Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission--a randomized trial.

Recent studies have suggested that procalcitonin (PCT) is a safe marker for the discrimination between bacterial and viral infection, and that PCT-guided treatment may lead to substantial reductions in antibiotic use. The present objective was to evaluate the effect of a single PCT measurement on antibiotic use in suspected lower respiratory tract infections (LRTIs) in a Danish hospital setting. In a randomized, controlled intervention study, 223 adult patients admitted to the hospital because of suspicion of LRTI were included with 210 patients available for analysis. Patients were randomized to either PCT-guided treatment or standard treatment. Antibiotic treatment duration in the PCT group was based on the serum PCT value at admission. The cut-off point for recommending antibiotic treatment was PCT > or =0.25 microg/L. Physicians could overrule treatment guidelines. The mean duration of hospital stay was 5.9 days in the PCT group vs. 6.7 days in the control group (p 0.22). The mean duration of antibiotic treatment during hospitalization in the PCT group was 5.1 days on average, as compared to 6.8 days in the control group (p 0.007). In a subgroup analysis of chronic obstructive pulmonary disease patients, the mean length of stay was reduced from 7.1 days in the control group to 4.8 days in the PCT group (p 0.009). It was concluded that the determination of a single PCT value at admission in patients with suspected LRTIs can lead to a reduction in the duration of antibiotic treatment by 25% without compromising outcome. No effect on the length of hospital stay was found.

No evidence of parvovirus B19, Chlamydia pneumoniae or human herpes virus infection in temporal artery biopsies in patients with giant cell arteritis.

OBJECTIVES: Recent studies have suggested that infective agents may be involved in the pathogenesis of giant cell arteritis (GCA), in particular Chlamydia pneumoniae and parvovirus B19. We investigated temporal arteries from patients with GCA for these infections as well as human herpes viruses using the polymerase chain reaction (PCR). METHODS: Thirty temporal artery biopsies from 30 patients suspected of having GCA within a period of 1 yr were examined. Thirteen patients had classical GCA, two had biopsy-negative GCA, 10 patients had polymyalgia rheumatica and five patients had other conditions. DNA was extracted from frozen biopsies and PCR was used to amplify genes from Chlamydia pneumoniae, parvovirus B19 and each of the eight human herpes viruses: herpes simplex viruses HSV-1 and 2, Epstein-Barr virus, cytomegalovirus, varicella zoster virus and human herpes viruses HHV-6, -7 and -8. RESULTS: In all 30 biopsies, PCR was negative for DNAs of parvovirus B19, each of the eight human herpes viruses and C. pneumoniae. CONCLUSIONS: We found no evidence of DNA from parvovirus B19, human herpes virus or C. pneumoniae in any of the temporal arteries. These agents do not seem to play a unique or dominant role in the pathogenesis of GCA.

The occurrence of sinusitis in HIV-infected patients with fever.

Sinusitis is commonly occurring in patients infected with Human Immunodeficiency Virus I (HIV), but the occurrence and etiology have not been established. The purpose of this study was prospectively to determine the occurrence, site and type of paranasal sinus abnormalities seen on MRI in HIV-infected patients with fever, to relate the abnormalities to clinical and immunological parameters, and to determine the microbiological agents found in the sinus aspirates. MRI was performed in 54 HIV-infected patients with 70 evaluable episodes of fever. Patients receiving antibiotics were excluded. Bactrim was permitted, when given as prophylaxis of Pneumocystis carinii pneumonia. If abnormalities were found on MRI, sinus aspiration was performed and the aspirate investigated. MRI abnormalities were found in 54.3% of the patients with a significantly higher occurrence of pathological changes in AIDS patients compared with HIV-infected without AIDS. In approximately 2/3 of the aspirates a probable, etiologic agent was found. However, 1/3 of these agents were atypical such as cytomegalovirus and mycobacteriae; in one patient Non-Hodgkin's lymphoma was found. The high occurrence of sinusitis in HIV-infected patients and the atypical findings in the sinus aspirates stress the importance of searching for sinusitis and the etiology to ensure the correct treatment.

Herpesvirus type 1-8 in sinus aspirates from HIV-infected patients and immunocompetent individuals.

Sinusitis is frequently occurring in HIV-infected patients, but in a substantial number of cases the etiology is unknown. The purpose of this study was by PCR 1) to determine the prevalence of the eight human herpesviruses in sinus aspirates from 24 HIV-positive/AIDS patients with sinusitis 2) to relate the presence of herpesvirus DNA to clinical and immunological parameters and 3) to compare the prevalence of herpesvirus DNA in sinus aspirates from HIV-infected patients with the prevalence observed in 50 immunocompetent patients with sinusitis. DNA from HSV-1, EBV, CMV and HHV-8 was detected in 8 (33%) of the sinus aspirates from HIV-infected patients. In the immunocompetent patients, one of the herpesviruses, HHV-6, was found in one sinus aspirate. These data indicate that herpesviruses are frequently found in sinus aspirates from HIV-infected patients with sinusitis, whereas they do not seem to be related to clinical signs of sinusitis in immunocompetent individuals. The cause of these discrepancies may be due to uncontrolled reactivation of herpesviruses, which is known to occur in immunocompromised individuals. It remains to be established whether the herpesviruses play a pathogenic role in the development of sinusitis in HIV-infected patients.

Herpesvirus type 1-8 in BAL fluid from HIV-1-infected patients with suspected pneumonia and from healthy individuals.

Pneumonia is still a major problem in human immunodeficiency virus (HIV)-infected patients, and despite extensive investigation the aetiology remains unknown in many cases. The prevalence of the eight human herpesviruses was determined by polymerase chain reaction in 91 samples of bronchoalveolar lavage (BAL) fluid from 72 HIV-infected patients with 91 episodes of suspected pneumonia. The presence of herpesviruses was related to clinical and immunological findings and the prevalence of herpesviruses in HIV-infected patients was compared with the prevalence in BAL fluid from 50 healthy, immunocompetent individuals. Epstein-Barr virus, cytomegalovirus and human herpesvirus-8 (HHV8) were found in 5.5%, 36% and 5.5% of BAL fluid samples from HIV-infected patients. No herpesviruses were detectable in BAL fluid from healthy, immunocompetent individuals. The herpesviruses occurred mainly in patients with CD4+ counts <200 x 10(6) L(-1). All patients with herpesviruses recovered without specific antiviral treatment. Two patients with HHV8 had the diagnosis of Kaposi's sarcoma. It is concluded that cytomegalovirus, Epstein-Barr virus, and human herpesvirus-8 are frequently present in bronchoalveolar lavage fluid from severely immunocompromised human immunodeficiency virus-infected patients with pulmonary symptoms. In bronchoalveolar lavage fluid from healthy, immunocompetent individuals, herpesviruses are absent. Apart from human herpesvirus-8, the present results indicate that the herpesviruses do not play a serious pathogenic role in the development of pulmonary symptoms in human immunodeficiency virus-infected patients.

[Familial Mediterranean fever with pseudodominant inheritance]. / Familiaer middelhavsfeber med pseudodominant arvegang.

Familial Mediterranean fever (FMF) is an autosomal, recessively inherited disease, mainly affecting patients from the Mediterranean basin. Owing to the recessive transmission, the disease in most of the affected families only occurs in the members of one generation. However, high consanguinity rates in populations with carrier frequencies as much as 1:5 may account for the occurrence of FMF in two or more successive generations, so-called pseudodominant inheritance. We report a case of pseudodominant inheritance in a Turkish family living in Denmark.

Familial Mediterranean fever diagnosed by PCR.

The diagnosis of familial Mediterranean fever (FMF) was, until recently, based on exclusion of diseases with related clinical signs. Now an exact diagnosis of FMF is possible by polymerase chain reaction (PCR). We report here a case with 2 different mutations in the gene responsible for FMF, thereby being a compound heterozygote (M694V/V726A).

[Microbiological examination of patients hospitalized in Aarhus municipal hospital]. / Mikrobiologisk udredning af patienter indlagt på Arhus Kommunehospital.

The purpose of this retrospective study was to evaluate 1) the nature, extent and relevance of the microbiological examination performed before institution of antibiotic treatment, 2) the relevance of the instituted treatment in the light of the microbiological findings or clinical diagnosis of infection. A minimum of requirements concerning microbiological examination was put forward for each clinical diagnosis of infection. Among patients with the diagnosis of sepsis, cystitis or pneumonia, 33%, 80% and 6.5%, respectively, fulfilled the minimum requirements, no attempt at microbiological examination was performed in 4.8%, 10%, and 32%, respectively. There is a need for education in relevant use of clinical microbiology e.g. samples related to focus of infection, and more consistency in the use of microbiological results.

The prevalence and significance of incidental paranasal sinus abnormalities on MRI.

Morphological changes in the paranasal sinuses are regularly noted on MRI, but little is known about the incidence and significance of these changes in the general population. The purpose of this study was 1) to classify the morphological changes in the paranasal sinuses seen on MRI 2) to investigate the prevalence, site and type of paranasal abnormalities and 3) to evaluate the significance of the findings by relating them to the presence of sinusitis symptoms, allergy, smoking habits and seasonal variations. In a one-year period, 404 patients referred to MRI for suspected intracranial neurological pathology were prospectively investigated. Before undergoing the scan the patients completed a questionnaire. The observed morphological conditions were classified so that mucous thickening < 5 mm was recorded as normal; > or = 5 mm, total sinus opacification or fluid and polyps as pathological. According to this classification 31.7% of the patients had pathological findings in the sinuses. A significantly higher incidence was found in the winter period and in patients with symptoms associated to sinusitis. "Blocked nose" was the only symptom occurring significantly more often in patients with pathological changes. There was no significant relationship between paranasal sinus abnormalities and sex, age, allergy, smoking habits, previous events of sinusitis or frequent events of colds. Criteria for pathological MRI findings in the paranasal sinuses are desirable and might improve the basis for a decision on the correct medical or surgical treatment.

The immunofluorescence antibody test (IFAT) for the diagnosis of schistosomiasis used in a non-endemic area.

OBJECTIVE: To evaluate an immunofluorescence antibody test (IFAT) for diagnosis of schistosomiasis in nonimmune travellers and immigrants from endemic areas. METHODS: 65 patients (48 Danes and 17 immigrants) with schistosomiasis were included. The diagnosis of schistosomiasis was based on the presence of schistosome eggs in faeces, urine, sperm, rectal or bladder biopsies and/or the presence of specific antibodies determined by the serological immunofluorescence antibody test (IFAT). Egg excretion was detected using conventional methods and the IFAT performed on whole S. mansoni schistosomula worms, harvested after 8 weeks from mice. Two patterns of immunofluorescence were observed: Fluorescence in the gut of the schistosome called 'Gut Associated Antigen, GAA', and fluorescence of the surface of the schistosomula called 'Membrane Bound Antigen, MBA'. RESULTS: Eggs were found in 44% of the Danish patients and in 76% of immigrants. The diagnosis was based on a positive IFAT in 48% of the patients. In patients from nonendemic areas, the finding of antibodies against GAA was diagnostic while optimal sensitivity in the immigrants was reached by measuring antibodies against both GAA and MBA. CONCLUSION: In patients from nonendemic areas GAA is a sensitive marker of acute infection with schistosomiasis. In patients from endemic areas the demonstration of both GAA and MBA is necessary to properly identify long-lasting, nonacute infections. Egg-detection and/or measurement of CAA and CCA remain the methods of choice to monitor treatment as the immunofluorescence assay may remain positive for several years after treatment.

Absence of human herpes virus 8 in semen from healthy Danish donors.

Epidemiological data indicate a sexual route of transmission of acquired immune deficiency syndrome (AIDS) associated Kaposi's sarcoma. Recently human herpes virus 8 (HHV-8) has been proposed as the aetiological agent for development of Kaposi's sarcoma. Further the virus has been reported in semen obtained from healthy men. In Denmark strict biochemical and microbiological criteria are used in combination with an intensive interview to select semen donors. Despite these strict criteria, HHV-8 may be transmitted to a recipient and even the child by the use of donor semen. We used four different polymerase chain reaction (PCR) and one nested PCR to test semen from 100 Danish donors for the presence of HHV-8 DNA. All 100 samples were consistently negative for HHV-8 DNA, while only one sample (1%) was positive for cytomegalovirus DNA. As HHV-8 was not demonstrated in any of the semen samples, we conclude that the frequency of HHV-8 in semen from Danish donors is very low.

Search for agents causing atypical pneumonia in HIV-positive patients by inhibitor-controlled PCR assays.

Pneumonia is one of the most frequent complications in acquired immunodeficiency syndrome-patients with Pneumocystis carinii as the leading cause. The true prevalence of atypical agents such as Chlamydia pneumoniae, C. trachomatis, Legionella pneumophila and Mycoplasma pneumoniae in this population of patients is unknown as the currently used method for diagnosing these agents is measurement of antibody levels. However, this method is of limited value in human immunodeficiency virus (HIV)-positive patients who may have a compromised antibody response. To evaluate the prevalence of Chlamydia spp., Legionella spp. and M. pneumoniae in HIV-infected patients with pulmonary disease, this retrospective study has applied inhibitor-controlled polymerase chain reaction analyses on 103 bronchoalveolar lavage (BAL) fluids representing 103 episodes of pneumonia in 83 HIV-positive patients. L. pneumophila was detected in 1% of the BAL fluids and M. pneumoniae was found as a coexisting pathogen in 2% of the samples. Chlamydia spp. could not be detected in any of the BAL fluids. By culture and staining methods 106 other microorganisms were detected with P. carinii and Streptococcus pneumoniae as the most frequently occurring. Pneumonia due to Chlamydia pneumoniae, Legionella pneumophila or Mycoplasma pneumoniae seems to be rare in Danish human immunodeficiency virus-infected patients, but might be considered as a possible cause in cases of treatment failure.

[Should recurrent Cytomegalovirus infections in patients with liver transplantation be treated?]. / Skal recidiverende cytomegalovirus-infektioner hos levertransplanterede patienter behandles?

Cytomegalovirus (CMV) is the single most important viral pathogen in organ transplantation. Treatment strategy for CMV infection and disease is not well established in transplantation. We report a case of primary CMV infection and two relapses in a woman with a liver transplant in whom spontaneous clearing of the second CMV relapse was seen. A 23 year-old CMV-seronegative woman received a liver transplant with a CMV-negative organ. Six weeks after transplantation she had her primary CMV infection proved by seroconversion and virus isolation. She had no clinical symptoms. Treatment with ganciclovir for five weeks resulted in declining CMV-antigen positive cells from 300/200.000 PMNs to CMV-antigen negativity. Only a slight antibody response was seen. At week 13 the first relapse occurred evidenced by antigenaemia. Ganciclovir was reinstituted for six weeks resulting in reduced antigenaemia. At week 22 liver biopsy was performed due to slightly elevated ALAT. The biopsy showed evidence of focal CMV hepatitis and blood analysis showed 120 CMV-antigen positive cells/200.000 PMNs. In spite of this, ganciclovir was not reinstituted, but the immunosuppressive treatment was reduced to a minimum to stimulate the patient's immune response to CMV. During the following months the patient gradually developed IgG antibody, cleared the antigen and levels of liver enzymes returned to normal. We suggest that ganciclovir treatment, may be omitted in cases of relapse with minimal clinical symptoms, slight antigenaemia and a beginning antibody response and that, the immunosuppressive treatment should be reduced instead. Such an approach requires careful clinical monitoring of the patient.

[Utilization of antibiotics at the Arhus Municipal Hospital. A prevalence study]. / Antibiotikaforbruget på Arhus Kommunehospital. En praevalensundersøgelse.

The hospital charts of 689 patients in Aarhus Municipal Hospital were surveyed on a single day in the autumn of 1994. Antibiotics were administered to 22% of the patients. In the intensive care unit, 69% of the patients received antibiotics, while 24% of the surgical patients and 17% of medical patients received antibiotics. Twenty-seven percent of 203 prescriptions were given as prophylaxis, mainly to surgical patients. Sixty-four percent were prescribed as monotherapy. Penicillins constituted 41% of the total usage of antibiotics. Antibiotics were administered orally in 55%, intravenously in 37%, topically in 5% and rectally in 3%. The prescription was noted in the medical chart for 96%, the indication in 74% and the planned duration of treatment in only 58% of the cases. Information concerning previous allergic reactions to penicillin was noted for 7% of the patients. It is concluded that the usage of antibiotics and the microbiological findings in the departments should be evaluated regularly, and the antibiotic regime and the practice of prescription adjusted accordingly.

[Schistosomiasis at Marselisborg hospital 1981-1990]. / Schistosomiasis på Marselisborg Hospital fra 1981 til 1990.

Schistosomiasis cases diagnosed and treated at Marselisborg Hospital, Denmark from 1.1.1981 to 31.12.1990 were reviewed. In all cases the infection was acquired in Africa. Among 41 patients 15 were Danes and 26 were immigrants, and a total of 57 episodes of schistosomiasis was recorded. Schistosoma mansoni was found in 27 patients, Schistosoma haematobium in 11 patients and in three cases the diagnosis was based on serology. Forty-eight percent of patients with S. mansoni had symptoms, compared to 82% of the patients with S. haematobium. The immigrants more often had symptoms than the Danes, possibly due to the occurrence of other infections. The treatment was in all cases praziquantel. Residual infection was observed in 24%. We recommend that subjects from endemic areas who may have been exposed to infection should be tested for schistosomiasis by examination of urine, stool, or snips of the rectal mucosa. Re-examination after treatment is recommended especially in cases of S. mansoni infection due to risk of residual infection.

Glutathione peroxidase activity in patients with rheumatoid arthritis and in normal subjects: effects of long-term selenium supplementation.

The effects of dietary supplementation with selenium were studied in 6 patients with severe, active rheumatoid arthritis (RA) and in 6 healthy control subjects. Initial concentrations of Se in red blood cells and in serum, and the activity of the Se-dependent enzyme glutathione peroxidase (GSH-Px) in red blood cells, serum, and granulocytes were significantly lower in RA patients compared with controls. During Se supplementation, however, the differences in Se levels and in GSH-Px activity between the 2 groups disappeared, except that, in RA patients, GSH-Px activity in granulocytes increased but remained significantly lower than in controls.

Prognosis in infantile hydrocephalus. Follow-up in adult patients, born 1946-1955.

Twenty-six patients with infantile hydrocephalus were re-examined at ages ranging from 21-32 years. Operations had been performed in 11, but abnormal head growth continued post-operatively in 9. One third of the patients lead a normal life, while half of the patients are mentally deficient. All patients have neurological signs, poor dexterity and clumsiness being present in all. Psychological testing reveals uneven profiles, in 4 patients with performance IQ considerably lower than verbal IQ. Computerised tomography demonstrates all degrees of hydrocephalus with no correlation between ventricular-brain ratio and IQ or between ventricular-brain ratio and operative procedures. Full otoneurological investigation shows differential-caloric examination to be abnormal in 60%, although none of the patients have complaints referring to the vestibular system.