Assuring the continued safety of lactic acid bacteria used as probiotics

Lactic acid bacteria have long been used to improve the safety of foods through fermentation. Some fermented products were also early used for their perceived health benefits, which lead to the development of probiotics as we now know them. Probiotics mainly belong to the genera Lactobacillus and Bifidobacterium. Most members of these genera are not considered pathogens or even opportunistic pathogens. Nevertheless, rare cases of Lactobacillus and Bifidobacterium infection have been reported, possibly even associated with the consumption of probiotic products. Such cases are extremely rare and the subjects always had severe underlying conditions most often affecting the immune system. There does not seem to be any risk for the general population. Safety assessments can be performed and many possible tests exist. It is, however, not certain these tests will prevent rare case of Lactobacillus infection in certain high-risk patients. The benefits of probiotic use should be weighed against the possible small risk. Such an evaluation will, in most cases, be favourable and should therefore not discourage consumption of probiotics. Presented at the Second Probiotic Conference, Košice, 15–19 September 2004, Slovakia.     

Inflammatory bowel disease in the West Indies.

Inflammatory bowel disease is generally assumed to be rare among negroes and Indians. Over 10 years 34 cases of ulcerative colitis and 14 cases of Crohn''s disease were seen in one medical and one surgical unit in Port-of-Spain, Trinidad. Twenty-six patients were Negroes, 18 were Indians, three were of mixed race, and one was Caucasian. In many of these patients the disease was extensive and several of those with Crohn''s disease suffered severe complications. The assumption that inflammatory bowel disease is rare among West Indians of African and Indian origin therefore seems to be wrong.     

Current treatment of hepatitis C-associated rheumatic diseases

The hepatitis C virus (HCV) is both hepatotropic and lymphotropic, responsible for a great number of hepatic and extrahepatic immune-system disorders that comprise the so-called HCV syndrome. HCV-associated rheumatic diseases are characterized by frequent clinico-serological overlap; therefore, correct classification of individual patients is necessary before therapeutic decisions are made. This is particularly difficult to do, however, because of the coexistence of viral infection and complex autoimmune alterations. In this context, mixed cryoglobulinemia syndrome (MCs) represents the prototype of virus-related autoimmune-lymphoproliferative diseases. MCs can be treated at different levels by means of etiological treatment with antivirals (peg-interferon-alpha plus ribavirin) aimed at HCV eradication and/or pathogenetic/symptomatic treatments directed to both immune-system alterations and the vasculitic process (rituximab, cyclophosphamide, steroids, plasmapheresis, and so on). In clinical practice, the therapeutic strategy should be modulated according to severity/activity of the MCs and possibly tailored to each individual patient''s conditions. Cryoglobulinemic skin ulcers may represent a therapeutic challenge, which should be managed by means of both local and systemic treatments. HCV-associated arthritis should be differentiated from the simple comorbidity of HCV infection and classical rheumatoid arthritis. It may be treated with low doses of steroids and/or hydroxychloroquine; the use of biologics (rituximab) may be considered in more severe cases. Primary Sjögren''s syndrome is rarely associated with HCV infection, while sicca syndrome and myalgia are frequently detectable in hepatitis C patients, with or without cryoglobulinemic vasculitis. Other autoimmune rheumatic disorders (poly/dermatomyositis, polyarteritis nodosa, osteosclerosis, fibromyalgia, and so on) have been reported as potentially associated with HCV infection in patient populations from different countries, suggesting the role of genetic and/or environmental co-factors. The therapeutic approach to these disorders should be decided according to each individual patient''s evaluation, including hepatic, virological, and immunological findings.     

Intravenous gammaglobulin treatment in patients with hypogammaglobulinaemia.

Intravenous gammaglobulin was compared with the standard British intramuscular preparation in patients with hypogammaglobulinaemia and chronic bronchitis. Five patients were given six months'' treatment with the weekly intramuscular preparation and six months'' treatment with intravenous gammaglobulin given once every 18 days. During the trial they recorded symptoms of infection, absence from work, and sputum volume; lung function tests were performed during the intravenous treatment. The half life of the intravenous IgG and changes in serum IgG and C1q concentrations were also measured in seven other patients who received intravenous gammaglobulin every two weeks for 12 weeks. IgG concentrations, sputum volume, and infection scores were significantly better during intravenous treatment and there were no adverse effects from the intravenous gammaglobulin. These five patients were significantly more healthy when they received an intravenous gammaglobulin preparation, probably because the intravenous preparation increased serum IgG concentrations. Although longer studies are needed, intravenous gammaglobulin should be considered for patients with severe chest disease and those who cannot tolerate intramuscular injections.     

Severe invasive streptococcal infection by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Streptococcus pyogenes, a group A Streptococcus (GAS), has been recognized as the causative pathogen in patients with severe invasive streptococcal infection with or without necrotizing fasciitis. In recent epidemiological studies, Streptococcus dysgalactiae subsp. equisimilis (SDSE) has been isolated from severe invasive streptococcal infection. Complete genome sequence showed that SDSE is the closest bacterial species to GAS, with approximately 70% of genome coverage. SDSE, however, lacks several key virulence factors present in GAS, such as SPE‐B, the hyaluronan synthesis operon and active superantigen against human immune cells. A key event in the ability of GAS to cause severe invasive streptococcal infection was shown to be the acquisition of novel genetic traits such as phages. Strikingly, however, during severe invasive infection, GAS destroys its own covRS two‐component system, which negatively regulates many virulence factor genes, resulting in a hyper‐virulent phenotype. In contrast, this phenomenon has not been observed in SDSE. The present review describes the epidemiology of severe invasive streptococcal infection and the detailed pathogenic mechanisms of GAS and SDSE, emphasizing findings from their genome sequences and analyses of gene expression.     

Septicemia due to Yersinia enterocolitica

Despite the increasing number of reports of Yersinia enterocolitica infection in humans, septicemia with this organism has remained a rare complication. A 73-year-old woman presented with fever, jaundice, hepatomegaly and cellulitis. Microorganisms isolated from both skin lesion and blood were biochemically and serologically identified as Yersinia enterocolitica, biotype 4, serotype 3 and lysotype 9b. High agglutinating titres against this organism were demonstrated in the patient''s serum. Complete recovery followed a course of gentamicin sulfate. A household pet was considered, but not proved, to be the source of this infection.     

Enhanced allergic tissue injury in Goodpasture's syndrome by intercurrent bacterial infection.

Studies of 16 relapses in seven patients receiving treatment for Goodpasture''s syndrome showed that intercurrent bacterial infection seemed to be the precipitating event in 13 cases, whereas a rising antibody titre to glomerular basement membrane was responsible in only one. This association between infection and relapse in Goodpasture''s syndrome has several implications for the pathogenesis of antibody-mediated tissue damage, and, clearly, more experiments are needed. Whatever the explanation, however, prevention and early diagnosis and treatment of infection in anti-GBM disease are important.     

Therapy and prevention of gastric ulcer.

After establishing the benign nature of a gastric ulcer, the treatment is primarily medical. This medical therapy is aimed to alleviate symptoms, to heal the ulcer and to prevent relapses. Based on the history of non-steroidal anti-inflammatory drugs (NSAIDs) and the Helicobacter pylori-status, gastric ulcer patients can be divided into four categories (1) H. pylori positive plus NSAID-use, (2) H. pylori positive without NSAID use, (3) NSAID use with negative H. pylori-status, (4) Negative H. pylori-status and no NSAID use. Patients taking NSAIDs should stop this therapy if possible. Patients with gastric H. pylori infection should be treated by a regimen of a proton pump inhibitor with at least two appropriate antibiotics. This treatment will result in early alleviation of symptoms, rapid healing of the ulcer and prophylaxis of ulcer relapse. In patients with gastric ulcer who cannot stop NSAIDs, maintenance therapy with prostaglandins or potent antisecretory drugs should be considered. The few patients with gastric ulcer who do not take NSAIDs and do not have gastric H. pylori infection should be treated by antisecretory drugs, and they should be carefully followed endoscopically to exclude malignant (carcinoma, lymphoma) or non-peptic (Crohn''s disease) disease. All patients with gastric ulcer should be re-endoscoped to verify complete ulcer healing. Surgery may be considered in gastric ulcer patients with complications, in those with severe dysplasia of the gastric mucosa, and in those who are not able or willing to take the medication.     

Haemoglobin Bart's hydrops syndrome in Greece.

A case of haemoglobin Bart''s hydrops syndrome was characterised in a Greek family with a history of three other fetuses with hydrops. Family studies showed that both the mother and father carried alpha-thalassaemia genes, and globin-chain synthesis analysis of the present fetus showed a total absence of alpha-chain production. The haemoglobin composition of the fetus was similar to that seen in cases in south-east Asia, and analysis of DNA from the Greek case confirmed the total deletion of the alpha-chain genes. The extent of the deletion, however, differed from that seen in south-east Asian cases and included the loss of one of the embryonic zeta-chain genes. Thus the severe form of alpha-thalassaemia occurs in Greece but has arisen independently from the similar condition in south-east Asia. The condition must be considered in any woman of this racial background who gives a history of unexplained stillbirths.     

Investigation of the role of endosomal Toll-like receptors in murine collagen-induced arthritis reveals a potential role for TLR7 in disease maintenance

The hepatitis C virus (HCV) is both hepatotropic and lymphotropic, responsible for a great number of hepatic and extrahepatic immune-system disorders that comprise the so-called HCV syndrome. HCV-associated rheumatic diseases are characterized by frequent clinico-serological overlap; therefore, correct classification of individual patients is necessary before therapeutic decisions are made. This is particularly difficult to do, however, because of the coexistence of viral infection and complex autoimmune alterations. In this context, mixed cryoglobulinemia syndrome (MCs) represents the prototype of virus-related autoimmune-lymphoproliferative diseases. MCs can be treated at different levels by means of etiological treatment with antivirals (peg-interferon-alpha plus ribavirin) aimed at HCV eradication and/or pathogenetic/symptomatic treatments directed to both immune-system alterations and the vasculitic process (rituximab, cyclophosphamide, steroids, plasmapheresis, and so on). In clinical practice, the therapeutic strategy should be modulated according to severity/activity of the MCs and possibly tailored to each individual patient's conditions. Cryoglobulinemic skin ulcers may represent a therapeutic challenge, which should be managed by means of both local and systemic treatments. HCV-associated arthritis should be differentiated from the simple comorbidity of HCV infection and classical rheumatoid arthritis. It may be treated with low doses of steroids and/or hydroxychloroquine; the use of biologics (rituximab) may be considered in more severe cases. Primary Sj?gren's syndrome is rarely associated with HCV infection, while sicca syndrome and myalgia are frequently detectable in hepatitis C patients, with or without cryoglobulinemic vasculitis. Other autoimmune rheumatic disorders (poly/dermatomyositis, polyarteritis nodosa, osteosclerosis, fibromyalgia, and so on) have been reported as potentially associated with HCV infection in patient populations from different countries, suggesting the role of genetic and/or environmental co-factors. The therapeutic approach to these disorders should be decided according to each individual patient's evaluation, including hepatic, virological, and immunological findings.     

Malaria in Birmingham and a London teaching hospital.

During the past five years the incidence of imported malaria increased among patients seen in East Birmingham Hospital and in St Thomas''s Hospital, London. Plasmodium vivax was the predominant species in Birmingham, and was almost always acquired by Asian immigrants visiting the Indian subcontinent. In St Thomas''s P falciparum was most commonly imported, usually by African immigrants visiting Nigeria and Ghana. Two patients (one Irish, one Japanese) died of falciparum malaria after visiting tropical Africa. In both hospitals the immigrant patients had seldom taken prophylactic drugs, and the few who had, ceased to do so on arrival in the UK and sometimes before leaving the malarious country. Apparently immigrants who visit their homeland do not consult their general practitioners before travelling, are given inappropriate advice, or do not take appropriate advice when given. Since the incidence of imported falciparum malaria in the UK is rising, the following points should be considered: the infection may be lethal, particularly in patients lacking immunity; it can mimic other diseases, which may lead to delayed diagnosis; severe disease may be associated with few parasites on a blood film, and even if the result is negative further tests should be performed; clinicians and hospital pharmacists should be aware of the need to keep permanent stocks of parenteral chloroquine and quinine preparations.     

Neuronal Antibody Biomarkers for Sydenham’s Chorea Identify a New Group of Children with Chronic Recurrent Episodic Acute Exacerbations of Tic and Obsessive Compulsive Symptoms Following a Streptococcal Infection

Several autoantibodies (anti-dopamine 1 (D1R) and 2 (D2R) receptors, anti-tubulin, anti-lysoganglioside-GM1) and antibody-mediated activation of calcium calmodulin dependent protein kinase II (CaMKII) signaling activity are elevated in children with Sydenham’s chorea (SC). Recognizing proposed clinical and autoimmune similarities between SC and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection), we sought to identify serial biomarker changes in a slightly different population. Antineuronal antibodies were measured in eight children (mean 11.3 years) with chronic, dramatic, recurrent tics and obsessive-compulsive disorder (OCD) associated with a group A β-hemolytic streptococcal (GABHS) respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac), one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects), and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years) obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control’s 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group’s 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1) a cohort, represented by this study, which lacks choreiform movements and elevated antibodies against D2R; 2) the originally reported group with choreiform movements and elevated anti-D2R antibodies, similar to SC. Increased antibody mediated CaMKII activation was found in both groups and requires further study as a potential biomarker.     

Are general practitioners ready to prevent the spread of HIV?

General practitioners are excellently placed to assess a person''s risk of being infected with the human immunodeficiency virus (HIV) and to give advice on reducing that risk. Their attitudes to the acquired immune deficiency syndrome (AIDS) and infection with HIV are, however, unknown. A questionnaire survey of 196 general practitioners in East Berkshire Health District was used to assess general practitioners'' readiness to undertake opportunistic health education to prevent the spread of infection with HIV. Altogether 132 replied. Sixty four of them expressed little interest in health education about HIV, and one in six would not dissent from the notion that AIDS could be controlled only by criminalising homosexuality. Only 75 of them had initiated discussions about HIV with patients. Moreover, many underestimated the risks from heterosexual sex while exaggerating the risks from non-sexual contact.Advice from general practitioners if given extensively might reduce the spread of infection with HIV. How best this may be achieved needs to be considered urgently.     

Genital herpes simplex.

Genital herpes is a sexually transmitted disease caused by the herpes simplex virus. Following the initial infection the virus becomes latent in the sacral ganglia. Approximately 80% of patients are then subject to milder but unpredictable recurrences and may shed the virus even when they are asymptomatic. The disorder causes concern because genital herpes in the mother can result in rare but catastrophic neonatal infection and because of a possible association between genital herpes and cancer of the cervix. No effective treatment is as yet available. Weekly monitoring for virus by cervical culture from 32 weeks'' gestation is recommended for women with a history of genital herpes and for those whose sexual partner has such a history.     

The acutely painful scrotum in children: review of 113 consecutive cases

A young boy who presents with an acutely painful scrotum can be a diagnostic challenge to his physician. It is important to differentiate the various causes of this symptom and to institute prompt management. Failure to do so could jeopardize the patient''s future fertility. In a review of 113 consecutive cases of a painful scrotum at a children''s hospital, torsion of the testicle was found in 51 patients (45%). Torsion of the appendix testis was found in 40 patients (35%) and acute epididymitis, once considered rare in children, was diagnosed in 17 (15%). The importance of prompt diagnosis of torsion is emphasized. The clinical diagnosis of the acutely painful scrotum is notoriously difficult, and in this series of cases surgical exploration was required in 92%. Only 2 of the 17 cases of epididymitis were associated with a bacterial urinary tract infection.     

Motor neurone disease: towards better care.

Even in the most severe forms of motor neurone disease--progressive bulbar palsy and amyotrophic lateral sclerosis--the symptoms and disabilities from progressive paralysis may be relieved in many patients by various symptomatic treatments. Quality of life may be improved even in the terminal stage, when narcotic administration should be considered. The physician''s proper role is to offer and carefully supervise these treatments, not withhold them. Home care is recommended even for the most severely paralysed, though hospice care may be a good alternative. The underlying principle--to alleviate symptoms--applies to the management of all progressive incurable diseases.     

Mechanisms of innate resistance to Toxoplasma gondii infection.

The interaction of protozoan parasites with innate host defences is critical in determining the character of the subsequent infection. The initial steps in the encounter of Toxoplasma gondii with the vertebrate immune system provide a striking example of this important aspect of the host-parasite relationship. In immuno-competent individuals this intracellular protozoan produces an asymptomatic chronic infection as part of its strategy for transmission. Nevertheless, T. gondii is inherently a highly virulent pathogen. The rapid induction by the parasite of a potent cell-mediated immune response that both limits its growth and drives conversion to a dormant cyst stage explains this apparent paradox. Studies with gene-deficient mice have demonstrated the interleukin-12 (IL-12)-dependent production of interferon gamma (IFN-gamma) to be of paramount importance in controlling early parasite growth. However, this seems to be independent of nitric oxide production as mice deficient in inducible nitric oxide synthase (iNOS) and tumour necrosis factor receptor were able to control early growth of T. gondii, although, they later succumbed to infection. Nitric oxide does, however, seem to be important in controlling persistent infection; treating chronic infection with iNOS metabolic inhibitors results in disease reactivation. Preliminary evidence implicates neutrophils in effector pathways against this parasite distinct from that described for macrophages. Once initiated, IL-12-dependent IFN-gamma production in synergy with other proinflammatory cytokines can positively feed back on itself to induce ''cytokine shock''. Regulatory cytokines, particularly IL-10, are essential to down-regulate inflammation and limit host pathology.     

Male Relationships and Infant Deaths in Red Howler Monkeys (Alouatta seniculus)

For decades howler monkeys were considered to be among the most peaceful animals. Recent investigators, however, have noted that, although male aggression is rare, it may be extremely severe; the criteria used to quantify howler relationships should therefore be different from those used for other primates. This paper describes the pattern of male relationships in the red howler monkey Alouatta seniculus, and examines its effect on reproductive success within the troop and the ability of troop males to resist intrusion by competing males. 4 of the 8 infants born during the study period were killed or disappeared when change occurred in relative status between two adult males.     

Nubidites omarai n. g. n. sp., ein neuer ammonit aus dem nubischen sandstein Ägyptens

A loose ammonite from the Nubian Sandstone near Abu Darag, Eastern Desert, Egypt, is described asNubidites omarai n. g. n. sp. Since ammonites from the Nubian Sandstone (Carboniferous to Cretaceous) are extremely rare, the new form is of great importance. The specimen has been found in a Carboniferous section of the Sandstone, but since Jurassic and Cretaceous outcrops occur in the neighbourhood, also these ages have to be considered. An Upper Cretaceous age of the new genus, however, is suggested.