSION: To our knowledge, this is the first report of the isolation of B burgdorferi from ligamentous tissue. This suggests that tendon tissues serve as a specific site of spirochete residence in human hosts.

Cellular immune reactivity to recombinant OspA and flagellin from Borrelia burgdorferi in patients with Lyme borreliosis. Complexity of humoral and cellular immune responses.

Patients with Lyme borreliosis (LB) usually develop a vigorous T cell response against the causative pathogen Borrelia burgdorferi, but little is known about the antigens recognized in the cellular response. Therefore, T cell reactivities against whole bacteria, recombinant 31-kD (outer surface protein A, [OspA]), and 41-kD proteins (flagellin) from B. burgdorferi were studied in patients with LB, non-LB patients, and healthy donors. In parallel, specific antibodies were determined by Western blot analysis. Virtually all patients with LB exhibited marked cellular responses to whole B. burgdorferi, which were significantly elevated compared with the control groups in both early and late disease stages. However, analyses using the purified antigens OspA and flagellin revealed considerable heterogeneity in the cellular reactivities among individuals as well as variations during the course of infection. T cell responses to OspA were significantly increased in patients with early LB compared with both control groups whereas in late-stage disease responses only exceeded those of non-LB patients and were not different from normal donors. Cellular immune reactivities to flagellin were significantly higher only in early LB compared with both control groups. Reciprocally, several control subjects demonstrated marked cellular responses to OspA and flagellin, suggesting that reactions to these proteins may not always be related to LB. T cell reactivity did not correlate well with the presence of specific antibodies. Almost all seropositive patients in both early and late stage LB had serum antibodies against flagellin, but antibodies to OspA were detectable only in a subset of late LB sera. These data demonstrate the complexity of the humoral and the cellular immune responses to components of B. burgdorferi.

T cell proliferation induced by Borrelia burgdorferi in patients with Lyme borreliosis. Autologous serum required for optimum stimulation.

The cellular immune response to Borrelia burgdorferi was studied in 24 patients with seropositive and seronegative Lyme borreliosis, 30 patients with arthritides of different origin (non-Lyme arthritides), and 20 normal blood donors. By far, the strongest T cell stimulation was induced by incubation with autologous serum; there was a significantly lower response or no response after incubation with allogeneic or heterologous sera. In patients with Lyme borreliosis, including seronegative patients, there was a strikingly elevated proliferation in response to whole B burgdorferi bacteria (mean 64,750 dpm) compared with that of normal donors (mean 19,700 dpm; P less than 0.0001) and especially that of non-Lyme arthritis patients (mean 11,600 dpm; P less than 0.0001). Levels of proliferation declined significantly in patients with Lyme borreliosis after successful antibiotic treatment. Parallel cultures using B burgdorferi and Treponema phagedenis as antigens showed that cells from patients with Lyme borreliosis responded significantly more to B burgdorferi than to T phagedenis, but this did not occur with cells from individuals with non-Lyme arthritides. There was no correlation between disease stages and proliferation values. These data indicate that lymphocyte proliferation assays may provide an important tool for the diagnosis of Lyme borreliosis, most notably in patients with arthritides and in those who are seronegative. Conversely, the lack of reactivity appears to be a strong indicator of the absence of active Lyme disease. It seems to be crucial, however, to use autologous sera in these assays.

Differentiation of serological responses to Yersinia enterocolitica serotype O9 and Brucella species by immunoblot or enzyme-linked immunosorbent assay using whole bacteria and Yersinia outer membrane proteins.

Serum samples from 134 patients showing by the microagglutination test serological cross-reactivity between Yersinia enterocolitica serotype O9 and Brucella spp. were analyzed by immunoblot and enzyme-linked immunosorbent assay techniques for the presence of antibodies directed against plasmid-encoded, yersinia-associated outer membrane proteins (OMPs). Since these OMPs are exclusively expressed in pathogenic strains of Yersinia spp., this characteristic was chosen for serological differentiation of infections caused by these bacteria. The presence of antibodies against plasmid-encoded OMPs of pathogenic Yersinia spp. in patient sera appeared to be a suitable means to identify acute or recent infection with Y. enterocolitica serotype O9, whereas the failure to detect such antibodies indicated an acute or recent infection with Brucella spp.