Delivery of the posterior arm reduces shoulder dimensions in shoulder dystocia.

OBJECTIVE: To evaluate a possible reduction in shoulder diameter and circumference by extending the posterior arm during delivery, for an easier birth in cases of shoulder dystocia. METHODS: In this study of 33 neonates the bisacromial diameter and axilloacromial circumference were measured within 72 h of birth, first with the neonate's arms by its chest and then with 1 arm extended above its head. Reductions in diameter and circumference were evaluated. RESULTS: The mean +/- SD differences in bisacromial diameter and axilloacromial circumference were 1.9 +/- 0.69 cm and 2.52 +/- 1.18 cm, respectively. A greater reduction was observed in neonates with a greater shoulder diameter. CONCLUSION: In cases of shoulder dystocia, delivery of the posterior arm should significantly reduce shoulder dimensions, especially in larger fetuses, and prevent a need for excessive traction.

Corticosteroids for Guillain-Barré syndrome.

BACKGROUND: The cause of Guillain-Barré syndrome is inflammation of the peripheral nerves, which corticosteroids would be expected to benefit. OBJECTIVES: To examine the ability of corticosteroids to hasten recovery and reduce the long-term morbidity from Guillain-Barré syndrome. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register (May 2005), MEDLINE (January 2000 to May 2005) and EMBASE (January 1980 to May 2005) and contacted trial authors and other experts. SELECTION CRITERIA: We included quasi-randomised or randomised controlled trials of people of all ages and all degrees of severity of Guillain-Barré syndrome who were treated with any form of corticosteroid or adrenocorticotrophic hormone. Our primary outcome measure was change in disability grade on a commonly used, validated seven-point scale at four weeks after randomisation. Secondary outcome measures were: time from randomisation until recovery of unaided walking, time from randomisation until discontinuation of ventilation (for those ventilated), mortality, proportion of participants dead or disabled (unable to walk without aid) after 12 months, improvement in disability grade after six and 12 months, relapse, and adverse events related to corticosteroid treatment. DATA COLLECTION AND ANALYSIS: Two authors extracted the data. MAIN RESULTS: Six trials with 587 participants provided data for our primary outcome measure . The overall evidence showed no significant difference between the corticosteroid and non-corticosteroid treated patients in disability grade. In four trials of oral corticosteroids with 120 participants in total, there was significantly less improvement after four weeks with corticosteroids than without corticosteroids (weighted mean difference of 0.82 of a disability grade less improvement, 95% confidence intervals 0.17 to 1.47). In two trials with a combined total of 467 participants, there was a trend towards more benefit from intravenous corticosteroids which was not quite significant, weighted mean difference 0.17 (95% confidence intervals -0.06 to 0.39) of a disability grade more improvement after four weeks than with placebo. There were no important significant differences between the corticosteroid-treated participants and the control group in any of the secondary outcome measures. Diabetes was significantly more common and hypertension much less common in the corticosteroid-treated participants. AUTHORS' CONCLUSIONS: Limited evidence shows that oral corticosteroids significantly slow recovery from Guillain-Barré syndrome. Substantial evidence shows that intravenous methylprednisolone alone does not produce significant benefit or harm. In combination with intravenous immunoglobulin, intravenous methylprednisolone may hasten recovery but does not significantly affect the long-term outcome. More research is needed and more effective treatments for Guillain-Barré syndrome should be sought.

Reliability of the Hammersmith functional motor scale for spinal muscular atrophy in a multicentric study.

The aim of this study was to validate the Hammersmith functional motor scale for children with spinal muscular atrophy in a large cohort of 90 non-ambulant children with spinal muscular atrophy type 2 or 3. All had a baseline assessment (T0) and were reassessed either at 3 months (T1) (n = 66) or at 6 months (T2) (n = 24). Inter-observer reliability, tested on 13 children among 3 examiners, was > 95%. Of the 66 children examined after 3 months 4 had adverse effects in between assessments and were excluded from the analysis. Forty-two (68%) of the remaining 62 reassessed had no variation in scores between T0 and T1 and 13 (21%) were within +/- 1 point. 9 (37.5%) of the 24 children reassessed after 6 months had no variation in scores between T0 and T2 and another 9 (37.5%) had variations within +/- 1 point. Our study confirms previous observations of the reliability of the scale and helps to establish a baseline for assessing changes of functional ability over 3 and 6 month intervals. This information can be valuable in view of therapeutic trials.

Intravenous immunoglobulin for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome is an acute, paralysing, inflammatory peripheral nerve disease. Intravenous immunoglobulin is beneficial in other autoimmune diseases. OBJECTIVES: We aimed to determine the efficacy of intravenous immunoglobulin for treating Guillain-Barré syndrome. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (March 2005), MEDLINE (January 1966 to March 2005) and EMBASE (January 1980 to March 2005) using the terms 'Guillain-Barré syndrome' and 'acute polyradiculoneuritis'. SELECTION CRITERIA: We included all randomised and quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, extracted data and assessed quality. MAIN RESULTS: Another Cochrane systematic review has shown that plasma exchange significantly hastens recovery. We found six randomised trials comparing intravenous immunoglobulin with plasma exchange. We undertook a meta-analysis of five trials involving 536, mostly adult participants who were unable to walk unaided and had been ill for less than two weeks. Our primary outcome measure was the change in a seven-grade disability scale four weeks after randomisation. The weighted mean difference of this measure was not statistically significant, being only -0.02 (95% confidence interval -0.25 to 0.20) of a disability grade more improvement in the intravenous immunoglobulin than the plasma exchange group. There were no statistically significant differences in other measures. One trial involving 249 participants compared plasma exchange followed by intravenous immunoglobulin with plasma exchange alone. Another involving 37 participants compared immunoabsorption followed by intravenous immunoglobulin with immunoabsorption alone. Neither revealed significant extra benefit from intravenous immunoglobulin. One study with 39 participants showed a trend towards more improvement with high-dose compared with low-dose intravenous immunoglobulin. Another trial with 51 children found no significant difference in outcome when the standard dose was given over two days rather than five days. Three studies including a total of 75 participants suggested that in children intravenous immunoglobulin significantly hastens recovery compared with supportive care. AUTHORS' CONCLUSIONS: In adults, there are no adequate comparisons with placebo. Randomised trials in severe disease show that intravenous immunoglobulin started within two weeks from onset hastens recovery as much as plasma exchange, which is known to be more effective than supportive care. Treatment with intravenous immunoglobulin is significantly more likely to be completed than plasma exchange. Giving intravenous immunoglobulin after plasma exchange did not confer significant extra benefit. In children, intravenous immunoglobulin probably hastens recovery compared with supportive care alone. More research is needed in mild disease and in treatment starting more than two weeks after onset of the condition. Dose-ranging studies are also needed.

Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections.

BACKGROUND: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited. OBJECTIVE: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results. METHODS: CSF from patients with was tested for human herpesviruses types 1-6, JC virus, enteroviruses, and Toxoplasma gondii. The likelihood of central nervous system (CNS) infection was classified as likely, possible, or unlikely. PCR findings in these categories were compared using single variable and logistic regression analysis. RESULTS: Of 787 samples tested, 97 (12%) were PCR positive for one or more viruses. Of episodes likely to be CNS viral infections, 30% were PCR positive compared to 5% categorised as unlikely. The most frequent positive findings were Epstein Barr virus (EBV), enteroviruses, and herpes simplex virus (HSV). Enteroviruses and HSV were found predominantly in the likely CNS viral infection group, whereas EBV was found mainly in the unlikely group. Positive PCR results were more likely when there were 3-14 days between symptom onset and lumbar puncture, and when CSF white cell count was abnormal, although a normal CSF did not exclude a viral infection. CONCLUSIONS: The diagnostic yield of PCR can be maximised by using sensitive assays to detect a range of pathogens in appropriately timed CSF samples. PCR results, in particular EBV, should be interpreted cautiously when symptoms cannot readily be attributed to the virus detected.

Cytotoxic drugs and interferons for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is a disease causing progressive or relapsing and remitting weakness and numbness. It is probably due to an autoimmune inflammatory process. Immunosuppressive or immunomodulatory drugs would be expected to be beneficial. OBJECTIVES: We aimed to review systematically the evidence from randomised trials concerning cytotoxic drugs and interferons for chronic inflammatory demyelinating polyradiculoneuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (searched May 2004), MEDLINE (searched January 1977 to May 2004), EMBASE (January 1980 to May 2004), CINAHL (searched January 1982 to December 2001) and LILACS (searched January 1982 to December 2001). We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials. SELECTION CRITERIA: We sought randomised and quasi-randomised trials of all immunosuppressive agents such as azathioprine, cyclophosphamide, methotrexate, cyclosporin A, mycophenolate mofetil, and rituximab and all immunomodulatory agents such as alpha interferon and beta interferon in participants fulfilling standard diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. DATA COLLECTION AND ANALYSIS: Two of us independently selected the trials which met our criteria, judged their methodological quality and extracted the data onto specially designed forms. We wanted to measure the change in disability after one year as our primary outcome measure. MAIN RESULTS: We found one parallel group open trial of azathioprine for nine months involving 27 participants and another of interferon beta involving 10 participants in a double blind crossover trial with each treatment period lasting 12 weeks. Neither trial provided our primary outcome measure and neither showed a significant beneficial effect on any of the outcome measures selected by the authors or ourselves in the protocol for this review. REVIEWERS' CONCLUSIONS: The evidence is inadequate to decide whether azathioprine, interferon beta or any other immunosuppressive drug or interferon is beneficial in chronic inflammatory demyelinating polyradiculoneuropathy.

A controlled investigation of the cause of chronic idiopathic axonal polyneuropathy.

To investigate the aetiology of chronic idiopathic axonal polyneuropathy (CIAP), 50 consecutive patients were compared with 50 control subjects from the same region. There were 22 patients with painful neuropathy and 28 without pain, 26 with sensory neuropathy and 24 with sensory and motor neuropathy. The typical picture was a gradually progressive sensory or sensory and motor neuropathy. It caused mild or sometimes moderate disability, and reduced the quality of life. There was no evidence that alcohol, venous insufficiency, arterial disease or antibodies to peripheral nerve antigens played a significant part. There was a possible history of peripheral neuropathy in the first or second-degree relatives of six patients and no controls (P = 0.01), and claw toes were present in 12 patients and four controls (P = 0.03). Thirty-two per cent of the patients and 14% of the controls had impaired glucose tolerance or fasting hyperglycaemia but, after adjusting for age and sex, the difference was not significant (P = 0.45), even in the painful neuropathy subgroup. The mean (SD) fasting insulin concentrations were significantly (P = 0.01) higher in the patients [75.9 (44.4) mmol/l] than the controls [47.3 (37.9) mmol/l], and the mean was higher still in the painful neuropathy subgroup [92.2 (37.1) mmol/l] (P < 0.0001). However, insulin resistance as assessed using the homeostasis model assessment formula was not significantly greater in the patients, even in those with pain, than the controls. After adjustment for body mass index as well as age and sex, there was no significant difference in the serum cholesterol concentrations, but there were significantly higher triglyceride concentrations in the patients [mean 1.90 (1.41) mmol/l] than the controls [mean 1.25 (0.79] mmol/l) (P = 0.02). In the patients with painful peripheral neuropathy, the mean triglyceride concentration was 2.37 (1.72), which was even more significantly greater compared with the controls (P = 0.003). In conclusion, CIAP is a heterogeneous condition. A logistic regression analysis identified environmental toxin exposure and hypertriglyceridaemia, but not glucose intolerance or alcohol overuse as significant risk factors that deserve further investigation as possible causes of CIAP.

Intravenous immunoglobulin for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome is an acute, paralysing, inflammatory peripheral nerve disease. Intravenous immunoglobulin purified from donated blood is beneficial in other autoimmune diseases. OBJECTIVES: We aimed to determine the efficacy of intravenous immunoglobulin for treating Guillain-Barré syndrome. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (search updated 11 February 2003), MEDLINE and EMBASE (from January 2000 to February 2003) using Guillain-Barré syndrome and acute polyradiculoneuritis as the search terms. We also searched bibliographies of trials and made contact with their authors and other experts. SELECTION CRITERIA: We included all randomised and quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two reviewers examined the titles and abstracts of all the papers retrieved by the search, extracted the data and assessed the quality of the trials independently. MAIN RESULTS: Two trials comparing intravenous immunoglobulin with supportive treatment were inadequate to establish its value. Another Cochrane systematic review has shown that plasma exchange hastens recovery. We found six randomised trials that compared intravenous immunoglobulin with plasma exchange. In a meta-analysis of five trials involving 536, mostly adult, participants who were unable to walk unaided and had been ill for less than two weeks. The primary outcome measure in this review was the change in a seven grade disability scale four weeks after randomisation. The weighted mean difference of this measure was not statistically significant, being only 0.04 (95% CI -0.26 to 0.19) of a disability grade more improvement in the intravenous immunoglobulin group than the plasma exchange group. There were also no statistically significant differences in time to walk unaided, mortality, and proportion of participants unable to walk without aid after a year. One trial involving 249 participants compared plasma exchange followed by intravenous immunoglobulin with plasma exchange alone, and another involving 37 participants compared immunoabsorption followed by intravenous immunoglobulin with immunoabsorption alone. Neither revealed significant extra benefit from intravenous immunoglobulin. One study of only 39 participants showed a trend towards more improvement with high-dose compared with low-dose intravenous immunoglobulin. REVIEWER'S CONCLUSIONS: Although there are no adequate comparisons with placebo, intravenous immunoglobulin hastens recovery from Guillain-Barré syndrome as much as plasma exchange. Giving intravenous immunoglobulin after plasma exchange is not significantly better than plasma exchange alone. Randomised trials are needed to decide the effect of intravenous immunoglobulin in children, in adults with mild disease and in adults who start treatment after more than two weeks.

Neonatal 5HT activity antagonizes the masculinizing effect of testosterone on the luteinizing hormone release response to gonadal steroids and on brain structures in rats.

Hypothalamic 5HT concentrations are transiently lower in male compared to female Wistar rats in the second week post partum (pp) and our previous findings have shown that pharmacologically potentiating 5HT activity over this period feminizes certain aspects of sexually differentiated behaviours in adult males and androgenized females. In order to investigate whether neonatal testosterone and 5HT interact to influence physiological and morphological brain sexual differences, females, androgenized females and males were treated with the 5HT2 agonist (-) [2,5 dimethoxy-4-iodophenyl]-2-amino propane HCl [(-) DOI], over days 8-16 pp. In androgenized females (250 microg testosterone proprionate, day 2 pp) (-) DOI prevented the delay in vaginal opening, but did not prevent the androgen-induced constant oestrus in females treated with 100 microg TP, day 2 pp. (-) DOI overcame the neonatal androgen effect in suppressing the positive feedback of ovarian steroids in a few males and androgenized females. (-) DOI had a feminizing effect on the volume of the anteroventral periventricular nucleus (normally smaller in males), by significantly increasing its volume in male and androgenized females. It also had a significant antagonistic effect on the testosterone-induced increase in the volume of the sexually dimorphic nucleus of the preoptic area in males and androgenized females. These findings support the view that raised 5HT activity in the second week of life antagonizes the masculinizing effect of neonatal testosterone.

A randomized controlled trial of recombinant interferon-beta 1a in Guillain-Barré syndrome.

The authors recruited 19 nonambulant patients with Guillain-Barré syndrome into a pilot, double-blind, randomized, placebo-controlled safety trial of interferon beta 1a (IFN[beta]-1a) (Rebif). Participants received IFN[beta]-1a or placebo subcutaneously three times weekly, 22 microg for the first week and then 44 microg for up to 24 weeks, in addition to IV immunoglobulin (IVIg). IFN[beta] did not have any unexpected interaction with IVIg and there was no significant difference in rate of improvement.

Cytotoxic drugs and interferons for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is a disease causing progressive or relapsing and remitting weakness and numbness. It is probably due to an autoimmune inflammatory process. Immunosuppressive or immunomodulatory drugs would be expected to be beneficial. OBJECTIVES: We aimed to review systematically the evidence from randomised trials concerning cytotoxic drugs and interferons for chronic inflammatory demyelinating polyradiculoneuropathy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (searched December 2001), MEDLINE (searched January 1977 to December 2001), EMBASE (January 1980 to December 2001), CINAHL (searched January 1982 to December 2001) and LILACS (searched January 1982 to December 2001). We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials. SELECTION CRITERIA: We sought randomised and quasi-randomised trials of all immunosuppressive agents such as azathioprine, cyclophosphamide, methotrexate, cyclosporin A, mycophenolate mofetil, and rituximab and all immunomodulatory agents such as alpha interferon and beta interferon in participants fulfilling standard diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. DATA COLLECTION AND ANALYSIS: Two of us independently selected the trials which met our criteria, judged their methodological quality and extracted the data onto specially designed forms. We wanted to measure the change in disability after one year as our primary outcome measure. MAIN RESULTS: We found one parallel group open trial of azathioprine for nine months involving 27 participants and another of interferon beta involving 10 participants in a double blind crossover trial with each treatment period lasting 12 weeks. Neither trial provided our primary outcome measure and neither showed a significant beneficial effect on any of the outcome measures selected by the authors or ourselves in the protocol for this review. REVIEWER'S CONCLUSIONS: The evidence is inadequate to decide whether azathioprine, interferon beta or any other immunosuppressive drug or interferon is beneficial in chronic inflammatory demyelinating polyradiculoneuropathy.

Intravenous immunoglobulin for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome is a potentially serious, acute, paralysing, probably autoimmune disease caused by inflammation of the peripheral nerves. Recovery has been shown to be speeded by plasma exchange which replaces the patient's own plasma with a plasma substitute. Intravenous immunoglobulin purified from donated blood is beneficial in other autoimmune diseases and is easier to administer. OBJECTIVES: To determine the efficacy of intravenous immunoglobulin in comparison with no treatment or other treatments for treating Guillain-Barré syndrome and to determine the most efficacious dose. SEARCH STRATEGY: Search of the Cochrane Neuromuscular Disease Group register using Guillain-Barré syndrome and acute polyradiculoneuritis as the search terms, bibliographies of trials and contact with their authors and other experts. SELECTION CRITERIA: Randomised and quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two reviewers examined the titles and abstracts of all the papers retrieved by the search, extracted the data onto forms designed for this review, and independently assessed the quality of the trials. MAIN RESULTS: The only trial comparing intravenous immunoglobulin with supportive treatment was inadequate to establish its value. Another Cochrane systematic review has shown that plasma exchange (PE) hastens recovery. Plasma exchange has become the gold standard against which other treatments need to be compared. We found three randomised trials that compared intravenous immunoglobulin with PE. We were able to combine the results of the two largest trials in a metaanalysis involving 398 patients. The primary outcome measure in this review was the change in a 7 grade disability scale four weeks after randomisation. The weighted mean difference of this measure was not significant, being only 0.11 (95% CI -0.14 to 0.37) of a disability grade more improvement in the intravenous immunoglobulin group than the PE group. There were also no significant differences in other outcome measures, including time to walk unaided, mortality, and proportion of patients unable to walk without aid after a year but some of these outcome measures were only available for one trial. We also reviewed one trial involving 249 patients which compared PE followed by intravenous immunoglobulin with PE alone and another involving 37 patients which compared immunoabsorption followed by intravenous immunoglobulin with immunoabsorption alone. Neither revealed any significant differences between the regimens with and without intravenous immunoglobulin. We did not discover any dose ranging studies of intravenous immunoglobulin except for one that is ongoing. REVIEWER'S CONCLUSIONS: There are no adequate trials to determine whether intravenous immunoglobulin is more beneficial than placebo. Intravenous immunoglobulin and plasma exchange have a similar ability to speed the recovery from Guillain-Barré syndrome. Giving intravenous immunoglobulin after plasma exchange is not significantly better than plasma exchange alone. Randomised trials are needed to decide whether intravenous immunoglobulin helps in mild Guillain-Barré syndrome or in disease which has lasted more than two weeks. Randomised trials also need to establish the optimal dose.

The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England and the national burden imposed.

Between April 1994 and May 1995 4000 adult patients admitted to selected specialties of a district general hospital were recruited to this study. Hospital-acquired infections presenting during the in-patient stay were identified using previously validated methods of surveillance, and information on daily resource use by both infected and uninfected patients was recorded and estimates of their cost derived. Linear regression modelling techniques were used to estimate how much of the observed variation in resource use and costs could be explained by the presence of an infection. Complete in-patient data sets were obtained for 3980 patients. Of these, 309 patients (7.8%; 95% CI; 7.0, 8.6) presented with one or more hospital-acquired infections during the in-patient period. Infected patients, on average, incurred hospital costs 2.9 (regression model estimate: 2.8; 95% CI; 2.6, 3.0) times higher than uninfected patients, equivalent to an additional pound3154 (regression model estimate pound2917). Both the incidence and the economic impact varied with site of infection and with admission specialty. Estimates of the burden of hospital-acquired infections occurring in adult patients admitted to similar specialties at NHS hospitals in England were derived from the results of this study. An estimated 320 994 (95% CI; 288 071, 353 916) patients per annum acquire one or more infections which present during the in-patient period, and these infections cost the hospital sector an estimated 930.62 million pounds (95% CI; 780.26 pounds; 1080.97 million pounds) per annum. The results presented represent the gross economic benefits that might accrue if these infections are prevented. Further research is required to establish the net benefits of prevention.

Preceding infections, immune factors, and outcome in Guillain-Barré syndrome.

OBJECTIVE: To test the hypothesis that different preceding infections influence the neurophysiologic classification and clinical features of Guillain-Barré syndrome (GBS). METHODS: We tested pretreatment sera, 7 +/- 3 (mean +/- SD) days from onset, from 229 patients with GBS in a multicenter trial of plasma exchange and immunoglobulin, for serological markers of infection, adhesion molecules, and cytokine receptors, and compared these with neurophysiologic and clinical features. RESULTS: Recent infection by Campylobacter jejuni was found in 53 patients (23%), cytomegalovirus in 19 (8%), and Epstein-Barr virus in four (2%). Patients with C. jejuni infection were more likely than others to have neurophysiologic criteria of axonal neuropathy or inexcitable nerves, antiganglioside GM(1) antibodies, pure motor GBS, lower CSF protein, and worse outcome. Patients with cytomegalovirus infection were younger and more likely than others to have raised serum concentrations of molecules important in T lymphocyte activation and migration, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble leukocyte selectin, and soluble interleukin-2 receptor (sIL-2R). Concentrations of sICAM-1 and soluble tumor necrosis factor receptor were higher in patients with inexcitable nerves than those with demyelinating neurophysiology. Logistic regression analysis showed death or inability to walk unaided at 48 weeks were associated with diarrhea, inexcitable nerves, severe arm weakness, age over 50, raised sIL-2R concentration and absence of immunoglobulin (Ig) M antiganglioside GM(1) antibodies. CONCLUSIONS: Subtypes of GBS defined by preceding infections were only approximately associated with different patterns of clinical, neurophysiologic, and immunologic features. A single infectious agent caused more than one type of pathology in GBS, implying interaction with additional host factors. Most patients had no identified infection.

Effect of human immunodeficiency virus-1 protease inhibitors on the clearance of human herpesvirus 8 from blood of human immunodeficiency virus-1-infected patients.

The effect of human immunodeficiency virus-1 protease inhibitors on the frequency of human herpesvirus 8 DNA detection from peripheral blood of human immunodeficiency virus-positive persons was evaluated. Thirty-three human immunodeficiency virus-seropositive male patients were studied longitudinally. DNA from open reading frame 26 of the human herpesvirus 8 genome was amplified by the polymerase chain reaction from the CD45+ fraction of peripheral blood before and after the introduction of protease inhibitor therapy. Human herpesvirus 8 IgG status, CD4+ cell counts, and human immunodeficiency virus-1 plasma viral load were also assessed before and after therapy. When both reverse transcriptase inhibitor and protease inhibitor treatment were introduced at the same time, there was an increase in CD4+ T cell counts (P=0.0041), a decrease in human immunodeficiency virus plasma load (P=0.0584), and a decrease in the detection rate of human herpesvirus 8 DNA (P=0.0077). Introducing protease inhibitor to patients already receiving reverse transcriptase inhibitor treatment was associated with an increase in CD4+ T cell counts (P=0.0003), a decrease in human immunodeficiency virus plasma viral load (P=0.0911), and a decrease in the human herpesvirus 8 detection rate (P=0.0412). No significant changes in the titters of anti-human herpesvirus 8 IgG were observed. Treatment with human immunodeficiency virus-1 protease inhibitors is therefore associated with the clearance of human herpesvirus 8 DNA from peripheral blood of human immunodeficiency virus-infected patients. The concomitant decrease in the human immunodeficiency virus plasma load and increase in the peripheral CD4+ cell count suggest that an amelioration in the immune defect following reduction in the burden of human immunodeficiency virus-1 infection is responsible for the clearance of human herpesvirus 8 by protease inhibitors.

Compliance with advice to boil drinking water during an outbreak of cryptosporidiosis. Outbreak Investigation Team.

All 2000 employees of a hospital in an area of the North Thames region where 300,000 households were advised to boil tap water before consumption during a large outbreak of cryptosporidiosis were surveyed about compliance with and adverse events linked to the boil water notice. Eighty-five per cent (408/479) of respondents who lived in the boil water area said that they used boiled water while the notice was in place, 72% (347) used bottled water, and 12% (59) did not continue to boil water for the whole 16 days. Although 88% believed that they were following the advice, 20% washed food that would be eaten raw in unboiled tap water and 57% used it to clean their teeth. If a boil water notice is applied for more than a few days it may be helpful to issue a detailed follow up letter.

Are routine sensitivity test data suitable for the surveillance of resistance? Resistance rates amongst Escherichia coli from blood and CSF from 1991-1997, as assessed by routine and centralized testing.

Surveillance of antibiotic resistance can be undertaken by compilation of routine data or by central testing of isolates. Routine results can be obtained cheaply and in sufficient quantities for correlation with population and prescribing denominators but there is concern about their quality. As one of a series of ongoing studies to assess this quality, we compared the proportions of resistance amongst Escherichia coli from patients with bacteraemia or meningitis between 1991 and 1997 (i) as recorded in routine data reported to the PHLS and (ii) as found in tests performed at the PHLS Laboratory of Enteric Pathogens (LEP). These two data sets both showed an overall upward trend in the proportion of isolates resistant to ampicillin, trimethoprim, gentamicin and ciprofloxacin. The average annual percentage increase in resistance was estimated in separate logistic regression models, and 95% confidence intervals (CI) were determined. The annual percentage increases in the proportions of isolates reported resistant were similar in the two data sets for trimethoprim, gentamicin and ciprofloxacin but differed for ampicillin. The upward trends were statistically significant except for gentamicin resistance in the LEP data set, where the 95% CI straddled zero. The proportions of resistant isolates for each antibiotic in the two data sets each year were in poorer agreement than the trends; however, the 95% CI of the difference of proportions resistant between the routine and LEP data sets straddled zero in 4 or 5 of the 7 years studied. Some discrepancies might be explained by geographical bias in the sampling or by differences in definitions of resistance. Thus (i) the proportion of resistant isolates tested at LEP almost always fell within the ranges bounded by the highest and lowest proportions for individual Regional Health Authorities, as recorded in the routine data, and (ii) the fact that LEP consistently recorded less gentamicin resistance but more ciprofloxacin resistance than the routine could be explained by breakpoint differences. We conclude that routine susceptibility data for ampicillin, ciprofloxacin, gentamicin and trimethoprim appear sound for E. coli and might be suitable for correlation with other data, e.g. for prescribing.

Inter-laboratory validation of an ELISA for the determination of serum anti-ganglioside antibodies.

Anti-ganglioside antibodies are frequently sought in the sera of patients with autoimmune peripheral neuropathy, using an enzyme-linked immunosorbent assay (ELISA) as the principal method for antibody detection. Wide variations in assay performance between laboratories have been reported. In this study, we established a standardized ELISA method between laboratories within the European Inflammatory Neuropathy Cause and Treatment (INCAT) group and determined the inter-laboratory variance in assay performance using both the standardized INCAT method and in-house local methods. As expected, the inter-laboratory variances were greater using local methods than using the standardized method, producing titre estimates which could be 24.8 or 7.6 times larger or smaller, respectively, than the true means for these laboratories. Using the standardized method, the within laboratory measurement error accounted for 41% of the inter-laboratory variation, providing a theoretical upper limit to which technical improvements within laboratories could reduce inter-laboratory variation. These data describe the intrinsic weaknesses within the widely used ganglioside antibody ELISA methods and reinforce the importance of inter-laboratory cooperation within this area. Standardized serological reagents used in this study are available from INCAT members.

Asymptomatic urethritis and detection of HIV-1 RNA in seminal plasma.

OBJECTIVE: To define risk factors for detection of HIV-1 RNA in semen in men attending the two largest HIV clinics in the West Midlands. METHODS: 94 HIV-1 seropositive men at any stage of infection donated matched semen and blood samples. 36 subjects (38%) were on no antiretroviral treatment, 12 (13%) were on dual therapy, and 46 (49%) were on three or more drugs. Median CD4 count was 291 cells x 10(6)/l. 87 subjects underwent a urethritis screen (Gram stained urethral smear and culture for gonococcus, and LCR for Chlamydia trachomatis on first pass urine). Quantitative cell free HIV-1 RNA was determined by commercial nucleic acid sequence based assay with a lower detection limit of 800 copies/ml for semen and 400 copies/ml for blood. Independent risk factors for seminal HIV RNA detection were defined by logistic regression. RESULTS: In univariate analysis, subjects not taking antiretrovirals were 11 times more likely to shed HIV RNA (21/36 (58%) v 6/58 (10%); p < 0.0001). Seven subjects (8%) had urethritis (including one C trachomatis infection). Urethritis was significantly associated with detection of seminal HIV RNA (adjusted OR, 80.2; p = 0.006), as was blood plasma viral load (adj OR, 19.3 per factor 10 increase; p < 0.001) and age (adj OR, 1.16 per 1 year older; p = 0.001). Antiviral treatment status, absolute CD4 and CD8 count, clinical stage, treatment centre, ethnicity, and risk factor were not independent predictors. No subject with undetectable blood viral load had detectable seminal HIV RNA. CONCLUSION: Asymptomatic urethritis is independently associated with seminal HIV RNA shedding.