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Biomedical subjects

V Novelli

Publications and source records attributed to V Novelli.

At least 19 recordsLinked to original sources
PubMed2004

HIV evolution: CTL escape mutation and reversion after transmission.

Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

Adult↗
PubMed2004

Determination of cadmium and lead in vegetables by stripping chronopotentiometry.

A method for the determination of cadmium and lead in vegetables by stripping chronopotentiometric analysis, after digestion of the sample with concentrated sulphuric acid and dry-ashing, is described. Metal ions were concentrated as their amalgams on a glassy carbon-working electrode previously coated with a thin mercury film and then stripped by a suitable oxidant. Potential and time data were digitally derived and E was plotted versus dt/dE(-1), thus increasing both the sensitivity of the method and the resolution of the analysis. Quantitative analysis was carried out by the method of standard addition; good linearity was obtained in the range of examined concentrations, as was shown by the determination coefficients, which were 0.998 (n = 4) for cadmium and 0.993 (n = 4) for lead. Recoveries of 85-100% for cadmium and of 84-97% for lead were obtained from a sample spiked at different levels. Accuracy was demonstrated by analysis of a matching reference sample of cabbage. The detection limits were 1.8 ng g(-1) of wet mass for cadmium and 5.1 ng g(-1) of wet mass for lead. The relative standard deviations (mean of nine determinations), evaluated on a real sample, were 6.7 and 6.2%, respectively. Results obtained on 10 different commercial samples of pepper (Capsicum annuum), and egg plant (Solanum melongena) were not significantly different from those obtained by graphite furnace atomic absorption spectrophotometry technique. The average content was in the range 3.1-18.6 ng g(-1) for cadmium and 38.2-64.3 ng g(-1) for lead.

Cadmium↗
PubMed2003

Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland.

OBJECTIVE: To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV. DESIGN: Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and additional data from a subset of children in the collaborative HIV paediatric study (CHIPS). SETTING: United Kingdom and Ireland. PARTICIPANTS: 944 children with perinatally acquired HIV-1 under clinical care. MAIN OUTCOME MEASURES: Changes over time in progression to AIDS and death, hospital admission rates, and use of antiretroviral therapy. RESULTS: 944 children with perinatally acquired HIV were reported in the United Kingdom and Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged > or = 10 years at last follow up, 193 (20%) are known to have died. The proportion of children presenting who were born abroad increased from 20% in 1994-5 to 60% during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at risk but fell to 2.0 in 2001-2 (trend P < 0.001). Progression to AIDS also declined (P < 0.001). From 1997 onwards the proportion of children on three or four drug antiretroviral therapy increased. Hospital admission rates declined by 80%, but with more children in follow up the absolute number of admissions fell by only 26%. CONCLUSION: In children with HIV infection, mortality, AIDS, and hospital admission rates have declined substantially since the introduction of three or four drug antiretroviral therapy in 1997. As infected children in the United Kingdom and Ireland are living longer, there is an increasing need to address their medical, social, and psychological needs as they enter adolescence and adult life.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Retrospective screening for hepatitis C in a tertiary paediatric referral centre.

The true prevalence of hepatitis C virus in children in the UK is not known and targeted screening is not standard practice despite an anticipated rise in new cases due to vertical transmission. An extension of the Department of Health's 'look-back' exercise was undertaken in order to determine the prevalence of hepatitis C virus in high-risk patient groups who were transfused with blood and/or blood products before 1991. Five hundred and ninety-five patients transfused between 1971-91 were traced and offered counselling and testing. Blood samples from 405 were analysed for the presence of HCV antibodies and/or HCV RNA by RT-PCR and eight patients were found to be positive. The HCV seroprevalence rate in this cohort was 1.97% and the HCV genome detection rate was 1.72%. In view of the long-term complications from this infection and the availability of potentially effective anti-viral agents, we feel that targeted screening is of value in this setting.

Adolescent↗
PubMed2002

Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathway.

Patients with genetic lesions in the Type-1 cytokine/cytokine receptor pathway exhibit a selective susceptibility to severe infections with poorly pathogenic mycobacteria and non-typhi salmonella spp. These experiments of nature demonstrate that IL-12-dependent IFNgamma production is critical for granuloma formation and therefore host immunity against such pathogens. The essential role of granuloma formation for protective immunity to these organisms is emphasized by the differing granuloma forming capabilities and resultant clinical sequelae observed in these patients which seems to reflect their ability to produce or respond to IFNgamma (Fig. 9). At one pole of this spectrum, represented by the complete IFNgammaR1/2 deficient patients, there is a complete absence of mature granuloma formation, whereas with the less severe mutations (i.e. partial IFNgammaR1/2, complete IL-12p40 and complete IL-12Rbeta1 deficiency), granuloma formation is very heterogenous with wide variations in composition being observed. This suggests that in the latter individuals, who produce partial but suboptimal IFNgamma responses, other influences, including pathogen virulence and host genotype may also affect the type and scale of the cellular response elicited.

Genetic Predisposition to Disease↗
PubMed2001

Discitis in young children.

Discitis is uncommon in children and presents in different ways at different ages. It is most difficult to diagnose in the uncommunicative toddler of one to three years of age. We present 11 consecutive cases. The non-specific clinical features included refusal to walk (63%), back pain (27%), inability to flex the lower back (50%) and a loss of lumbar lordosis (40%). Laboratory tests were unhelpful and cultures of blood and disc tissue were negative. MRI reduces the diagnostic delay and may help to avoid the requirement for a biopsy. In 75% of cases it demonstrated a paravertebral inflammatory mass, which helped to determine the duration of the oral therapy given after initial intravenous antibiotics. At a mean follow-up of 21 months (10 to 40), all the spines were mobile and the patients free from pain. Radiological fusion occurred in 20% and was predictable after two years. At follow-up, MRI showed variable appearances: changes in the vertebral body usually resolved at 24 months and recovery of the disc was seen after 34 months.

Anti-Bacterial Agents↗
PubMed2000

Isolated cutaneous response to granulocyte-monocyte colony stimulating factor in fatal idiopathic disseminated Bacillus-Calmette-Guerin infection.

UNLABELLED: Severe disseminated Bacillus-Calmette-Guerin (BCG) infection is very rare and has been regarded as idiopathic when no immunodeficiency is present. This entity seems to be due to several new types of inherited abnormalities in the pathways important in defence against Mycobacteria. Although improvement with interferon-gamma (IFN-gamma) has been reported in some patients, to our knowledge there are no reports on the effect of other cytokines in the treatment of these patients. We report here the clinical response to IFN-gamma and granulocyte-monocyte colony stimulating factor (GM-CSF) treatment in a patient with idiopathic disseminated BCG infection who failed to respond to multiple antimycobacterial agents. The patient showed partial and transitory response to IFN-gamma, however, GM-CSF treatment led to rapid improvement of skin lesions within 2 weeks without any effect on the progression of the disease in the other organ systems. CONCLUSION: The response of idiopathic disseminated Bacillus-Calmette-Guerin infection to granulocyte-monocyte colony stimulating factor treatment was limited to cutaneous lesions. Granulocyte-monocyte colony stimulating factor may have acted to promote wound healing or the levels of this factor achieved in other affected organs may have been inadequate.

BCG Vaccine↗
PubMed2000

A preliminary investigation of dental disease in children with HIV infection.

OBJECTIVE: To establish the levels of dental caries and gingivitis in a group of HIV-positive children. STUDY GROUP: The study group comprised 35 children with the Human Immunodeficiency Virus attending The Great Ormond Street Hospital For Children. OUTCOME MEASURES: Outcome measures included the number of decayed, missing and filled teeth and surfaces in both the primary and permanent dentitions; plaque and gingivitis scores. RESULTS: The children included 18 boys and 17 girls. They were aged from 6 months to 18 years, with 17 aged 5 years or less and 15 aged 6 years or older. Twenty-four of the 35 children had some caries experience. The mean DMFT was 4.4 and for those with permanent teeth the mean DMFT was 0.7. Mean plaque and gingivitis scores were 16.7 and 5.1 for plaque and gingivitis adjacent to primary teeth and 8.0 and 5.7 for that related to permanent teeth. CONCLUSIONS: There is a significant treatment need for children with HIV.

Adolescent↗
PubMed2000

Exotic pulmonary infections.

Pulmonary infections are the commonest type of illnesses seen in everyday practice. Although most infections are caused by a few familiar pathogens, an increase in global travel has led to the occurrence of rare and exotic diseases that often do not manifest until after the traveller returns home. Previously innocuous organisms may also be the cause of exotic infections in patients undergoing transplantation, or very aggressive immunosupression. Such treatment regimes may reactivate quiescent organisms acquired years previously, for example melioidosis and strongyloides stercoralis. In most developed countries there is also an increasing incidence of zoonotic infections, with a number of these presenting with mainly pulmonary symptoms. A carefully taken history of recent travel, exposure to wild or domestic animals or the presence of immunosuppression, is extremely helpful in identifying problematic infections that fall into the realm of the exotic. This review discusses some of the respiratory infections in each of these groups with an emphasis on imported infections.

Animals↗
PubMed1999

A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection.

The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

Adolescent↗
PubMed1999

Safety and tolerability of fluconazole in children.

The safety profile of fluconazole was assessed for 562 children (ages, 0 to 17 years) comprising 323 males and 239 females. The data are derived from 12 clinical studies of fluconazole as prophylaxis or treatment for a variety of fungal infections in predominantly immunocompromised patients. Most children received multiple doses of fluconazole in the range of 1 to 12 mg/kg of body weight; a few received single doses. Administration was mainly by oral suspension or intravenous injection. Overall, 58 (10.3%) children reported 80 treatment-related side effects. The most common side effects were associated with the gastrointestinal tract (7.7%) or skin (1.2%). Self-limiting, treatment-related side effects affecting the liver and biliary system were reported in three patients (0.5%). Overall, 18 patients (3.2%) discontinued treatment due to side effects, mainly gastrointestinal symptoms. Dose and age did not appear to influence the incidence and pattern of side effects. Treatment-related laboratory abnormalities were uncommon, the most frequent being transient elevated alanine aminotransferase (4.9%), aspartate aminotransferase (2.7%), and alkaline phosphatase (2.3%) levels. Although 98.6% of patients were taking concomitant medications, no clinical or laboratory interactions were observed. The safety profile of fluconazole was compared with those of other antifungal agents, mostly oral polyenes, by using a subset of data from five controlled studies. Side effects were reported by more patients treated with fluconazole (45 of 382; 11.8%) than by those patients treated with comparable agents (25 of 381; 6.6%); vomiting and diarrhea were the most common events in both groups. The incidence and type of treatment-related laboratory abnormalities were similar for the two groups. In conclusion, fluconazole was well tolerated by the pediatric population, many of whom were suffering from severe underlying disease and were taking a variety of concurrent medications. The safety profile of fluconazole in children mirrors the excellent safety profile seen in adults.

Adolescent↗
PubMed1999

Management of occupational exposure to HIV--what actually happens.

A year after the Department of Health issued guidelines on post exposure prophylaxis (PEP) for health care workers exposed to HIV, we conducted a telephone survey of occupational health nurses and junior doctors in London teaching hospitals, to assess implementation of the guidelines and awareness among junior doctors of local policies. The management and administration of PEP for HIV differed considerably between hospitals. Many junior doctors did not know what to do in the event of a needlestick injury. Both the implementation of and the briefing of staff about current management policies need to improve.

Data Collection↗
PubMed1998

Otitis media in children with vertically-acquired HIV infection: the Great Ormond Street Hospital experience.

Human immunodeficiency virus (HIV) infection continues to be a vexing problem in the pediatric population. Otitis media, a common entity in immunocompetent as well as immunocompromised children, is prevalent in pediatric patients with HIV infection. Recurrent infections and complications secondary to otitis media are also common in this population. The purpose of this review was to evaluate the records of a large group of children with HIV infection undergoing treatment for otitis media at a tertiary care center. Incidence of infections, severity of infections, and pathogens responsible were the key points of data collection in relation to each patient's HIV clinical and immunologic classification. We reviewed 72 patients with vertically-acquired HIV infection undergoing treatment at the Hospital for Sick Children, Great Ormond Street, London. All patients were born to HIV infected mothers of sub-Saharan African origin. A total of 32 (44.4%) of these children presented to our institution with one or more episodes of otitis media, six of whom suffered systemic complications secondary to middle ear pathology. Middle ear culture data, when available from actively draining ears, was similar to those of immunocompetent children in the general population. The most common complications were systemic bacteremia and recalcitrant infections requiring intravenous antibiotic therapy. Severity of immunosuppression was associated with higher incidence and severity of otitis media. Otitis media in an HIV infected child must be treated aggressively at its outset in an attempt to minimize possible complications. Administration of prophylactic antibiotics to these children may reduce the frequency of acute and chronic infections. Improvement in immunologic status using antiretrovirals or protease inhibitors is a primary goal in diminishing the severity of otitis media as well as other infections in these children.

AIDS-Related Opportunistic Infections↗
PubMed1997

Salmonella osteomyelitis in sickle cell disease children in the east end of London.

Five cases of Salmonella osteomyelitis are presented in children with sickle cell disease living in the East End of London. Four of these had involvement of the long bones and one (an infant) presented with hand-foot syndrome. Four required surgical drainage of pus and all required lengthy therapy with antibiotics. Factors contributing to the increased susceptibility of these patients to invasive disease with Salmonella sp. are discussed as are the clinical features, surgical and antibiotic management and possible preventative measures.

Anemia, Sickle Cell↗
PubMed1997

High-performance liquid chromatographic determination of 2-furaldehyde and 5-hydroxymethyl-2-furaldehyde in fruit juices.

A method for the determination of 2-furaldehyde (F) and 5-hydroxymethyl-2-furaldehyde (HMF) in fruit juices by high-performance liquid chromatography (HPLC) is described. The method is based on the formation of the 2,4-dinitrophenylhydrazones of carbonyl compounds and subsequent separation of these derivatives. Derivatization is carried out by utilizing an acidic solution of 2,4-dinitrophenylhydrazine in acetonitrile. Precipitation of the derivatives of carbonyl compounds is thus avoided, and direct injection of the sample into the HPLC system is allowed. The procedure offers a high specificity and a detection limit of the order of 10(-8) mol/L. Recoveries of 95-98% are obtained from apple juice spiked at different levels with both analytes. The reproducibility (mean of six determinations) is +/- 2% for F and +/- 3% for HMF.

Beverages↗