Acetazolamide for the prevention of acute mountain sickness--a systematic review and meta-analysis.

BACKGROUND: Acetazolamide has been reported to be effective in the prevention of acute mountain sickness (AMS). Our aim was to conduct a systematic review of randomized, placebo-controlled trials of acetazolamide in the prevention of AMS. METHODS: Studies were identified by searching the MEDLINE, Embase, Cochrane Clinical Trials Register, and ClinicalTrials.gov databases. Primary end point was difference in incidence of AMS between acetazolamide and placebo groups. RESULTS: Acetazolamide prophylaxis was associated with a 48% relative-risk reduction compared to placebo. There was no evidence of an association between efficacy and dose of acetazolamide. Adverse effects were often not systematically reported but appeared to be common but generally mild. One study found that adverse effects of acetazolamide were dose related. CONCLUSIONS: Acetazolamide is effective prophylaxis for the prevention of symptoms of AMS in those going to high altitude. A dose of 250 mg/day has similar efficacy to higher doses and may have a favorable side-effect profile.

Clinical surveillance of thrombotic microangiopathies in Scotland, 2003-2005.

The prevalence, incidence and outcomes of haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP) are not well established in adults or children from prospective studies. We sought to identify both outcomes and current management strategies using prospective, national surveillance of HUS and TTP, from 2003 to 2005 inclusive. We also investigated the links between these disorders and factors implicated in the aetiology of HUS and TTP including infections, chemotherapy, and immunosuppression. Most cases of HUS were caused by verocytotoxin-producing Escherichia coli (VTEC), of which serotype O157 predominated, although other serotypes were identified. The list of predisposing factors for TTP was more varied although use of immunosuppressive agents and severe sepsis, were the most frequent precipitants. The study demonstrates that while differentiating between HUS and TTP is sometimes difficult, in most cases the two syndromes have quite different predisposing factors and clinical parameters, enabling clinical and epidemiological profiling for these disorders.

Potential therapeutic agents for the prevention and treatment of haemolytic uraemic syndrome in shiga toxin producing Escherichia coli infection.

PURPOSE OF REVIEW: Shiga toxin producing Escherichia coli (STEC) cause a wide spectrum of disease ranging from asymptomatic carriage through to haemorrhagic colitis and the haemolytic uraemic syndrome. There are no current therapeutic interventions available in clinical practice that can prevent the development of haemolytic uraemic syndrome. A number of newly developed agents offer the potential for the treatment of STEC-associated disease. RECENT FINDINGS: Three different classes of agent designed to bind and inactivate shiga toxin have now been developed. Synthetic toxin binders, recombinant bacteria and monoclonal antibodies provide potentially potent agents that could prevent the development of haemolytic uraemic syndrome. These agents have been shown in animal models of STEC disease to be effective. A recent clinical trial of one synthetic toxin binder showed no benefit in established haemolytic uraemic syndrome. More potent toxin binders, however, have since been developed and await human clinical trials. It is likely to be important that these agents are administered early in the course of disease in order to have maximum efficacy. Although rapid diagnostic techniques are available for the diagnosis of STEC disease, they still rely on stool culture. SUMMARY: Clinicians need to maintain a high level of suspicion of STEC disease as the diagnosis is often made on epidemiological and clinical grounds. This will allow potential cases to be identified early and treated appropriately.

Blood group and susceptibility to disease caused by Escherichia coli O157.

Patients (n=186) infected during the Escherichia coli O157 outbreak in Scotland in 1996 were assessed for blood group markers (ABO, Lewis, and P) associated with other gastrointestinal infections. Binding of bacteria to epithelial cells was assessed by flow cytometry. Buffy coats from blood donors were examined for inflammatory responses to culture filtrates of the outbreak strain. Individuals of blood group O comprised 63.4% of patients, compared with 53.4% (P <.05) and 53.9% (P <.01) of neighboring populations in Airdrie and Glasgow, respectively; group O also comprised 64.3% of patients with hemolytic uremic syndrome (HUS) and 87.5% of patients who died (P <.05). No or weak agglutination by anti-P antiserum was observed for 40.7% of control persons (n=122), 61.5% of all patients (P =.0027), and 83.3% of patients with HUS (P =.013). The susceptibility of group O to E. coli was not associated with increased binding of bacteria to epithelial cells or with higher production of tumor necrosis factor (TNF)-alpha or interleukin-6. Leukocytes of P-negative blood donors produced higher levels of TNF-alpha than those of P-positive donors.

The central Scotland Escherichia coli O157:H7 outbreak: risk factors for the hemolytic uremic syndrome and death among hospitalized patients.

Little is known about risk factors for complications of Escherichia coli O157:H7 infection in adults. The 1996 outbreak in central Scotland involved the largest number of adult case patients in whom hemolytic uremic syndrome (HUS) developed and, ultimately, the largest number of deaths associated with E. coli O157:H7 infection that has yet been recorded. We investigated risk factors for HUS in a retrospective study of all hospitalized case patients in this outbreak. Of 120 case patients, 34 had HUS develop, 28 of whom were adults. Sixteen adults died. Significant risk factors for HUS were age <15 years or >65 years (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.3-14.4), hypochlorhydria (OR, 6.7; 95% CI, 1.9-24.0), and coincidental antibiotics (OR, 4.7; 95% CI 1.4-16.5). Factors associated with HUS were as follows: white blood cell count >20 x 10(9) cells/L (OR, 8.25; 95% CI, 1.1-60.3), neutrophil count >15 x 10(9) cells/L (OR, 8.5; 95% CI, 1.5-50.1), and serum albumin level <35 g/L (OR, 7.2; 95% CI, 1.2-42.5) < or =3 days after symptom onset. Deaths were confined to case patients >65 years of age. Early identification of risk factors for HUS is vital and could select case patients for trials of preventative and treatment therapies.

The management of VTEC O157 infection.

VTEC O157 infections, although showing a relentless rise in incidence over the last decade, only account for less than 10% of total food poisoning notifications in the UK. Despite this, the propensity for this infection to cause the serious and life-threatening clinical complications of haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP), in a significant proportion (2-15%) of sufferers, highlights the need to focus on it both epidemiologically and clinically. The mortality rate of these complications (3-17% and up to 30% in outbreaks) adds urgency to this consideration. The pathogenesis and epidemiology of the illness caused by VTEC O157 is now well described, allowing the potential for appropriate intervention in outbreak and individual clinical management. The presence or absence of symptoms, e.g. bloody diarrhoea, fever, vomiting, in VTEC O157 infections compared with other causes of gastroenteritis may allow some selection of cases for more intensive management. Age (< 15, > 65 years), clinical hypochlorhydria. and a short incubation period have been associated with complication (HUS/TTP) development. Antibiotic therapy in the pre-infection period may predispose to complication development and there is evidence that it may increase complications if used in the management of acute illness. Laboratory markers such as early neutrophil leukocytosis have been shown both to correlate with VTEC O157 infection and to predict complications in central Scotland and Japan. The serum albumin and the C-reactive protein may act as additional markers for HUS development. Laboratory markers may be differentiated into those predicting HUS/TTP and those useful in monitoring its development. A scheme for clinical management of affected cases is presented to allow the attending clinician to select cases that may benefit from further intervention to prevent or treat complications.

Clinical presentation, complications and treatment of infection with verocytotoxin-producing Escherichia coli. Challenges for the clinician.

Seventeen years after its recognition, outbreaks and sporadic infections attributed to Escherichia coli O157 continue to increase. Acute gastrointestinal, and the systemic complications haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), are frequent and severe. Current challenges that face clinicians are the early recognition of infection, identification of risk factors for poor prognosis, determination of appropriate monitoring for the development of complications, establishment of a therapeutic strategy and, finally, advice for patients about their long-term prognosis. Clinical features which, in combination, have been shown to distinguish E. coli O157 infection from other enteric pathogens are a history of bloody diarrhoea, visibly bloody stools, absence of fever, a leucocyte count greater than 10 x 10(9) l(-1) and abdominal tenderness on physical examination. The most consistent risk factors for the development of HUS/TTP are the extremes of age and a raised leucocyte count. Bloody diarrhoea and 'antimotility' drugs are also likely to be important risk factors. Recent evidence from the central Scotland outbreak suggests that individuals who are taking drugs that reduce gastric acidity or antibiotics at the time of infection with E. coli O157, or who have a short incubation period, may also be at increased risk of progression to HUS/TTP. Clinical management, in particular the role of antibiotics in gastrointestinal infection, remains controversial, and retrospective assessment of the 1996 outbreaks from central Scotland and Japan only adds to this controversy. Therapeutic plasma exchange is a promising treatment for adults who develop HUS/TTP, but its role has yet to be determined definitively, either in a randomized controlled trial or by an international register of cases. Significant chronic sequelae of infection occur, particularly irritable bowel syndrome after uncomplicated gastrointestinal infection, and renal failure after HUS/TTP. Their frequency and severity are likely to become evident over the next decade.

Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak.

BACKGROUND: The largest number of adult cases of haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) during an Escherichia coli O157 outbreak occurred in 1996 in central Scotland. Adults who develop HUS/TTP induced by E. coli O157 tend to be elderly and have a historical mortality rate of almost 90% when treated conservatively. Therefore the decision was made to treat adults who developed HUS/TTP during this outbreak with therapeutic plasma exchange (TPE). We report our outcome with this controversial treatment. METHODS: A case definition for HUS/TTP was developed at the beginning of the outbreak. All cases meeting this definition were considered for TPE. Information on demographics, clinical features, treatment and outcome of patients was obtained by retrospective case note review. FINDINGS: 22 adults developed HUS/TTP. They had a mean age of 71 years. 16 cases received TPE. Six cases had contraindications to TPE or died before the procedure could be done. Ten of the 22 (45%) adults with HUS/TTP died. Five of the 16 (31%) TPE-treated cases died, four of eight aged over 70 years compared with one of eight aged less than 70 years. Premorbid illness, neurological features, treatment with ciprofloxacin or prostacyclin, and the laboratory severity of HUS/TTP were not associated with death; the number of cases, however, was too small to allow statistical conclusion. INTERPRETATION: The mortality rate is high in adults who develop HUS/TTP induced by E. coli O157. TPE appears to be a promising treatment that was well tolerated in our elderly patients. A national register of adult cases of HUS/TTP induced by E. coli O157 should be established.

The role of a medical illustration department during the Lanarkshire E. coli O157 outbreak.

In November and December 1996 an outbreak occurred of Escherichia coli (E. coli) O157 gastro-enteritis, centred on the Lanarkshire town of Wishaw, in central Scotland. The majority of resultant admissions were received by a single local general hospital. Monklands Hospital, in Airdrie, is the site of the Lanarkshire Area Infectious Diseases (ID) Unit and over the period of the outbreak one hundred and thirteen cases were admitted. This placed considerable strain on the resources of the hospital; at one stage the hospital was closed to all but emergency admissions. The hospital Medical Illustration Department was involved in a supporting role to the clinical team dealing with the outbreak as well as assisting the hospital management team with other duties. This paper gives a brief history of the event and describes the range of duties undertaken by the department during the incident. It is hoped that it will raise awareness, within the medical illustration profession, of the role that Medical Illustration Departments can play in major medical incidents.

Escherichia coli O157 and human disease.

In the 15 years since its discovery, Escherichia coli O157 infection has become an important public health problem of the developed world, causing concern not only because of its rise in incidence, but also because of the severity of its complications. Research is still at an evolutionary phase, often providing more questions than answers. The most recent developments in human infection are presented in this review.

A severe outbreak of E. coli O157 in two psychogeriatric wards.

In October 1990 there was a severe outbreak of Escherichia coli O157 in two psychogeriatric wards of a large psychiatric hospital in Lanarkshire. There were 11 cases (eight patients and three staff), of whom four died (all patients). Two cases, one staff and one patient (the likely index case) were identified serologically after the outbreak was over. E. coli O157 was not cultured from any food, water or milk samples, and the evidence suggests that the index case had eaten food brought into the hospital. The results also suggest that the incubation period of the organism may be longer than is currently recognized, particularly for person-to-person spread. A Fatal Accident Inquiry was held into the deaths, and the Sheriff's Determination is discussed together with the implications of the results for infection control procedures.

Viral-associated haemophagocytosis with parvovirus-B19-related pancytopenia.

Viral-associated haemophagocyte syndrome in response to infection with human parvovirus B19 was seen in 2 patients with hereditary spherocytosis. Depressed reticulocyte response during acute parvovirus infection is a known cause of hypoproliferative crises in patients with reduced erythrocyte lifespan; the observation of parvovirus-associated haemophagocytosis could account for the pancytopenia that may accompany human parvovirus B19 infection.

Transient leukaemia cutis in hairy-cell leukaemia.

Leukaemic skin infiltration is uncommon in hairy-cell leukaemia (HCL), a neoplasm characterized by the presence of uniform mononuclear cells with cytoplasmic projections in the blood, bone marrow and spleen. A case is reported in which leukaemia cutis was a transient phenomenon, appearing soon after the onset of a continuous pyrexia associated with marked systemic upset which was subsequently shown to be due to pulmonary tuberculosis.