Michael W. McKendrick

Psychometric scores and persistence of irritable bowel after infectious diarrhoea.

BACKGROUND Although previous studies have shown that psychological disturbances are frequently associated with the irritable bowel syndrome (IBS), the relation was not necessarily cause and effect. The development of chronic bowel symptoms resembling IBS after an episode of acute gastroenteritis has allowed us to examine prospectively the role of psychological factors. METHODS 75 patients with acute gastroenteritis completed a series of psychometric tests soon after admission to hospital. Of these, 22 had persistent symptoms compatible with IBS after the acute illness, and in 20 of these the symptoms were still present at six months. FINDINGS At the time of their initial illness, patients who subsequently developed IBS symptoms had higher scores for anxiety, depression, somatisation, and neurotic trait than those who returned to normal bowel function. The psychometric scores had not changed when remeasured three months after the acute illness. Lactose malabsorption was not an important factor. INTERPRETATION These results support the hypothesis that psychological factors are important in IBS.

Increased rectal mucosal expression of interleukin 1β in recently acquired post-infectious irritable bowel syndrome

Background and aims: Chronic bowel disturbances resembling irritable bowel syndrome (IBS) develop in approximately 25% of patients after an episode of infectious diarrhoea. Although we have previously shown that psychosocial factors operating at the time of, or prior to, the acute illness appear to predict the development of post-infectious IBS (PI-IBS), our finding of an increased inflammatory cell number in the rectum persisting for at least three months after the acute infection suggested that there is also an organic component involved in the development of PI-IBS. To evaluate this further, we measured expressions of interleukin 1β (IL-1β) and its receptor antagonist (IL-1ra) in these patients to provide additional evidence that the pathogenesis of PI-IBS is underpinned by an inflammatory process. Methods: Sequential rectal biopsy samples were prospectively obtained during and three months after acute gastroenteritis, from eight patients who developed post-infectious IBS (INF-IBS) and seven patients who returned to normal bowel habits after acute gastroenteritis (infection controls, INF-CON). Eighteen healthy volunteers who had not suffered from gastroenteritis in the preceding two years served as normal controls (NOR-CON). IL-1β and IL-1ra gene expressions were assayed by reverse transcriptase-polymerase chain reaction, and their levels of expression were quantitated by optical densitometry after electrophoresis on agarose gel. Results: INF-IBS patients exhibited significantly greater expression of IL-1β mRNA in rectal biopsies than INF-CON patients both during and three months after acute gastroenteritis. Moreover, IL-1β mRNA expression had increased in biopsies taken from INF-IBS patients at three months after the acute infection but no consistent change was observed in INF-CON patients. IL-1β mRNA expression of INF-IBS patients at three months post gastroenteritis was significantly greater than NOR-CON whereas that of INF-CON patients was not significantly different from NOR-CON. Despite these differential changes in IL-1β mRNA expression, no significant changes were observed in IL-1ra mRNA expression among the three groups. Conclusions: These findings indicate that those patients who develop IBS post infection exhibit greater IL-1β mRNA expression, both during and after the infection, compared with individuals who do not develop PI-IBS. We conclude that such patients may be susceptible to inflammatory stimuli, and that inflammation may play a role in the pathogenesis of PI-IBS.

Clinical Features of Viral Meningitis in Adults: Significant Differences in Cerebrospinal Fluid Findings among Herpes Simplex Virus, Varicella Zoster Virus, and Enterovirus Infections

BACKGROUND In this retrospective study, our objective was to review the epidemiology of viral meningitis and to compare clinical features associated with enterovirus, herpes simplex virus (HSV), and varicella zoster virus (VZV) infections in immunocompetent adults. METHODS Data on cerebrospinal fluid (CSF) samples submitted to the Trust Virology Laboratory (Sheffield, UK) from April 2004 through April 2007 were reviewed. Notes on immunocompetent adults who were polymerase chain reaction (PCR) positive for enterovirus, HSV type 2, or VZV and who had presented to local clinical departments were scrutinized (4 patients were positive for HSV type 1 and did not meet the inclusion criteria). RESULTS A total of 2045 samples were analyzed for viral pathogens during the 3-year period. Of the 109 PCR-positive samples, 38 (35%) were from immunocompetent adults, of whom 22 were infected with enterovirus, 8 were infected with HSV type 2, and 8 were infected with VZV. The median ages were 32 years (range, 16-39 years), 39 years (range, 22-53 years), and 47.5 years (range, 26-80 years), respectively. Rash occurred after the meningitis symptoms in 5 patients infected with VZV (median time from meningitis symptoms to rash, 6 days). Protein levels were significantly higher in CSF samples from patients infected with HSV type 2 (median, 1205 mg/L) and in samples from those infected with VZV (median, 974 mg/L) than in samples from those infected with enterovirus (median, 640 mg/L; P = .001 and P = .01, respectively). White blood cell counts were significantly higher in CSF samples from patients infected with HSV type 2 (median, 240 x 10(6) cells/L) than in samples from those infected with enterovirus (median, 51 x 10(6) cells/L; P = .01). CONCLUSIONS Enterovirus infection was the most common cause of viral meningitis in immunocompetent adults in this study. White blood cell counts and protein levels were significantly higher in CSF samples from patients infected with HSV type 2 than in samples from patients with enterovirus infection. Zoster rash often occurs after meningitis. PCR testing provides a rapid and specific etiological diagnosis.

Assessment of pain in herpes zoster: lessons learned from antiviral trials

Pain typically accompanies acute herpes zoster and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes zoster, but different methods have been used to analyze pain in recent published trials. These reports are reviewed and their methodological strengths and weaknesses examined. Based on this review, recommendations for the design and analysis of future trials of antiviral agents in herpes zoster are proposed. The principal recommendation is that antiviral efficacy should be evaluated both by distinguishing post-herpetic neuralgia from acute pain and by considering pain as a continuum. The primary endpoint should address both the prevalence and duration of post-herpetic neuralgia and should be examined in those patients who have post-herpetic neuralgia. Adopting the proposed recommendations in design and analysis of future trials should facilitate comparison across trials of the efficacy of antiviral agents in the treatment of herpes zoster.

Propionibacterium acnes Endocarditis in a Native Valve Complicated by Intraventricular Abscess: A Case Report and Review

Propionibacterium acnes is a constituent of the normal skin flora. It has been described as causing infection on prosthetic valves but very rarely on native valves. We describe a case of aggressive P. acnes endocarditis in a healthy 36-y-old man which infected a native aortic valve and was complicated by an aortic root abscess and review the literature.Propionibacterium acnes is a constituent of the normal skin flora. It has been described as causing infection on prosthetic valves but very rarely on native valves. We describe a case of aggressive P. acnes endocarditis in a healthy 36-y-old man which infected a native aortic valve and was complicated by an aortic root abscess and review the literature.

Primary group A streptococcal peritonitis.

Primary peritonitis caused by Group A beta-haemolytic streptococci (GAS) is extremely rare and is usually only seen in the presence of underlying disease. This report describes the case of a previously fit young woman who developed primary GAS peritonitis. She had a laparotomy performed at which large amounts of intra-peritoneal pus was identified but no focus of infection was found. Broad spectrum antibiotics were initially used, these were changed to intravenous benzylpenicillin when GAS was isolated. She made a good recovery and was discharged 2 weeks after admission on oral amoxycillin. The organism was serotyped as T3/M3/R3 (opacity factor negative) and it is interesting that the same serotype was isolated from a throat swab taken from her daughter. We also discuss the possible routes of infection and the epidemiology of invasive GAS disease.

Group G Streptococcal Bacteraemia: An Opportunistic Infection Associated with Immune Senescence

The number of cases of group G streptococcal bacteraemia reported worldwide is increasing. Twenty-six cases of group G streptococcal bacteraemia were identified during a 70-month period at a single university teaching hospital in Sheffield, UK. These cases represented 20% of all bacteraemias due to β-hemolytic Streptococci, a higher proportion than previously reported. The median age of these cases was 72 y and although medical comorbidities were common only cutaneous ulceration was clearly linked to the presenting syndromes. The skin was the source of infection in 16 cases (62%) and the most frequent clinical presentations were cellulitis in 13 cases (50%) and endovascular infection in 5 (19%). Eight (31%) of the cases died during the period of follow-up but only 2 deaths were related to the streptococcal infection. Immunosenescence represents the major risk factor for group G streptococcal infection in this population and comorbidities, including carcinoma, may be markers of the senescent immune system rather than direct contributing factors to group G streptococcal bacteraemia.

Prolonged cryptosporidiosis during primary HIV infection

Primary infection with the human immunodeficiency virus causes profound immunosuppression with a decrease in lymphocyte numbers and function. However, this immunosuppression is transient and most individuals regain normal immune function. Infection with opportunist pathogens during the period of immunosuppression is rare. We report a case of severe prolonged cryptosporidiosis complicating primary HIV infection. This has not previously been described. A review of other cases of opportunist infections in primary HIV infection suggests that various pathogens may take advantage of the transient immunosuppression. This has important implications for the diagnosis and management of acute HIV infection, and for the diagnostic criteria currently used for AIDS.

Functional T-Cell Deficiency in Adolescents Who Experience Serogroup C Meningococcal Disease despite Receiving the Meningococcal Serogroup C Conjugate Vaccine

ABSTRACT Some individuals have experienced meningococcal disease despite receiving the meningococcal serogroup C conjugate (MCC) vaccine in adolescence. We sought to determine whether this is due to subclinical functional B- or T-cell immunodeficiency. Of 53 vaccine failures identified by enhanced surveillance of England and Wales from 1999 to 2004, 15 received MCC vaccine in adolescence, 9 of whom were recruited 2 to 6 years following convalescence from meningococcal disease. Their peripheral blood mononuclear cells (PBMCs) were incubated with polyclonal activators designed to mimic T-cell-independent B-cell stimulation by bacterial polysaccharides and the T-cell stimulation provided by the protein component of the conjugate vaccine. Subsequent proliferation and activation of T and B lymphocytes were measured, along with T-cell help to B cells. Compared to age-, sex-, geographically, and ethnicity-matched controls, CD4 T-cell proliferation rates in response to both anti-CD3 (T-cell receptor [TCR]) stimulation and anti-CD3 in the presence of B cells activated through anti-IgD conjugated to dextran (α-δ-dex) were lower in PBMCs derived from vaccine failures (P = 0.044 and P = 0.029, respectively). There was reduced CD4 cell activation of the patient cells compared to controls following stimulation by CD3 (P = 0.048). B-cell activation during incubation of PBMCs with the T-cell stimuli, anti-CD3 (P = 0.044), or anti-CD3 plus anti-CD28 (P = 0.018) was relatively impaired in patients. Anti-tetanus toxoid IgG concentrations were lower in the vaccine failure group (P = 0.0385). There was a relative defect of T-cell responsiveness to T-cell-dependent antigen stimulation in MCC vaccine failures, which was manifested in reduced T-cell help to B cells.

Evidence of a Functional B-Cell Immunodeficiency in Adults Who Experience Serogroup C Meningococcal Disease

ABSTRACT After adolescence, the incidence of meningococcal disease decreases with age as a result of the cumulative immunizing effect of repeated nasopharyngeal colonization. Nevertheless, some adults succumb to meningococcal disease, so we hypothesized that this is due to a subtle functional immunological defect. Peripheral blood lymphocytes derived from survivors of serogroup C meningococcal disease and from age- and sex-matched controls were incubated with a polyclonal B-cell activator containing anti-immunoglobulin D (α-δ-dex) employed to mimic antigen-specific stimuli encountered during immune responses to bacterial polysaccharides, with and without T-cell activation (using anti-CD3/anti-CD28). Subsequent proliferation and activation of T and B lymphocytes were measured. In patients, T-cell responses to polyclonal stimuli and the delivery of T-cell help to B cells were unimpaired. Levels of B-cell proliferation in response to α-δ-dex stimulation alone were low in all samples but were significantly lower in patients than in controls, and these differences were more pronounced with the addition of T-cell help. The data are consistent with the presence of a subtle immunodeficiency in adults who have exhibited susceptibility to meningococcal disease. This defect is manifested as an impaired B-cell response to T-cell-independent type 2 antigens analogous to bacterial capsular polysaccharide.