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Biomedical subjects

L Hagberg

Publications and source records attributed to L Hagberg.

At least 73 records · Page 4Linked to original sources

Markers of immune stimulation in the cerebrospinal fluid during HIV infection: a longitudinal study.

Markers of immune stimulation were studied in 76 sequential cerebrospinal fluid (CSF) samples from 19 patients infected with HIV-1 without antiretroviral treatment during observation periods ranging from 22 months to 6 years. Eight of these patients were further followed with 14 CSF samples for 3-24 months of zidovudine treatment. During the course of HIV-1 infection, the mean CSF neopterin and beta 2-microglobulin (beta 2M) concentrations increased from 12.7 to 20.4 nmol/l (p < 0.01) and from 1.93 to 2.17 mg/l (p < 0.05), respectively, while the mean peripheral CD4 + T cell count decreased from 624 to 320 cells x 10(6)/l (p < 0.001). The IgG index, reflecting intrathecal immunoglobulin production, increased from 0.72 to 0.92 (p = 0.08). The number of patients with CSF pleocytosis did not change significantly during follow-up (8/19 at baseline, 7/19 at endpoint). In the 8 patients followed up during antiretroviral treatment, a significant reduction in mean CSF levels of neopterin and beta 2M (-48% and -32%, respectively, p < 0.01) was seen after 3-12 months on zidovudine. We suggest that gradual increase in immune stimulation reflected by the rising CSF concentrations of neopterin and beta 2M indicates that HIV-1 infection in the central nervous system is progressive even in neurologically asymptomatic stages.

Adult↗

V3 sequences of paired HIV-1 isolates from blood and cerebrospinal fluid cluster according to host and show variation related to the clinical stage of disease.

The spread of HIV-1 to the nervous system occurs early during infection in a large number of asymptomatic virus carriers. In order to address the question whether the brain is targeted by a group of HIV-1 variants with increased neurotropic properties we have obtained 20 paired isolates from the blood and cerebrospinal fluid (CSF) of patients with varying severity of HIV-1 infection. We determined the nucleotide sequence of variable region 3 (V3) of the gp 120 envelope protein and studied the growth capacity of the virus isolates in primary monocyte/macrophage cultures. Blood and CSF V3 sequences could be grouped according to the host, whereas particular amino acid sequences related to tissue specificity were not identified. Moreover, the majority of HIV-1 isolates, independently of the tissue source, replicated in macrophage cultures. The isolates derived from the brain and blood compartments thus appeared genetically similar and could not be grouped according to their replicative capacities. The genetic distance between paired CSF and blood sequences was more pronounced in the group of patients with AIDS than in asymptomatic virus carriers. These observations indicate that the viruses present in the blood and CSF in the early stage of infection are genetically similar. Different mechanisms of adaptation or immunomodulation of the virus in CSF and blood may account for the increased intra-patient variability observed in the AIDS group.

Acquired Immunodeficiency Syndrome↗

Doxycycline and pyrimethamine for toxoplasmic encephalitis.

Clinical improvement is reported in a 40-year-old man with AIDS and presumed toxoplasmic encephalitis, who was treated with doxycycline, 400 mg, and pyrimethamine, 25 mg, daily. Computerised tomography (CT) scanning of the brain showed complete resolution of 2 ring-enhanced lesions within 5 weeks.

AIDS-Related Opportunistic Infections↗

Cerebrospinal fluid neopterin concentrations in central nervous system infection.

Cerebrospinal fluid (CSF) neopterin levels were determined by RIA in individuals with central nervous system (CNS) or human immunodeficiency virus (HIV) infections and in healthy controls. The mean CSF neopterin concentrations were 63.0 nmol/L in 15 patients with acute bacterial meningitis, 54.9 nmol/L in 15 patients with Lyme neuroborreliosis, 32.5 nmol/L in 10 patients with viral meningitis, 130.9 nmol/L in 8 patients with viral encephalitis, 13.9 nmol/L in 15 patients with asymptomatic HIV infection, 26.0 nmol/L in 11 patients with AIDS without dementia, 65.4 nmol/L in 4 patients with AIDS dementia, and 4.2 nmol/L in 24 healthy controls. Although patients with viral encephalitis had higher mean neopterin levels than any other patient category studied, the CSF neopterin concentrations cannot be used to discriminate between viral and bacterial infections. Analysis of CSF levels of neopterin may be useful as guidance in following clinical course and effect of treatment and can provide information of value in addition to CSF cell count as a measurement of CNS immune stimulation.

Adolescent↗

Intestinal antibody responses to oral vaccination in HIV-infected individuals.

OBJECTIVE: To examine whether and at what stage mucosal immune responsiveness is impaired during HIV-1 infection. DESIGN: Intestinal and systemic antibody-secreting cell (ASC) responses were examined in eight HIV-1-infected volunteers and 10 seronegative control subjects after oral cholera and parenteral tetanus vaccinations. METHODS: ASC numbers were determined before and after booster vaccinations by the enzyme-linked immunospot (ELISPOT) technique. This technique was performed on cell suspensions obtained from enzymatically dispersed duodenal biopsies and from peripheral blood. RESULTS: Oral cholera vaccination evoked ASC responses in the intestinal mucosa of six out of eight HIV-1-infected volunteers, including patients with advanced disease and very low levels of circulating CD4+ T cells. The intestinal cholera ASC responses in HIV-infected volunteers were comparable to those in uninfected controls with regard to both magnitude and distribution of antibody classes. Most HIV-infected volunteers with only moderately reduced CD4+ T-cell counts also responded with vaccine-specific ASC in the blood, whereas none of the patients with < 200 x 10(6)/l CD4+ T cells per litre blood had detectable circulating ASC. CONCLUSION: These findings indicate that mucosal humoral immune responsiveness to a T-cell dependent antigen is maintained in HIV-infected individuals, despite concomitant systemic humoral hyporesponsiveness.

Administration, Oral↗

Hemagglutination (fimbriae) and hydrophobicity in adherence of Serratia marcescens to urinary tract epithelium and contact lenses.

The capacity of 59 isolates of Serratia marcescens, obtained from urinary tract infections, wounds, and contact lenses or their paraphernalia, to agglutinate erythrocytes from different animal species was tested. Three main patterns were found: mannose-sensitive agglutination of guinea-pig, fowl or horse erythrocyte; mannose-resistant agglutination of chicken or pigeon erythrocytes alone or in combination with mannose-sensitive agglutination; and no agglutination. Hemagglutination capacity was associated with isolates from urinary tract infection, but not with isolates associated with contact lenses. Adherence to human urinary tract epithelium did not correlate with the hemagglutination patterns nor with the origin of the isolates. Some strains of different hemagglutination pattern were selected for the study of hydrophobicity and adherence to contact lens polymers. Hydrophobicity, as determined by degree of partition in hexadecane and water (BATH-values), correlated neither with degree of adherence to contact lens polymers nor with the hemagglutination pattern. For a representative strain there was an excellent correlation (r2 = 0.98) between adherence and the water content (hydrophobicity) of the lens polymers. These results suggest that, as with tissues, other factors interact with hydrophobicity in causing adherence to plastics.

Alkanes↗

Cerebrospinal fluid anti-cerebellar soluble lectin antibodies in human immunodeficiency virus type 1 infection.

Cerebrospinal fluid samples from 14 human immunodeficiency type 1 (HIV-1) seropositive patients in various stages of HIV infection were tested for the presence of autoantibodies to an endogenous manose-binding protein, the cerebellar soluble lectin (CSL), which has recently been found to be detected in a high proportion of patients with multiple sclerosis. An immunoblotting test was used with rat CSL as antigen. Seven patients were positive for anti-CSL and seven were negative. The seven anti-CSL-positive patients had signs of intrathecal immunoglobulin G production measured as an elevated IgG index, while the seven anti-CSL-negative patients had a normal IgG index. There was no apparent relation between infectious stage and the presence of anti-CSL. Immunological reactions such as anti-CSL autoantibodies may be a similar pathogenic mechanism in HIV and multiple sclerosis brain disease.

Acquired Immunodeficiency Syndrome↗

The contents of macromolecule solutes in flexor tendon sheath fluid and their relation to synovial fluid. A quantitative analysis.

The importance of synovial environment for minimal adhesion formation in flexor tendon healing has recently gained attention. Various techniques have been used to restore an injured synovial tendon sheath. Therefore a quantitative analysis of flexor tendon sheath fluid is of interest to increase our knowledge about the specific synovial milieu and to evaluate the success of different types of sheath reconstructions from a biochemical point of view. Samples of tendon sheath fluid from trigger digits and tendon sheaths containing ganglions have been assayed for contents of hyaluronic acid and proteins of different molecular weights. The results show concentrations of hyaluronate and several proteins similar to those in normal joint fluid. These results indicate that flexor tendon sheath fluid has a character similar to synovial fluid of joints and apparently has specific functions such as soft tissue lubrication and nutrition of avascular tendon tissue.

Adult↗

Exogenous hyaluronate as an adjunct in the prevention of adhesions after flexor tendon surgery: a controlled clinical trial.

Postoperative adhesions that restrict tendon gliding are a major cause of failure after tendon repair and grafting in zone II. Several experimental reports have claimed that exogenously administered sodium hyaluronate helps to prevent the formation of such adhesions. In a prospective double-blind, randomized, clinical study with open therapeutic control sodium hyaluronate or physiologic saline solution was injected into the tendon sheath after completion of tenorrhaphy or tendon grafting in 120 digits. Sodium hyaluronate had no statistically significant effect as evaluated on total active motion at follow-up.

Adult↗

Sodium hyaluronate as an adjunct in adhesion prevention after flexor tendon surgery in rabbits.

Topical application of sodium-hyaluronate (NaHe) has been proposed to decrease the formation of adhesions after tendon surgery, but reports published thus far have been contradictory. A new test instrument capable of simultaneous registration of tensile load, tendon excursion, and joint motion was therefore developed and used to evaluate the effect of locally administered NaHe of different concentrations and molecular weights on the outcome after tenorrhaphy of rabbit hindlimb flexor tendons. Immediately after tenorrhaphy, NaHe or saline solution was deposited into the tendon sheath. The functional characteristics of the digits were evaluated 15 days after surgery. NaHe with a concentration of 19 mg/ml and a molecular weight of 6 x 10(6) significantly limited the strength of the adhesions formed without impairment of tensile strength. These results suggest that the efficacy of NaHe is affected by both the concentration and the molecular weight of the NaHe preparation used.

Animals↗

Lack of autologous neutralizing antibodies in the cerebrospinal fluid of HIV-1 infected individuals.

The cerebrospinal fluids (CSF) and sera from HIV-1-infected individuals at different clinical stages were monitored for neutralizing activity against CSF-derived HIV-1 isolates. None of the CSF samples and only one of seven serum samples could neutralize the autologous CSF isolate. CSF samples collected one to two years later from the same patients also lacked autologous neutralizing antibodies against these isolates. However, some CSF samples were able to neutralize heterologous CSF isolates albeit in low titers. HIV antibody positive control sera could readily neutralize all of the CSF isolates demonstrating that these isolates were not resistant to neutralization per se. IgG antibodies against the HIV-1 envelope protein and, specifically, against the V3 loop of HIV-1 gp120 (MN) were present in some CSF samples, although the samples lacked neutralizing activity. In summary, this study demonstrates a lack of autologous neutralizing antibodies in CSF samples when assayed against CSF-derived HIV-1 isolates.

Amino Acid Sequence↗

Human immunodeficiency virus type 1 is present in the cerebrospinal fluid of a majority of infected individuals.

Cerebrospinal fluid (CSF) specimens from 63 patients with different severities of human immunodeficiency virus (HIV-1) infection, including asymptomatic virus carriers, were examined for the presence of HIV-1 by using polymerase chain reaction (PCR) and virus isolation. Polyadenylated RNA, presumably associated with virus particles, was extracted and reverse transcribed, and the pol region was amplified in a nested PCR. Virus could be detected in 90% of the CSF specimens examined by PCR, and data on isolation of virus from CSF were in agreement with these figures. In fact, when several CSF specimens from the same individual were studied, HIV-1 could be isolated from 80% of the patients. The presence of the viral RNA in CSF was independent of the clinical stage of infection and of neurological symptoms. These results show that the spread of HIV-1 to the brain represents an early event during infection and occurs in the majority of asymptomatic individuals.

Blood↗

Cerebrospinal fluid catecholamine metabolites in HIV-infected patients.

Twenty-eight HIV-seropositive individuals--11 asymptomatic cases, 8 with lymphadenopathy syndrome (LAS), and 9 with AIDS--were investigated. Clinical staging of the AIDS dementia complex was done in the 9 AIDS patients. The catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in CSF were determined in all the HIV patients and in 20 healthy volunteers. The CSF MHPG levels did not differ significantly between healthy subjects and HIV-infected patients at any stage of the infection. The CSF concentrations of HVA differed between the groups only during the AIDS stage. The mean CSF HVA value in the AIDS patients was 42% lower than in the healthy subjects and significantly lower than in any other stage of HIV infection (P less than .01). Patients with signs of the AIDS dementia complex had reduced CSF HVA levels, but there was no clear relationship between HVA concentration and stage of the AIDS dementia complex.

AIDS Dementia Complex↗

Elimination of exogenously injected sodium-hyaluronate from rabbit flexor tendon sheaths.

To obtain information about the elimination of Na hyaluronate (NaHe) deposited in flexor tendon sheaths in rabbits, two flexor tendon sheaths from each hind limb were operatively exposed in 15 animals and each filled with one of four different NaHe preparations, namely: 10 mg/ml, MW 2.6 x 10(6); 10 mg/ml, MW 6.3 x 10(6); 19 mg/ml, MW 3.0 x 10(6); and 19 mg/ml, MW 6.5 x 10(6). One, 3, and 7 days after surgery, the NaHe concentration was measured in frozen specimens from the tendon sheaths. One day after surgery, NaHe concentration in the tendon sheath fluid was close to 10 mg/ml in all groups. Three and 7 days after surgery it was higher in tendon sheaths in which NaHe preparations with a high (19 mg/ml) rather than with a low concentration (10 mg/ml) had been deposited. At 3 days, NaHe concentration was also higher in sheaths that had received a preparation with a high MW (6.5 x 10(6)) than those with a lower MW (2.6 or 3.0 x 10(6)). The findings suggest that within the first 24 h, a dilution of concentrated NaHe preparations takes place, probably as a result of their hyperoncotic properties. After 24 h, there was a slower decline in NaHe concentration when more concentrated solutions (19 mg/ml) and solutions with high MWs (6.5 x 10(6)) were administered. Development of pharmaceutical NaHe preparations with slow elimination from tendon sheaths should reasonably be focused on a solution with a high MW and high concentration.

Animals↗

Determination of biomechanical characteristics of restrictive adhesions and of functional impairment after flexor tendon surgery: a methodological study of rabbits.

Formation of restrictive adhesions is one of the main obstacles in rehabilitation following hand surgery. Most experimental work, however, involves only a macroscopic and/or histologic evaluation of the amount of adhesions, and their functional characteristics are poorly described. The aim of this study was to develop an experimental technique for characterization of the biomechanical properties of the finger-tendon unit. An instrument was developed for continuous and simultaneous recording of tensile load, tendon excursion and angular rotation in the distal interphalangeal joint of rabbit digits. Utilizing this instrument, it was revealed that the first 50 degrees of flexion required virtually no tensile load either in unoperated digits or immediately after tenorrhaphy. Thereafter, the load required to obtain further flexion was progressively increased. The strength of adhesions, determined 2 weeks after tenorrhaphy, was best expressed as the maximum tensile load recorded before 50 degrees of flexion was reached. This measurement could also be used to register the strength of the tendon repair and to detect partial tendon rupture during the measurement. The technique allows both adequate measurements of the strength of the adhesions and of the tendon gliding ability after flexor tendon surgery.

Animals↗