Clinical features of patients with homozygous complement C4A or C4B deficiency.

INTRODUCTION: Homozygous deficiencies of complement C4A or C4B are detected in 1-10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. MATERIAL AND METHODS: Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients' files. RESULTS: Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%CI = 1.83-158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%CI = 1.00-1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%CI = 1.79-2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%CI = 1.30-7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%CI = 1.22-4.88, p = 0.010). CONCLUSION: This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations.

Clinical Diagnosis of the Dampness and Mold Hypersensitivity Syndrome: Review of the Literature and Suggested Diagnostic Criteria.

A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient's history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS.

Complement C4 deficiency--a plausible risk factor for non-tuberculous mycobacteria (NTM) infection in apparently immunocompetent patients.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are ubiquitous in the environment and they infect mainly persons with underlying pulmonary diseases but also previously healthy elderly women. Defects in host resistance that lead to pulmonary infections by NTM are relatively unknown. A few genetic defects have been associated with both pulmonary and disseminated mycobacterial infections. Rare disseminated NTM infections have been associated with genetic defects in T-cell mediated immunity and in cytokine signaling in families. We investigated whether there was an association between NTM infections and deficiencies of complement components C4A or C4B that are encoded by major histocompatibility complex (MHC). METHODS: 50 adult patients with a positive NTM culture with symptoms and findings of a NTM disease were recruited. Patients' clinical history was collected and symptoms and clinical findings were categorized according to 2007 diagnostic criteria of The American Thoracic Society (ATS). To investigate the deficiencies of complement, C4A and C4B gene copy numbers and phenotype frequencies of the C4 allotypes were analyzed. Unselected, healthy, 149 Finnish adults were used as controls. RESULTS: NTM patients had more often C4 deficiencies (C4A or C4B) than controls (36/50 [72%] vs 83/149 [56%], OR = 2.05, 95%CI = 1.019-4.105, p = 0.042). C4 deficiencies for female NTM patients were more common than for controls (29/36 [81%] vs 55/100 [55%], OR = 3.39, 95% CI = 1.358-8.460, p = 0.007). C4 deficiences seemed not to be related to any specific underlying disease or C4 phenotype. CONCLUSIONS: C4 deficiency may be a risk factor for NTM infection in especially elderly female patients.

Prognostic value of American Thoracic Society criteria for non-tuberculous mycobacterial disease: a retrospective analysis of 120 cases with four years of follow-up.

BACKGROUND: Non-tuberculous mycobacteria (NTM) cause disease in healthy and immunocompromised patients. The American Thoracic Society (ATS) 2007 diagnostic criteria were devised to distinguish NTM disease from airway colonization. The aim of this study was to evaluate the prognostic value of the ATS criteria. METHODS: In a 4-y follow-up study that ended on 8 June 2006, we retrospectively analyzed the symptoms, underlying diseases, and mortality of 120 adult non-HIV patients with NTM culture findings obtained between 1990 and 1998. We categorized the patients according to the 2007 ATS NTM case definition into positive and negative groups. RESULTS: Only 61/120 patients (51%) fulfilled the ATS criteria for NTM disease. As compared to ATS-negative subjects, the ATS-positive group showed lower age, a higher proportion of females, and fewer fatal underlying diseases. Among ATS-negative subjects, 46/59 (78%) did not fulfil the microbiological criteria and 43/59 (73%) did not fulfil the radiological criteria. Mycobacterium avium complex (MAC) comprised 61% of isolations in the ATS-positive and 47% in the ATS-negative group (p = 0.15). No significant difference in median survival time was found between the groups: ATS-positive 7.4 y (95% confidence interval (CI) 0.2-14.6) and ATS-negative 5.3 y (95% CI 3.0-7.6). No significant difference was found in symptoms except fatigue, which was more common in the ATS-positive (56% vs 37%, p = 0.04). Symptoms lasted for less than a year in 48%, which suggests a more rapid disease progression than has previously been reported. CONCLUSIONS: The fulfillment of ATS criteria was poorly associated with any difference in prognosis, and based on our findings would be a poor prognostic marker.

The association of serum neutrophil markers and acute coronary syndrome.

An association exists between chronic infection-induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-8, tissue inhibitor of metalloproteinase (TIMP)-1 concentrations and MMP-8/TIMP-1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months. Serum samples were collected within arrival to the hospital, at 1 week, 3 months and 1 year. Recurrent ACS events were registered during the 1-year follow-up. In the whole population, high serum MPO concentrations at 1 week (fourth quartile versus quartiles 1-3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277-4.980; P = 0.008). In patients without periodontal disease, high MPO concentration at 1 week and 1 year predicted recurrent ACS with RRs of 3.54 (1.600-7.831; P = 0.002) and 2.87 (1.171-7.038; P = 0.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP-8/TIMP-1 ratio at 1 week predicted recurrent ACS with an RR of 3.23 (1.295-8.063; P = 0.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication.

Clinical symptoms and survival in non-smoking and smoking HIV-negative patients with non-tuberculous mycobacterial isolation.

BACKGROUND: Non-tuberculous mycobacteria (NTM) cause infections in patients with smoking-related chronic lung diseases and also in non-smoking healthy elderly women. We analyzed the clinical symptoms, underlying diseases and mortality in patients with NTM culture findings, with special emphasis on smoking status. METHODS: A total of 120 consecutive adult HIV-negative patients with NTM isolation were followed between 1990 and 1998 by retrieving data from their medical records for a period of at least 4 y, until 8 June 2006. Their clinical pictures and outcomes were analysed according to smoking status. RESULTS: In this study, 42% of the patients had never smoked. Females accounted for 72% of non-smokers, but only 30% of smokers (p < 0.001). Mycobacterium avium complex (MAC) accounted for 72% of all isolates in non-smokers and 41% in smokers (p = 0.001). Furthermore, 28% of non-smokers and 19% of smokers had no previous pulmonary diseases (p = 0.223). In nearly half of all patients (48%), symptoms of NTM infection started within a year prior to NTM isolation. Smokers had a higher risk of mortality compared to non-smokers (hazard ratio 1.64, p = 0.049), though this was not found after adjusting for underlying diseases. No fatal underlying diseases were found for 82% of non-smokers and 59% of smokers (p < 0.01). CONCLUSIONS: Non-smokers with NTM isolates had fewer previous lung diseases but had a higher incidence of MAC and bronchiectasis. Time from symptoms to NTM isolation was shorter than previously reported.

HLA-DRB1*01 allele and low plasma immunoglobulin G1 concentration may predispose to herpes-associated recurrent lymphocytic meningitis.

Recurrent lymphocytic meningitis (RLM) is a rare illness caused mostly by herpes simplex virus type 2 (HSV-2). Predisposing factors are not known. Deficiencies in immunoglobulin (Ig) G subclasses 1 (IgG1) and 3 (IgG3) and complement protein C4 are associated with susceptibility to and persistence of bacterial and viral infections. Selected HLA and mannose-binding lectin (MBL) alleles have previously been associated with recurrent genital herpes or herpetic meningitis. We assessed the frequencies of low IgG1 and IgG3, their allotypes (Gm), and HLA-A*, -B*, -DRB1*, and MBL2 alleles, as well as deficiencies in C4A and C4B genes, as potential predisposing factors for HSV-2-associated RLM. The level of IgG1 was lower (p = 0.009) and the frequency of low IgG1 was higher (p < 0.001) in patients than in controls. Furthermore, the risk for a new meningitis episode was increased in patients with low IgG1 (incident ratio 2.05). HLA-DRB1*01 (p = 0.009) and -B*27 (p = 0.050) were more common among patients than controls. We conclude that HLA-DRB1*01 and -B*27 alleles and low plasma IgG1 levels may be significant risk factors for RLM.

Recurrent lymphocytic meningitis positive for herpes simplex virus type 2.

We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996-2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2-5 days after symptom onset.

[Treatment path of wound patient in the HUC medical care district]. / Haavapotilaan hoitopolku HYKS:n sairaanhoitoalueella.

Unorganized care on chronic wounds is expensive. Resources are focused on the care of complicated wounds, although a significant proportion of the wounds could be prevented or treated at an early stage. Good care is cost-effective, a delayed care and inoperative treatment chain will waste money and resources. Specialization of medical and nursing staff in wound care will improve treatment outcome. Prerequisites for the necessary care must be guaranteed by creating a complete treatment path for problematic wounds in the capital region.

Widespread unilateral pain associated with herpes simplex virus infections.

UNLABELLED: We describe a patient group with unexplained widespread pain on one side of the body and pain exacerbations during active labial or genital herpes and during herpetic central nervous system infections. The patients had no visible lesion of the central nervous system on magnetic resonance imaging or abnormality in electrophysiological studies. To understand the nature of the pain and its possible relation to herpes simplex virus (HSV) infections, a clinical neurological examination was performed and quantitative sensory testing and skin biopsies were assessed in 17 patients. The levels of serum total immunoglobulins and IgG subclasses and the frequencies of the immune response genes at the IGH@, HLA-A, -B, -DRB1, C4A, and C4B loci were analyzed in the patients and in control subjects. The patients manifested a uniform clinical syndrome with unilateral pain that was best described as neuropathic and that was exacerbated by HSV reactivations. Low plasma IgG3 concentrations, the presence of either low plasma IgG1 or IgG3 or both, and high anti-HSV-2-IgG titers were more common in the patients than in the control subjects, which rendered the patients more vulnerable to HSV recurrences. PERSPECTIVE: We suggest that low immunoglobulin subclass levels and certain MHC alleles render the patients susceptible to recurring HSV infections. HSV reactivations and the accompanying inflammatory process cause dysfunction of the central nervous system that manifests as neuropathic pain. Studies using functional brain imaging are needed to clarify this syndrome.

Methicillin-sensitive Staphylococcus aureus bacteraemia and endocarditis among injection drug users and nonaddicts: host factors, microbiological and serological characteristics.

BACKGROUND: Endocarditis has been associated with lower mortality and fewer complications among injection drug users (IDUs) than nonaddicts in Staphylococcus aureus bacteraemia (SAB). The better prognosis of IDUs has not been clarified but it has generally been explained by younger age and other host factors. In this study, bacterial strains, their virulence factors, and host immune responses were compared among IDUs and nonaddicts with SAB, including those with and without endocarditis. METHODS: A total of 430 consecutive adult patients with methicillin-sensitive SAB were followed prospectively for 3 months. All 44 IDUs were included, and 44 nonaddicts as controls for them. According to the modified Duke criteria, 20 patients in both groups had endocarditis. For each addict without endocarditis, an age and sex matched nonaddict was selected as a control. S. aureus isolates were assigned a genotype by PFGE, Panton-Valentine leukocidin (PVL), staphylokinase (SAK), protease, and haemolysin production. Acute and convalescent sera were tested for antibodies to alpha-haemolysin (ASTA) and teichoic acid (TAA). RESULTS: There were no differences between IDUs and nonaddicts with SAB in the proportion of patients with a deep infection (98% vs 86%, P=0.06) or a thromboembolic complication (30% vs 14%, P=0.12). Endocarditis among IDUs was not associated with any specific strains, and only the FIN-4 strain was observed more often in IDUs than in nonaddicts (21% vs 5%, P=0.03). The majority of isolates (98%) were PVL negative, and there were no differences in the numbers of SAK, protease and haemolysin production among strains between IDUs and nonaddicts. However, haemolytic properties were found more frequently in strains from IDUs without endocarditis than those with endocarditis (88% vs 47%, P=0.007). IDUs displayed more often elevated TAA titers than nonaddicts, especially in endocarditis at acute phase (33% vs 5%, P=0.04) and at convalescent phase (50% vs 10%, P=0.01). The ASTA titer was more frequently initially positive among IDUs without endocarditis than with endocarditis (44% vs 6%, P=0.01). CONCLUSIONS: Characterization of the bacterial strains and their virulence factors, and host immune responses did not reveal significant differences between IDUs and nonaddicts with similar clinical picture of SAB. Serological tests were not helpful in identifying patients with endocarditis.

Association of Chlamydia pneumoniae infection with HLA-B*35 in patients with coronary artery disease.

The immune system may interplay between Chlamydia pneumoniae infection and coronary artery disease (CAD). Major histocompatibility complex genes regulate innate and adaptive immunity. Patients with CAD (n = 100) and controls (n = 74) were enrolled. Human leukocyte antigens (HLA-A, HLA-B, and HLA-DRB1), four lymphotoxin alpha single-nucleotide polymorphisms, and complement C4A and C4B allotypes were typed, and their haplotypes were inferred. The presence of serum C. pneumoniae immunoglobulin A (IgA) (titer, > or =40) or IgG (titer, > or =128) antibodies or immune complex (IC)-bound IgG antibodies (titer, > or =2) was considered to be a serological marker suggesting chronic C. pneumoniae infection. C. pneumoniae IgA antibodies were found more frequently in patients than in controls (P = 0.04). Among the patients, multiple logistic regression analysis showed the HLA-B*35 allele to be the strongest-risk gene for C. pneumoniae infection (odds ratio, 7.88; 95% confidence interval, 2.44 to 25.43; P = 0.0006). Markers of C. pneumoniae infection were found more frequently in patients with the HLA-A*03-B*35 haplotype than in those without the haplotype (P = 0.007 for IgA; P = 0.008 for IgG; P = 0.002 for IC). Smokers with HLA-B*35 or HLA-A*03-B*35 had markers of C. pneumoniae infection that appeared more often than in smokers without these genes (P = 0.003 and P = 0.001, respectively). No associations were found in controls. In conclusion, HLA-B*35 may be the link between chronic C. pneumoniae infection and CAD.

Serum complement C3/C4 ratio, a novel marker for recurrent cardiovascular events.

Acute coronary syndrome is an inflammatory disease, during which the complement cascade is activated. We assessed the complement C3 and C4 concentration ratio (C3/C4 ratio) in serum as a potential measurement to predict cardiovascular attacks. Patients with acute coronary syndrome (n=148) were followed after an initial attack for subsequent ischemic cardiovascular events (composite end point of death, myocardial infarction, recurrent unstable angina, or stroke). During the follow-up period (average 555 days), 44 patients met an end point. Blood samples were taken at hospitalization, 1 week, 3 months, and 1 year after hospital admission. Serum complement C3 and C4 concentrations and the C3/C4 ratio were analyzed. Patients with an end point had, throughout the follow-up period, a higher C3/C4 ratio than patients without these end points (repeated measures analysis of variance, p=0.007). When all traditional cardiovascular risk factors and other potential confounding factors were included in a Cox multivariate logistic regression survival analysis, the C3/C4 ratio emerged as the novel risk factor for any new cardiovascular event (odds ratio 1.33, 95% confidence interval 1.08 to 1.63, p=0.007). When the C3/C4 ratio was divided into 4 quartiles, 24% in quartiles 1 and 2 (lowest) and 48% in quartile 4 (highest) had end points during follow-up (odds ratio 3.04, 95% confidence interval 1.27 to 7.29, p=0.01). In conclusion, increased serum C3/C4 ratio is a readily available and novel marker for recurrent cardiovascular events in acute coronary syndrome. The relative increase in serum C3 protein and decrease in C4 protein could explain changes in the C3/C4 ratio.

Is periodontal infection behind the failure of antibiotics to prevent coronary events?

The use of antimicrobial agents to prevent coronary events is under debate. They have reduced cardiovascular events in some studies, but in others, their effect has not been distinguishable from that of placebo. In addition to Chlamydophila (Chlamydia) pneumoniae as a target pathogen, very few other microbes or infections have been targeted, although an association for instance between cardiovascular disease and periodontitis has been established. In our recent pilot study, long-term clarithromycin treatment reduces recurrent cardiovascular events in subjects without periodontitis, but in subjects with periodontitis, fails to show any effect. As a background infection, periodontitis may overpower the beneficial effects of antibiotics. This paper presents the hypothesis that periodontitis is behind the failure of antibiotics to prevent coronary events. We discuss the systemic effects of periodontal infection and consider studies to test our hypothesis, which offers a novel viewpoint for discussion of antibiotics in coronary-disease prevention.

Clinical manifestations and outcome in Staphylococcus aureus endocarditis among injection drug users and nonaddicts: a prospective study of 74 patients.

BACKGROUND: Endocarditis is a common complication in Staphylococcus aureus bacteremia (SAB). We compared risk factors, clinical manifestations, and outcome in a large, prospective cohort of patients with S. aureus endocarditis in injection drug users (IDUs) and in nonaddicts. METHODS: Four hundred and thirty consecutive adult patients with SAB were prospectively followed up for 3 months. Definite or possible endocarditis by modified Duke criteria was found in 74 patients: 20 patients were IDUs and 54 nonaddicts. RESULTS: Endocarditis was more common in SAB among drug abusers (46%) than in nonaddicts (14%) (odds ratio [OR], 5.12; 95% confidence interval [CI], 2.65-9.91; P < 0.001). IDUs were significantly younger (27 +/- 15 vs 65 +/- 15 years, P < 0.001), had less ultimately or rapidly fatal underlying diseases (0% vs 37%, P < 0.001) or predisposing heart diseases (20% vs 50%, P = 0.03), and their SAB was more often community-acquired (95% vs 39%, P < 0.001). Right-sided endocarditis was observed in 60% of IDUs whereas 93% of nonaddicts had left-sided involvement (P < 0.001). An extracardiac deep infection was found in 85% of IDUs and in 89% of nonaddicts (P = 0.70). Arterial thromboembolic events and severe sepsis were also equally common in both groups. There was no difference in mortality between the groups at 7 days, but at 3 months it was lower among IDUs (10%) compared with nonaddicts (39%) (OR, 5.73; 95% CI, 1.20-27.25; P = 0.02). CONCLUSION: S. aureus endocarditis in IDUs was associated with as high complication rates including extracardiac deep infections, thromboembolic events, or severe sepsis as in nonaddicts. Injection drug abuse in accordance with younger age and lack of underlying diseases were associated with lower mortality, but after adjusting by age and underlying diseases injection drug abuse was not significantly associated with mortality.

Subtly impaired humoral immunity predisposes to frequently recurring genital herpes simplex virus type 2 infection and herpetic neuralgia.

BACKGROUND: Immunogenetic factors predisposing to recurrent genital herpes remain poorly characterized. METHODS: In a prospective case-control study, 52 consecutive patients with frequently recurring outbreaks of genital herpes were compared with 80 herpes simplex virus (HSV)-seropositive (types 1 and 2) and 70 HSV-seronegative control subjects. Immunoglobulins (Igs), type-specific anti-HSV-2 IgG and IgG subclass antibodies against glycoprotein G, levels of C3 and C4, and classical pathway hemolytic complement activity were measured, and IgG1 and IgG3 allotyping; C4 immunophenotyping; C4* real-time polymerase chain reaction (PCR) genotyping; and HLA-A*, B*, and DR* typing were performed. RESULTS: The G3m(g),G1m(a/a(x)) haplotype was more frequent in patients than in HSV-seronegative control subjects (P=.047). Compared with all control subjects, low levels of total IgG1 (odds ratio [OR], 4.9 [95% confidence interval {CI}, 2.0-12.5]; P=.001) and IgG3 (OR 3.6 [95% CI 1.7-7.8]; P=.001), but not of anti-HSV-2 antibodies, were associated with recurrences. Levels of complement were lowest in patients. The C4* null type was negatively associated with neuralgia (OR, 0.2 [95% CI, 0.06-0.81]; P=.022). CONCLUSIONS: Low levels of antibody-dependent cellular cytotoxicity-mediating IgG1 and IgG3 antibodies, partly dependent of allotype, may predispose to recurrent genital herpes. Antibodies produced by T helper type 1 responses, potentially against an unknown epitope, appear to be relevant in recurrences. In patients, C4* deficiencies are associated with protection from herpetic neuralgias, possibly through reduced inflammation.

Clarithromycin reduces recurrent cardiovascular events in subjects without periodontitis.

Inflammation leading to acute coronary syndrome may be triggered by bacteria causing periodontal infection. We investigated if recurrence of cardiovascular events in unstable coronary patients are associated with periodontitis or microbiological/serological markers of it. Periodontitis-related parameters of 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months, were adjusted to the occurrence of a recurrent cardiovascular event during a follow-up period (average 519 days). In the age group under 65 years the patients with periodontitis had a univariate odds ratios (OR) 95% confidence intervals (95% CI) of 5.0 (1.02-24.55) for a recurrent cardiovascular event in comparison with patients without periodontitis. Dental status correlated positively with serum lipopolysaccharide concentrations and combined IgG antibody response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. The end point frequency did not differ between clarithromycin and placebo groups in bacterium-positive, seropositive, or periodontitis patients. Fewer end points in clarithromycin group were seen in bacterium-negative, seronegative, edentulous, and non-periodontitis patients. Periodontitis and edentulousness are associated with recurrent cardiovascular events, especially in younger patients. Long-term clarithromycin therapy seems to be beneficial in prevention of recurrent cardiovascular events in non-periodontitis but not in periodontitis patients.

The efficacy and safety of probiotic Lactobacillus rhamnosus GG on prolonged, noninfectious diarrhea in HIV Patients on antiretroviral therapy: a randomized, placebo-controlled, crossover study.

PURPOSE: The aim of this placebo-controlled, crossover study was to evaluate the efficacy and safety of probiotic Lactobacillus rhamnosus GG (LGG) in ameliorating gastrointestinal symptoms in HIV-infected patients on antiretroviral therapy. METHOD: Infectious causes for diarrhea (bacteria, ova, parasites, and viruses including cryptosporidium, microsporidia, and cyclospora) were excluded with fecal samples before the study. HIV-infected patients with diarrhea for more than 1 month received in randomized order probiotic LGG preparation (containing viable LGG 1-5 x 1010 cfu/dose) and placebo twice a day for 2 weeks. Gastrointestinal symptoms were assessed daily and included the daily number of bowel movements, classification of stool consistency (watery, semi-watery, loose, firm, or foaming), and Visual Analog Scale (VAS) of gastrointestinal symptoms (flatulence, stomach pain, bloating disorders, general well-being). RESULTS: Seventeen HIV-infected patients completed the study. There were no significant differences between the treatment groups in the frequency or the consistency of diarrhea. In the VAS assessments of gastrointestinal symptoms, no difference between LGG and placebo could be detected. No adverse events were reported. The number of HIV RNA copies in the blood and CD4 cell counts remained stable during the study. CONCLUSION: Probiotic LGG preparation was well-tolerated in HIV infected patients. No significant differences in noninfectious diarrhea or gastrointestinal symptoms compared to placebo could be observed in this crossover study.