Biomedical subjects

L Hagberg

Publications and source records attributed to L Hagberg.

At least 19 recordsLinked to original sources

PubMed2006

Clinical and bacteriologic efficacy of telithromycin in patients with bacteremic community-acquired pneumonia.

This retrospective analysis was performed to determine the clinical and bacteriologic efficacy of the ketolide antibacterial telithromycin in patients with community-acquired pneumonia (CAP) with pneumococcal bacteremia. Patients 13 years old with radiologically confirmed CAP and a positive blood culture for Streptococcus pneumoniae at screening were analyzed from eight multicenter Phase III/IV clinical trials. In four open-label, non-comparative studies, patients received telithromycin 800 mg once daily for 7-10 days. In four randomized, controlled, double-blind, comparative studies, patients received telithromycin 800 mg once daily for 5-10 days or a comparator antimicrobial (amoxicillin 1000 mg three times daily, clarithromycin 500 mg twice daily, or trovafloxacin 200 mg once daily) for 7-10 days. In total, 118 patients (telithromycin, 94/1061 [8.9%]; comparator, 24/244 [9.8%]) had documented pneumococcal bacteremia. Those who were treated with telithromycin achieved a clinical cure rate of 90.2% (74/82, per-protocol population); S. pneumoniae was eradicated in 77/82 (93.9%) bacteremic patients who received telithromycin and 15/19 (78.9%) comparator-treated patients. Clinical cure was also observed among telithromycin-treated bacteremic patients who were infected with penicillin- or erythromycin-resistant strains of S. pneumoniae (5/7 and 8/10, respectively). In conclusion, telithromycin achieves high clinical and bacteriologic cure rates in CAP patients with pneumococcal bacteremia.

Adolescent↗

PubMed2005

CSF amyloid beta42 and tau levels correlate with AIDS dementia complex.

There is concern that AIDS dementia complex (ADC) may be complicated by Alzheimer disease (AD). Because AD presence and risk are related to CSF beta-amyloid(1-42) (Abeta42), total tau (t-tau), and phosphorylated tau (p-tau), the authors examined these in ADC, AD, and controls. ADC had significantly decreased CSF Abeta42 and increased t-tau and p-tau concentrations similar to AD, suggesting that ADC may be associated with AD or an AD-like process.

AIDS Dementia Complex↗

PubMed2005

Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.

OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.

Adolescent↗

PubMed2005

Effects of antiretroviral treatment on blood-brain barrier integrity and intrathecal immunoglobulin production in neuroasymptomatic HIV-1-infected patients.

OBJECTIVES: To study the effect of antiretroviral combination therapy on blood-brain barrier (BBB) integrity and intrathecal immunoglobulin G (IgG) production. METHODS: Lumbar punctures were performed on 38 neurologically asymptomatic, treatment-naive HIV-1-infected patients prior to and during treatment at intervals of approximately 4 months, 1 year and 2 years. Albumin ratio and IgG index were analysed as markers of BBB integrity and intrathecal IgG synthesis. RESULTS: HIV-1 RNA decreased to < 50 HIV-1 RNA copies/mL in the cerebrospinal fluid (CSF) of all patients and in the plasma of all but one patient. Only 5% of patients had elevated albumin ratio values at baseline, while 56% had an elevated IgG index. There was no significant reduction of the albumin ratio or the IgG index. After 2 years of treatment all patients had normal albumin ratio values, while 41% still had increased IgG index levels. CONCLUSIONS: Up to 2 years after the initiation of treatment, the favourable impact of antiretroviral combination treatment on CSF viral load was not accompanied by a similar reduction of intrathecal IgG production. BBB function, measured as the albumin ratio, was not significantly changed in this cohort of neurologically asymptomatic HIV-1-infected patients.

Adolescent↗

PubMed2003

Telithromycin in the treatment of community-acquired pneumonia: a pooled analysis.

The efficacy of telithromycin has been assessed in six Phase III studies involving adults with mild to moderate community-acquired pneumonia (CAP) with a degree of severity compatible with oral therapy. Patients received telithromycin 800 mg once daily for 7-10 days in three open-label studies (n=870) and three randomized, double-blind, comparator-controlled studies (n=503). Comparator antibacterials were amoxicillin 1000 mg three-times daily, clarithromycin 500 mg twice daily and trovafloxacin 200 mg once daily. Clinical and bacteriological outcomes were assessed 7-14 days post-therapy. Among telithromycin-treated patients, per-protocol clinical cure rates were 93.1 and 91.0% for the open-label and comparative studies, respectively. Telithromycin treatment was as effective as the comparator agents. High eradication and clinical cure rates were observed for infections caused by key pathogens: Streptococcus pneumoniae including isolates resistant to penicillin G and/or erythromycin A (95.4%), Haemophilus influenzae (89.5%) and Moraxella catarrhalis (90%). Telithromycin was also highly effective in patients with infections caused by atypical and/or intracellular pathogens and those at increased risk of morbidity. Telithromycin was generally well tolerated. Telithromycin 800 mg once daily for 7-10 days offers a convenient and well-tolerated first-line oral therapy for the empirical treatment of mild to moderate CAP.

Aged↗

PubMed2002

Efficacy and tolerability of once-daily telithromycin compared with high-dose amoxicillin for treatment of community-acquired pneumonia.

BACKGROUND: This randomized, double-blind study compared the efficacy and tolerability of the new ketolide antimicrobial telithromycin with that of high-dose amoxicillin in the treatment of community-acquired pneumonia (CAP). PATIENTS AND METHODS: Adult patients (n = 404), with signs and symptoms of CAP and radiologic confirmation were randomized to receive telithromycin 800 mg once daily (n = 199) or amoxicillin 1,000 mg three times a day (n = 205) for 10 days. Clinical and bacteriologic outcomes were assessed at post-therapy test-of-cure (days 17-24) and late post therapy (days 31-36). RESULTS: The clinical cure rate for telithromycin-treated patients (per protocol) pst therapy (days 17-24) was 141/149 (94.6%) and compared well with that for amoxicillin (137/152 (90.1%)). Subset analysis of patients (per protocol) showed high clinical cure rates for patients aged >/= 65 years (telithromycin 21/24, 87.5%; amoxicillin 22/29, 75.9%); those with documented pneumococcal bacteremia (telithromycin 10/10, 100%; amoxicillin 7/9, 77.8%); and patients with a Fine score >/= III (telithromycin 31/34, 91.2%; amoxicillin 38/47, 80.9%). Bacterial eradication rates were comparable between treatments (telithromycin 42/48, 87.5%; amoxicillin 39/45, 86.7%), with 22/23 vs 18/21 Streptococcus pneumoniae strains 9/12 vs 11/13 Haemophilus influenzae strains and all Moraxella catarrhalis isolates (five and three patients, respectively) eradicated at the test-of-cure visit. Both treatments were generally well tolerated. CONCLUSION: Telithromycin 800 mg once daily is a convenient, optimal-spectrum, first-line treatment for CAP in adults, at least as effective and well tolerated as high-dose amoxicillin.

Adolescent↗

PubMed2001

Elevated levels of soluble Fas and Fas ligand in cerebrospinal fluid of patients with AIDS dementia complex.

We measured the levels of sFas and sFasL in CSF and serum of HIV-1 infected patients and related them to AIDS dementia complex (ADC). Specimens were obtained from 51 HIV-1 infected individuals (29 with ADC) and 39 HIV negative individuals. The sFas was detectable in all sera and 98% of CSF specimens. Measurable levels of sFasL were found in 79% of the CSF and 98% of sera samples. According to the presence or absence of ADC, we observed significant differences in CSF sFas (median and IQR 116, 132 vs. 30, 23 pg/ml, P<0.001) and sFasL (median and IQR 127, 290 vs. 15, 73 pg/ml, P<0.001) levels. The sFas in serum differed significantly between HIV-1 infected subjects and non-infected controls (P<0.001), with no correlation to ADC. On the contrary, sFasL in serum differed among HIV-1 infected subjects according to clinical signs of ADC. In the cross-sectional study, the number of cells present in CSF and CD4+ T cell counts in blood did not correlate to the levels of CSF sFas and sFasL. Interestingly, the number of HIV RNA copies in CSF correlated significantly to the levels of CSF sFasL (P=0.001) but not to sFas in the same compartment. Antiretroviral therapy reduced viral load and sFas levels in CSF in the majority of patients. sFas is a useful marker for ADC diagnosis and follow-up during antiviral treatment.

AIDS Dementia Complex↗

PubMed2001

Antiretroviral treatment of central nervous system HIV-1 infection: a review.

HIV-1 infects the central nervous system (CNS) and it has been feared that the CNS may be a sanctuary site where HIV-1 could hide and continue to replicate despite otherwise effective antiretroviral treatment. Neurological HIV-1 related symptoms, cerebrospinal fluid (CSF) viral load, intrathecal immunoactivation and CSF drug concentration measurements are considered in this review of antiretroviral treatment effects on CNS HIV-1 infection. We conclude that antiretroviral combination treatment regimens improve neurocognitive symptoms in HIV-1 infection and substantially lower CSF viral load. The threat of an increasing number of patients with neurological symptoms and continued HIV-1 replication in the brain despite otherwise effective antiretroviral therapy has not yet proved to be a problem. It is, however, important to keep this potential risk in mind, and more longitudinal prospective studies addressing the issue of antiretroviral treatment effects on CNS HIV-1 infection are needed.

Anti-HIV Agents↗

PubMed2001

Clinical and laboratory signs of mitochondrial dysfunction secondary to nucleoside analogue antiretroviral therapy are reversible.

During 27 months treatment with 400 mg didanosine and 80 mg stavudine daily but no protease inhibitor therapy, a 50-y-old HIV-positive woman gradually lost 13 kg in weight, her arms, legs and buttocks decreased in volume and she experienced fatigue and polyneuropathy. Laboratory tests showed slight increases in plasma lactate and liver enzyme levels. Eighteen months after withdrawal of antiretroviral drug, the patient was free of fatigue and polyneuropathy and had regained 7 kg in weight as well as most of the volume of her arms, legs and buttocks.

Anti-HIV Agents↗

PubMed2001

Increased blood-brain barrier permeability in neuro-asymptomatic HIV-1-infected individuals--correlation with cerebrospinal fluid HIV-1 RNA and neopterin levels.

The objective of this study was to assess the frequency of blood-brain barrier (BBB) impairment, as measured by the albumin ratio, in neuro-asymptomatic HIV-1-infected individuals without antiretroviral treatment and the correlation between BBB disruption and intrathecal immune activation and HIV-1 RNA levels. Serum and cerebrospinal fluid (CSF) albumin, neopterin, and HIV-1 RNA levels were analysed in 110 neuro-asymptomatic HIV-1-infected individuals at different stages of disease; 63 classified as CDC A, 25 as CDC B, and 22 as CDC C. Increased BBB permeability was found in 17 of 110 (15%) of HIV-1-infected individuals. This proportion was sustained throughout the CDC stages. The albumin ratio was correlated with the CSF neopterin levels (r(s) = 0.36, P < 0.001), the serum neopterin levels (r(s) = 0.37, P < 0.001), and the CSF HIV-1 RNA levels (r(s) = 0.26, P < 0.01), but not with the plasma HIV-1 RNA levels. The correlations between the albumin ratio and the CSF and serum neopterin concentrations and the CSF HIV-1 RNA levels indicate that immune activation and, possibly, intrathecal HIV-1 virus replication are important factors associated with increased BBB permeability in HIV-1 infection.

Adolescent↗

PubMed2000

Hepatocyte growth factor levels in cerebrospinal fluid: a comparison between acute bacterial and nonbacterial meningitis.

The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P<.001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.

Acute Disease↗

PubMed2000

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open iup new perspectives in the coming millennium.

Amputation, Surgical↗

PubMed2000

Intrathecal immune activation is associated with cerebrospinal fluid markers of neuronal destruction in AIDS patients.

We analysed the relationship between cerebrospinal fluid (CSF) concentrations of the light subunit of the neurofilament protein (NFL, a marker of neurons, mainly axons), neopterin (a marker of immune activation), and quantitative HIV RNA levels in 47 patients with HIV-1 infection, 25 of whom had AIDS. In the AIDS patients, the mean levels of CSF NFL were high indicating neuronal destruction. The CSF NFL and the CSF neopterin concentrations were correlated in the subgroup of patients without CNS opportunistic infection (p < 0.05). There was no significant correlation between NFL and HIV RNA levels in CSF. In HIV seropositive patients without AIDS, only 3/22 had CSF NFL concentrations above the upper normal reference value. The results suggest that CNS neuronal destruction occurs frequently in patients with AIDS but rarely in those without AIDS, and that immune activation rather than the HIV viral load is associated with neurochemical signs of axonal destruction.

AIDS-Related Opportunistic Infections↗

PubMed2000

Higher HIV-1 RNA cutoff level required in cerebrospinal fluid than in blood to predict positive HIV-1 isolation.

HIV-1 can be isolated from the vast majority of blood samples taken from HIV-1-seropositive patients not treated with antiretroviral drugs. Isolation rates from cerebrospinal fluid (CSF) samples are considerably lower, ranging between 20-70%. The objective of this study was to determine the cutoff levels for HIV-1 RNA that would yield a positive predictive value > or =90% for positive virus isolation from CSF and blood. Quantitative HIV-1 RNA PCR (Amplicor HIV monitor, version 1.0, Roche Diagnostic Systems) and virus isolation were used to examine 303 CSF samples and 278 paired blood samples from 157 HIV-1-seropositive patients. Patients on antiretroviral treatment provided 140 of the CSF samples and 131 of the blood samples. CSF samples that were positive by culture numbered 137 of 303 (45%), as compared with 216 of 278 (78%) blood samples. In the case of samples taken from patients with antiretroviral treatment, 28% were positive by culture from CSF and 63% from blood. As expected, mean HIV-1 RNA levels were higher in CSF and blood samples positive by culture than in samples negative by culture. A cutoff level of >5,000 HIV-1 RNA copies/ml was required to yield a positive predictive value for positive virus isolation from CSF samples of > or =90%, whereas the cutoff level for blood samples was just above the detection limit of the assay (>200 HIV-1 copies/ml).

Acquired Immunodeficiency Syndrome↗

PubMed2000

Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction.

We determined the extent of neuronal and glial cell destruction in 13 patients with herpes simplex type 1 (HSV-1) encephalitis, 15 patients with tick-borne encephalitis (TBE), and 20 noninfectious controls by analyzing the cerebrospinal fluid (CSF) concentrations of neurofilament protein (a marker of neurons, mainly axons), neuron-specific enolase (a marker of neurons, mainly somas), glial fibrillary acidic protein, and S-100 protein (markers of astrocytes). In addition, in patients with HSV-1 encephalitis CSF samples were collected serially before 7, 8-14, and 18-49 days and 3-10 months after the onset of neurological symptoms. In the acute stage of HSV-1 encephalitis we found markedly higher CSF levels of the cell damage markers than in patients with TBE. The concentration of cell damage markers in HSV-1 encephalitis decreased within 45 days after acute infection, except for neurofilament protein. The CSF concentrations of neurofilament protein increased during the second week, remained extremely high throughout the next month, and decrease thereafter. The changes in these markers of neuronal and glial destruction demonstrate the neuronal and astroglial cell damage during the first month after HSV-1 encephalitis. In contrast, most patients with TBE had signs only of slight astrogliosis, except for two patients with paresis.

Adult↗

PubMed2000

Booster effect of low doses of tetanus toxoid in elderly vaccinees.

In order to improve the immunity to diphtheria, the recommended booster dose of diphtheria/tetanus vaccine for adults in Sweden was changed in 1986 from 0.5 ml of tetanus vaccine with a small diphtheria dose to 0.25 ml of a diphtheria/tetanus vaccine containing 7.5 Lf tetanus toxoid and 30 Lf diphtheria toxoid/ml. This change resulted in an increase in the dose of diphtheria toxoid from 0.5 Lf to 7.5 Lf, but a decrease in the recommended booster dose of tetanus toxoid from 3.75 Lf to 1.9 Lf. The aim of the present study was to investigate whether this lower dose of tetanus toxoid was also sufficiently protective for elderly people. Two hundred adults (median age 76 years, range 60-92 years) with no history of tetanus vaccination during the past 10 years volunteered for the study. One hundred two vaccinees were inoculated with 1.9 Lf tetanus toxoid (0.25 ml) and 98 with 3.75 Lf tetanus toxoid (0.5 ml). Paired serum samples were analysed by the toxin-binding inhibition assay. Side effects were few and mild, without significant differences between the groups. Response rates were similar, with the 3.75 Lf dose eliciting a marginally higher antitoxin response. The prevaccination geometric mean titre was the same for both groups: 0.03 IU/ml. Postvaccination geometric mean titres were 1.18 IU/ml for the 3.75 Lf group and 1.93 IU/ml for the 7.5 Lf group, respectively (difference not significant). Forty-seven percent of the vaccinees had a prevaccination titre of < or =0.01 IU/ml. Postvaccination, 85% had a titre >0.01 IU/ml. Booster vaccination with tetanus vaccine containing only 1.9 Lf of tetanus toxoid was thus found to induce an excellent immune response in elderly people, with few side effects resulting.

Aged↗

PubMed2000

Slowed reaction time in HIV-1-infected patients without AIDS.

OBJECTIVES: To investigate if HIV-1-infected patients without acquired immunodeficiency syndrome (AIDS) have cerebral dysfunction as reflected by impaired reaction times compared to patients with chronic hepatitis C. MATERIAL AND METHODS: Forty-one HIV-1-infected patients not fulfilling the AIDS criteria, were tested with three reaction time tests and compared to controls with chronic hepatitis C, matched according to gender and age. RESULTS: HIV-1-infected individuals had, in mean, 5-47 ms longer reaction time than patients with hepatitis C (statistically significant in two of three tests). All but 9 HIV-1-infected individuals had, however, reaction times within the normal range defined by the control group (mean +/- 2 SD). No correlation was found between reaction time and immune status measured as CD4-cell count. CONCLUSION: This study indicates that a subgroup of HIV-1-infected individuals have slower reaction time compatible with cerebral deterioration early in the course of the infection.

AIDS Dementia Complex↗

PubMed2000

Herpesvirus DNA detection in cerebral spinal fluid: differences in clinical presentation between alpha-, beta-, and gamma-herpesviruses.

To evaluate the role of 6 human herpesviruses (cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV)) in infections of the nervous system, cerebrospinal fluid (CSF) samples from 662 patients with suspected viral aetiology to neurological symptoms were investigated for presence of herpesviral DNA in a PCR-based study. Of the 69 patients (2 patients had 2 herpesvirus DNA detected in CSF) who had herpesvirus DNA detected in the CSF, 60 (87%) were non-immunocompromised (CMV 7; HHV-6 6; EBV 16; HSV-1 18; HSV-2 9 and VZV 6) and 9 (13%) were immunocompromised (CMV 3; HHV-6 0; EBV 5; HSV-1 0; HSV-2 1 and VZV 0). The study was performed in a retrospective/prospective manner. The HSV-1, HSV-2, VZV and CMV DNA-positive patients usually had typical clinical syndromes, such as encephalitis/myelitis and meningitis, but also other neurological conditions were associated with findings of these viruses. HHV-6 and EBV DNA were detected in patients presenting with a variety of neurological symptoms, and in some of the cases, concurrent with diagnosis of other infections of the central nervous system. Despite the overall variability of clinical conditions seen, a pattern associated with each investigated herpesvirus was discernable as regards clinical presentation.

Adolescent↗