Search PubMed⌕ Search

Biomedical subjects

N Francis

Publications and source records attributed to N Francis.

At least 55 records · Page 3Linked to original sources

Chronic erosive herpes simplex virus infection of the penis, a possible immune reconstitution disease.

OBJECTIVE: To report a novel clinical presentation: a chronic erosive herpes simplex virus (HSV) infection of the penis which developed in AIDS patients following the commencement of highly active antiretroviral therapy (HAART). The lesions were unresponsive to antiviral treatments which had previously been effective, and this could not be accounted for in terms of increased antiviral resistance. DESIGN: Detailed case-note review and investigation of three cases which presented at two large HIV units in London. METHODS: Review of all histology with immunohistochemistry for HSV, HSV drug susceptibility assays, tissue typing and measurement of in vitro lymphocyte functional activity against HSV. RESULTS: The histology of the lesions was the same in each case, with the presence of HSV on immunohistochemistry and an unusual prominence of plasma cell and eosinophils in the inflammatory infiltrate. HSV-specific lymphoproliferative responses were normal in two cases, but subnormal in a third case. All individuals shared the HLA class I molecules B72 and Cw0202 and the class II allele DRB4. CONCLUSION: We believe this to be a previously unreported adverse consequence of HAART, the result of partial immune restoration, reminiscent of the the recently described syndrome of immune recovery vitritis.

AIDS-Related Opportunistic Infections↗

Diagnosis of Helicobacter pylori gastritis in children using the 13C urea breath test.

The clinical recognition of Helicobacter pylori gastritis in children with recurrent abdominal pain is difficult. We assessed the value of a simplified 13C urea breath test (13C-UBT) in a selected group of children with nocturnal waking and disruptive recurrent abdominal pain who fulfilled criteria for endoscopy. Gastric antral biopsies were examined histologically and by the quick urease test and were compared with H. pylori serology and the 13C-UBT in a prospective study of 50 children referred to a tertiary center. Thirty-two patients had gastritis and of these, 19 had histologically proven H. pylori gastritis. Seventeen of these 19 patients had a positive 13C-UBT. The sensitivity and specificity of the 13C-UBT compared with the histologic diagnosis of H. pylori was 89 and 90% respectively. The 13C-UBT was more specific than the H. pylori serology. The 13C-UBT using two breath collections is a reliable and noninvasive diagnostic test for H. pylori infection in children.

Adolescent↗

Peripheral muscle ergoreceptors and ventilatory response during exercise recovery in heart failure.

Recent studies have suggested that the increased ventilatory response during exercise in patients with chronic heart failure was related to the activation of muscle metaboreceptors. To address this issue, 23 patients with heart failure and 7 normal subjects performed arm and leg bicycle exercises with and without cuff inflation around the arms or the thighs during recovery. Obstruction slightly reduced ventilation and gas exchange variables at recovery but did not change the kinetics of recovery of these parameters compared with nonobstructed recovery: half-time of ventilation recovery was 175 +/- 54 to 176 +/- 40 s in patients and 155 +/- 66 to 127 +/- 13 s in controls (P < 0.05, patients vs. controls, not significant within each group from baseline to obstructed recovery). We conclude that muscle metaboreceptor activation does not seem to play a role in the exertion hyperventilation of patients with heart failure.

Arm↗

Thalidomide: a novel therapy for microsporidiosis.

BACKGROUND & AIMS: Microsporidiosis is a common cause of chronic diarrhea in human immunodeficiency virus (HIV)-seropositive individuals and often does not respond to treatment. Fecal tumor necrosis factor alpha (TNF-alpha) is elevated in microsporidiosis; therefore, thalidomide, an anti-TNF-alpha agent, was used as therapy. METHODS: Eighteen subjects with chronic diarrhea caused by Enterocytozoon bieneusi that had not responded symptomatically to albendazole and 1 untreated subject with Encephalitozoon intestinalis received 1 month of thalidomide, 100 mg nocte. Clinical response was assessed by stool frequency and body weight, histological response by light microscopy with villus height/crypt depth ratios and electron microscopy, and immunologic response by fecal TNF-alpha level. RESULTS: Seven subjects with chronic diarrhea due to E. bieneusi had a complete clinical response, and 3 had a partial response to thalidomide. There was a significant decrease in stool frequency from 5.3 to 3.1 per day (P = 0.001), and weight increased significantly by 1.2 kg (P < 0.02). Thalidomide significantly increased the villus height/crypt depth ratio (1.95 to 2.07; P = 0.045) and number of abnormal forms of microsporidia (P < 0.01). Fecal TNF-alpha level nonsignificantly decreased from 17.9 to 8.9 U/mL. There was apparent disruption of all stages of the life cycle of E. intestinalis. CONCLUSIONS: Thalidomide may be an effective therapy for diarrhea and weight loss from E. bieneusi.

Acquired Immunodeficiency Syndrome↗

Maternal immunization with Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in The Gambia.

OBJECTIVE: To evaluate maternal responses to Haemophilus influenzae type b (Hib) polysaccharide-tetanus protein conjugate (polyribosylribitol phosphate-tetanus or PRP-T) given to pregnant Gambian women, the transplacental transfer of antibody, and the effect of maternal immunization on infant responses to the vaccine. DESIGN: An open, randomized immunogenicity study. SETTING: A busy urban health center in The Gambia. STUDY PARTICIPANTS: A total of 451 pregnant women enrolled during the third trimester of pregnancy. INTERVENTION: Study participants were randomized to three groups. In one group, mothers were given PRP-T during the third trimester and their infants were given PRP-T at 2, 3, and 4 months of age. In the second group, mothers received PRP-T and infants were given inactivated poliovirus vaccine. In the third group, mothers received meningococcal A and C vaccine, and their infants received PRP-T. MAIN OUTCOME MEASURES: Anti-PRP antibody measurements of maternal cord, and infant blood. RESULTS: Vaccinated women had a marked increase in total anti-PRP antibody (geometric mean titer 9.0 micrograms/mL), which was greatest in women in their first or second pregnancy. Previous tetanus vaccination during the same pregnancy and high concentrations of antitetanus antibody were associated with lower anti-PRP responses. In infants of PRP-T recipients, cord blood anti-PRP IgG concentrations were 61% of simultaneous maternal concentrations. In vaccinated infants of vaccinated mothers, geometric mean anti-PRP antibody concentrations at birth, 2 months of age, and 5 months of age were 1.92, 0.35 and 2.84 micrograms/mL, respectively, while in vaccinated infants of unvaccinated mothers, the corresponding concentrations were 0.29, 0.12, and 3.91 micrograms/mL. At 2 months of age, 60% of infants of vaccinated mothers and 26% of infants of unvaccinated mothers had anti-PRP antibody concentrations considered to be protective (>0.15 micrograms/mL). CONCLUSIONS: In areas where much invasive Hib disease occurs in infants younger than 6 months, maternal immunization may help to reduce the risk of Hib disease in infants too young for immunization.

Antibodies, Bacterial↗

Immunization with a pneumococcal capsular polysaccharide vaccine during pregnancy.

The feasibility of preventing invasive pneumococcal infections during the first few months of life by immunization during pregnancy has been investigated. One hundred and fifty Gambian women were immunized with either a 23-valent pneumococcal polysaccharide vaccine or a meningococcal polysaccharide vaccine during the last trimester of pregnancy. Pregnant women showed a good antibody response to five of the six pneumococcal polysaccharides tested (types 1, 3, 5, 6, 14 and 19) but not to type 6 polysaccharide. Mean cord blood/maternal blood IgG antibody ratios varied from 24% (type 1) to 49% (type 3) and differed substantially between individual mother/infant pairs. Pneumococcal antibody levels were higher at birth in infants of women immunized with pneumococcal polysaccharide vaccine than in control infants. However, these antibodies disappeared rapidly during the first few months of life and it is uncertain how much clinical protection against pneumococcal infection maternal immunization would have provided.

Antibodies, Bacterial↗

Intestinal inflammation, ileal structure and function in HIV.

OBJECTIVES: This study examines small intestinal absorption-permeability, intestinal inflammation and ileal structure and function in HIV-positive male homosexuals. METHODS: Thirty HIV-seropositive male homosexuals at various stages of disease underwent intestinal absorption permeability and 111indium leukocyte studies (for quantification of intestinal inflammation). Twenty-six men with AIDS had a dual radioisotopic ileal function test (whole body retention of tauro 23-[75Se]-selena 25-homocholic acid and 58cobalt-labelled cyanocobalamine), and 17 underwent ileocolonoscopy with terminal ileal biopsy. RESULTS: Well, HIV-infected, subjects had normal intestinal absorption-permeability, but both functions were impaired upon the development of AIDS. The median faecal excretion of 111indium in well patients (0.66%) did not differ significantly (P > 0.5) from controls (0.46%), but subjects with AIDS who were well or who had diarrhoea had significant (P < 0.005) intestinal inflammation (1.33% and 2.18%, respectively). The median 7-day retention of tauro 23-[75Se]-selena 25-homocholic acid in well patients with AIDS (38.9%) did not differ significantly (P > 0.2) from controls (39.3%), whereas the absorption of 58cobalt-labelled cyanocobalamine was significantly (P < 0.05) lower than controls (32.1% and 59.4%). Patients with AIDS-diarrhoea had significant (P < 0.001) malabsorption of both the bile acid (7.7%) and vitamin B12 (8.9%) which was more severe than in Crohn's ileitis (14.2% and 30.3%, respectively). Morphometric analyses of ileal biopsies were unremarkable in AIDS. CONCLUSIONS: These studies demonstrate a low-grade enteropathy in patients with AIDS, severe ileal malabsorption in patients with AIDS diarrhoea and relatively minor ileal morphologic changes. Malabsorption of bile acids may play a pathogenic role in patients with AIDS and diarrhoea.

Acquired Immunodeficiency Syndrome↗

Meningococcal antibody titres in infants of women immunised with meningococcal polysaccharide vaccine during pregnancy.

Seventy five Gambian women were immunised with a single dose of a group A+group C meningococcal polysaccharide vaccine during the last trimester of pregnancy. IgG antibody titres were measured in mothers and in their infants by an enzyme-linked immunosorbent assay (ELISA). All women had a good response to vaccination and maternal antibodies were high at the time of delivery (23.2 micrograms/ml for group A antibodies and 14.3 micrograms/ml for group C antibodies). However, only a proportion of this antibody crossed the placenta; cord blood:maternal antibody ratios were 30% for group A antibody and 44% for group C antibody, respectively. Considerable variability in cord blood:maternal blood ratios was seen between individuals. This could not be related to age, parity, or ethnic group. Mean group A and group C cord blood:maternal blood ratios were lower in women with serological evidence of syphilis than in seronegative women, and diminished transfer of group A antibody was noted in women with active malarial infection of the placenta. Antibody titres declined rapidly in infants and by the age of 3-4 months these had reached control values. Maternal immunisation may give infants some protection against group A and group C meningococcal disease but only during the first few months of life.

Adult↗

Ulceration of the small intestine in children with coeliac disease.

BACKGROUND: Ulceration of the small intestine in children has not been previously described. PATIENTS: Two children, aged 12 and 18 months, presented with a history of failure to thrive and intractable diarrhoea. RESULTS AND CONCLUSIONS: Upper gastrointestinal endoscopy showed multiple ulcers involving the first and second parts of the duodenum. Histology of biopsy specimens taken from these sites confirmed ulceration and showed other features consistent with a diagnosis of coeliac disease. They both showed pronounced clinical improvement and satisfactory linear growth on a gluten free diet. A year later the diagnosis of coeliac disease was confirmed on a biopsy controlled gluten challenge, and repeat endoscopy showed complete resolution of the intestinal ulceration.

Celiac Disease↗

Investigation of chronic diarrhoea in acquired immunodeficiency syndrome. A prospective study of 155 patients.

BACKGROUND AND AIMS: The optimum diagnostic investigation for patients with acquired immunodeficiency syndrome (AIDS) and diarrhoea is not known. Often no pathogen is detected and it is unclear whether this is because pathogens are absent in some patients or the investigations used fail to detect them. The hypothesis that AIDS related diarrhoea is usually due to an infection, which can be identified by a simple diagnostic strategy based on the results of intensive investigation of a cohort of such patients, was investigated. METHODS: 155 patients with AIDS and chronic diarrhoea underwent contemporaneous examination of stools, duodenal, jejunal, and rectal biopsy specimens and duodenal aspirate for bacterial, protozoal, and viral pathogens. A decision tree analysis was used to determine the best sequential diagnostic strategy for clinicians. RESULTS: 128 of 155 patients investigated (83%) had at least one potential pathogen. The presenting clinical features could not predict the presence or site of the pathogens. Stool analysis identified the most pathogens (93 of 199, 47%). Rectal biopsy was essential for the diagnosis of cytomegalovirus and adenovirus. Duodenal biopsy was as helpful as jejunal biopsy and detected some treatable pathogens missed by other methods. Electron microscopy, impression smears, and duodenal aspirate yielded little extra information. If gut biopsy was reserved for patients without a stool pathogen, some treatable pathogens would have been missed. CONCLUSION: Most patients with AIDS and chronic diarrhoea have at least one gut pathogen, which can be identified by stool analysis and light microscopic examination of duodenal and rectal biopsies. Some pathogens will be missed unless all these investigations are done on all such patients.

Acquired Immunodeficiency Syndrome↗

Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes.

Adult↗

Reversible renal failure caused by a microsporidian infection.

OBJECTIVE: To report a case of renal failure associated with microsporidian infection in an HIV-seropositive patient. DESIGN: Case report. SETTING: Chelsea and Westminster Hospital, London, England, UK. PATIENT: An HIV-seropositive patient presented febrile with abdominal pain who developed renal failure. Renal biopsy and urinalysis showed infection with a microsporidian of the genus Encephalitozoon. INTERVENTION: Treatment with albendazole (400 mg) twice daily was associated with disappearance of infection from the urine, clinical improvement and return of renal function virtually to normal. CONCLUSION: HIV-seropositive individuals with renal failure should have urine screened for microsporidia. The administration of albendazole in such cases may reverse renal failure.

AIDS-Related Opportunistic Infections↗