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Biomedical subjects

P L Andersen

Publications and source records attributed to P L Andersen.

At least 19 recordsLinked to original sources

[Castleman's disease--difficult diagnosis].

A case of Mb. Castleman of the localized plasma cell type is reported. This disease expresses several symptoms from different organ systems and therefore an extensive investigation program is often performed. Diagnosis is possible through consideration of all clinical components at the same time: Refractory anaemia, high and refractory SR, weight loss, B-symptoms, but at the same time a relatively good health. CT-scan-demonstration of a localized tumour is an important clue. Histopathologically, the tumour shows vascular hyperproliferation and plasmacytosis of varying maturation. Immunophenotyping of the plasma cells and immunoblasts usually reveals a polyclonal population. Needle biopsies from several regions may be necessary to detect the polyclonality, because monoclonality is often widespread locally in the tumour. HHV8 is correlated to the multicentric PC-type of Mb. Castleman. However, no HHV8 was found in this case.

Adult

A randomized controlled trial of acyclovir versus netivudine for treatment of herpes zoster. International Zoster Study Group.

Oral acyclovir has become the standard of care for treatment of acute herpes zoster. Netivudine is a novel antiviral with greater in-vitro activity against varicella zoster virus. It was compared with acyclovir in a randomized, double-blind, controlled trial in immunocompetent adults with herpes zoster. Patients with rash for less than 72 h were assigned to receive either acyclovir or netivudine, then assessed regularly for 6 months. No evidence for a dose response with netivudine was found, so intent-to-treat analyses of all 511 enrolled patients compared acyclovir with netivudine. The time to complete cessation of pain (P = 0.007) and to cessation of moderate to excruciating pain (P = 0.005) was accelerated in acyclovir recipients. Rash outcomes and adverse event profiles were similar for both treatments. This study has confirmed the efficacy of acyclovir in decreasing the duration and severity of pain following herpes zoster. Greater in-vitro activity of newer agents may not necessarily provide greater benefit in humans.

Acyclovir

Viremia in chronic hepatitis C patients evaluated by the Amplicor RT-PCR, a nested RT-PCR, and transaminase levels.

A commercially available kit, Amplicor, was compared with a locally developed nested reverse-transcriptase (RT) PCR for qualitative detection of HCV-RNA. Sixty-one serum samples from sixty-one patients with liver disease, and 60 samples from 60 hemophiliacs without symptoms, but known to have been heavily exposed to hepatitis C virus, were investigated. There was a high degree of concordance between the two diagnostic tests (97%), the Amplicor kit being slightly more sensitive than the in-house PCR, when evaluated using serial dilutions of samples showing discrepant results. The relationship between viremia and abnormal ALT levels was studied in the two groups of patients. Among those with chronic liver disease, 8.3% of patients with viremia had normal ALT levels, whereas transaminases were normal in 20% of hemophiliacs with viremia. This points to ALT as being a poor marker of ongoing viral replication.

Adolescent

[Yellow fever vaccination as prophylaxis of herpes labialis].

At some vaccination centres, it seems to be a clinical observation, that there is a reduction in the number of attacks of herpes labialis following yellow fever vaccination. We therefore conducted a double blind, prospective, randomized study to evaluate the efficacy of yellow fever vaccination against recurrent herpes labialis. Twenty-four patients with culture proven herpes labialis were allocated to either yellow fever vaccination or placebo (saline), with 12 persons in each group. After vaccination/ placebo the patients were followed for one year. The patients returned a letter every other month with information concerning the number of attacks during the period. Comparison of the data from the two groups after one year revealed no significant difference in the number of attacks between the two groups. In conclusion evaluation of the data from this study does not confirm the clinical observation that yellow fever vaccination may act as prophylaxis against herpes labialis.

Adult

Quantitative analysis of GAP-43 expression by neurons in microcultures using cell-ELISA.

A cell-ELISA technique is described which allows the quantification of GAP-43 protein in a large number of microcultures of adult dorsal root ganglion neurons. GAP-43 is measured in the 1-10 ng range, corresponding to the amount of GAP-43 present in fewer than 500 DRG neurons. Specificity of the assay is confirmed using Western blotting and immunocytochemistry. The GAP-43 content of adult DRG microcultures rises during 2 weeks in culture, although the number of surviving neurons decreases. The GAP-43 content of cultured adult DRG neurons is not increased by chronic exposure to added nerve growth factor after 7 days in vitro. However, GAP-43 is increased in DRG taken from animals with prior peripheral nerve injury, and is decreased by chronic exposure to dibutyryl cyclic AMP after 7 days in vitro. The method affords the sensitivity and statistical power to document modest changes in GAP-43 protein abundance in complex cultures.

Animals

Chlamydia pneumoniae in children with otitis media.

In this study the polymerase chain reaction was used to test for the presence of Chlamydia pneumoniae DNA in 118 middle-ear aspirates from 20 children with acute otitis media (AOM) and 53 children with otitis media with effusion (OME). C. pneumoniae was detected in 8 samples obtained from 5 children with OME and, together with Streptococcus pneumoniae, in a sample from 1 child with AOM. The mean age of these five children (6.6 +/- 1.4 years) was significantly higher than that of the 48 children with OME in whom C. pneumoniae could not be detected (4.3 +/- 1.9 years). The presence of C. pneumoniae in 9.4% of the examined children with OME suggests that C. pneumoniae might be a significant supplementary factor in the etiology of this common children's disease.

Acute Disease

Interleukin-8 and chemotactic activity of middle ear effusions.

The importance of interleukin (IL)-8 in the chemotactic activity of middle ear effusions (MEEs) was evaluated. There was a significantly higher IL-8 concentration in MEEs of children with acute otitis media (AOM) (n = 17; 136 ng/mL) than in children with otitis media with effusion (OME) (n = 28; 65 ng/mL). The IL-8 concentration in MEEs with bacteria (149 ng/mL) was significantly higher than in MEEs without bacteria (66 ng/mL). MEEs from children with AOM and OME had equally higher chemotactic activity than the diluent alone (23.3% and 24.8% vs. 9.2%). The chemotactic activity was not altered by the presence of bacteria nor did it correlate with IL-8 concentration. Fractionation of MEEs by gel chromatography demonstrated that the main chemotactic activity could clearly be separated from the IL-8 activity, thus excluding IL-8 as a main chemotactic component in MEEs.

Bacterial Infections

The effect of quinolones on the intracellular killing of Staphylococcus aureus in neutrophil granulocytes.

The effect of ciprofloxacin, lomefloxacin, fleroxacin and ofloxacin on the intracellular killing of Staphylococcus aureus in human neutrophil granulocytes was studied. Each drug was tested in concentrations of 0.25, 1, 4, 16 and 64 times the MIC and the intracellular killing was measured for up to 5 h of incubation. All four quinolones increased the intracellular killing in a concentration- and time-dependent manner. When compared at concentrations of 4 x MIC, ofloxacin increased the killing significantly more than the other quinolones. All four quinolones increased the killing significantly more than the beta-lactam dicloxacillin. All five antibiotics increased the killing significantly relative to the control without antibiotics. None of the antibiotics affected the viability of the granulocytes or their ability to generate superoxide anion. In conclusion, the quinolones increased the intracellular killing of S. aureus in neutrophil granulocytes.

Adult

[Schistosomiasis at Marselisborg hospital 1981-1990].

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.

Africa

Relative bradycardia in infectious diseases.

Relative bradycardia in infectious diseases is a poorly defined term. No exact and useful definition exists and the underlying mechanisms are unknown. Despite this, the term is often used in the literature and in clinical practice both as a clinical sign for an individual patient and as a characteristic feature of certain specific diseases. In this study a definition of relative bradycardia as a clinical sign in an individual patient and a definition of relative bradycardia as a characteristic feature of a specific disease were established based on a reference population comprising 673 patients with various infectious diseases. Relative bradycardia as a clinical sign in an individual patient held no predictive value regarding the likely type of infection. Relative bradycardia as a characteristic feature of specific disease was found for typhoid fever (P = 0.003), Legionnaire's disease (P = 0.005), and pneumonia caused by Chlamydia sp. (P = 0.0005), but not for mycoplasma pneumonia. It was not found for other pulmonary infections, infections caused by other Salmonella sp., other extracellular Gram-negative infections, or viral infections. Thus, relative bradycardia as a clinical sign has no predictive value for obtaining a tentative diagnosis, but relative bradycardia as a feature of specific disease is seen in typhoid fever, Legionnaire's disease, and pneumonia caused by Chlamydia sp. It seems that relative bradycardia as a feature of specific disease only occurs in diseases caused by organisms that are both Gram-negative and intracellular.

Adolescent

Incidence and relative risk for hepatitis A, hepatitis B and tuberculosis and occurrence of malaria among merchant seamen.

The purpose of the study was to assess the incidence and relative risk of hepatitis A and B and tuberculosis among Danish merchant seamen. We also assessed the occurrence of malaria. The study was based on record linkage of a research database containing data on 24,132 Danish male seamen and the Registry for Notifiable Infectious Diseases in Denmark, supplemented by data from other sources. The standardized incidence ratio (SIR) for hepatitis A for male seamen was 1.77 (0.91-3.10) as compared with the incidence in the general population. The incidence was 0.9 notified cases/10,000 years. The SIR for hepatitis B for male seamen was 3.02 (1.79-4.78), the main risk factors being intravenous drug use and casual sex abroad. Tuberculosis was not more common among seamen than in non-seamen. The results have implications for vaccination strategies in this occupational group. Malaria occurred frequently in the seamen, especially among those involved in West African trade. Irregular use of malaria prophylaxis and probably chloroquine resistance were of importance in some cases. To detect further cases of hepatitis A and B and malaria, other sources were reviewed. Only a few extra cases were identified. The registry of notifiable infectious diseases was thus found to be rather complete.

Adolescent

Decreased activation of the respiratory burst in neutrophils from AIDS patients with previous Pneumocystis carinii pneumonia.

Neutrophils from human immunodeficiency virus (HIV)-negative blood donors, asymptomatic HIV-positive patients, AIDS patients with previous Pneumocystis carinii pneumonia (PCP), and AIDS patients without previous PCP were compared for their ability to activate the respiratory burst, measured as luminol-amplified chemiluminescence. P. carinii, Staphylococcus aureus, phorbol-12-myristate-13-acetate, and FMLP were used to stimulate the neutrophils. When stimulated with P. carinii, neutrophils from PCP patients had a significantly lower response than the other groups, whereas no difference was found when S aureus was used. A somewhat but not significantly lower response to P. carinii was also seen in non-PCP patients compared with HIV-negative donors. Priming of the neutrophils with recombinant granulocyte colony-stimulating factor (G-CSF) or recombinant human granulocyte-macrophage (GM)-CSF corrected this defect. A similar effect of these cytokines was seen on phagocytosis, whereas the chemiluminescence in unprimed cells did not correlate with phagocytosis.

Acquired Immunodeficiency Syndrome

The level of the serum opsonin, mannan-binding protein in HIV-1 antibody-positive patients.

The concentrations of mannan-binding protein (MBP) in consecutive samples from 10 HIV+ persons were estimated using an ELISA based on polyclonal rabbit anti-MBP. The changes in MBP with time were similar in HIV+ and HIV- persons, and did not appear to be of clinical significance. MBP was determined in a further 70 persons found HIV-1+ during a period of 2.5 years (1984-1986). Out of the total of 80 patients, 32 have by now died from AIDS. According to the serum level of MBP the HIV-infected persons were grouped into high (> 650 ng MBP/ml), intermediate (101-650 ng/ml), and low MBP (< 101 ng/ml). At the termination of the study the frequency of deaths/total in each of the groups were: high MBP, 14/39 (36%); intermediate MBP, 12/26 (46%); and low MBP, 6/14 (43%). There was no association between the MBP level of the individual and the progressive loss of CD4+ T cells, and the level of MBP was not predictive for the length of time between the detection of HIV antibodies and development of AIDS, nor for the duration of AIDS before death occurred. The number of HIV+ persons without detectable MBP (10%) was significantly higher than previously reported for healthy persons (2.4%, P = 0.027). The course of HIV infection does not seem to be influenced by the level of MBP, nor does the antimicrobial activity of MBP appear to affect the progression of AIDS. Further studies are required to substantiate the significance of absence of MBP in the susceptibility to HIV.

Adult

Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults.

Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three- to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged > or = 50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P = 0.001 and P = 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients > or = 50 years of age with localized herpes zoster, valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.

Acyclovir

Antibodies against hepatitis viruses in merchant seamen.

Seamen constitute a special group of international travellers who may run an increased risk of contracting hepatitis, because of visits to foreign ports and the particular environment on board ship. The purpose of the survey was to assess the prevalence of serological markers for hepatitis A, B and C virus infection among seamen and to identify present and previous risk factors for infection. 515 seamen were studied. The prevalence of antibodies against hepatitis A was 0.3% in subjects below 40 years of age, increasing with age above 40 years, and highest among those who had sailed in international trade. The prevalence of antibodies against hepatitis B was 2.7% in subjects below 40 years of age, increasing to 35.7% in the group above 60 years of age. Hepatitis C antibodies occurred in 1.2%. Vaccination of sailors against hepatitis A should follow the same recommendations as to other travellers. The prevalence of hepatitis B was higher than in reference groups of non-seamen but, because hepatitis B is only one of many blood-borne diseases, prevention should be directed towards changes in behaviour rather than vaccination, except for special groups. Young seamen in international trade were found to be most at risk of contracting sexually transmitted diseases.

Adult

[Purulent meningitis at the Marselisborg Hospital 1980-1990].

From 1980-1990 245 immunocompetent patients were admitted to The Department of Infectious Diseases, Marselisborg Hospital with purulent meningitis or meningococcal septicaemia. The clinical diagnosis was established by clinical examination and by neutrophil pleocytosis. The aetiological diagnosis was established by demonstration of bacteria in the cerebrospinal fluid by microscopy or culture and by blood culture. Clinical signs of disseminated intravascular coagulation (DIC) or demonstration of meningococcal antibodies (MAT) in serum were considered diagnostic for meningococcal disease. The group comprised 120 males and 125 females aged 0-90 years. One hundred and eleven (45%) had meningococcal disease, 69 (28%) had pneumococcal meningitis, and 20 (8%) had H. influenzae-meningitis. Other aetiologies occurred in one to six cases. No aetiology could be established in 25 (10%) patients. Patients with meningococcal and pneumococcal disease were treated with monotherapy with high doses of penicillin, and H. influenzae-meningitis was treated with ampicillin. In patients with meningitis of unknown aetiology penicillin was used, except in children below the age of five where ampicillin was used. In patients with meningococcal disease the mortality was 5.4%, and 17% developed sequelae. In pneumococcal meningitis the corresponding figures were 13% and 17%, and in H. influenzae-meningitis 0% and 5% respectively. Among 20 patients with other aetiologies one patient (5%) died, and eight (40%) developed sequelae, whereas one patient (4%) died, and one (4%) developed sequelae in the group with meningitis of unknown aetiology. No ampicillin-resistant H. influenzae-strains were demonstrated. We suggest that monotherapy with betalactam-antibiotics is still a valuable treatment for meningitis in Denmark.

Adult