Biomedical subjects

M A Johnson

Publications and source records attributed to M A Johnson.

At least 37 records · Page 2Linked to original sources

PubMed2004

Findings from the British HIV Association's national clinical audit of first-line antiretroviral therapy and survey of treatment practice and maternity care, 2002.

OBJECTIVES: To assess the impact of and adherence to the British HIV Association (BHIVA) guidelines in routine clinical practice in the UK and Ireland. METHODS: A self-completed postal survey of practice with regard to HIV management and maternity care of HIV-positive women was carried out. A case-note review of all patients starting their first antiretroviral (ART) therapy (up to a maximum of 25 patients) between April and September 2002 was also performed. RESULTS: A total of 113 treatment centres participated. Ninety-nine units (88%) use the BHIVA ART guidelines as part of their treatment policy. Problems revealed by the survey include limited access to some ARTs in a small number of units and a wait longer than 4 weeks before the first assessment of patients started on ART in some units. Thirty-one centres (33%) felt that their maternity services had reached the government target of >90% antenatal HIV testing by October 2002. A total of 942 case-notes audited showed shortfalls in reported pretreatment testing of blood glucose, lipids and hepatitis C virus. Three patients had not strictly met the BHIVA guidelines for starting ART, but all had a high viral load (>100 000 HIV-1 RNA copies/mL). The majority (844 patients; 90%) had started on recommended therapies, most commonly two nucleoside reverse transcriptase inhibitors and a nonnucleoside reverse transcriptase inhibitor. The other 98 patients (10%) were given a variety of nonstandard triple or quadruple ART. CONCLUSIONS: This audit again shows a high rate of consistency and quality of care of patients with HIV across the UK and Ireland. Problems with pretreatment assessment and early follow up of patients starting ART have been found.

Adult↗

PubMed2004

Changes in hospital admissions across Europe: 1995-2003. Results from the EuroSIDA study.

OBJECTIVES: To describe changes in the proportions of patients admitted to hospital and the duration of admission during the month of March between 1995 and 2003 and to describe the factors related to admission for 9802 patients from EuroSIDA, a pan-European, observational cohort study. METHODS: Generalized estimating equations were used to determine changes over time in the proportion of patients admitted and the median duration of admission. Logistic regression was used to determine factors related to admission in March 1995, March 1998 and March 2001. RESULTS: The proportion of patients admitted during March declined from 7.4% in 1995 to 2.6% in 2003. After adjustment, the estimated reduction in the proportion of patients admitted was 5.5% per year [95% confidence interval (CI) 2.5-8.5%; P=0.0004], a 26% reduction. The median duration of hospital admission declined by 58% from 12 days in 1995 [interquartile range (IQR) 5-19 days] to 5 days in 2003 (IQR 3-12 days), a significant decline of 0.7 days per year after adjustment (95% CI 0.5-0.9 days; P=0.031). Patients with a lower CD4 lymphocyte count, and with an AIDS diagnosis made within the 3 months prior to March, all had increased odds of admission during March 1995, 1998 or 2001. In March 2001, patients whose treatment regimen was changed as a consequence of toxicities had increased odds of admission [odds ratio (OR) 2.34; 95% CI 1.26-4.37; P=0.0074]. In addition, patients who were hepatitis C virus-positive during March 2001 (OR 1.66; 95% CI 1.02-2.68; P=0.041) had increased odds of admission. CONCLUSIONS: There has been a considerable decline in both the proportion of patients admitted to hospital and the median duration of the stay. Patients with hepatitis C had increased odds of admission, but there was little evidence of an increase in admissions among patients taking highly active antiretroviral therapy (HAART) associated with serious adverse events, although longer follow up is required.

Antiretroviral Therapy, Highly Active↗

PubMed2004

Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection.

BACKGROUND: It has been suggested that deterioration of tuberculosis (TB) during appropriate treatment, termed a paradoxical reaction (PR), is more common and severe in HIV positive individuals on highly active antiretroviral therapy (HAART). METHOD: A study was undertaken to determine the frequency of PR and its associated features in a population of HIV+TB+ patients and a similar sized group of HIV-TB+ individuals. RESULTS: PR occurred in 28% of 50 HIV+TB+ patients and 10% of 50 HIV-TB+ patients. Disseminated TB was present in eight of 13 HIV+TB+ patients and four of five HIV-TB+ patients with PR. In 28 HIV+TB+ patients starting HAART, PR was significantly associated with commencing HAART within 6 weeks of starting antituberculosis treatment (p = 0.03) and was more common in those with disseminated TB (p = 0.09). No association was found between development of PR and baseline CD4 count or CD4 response to HAART. CONCLUSIONS: PR is common in HIV infected and uninfected individuals with TB. Early introduction of HAART and the presence of disseminated TB appear to be important in co-infected patients.

AIDS-Related Opportunistic Infections↗

PubMed2004

The sociodemographic profile, risk categories and prevalence of HIV infection among people attending a London same-day testing clinic, 2000-2001.

The objectives were to determine the sociodemographic profile, risk category, and prevalence of HIV infection amongst people attending a confidential clinic providing counselling, medical advice and results of HIV antibody testing on the same day of consultation. Data were collected on all 1749 individuals attending the same-day HIV testing clinic at the Royal Free Hospital, London and proceeding to HIV testing between June 2000 and May 2001. One thousand, one hundred and forty-eight men and 601 women (mean age 33.3 years) were tested for HIV antibodies. The primary risk for HIV infection was heterosexual contact (69.9%; 1224/1749) and homosexual contact (27.7%; 485/1749). Fifty individuals tested HIV-positive (42 men and eight women). HIV seroprevalence was 2.8% (50/1749) and was highest among men who reported risk through homosexual contact (6.2%; 30/485). The rates for heterosexual men and women were 1.8% (12/648) and 1.4% (8/576), respectively, though they were highest among Black Caribbean (12%; 3/25) and Black African attendees from sub-Saharan African countries (11.2%; 18/160). Of the total number attending the clinic, more than half (56%; 981/1749) had previously been tested and received a negative test result. Of the fifty HIV antibody-positive individuals, 26%, (13) had previously received a negative result and had all reported risk through homosexual contact. Thirty of the HIV antibody-positive individuals were asymptomatic, 14 were symptomatic and three were diagnosed with an AIDS-defining condition. Half of all HIV-positive attendees (51.2%; 22/43) presented at the time of testing with CD4 cell counts below the normal range (>400x10(6)/l). The high HIV seroprevalence among homosexual men, some of whom had previously tested negative, suggests that HIV prevention strategies used within this group may need to be reassessed. The continuing high HIV seroprevalence among individuals from African countries suggests that this population require specific targeting for HIV risk reduction and information on the advantages of early diagnosis and treatment.

Adolescent↗

PubMed2003

Human immunodeficiency virus type 1-related pulmonary Mycobacterium xenopi infection: a need to treat?

We report treatment decisions and outcomes for 20 patients who were infected with human immunodeficiency virus type 1 (HIV-1) and were receiving highly active antiretroviral therapy (HAART) who had respiratory symptoms and from whom Mycobacterium xenopi was isolated. All patients also had coexisting pulmonary pathologic conditions. The median blood T cell CD4 count was 37 cells/microL (range, 2-480 cells/microL). Fifteen of 20 patients received no antimycobacterial therapy and remain healthy after a median of approximately 4 years of follow-up, and 2 patients required treatment specifically for M. xenopi infection, both showing clinical improvement. We conclude that pulmonary M. xenopi isolation in HIV-1 patients receiving HAART does not usually require specific treatment.

AIDS-Related Opportunistic Infections↗

PubMed2003

Clinical progression of mitochondrial myopathy is associated with the random accumulation of cytochrome c oxidase negative skeletal muscle fibres.

We studied the accumulation of cytochrome c oxidase (COX)-negative skeletal muscle fibres in six patients with a myopathy due to a mitochondrial DNA (mtDNA) defect. Each patient was biopsied on two or more occasions over a period of 3-15 years. Progressive proximal weakness was associated with an increase in the proportion of COX-negative fibres. These fibres were arranged randomly, indicating that each fibre became COX negative independently of the status of neighbouring fibres. The clinical progression of mtDNA myopathy is therefore a consequence of a biochemical defect that develops independently within individual muscle fibres. It is likely that this is due to the clonal expansion of mutant mtDNA.

Adult↗

PubMed2003

Bone turnover and body weight relationships differ in normal-weight compared with heavier postmenopausal women.

Low body weight is associated with increased risk for fractures, whereas higher body weight has been shown to be protective against osteoporosis. This study evaluated whether body weight plays a role regulating bone turnover and mass in normal-weight (body mass index (BMI) <25 kg/m2), overweight (BMI 25-29.9 kg/m2) and obese (BMI> or =30 kg/m2) postmenopausal women who were either receiving hormone replacement therapy [HRT(+)] or not [HRT(-)] (total of six groups). Body weight, BMI, total body bone mineral content (TBBMC), and markers of bone formation (serum osteocalcin) and bone resorption (urinary pyridinoline (PYD) and deoxypyridinoline) were retrospectively analyzed in 210 postmenopausal women. The mean age was 67+/-6 years, with mean body weight of 70.8+/-14.2 kg, ranging from 45.0 to 115.5 kg. Body weight was positively correlated with TBBMC ( r=0.50, p<0.0001). There was a lower TBBMC and higher bone formation rate in normal-weight than obese HRT(-) women, but in women taking HRT there were no differences between BMI categories. In addition, in normal-weight HRT(-) women only, PYD and body weight showed a negative correlation (r=-0.39, p=0.01). Among normal-weight, but not overweight or obese subjects, we observed higher TBBMC and lower bone turnover in the HRT(+) compared with the HRT(-) group. Regression models explained 36% of the variance in TBBMC, mainly through body weight. Additional models could only explain 11-15% of the variance in bone turnover. Taken together, these data suggest that among normal-weight but not obese postmenopausal women, higher bone turnover is associated with lower bone mass, and that only normal-weight women show a different bone turnover profile with HRT treatment. Body weight should be considered an important factor in bone metabolism with relevant clinical implications.

Aged↗

PubMed2003

Findings from the first national clinical audit of treatment for people with HIV.

OBJECTIVES: We reviewed the impact of and assessed adherence to British HIV Association (BHIVA) guidelines in routine clinical practice. Feedback has been provided to clinical centres to facilitate any necessary change. METHODS: We used a questionnaire to gauge clinicians' views on the guidelines and availability of antiretroviral therapy (ART) drugs and specialized tests. A case note review of 2044 patients was conducted to assess adherence to guideline recommendations plus patterns of use of HIV resistance testing. RESULTS: Most clinicians (74.1%) report that BHIVA guidelines have influenced care at their centres. A significant minority report problems with access to specialized tests. Most patients who started ART did so at CD4 counts lower than guidelines recommend but in most cases this reflected the CD4 count at diagnosis of HIV. Of patients on ART, an overwhelming majority (97.6%) were receiving three or more drugs. Of those on three or more drugs, 58.9% had latest viral load (VL) below 50 HIV-1 RNA copies/mL and a further 18.1% below 500 copies/mL. Only 19.3% of patients had been tested for HIV resistance, of whom more than half showed resistance to more than one class of drugs. CONCLUSIONS: This clinical audit provides encouraging evidence of the quality of care offered to people with diagnosed HIV in the UK. However late diagnosis means most people start ART at a more advanced stage than guidelines recommend.

Adolescent↗

PubMed2003

An audit of antiretroviral treatment use in HIV-infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use.

OBJECTIVE: To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines. METHODS: All patients under follow-up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow-up, were used to identify which patients should be receiving HAART according to the guidelines. RESULTS: One thousand two hundred and sixty-four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/ micro L and over 80% had previously had a viral load above 4 log10 HIV-1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty-five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it. CONCLUSION: Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.

Adult↗

PubMed2003

SPECT scans for monitoring response to pleconaril therapy in chronic enteroviral meningoencephalitis.

Chronic enteroviral meningoencephalitis (CEMA) is a rare complication of immunodeficient individuals and may present as insidious intellectual deterioration. Diagnosis requires isolation or PCR identification of enterovirus from the CSF. Pleconaril, a novel anti-picornaviral compound is available on a compassionate release basis to treat patients with potentially life threatening enteroviral infection. Non-invasive neuroimaging is an important new technique for both the diagnosis of encephalitis and as an objective assessment of response to treatment. We report two immunodeficient patients, one with common variable immunodeficiency and one with HIV, with an insidious presentation of CEMA. In both patients, perfusion single photon emission tomography scans were effective in monitoring treatment, correlating with clinical and virological response to pleconaril.

Adolescent↗

PubMed2003

A controlled study comparing visual function in patients treated with vigabatrin and tiagabine.

OBJECTIVE: Vigabatrin treatment is frequently associated with irreversible retinal injury and produces retinal electrophysiological changes in nearly all patients. Concern has been raised that tiagabine and other antiepilepsy drugs (AEDs) that increase brain gamma-aminobutyric acid (GABA) might produce similar electrophysiological and clinical changes in visual function. The study compared visual function between groups of patients with epilepsy treated long term with tiagabine, vigabatrin, and patients treated with other AEDs. METHODS: A cross sectional study comparing visual acuity, colour vision, static and kinetic perimetry, and electroretinograms between groups of patients treated with tiagabine, vigabatrin, and other AEDs (control patients). Patients were adults receiving stable AED treatment for >6 months. RESULTS: Vigabatrin treated patients had marked visual field constrictions in kinetic perimetry (mean radius 39.6 degrees OD, 40.5 degrees OS), while tiagabine patients had normal findings (mean 61 degrees OD, 62 degrees OS) (differences OD and OS, p=0.001), which were similar to epilepsy control patients (mean 60 degrees OD, 61 degrees OS). Vigabatrin patients had abnormal electroretinographic photopic B wave, oscillatory, and flicker responses, which correlated with visual field constrictions. These electroretinographic responses were normal for tiagabine patients and control patients. Patients were treated with vigabatrin for a median of 46 months compared with 29 months for tiagabine. Patients taking other AEDs that may change brain GABA had normal visual function. CONCLUSION: Unlike vigabatrin, tiagabine treatment is associated with normal electroretinography and visual fields and ophthalmological function similar to epilepsy control patients. Differences between vigabatrin and other GABA modulating AEDs in retinal drug concentrations and other effects might explain why tiagabine increases in GABA reuptake do not cause retinal injury.

Adult↗

PubMed2003

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

OBJECTIVE: Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. RESEARCH DESIGN AND METHODS: We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. RESULTS: Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. CONCLUSION: Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Alendronate↗

PubMed2002

The role of cytochrome c oxidase deficient hippocampal neurones in Alzheimer's disease.

Defects of mitochondrial function have been proposed as a potential mechanism in the development and pathogenesis of Alzheimer's disease (AD) and neuronal apoptosis. Mitochondrial enzyme-deficient pyramidal neurones are found in greater quantities in the hippocampus of AD patients than in age-matched controls. The presence of these neurones indicates that high levels of mutant mtDNA (mitochondrial DNA), sufficient to cause a biochemical deficiency within individual neurones, occur more frequently in AD than in normal ageing. This study analyses the relationship of cytochrome c oxidase (COX)-deficient neurones with the neuropathological markers of AD, neurofibrillary tangles (NFTs) and amyloid plaques, as well as markers of neuronal apoptosis known to occur in AD brains. Frozen sections of hippocampi from three AD patients were used to directly colocalize in situ the presence of histochemically COX-deficient neurones with immunohistology for the classical neuropathological markers of AD, tau and beta-amyloid. In addition, we also directly colocalized these mitochondrial-enzyme deficient neurones using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and cleaved caspase-3. The distribution of amyloid plaques is anatomically distinct from the COX-deficient hippocampal pyramidal neurones and the neurones that contained NFTs or apoptotic labelling were always COX-positive. COX-deficient, succinate dehydrogenase-positive hippocampal neurones indicative of high mtDNA mutation load do not appear to be prone to apoptosis or to directly participate in the over production of tau or beta-amyloid. Biochemically significant mitochondrial defects do occur in AD and are likely to contribute to the overall central nervous system dysfunction in impairing neuronal function and possibly causing neurodegeneration via mechanisms other than apoptosis.

Aged↗

PubMed2002

The cellular response associated with cervical intraepithelial neoplasia in HIV+ and HIV- subjects.

This study investigates local alterations in T-cell and macrophage subsets that occur in cervical epithelial neoplasia (CIN), in the presence and absence of human immunodeficiency virus (HIV) infection. Ectocervical biopsies from 10 women with CIN who were infected with HIV, and 10 women with CIN but no HIV infection were studied by immunocytochemistry. Significantly increased proportions of activated CD8+ T cells were seen in all CIN biopsies, and these proportions were further increased in the presence of HIV infection. Levels of CD8+TIA-1+ cells were particularly increased in the CIN+HIV+ group. There was a lack of expression of CD28 on the CD8+ cells of the epithelium of CIN+HIV+ samples. A significant reduction in the proportion of epithelial inductive D1+ macrophages and an increase in D1+D7+-suppressive cells were observed in the CIN+HIV+ cohort. The lack of expression of CD28 on the CD8+ cells of the epithelium of CIN+HIV+ samples in combination with the reduced CD4+ T-cell numbers seen in the presence of HIV infection may contribute to the development of higher grade CIN in this susceptible group. This may be aggravated by the reduction in the D1+ epithelial inductive macrophages, which might reflect recruitment of more suppressive D1+D7+ cells. This would further compromise the ability of the local T-cell system to respond to antigens and thus contribute to the development of neoplasia at this site. These results suggest that the increase in activated CD8+ T cells is a consequence rather than a cause of CIN.

Adolescent↗

PubMed2002

The changing demographics of new HIV diagnoses at a London centre from 1994 to 2000.

OBJECTIVE: To document the demographic changes in new HIV diagnoses at the Royal Free Hospital, London, UK, between 1994 and 2000. DESIGN: Retrospective case note review. METHODS: Data were extracted from the Royal Free HIV database identifying new diagnoses for 1994, 1997 and 2000. All case notes were reviewed and patients were included if they had their first positive HIV test at the Royal Free Hospital, or if they first tested positive elsewhere and attended the Royal Free HIV unit for their initial HIV care. Data extracted included sex, ethnicity, age, risk factor(s) for HIV, reason for test, clinical stage of disease, CD4 count and HIV RNA viral load at diagnosis. RESULTS: One hundred and forty-four patients were identified for 1994, 136 for 1997 and 110 for 2000. Over this time period the proportion of white patients dropped from 72% (n = 104) to 48% (n = 53), P = 0.0001, whilst the proportion of black Africans rose from 24% (n = 34) to 45% (n = 49), P = 0.0004. The median CD4 count at diagnosis of the white cohort was 475 cells/microL in 1994 and 286/microL in 2000, P = 0.005, whilst in the black African patients it was 240/microL and 230/microL for the same years. CONCLUSIONS: There has been a reduction in new HIV diagnoses among the white population and a rise in the black Africans at this centre between 1994 and 2000. The clinical and immunological parameters of HIV disease have worsened over this time period for the white group, but have remained stable in the black Africans.

Black or African American↗

PubMed2002

Immune reconstitution pneumonitis following Pneumocystis carinii pneumonia in HIV-infected subjects.

An HIV-infected man presented with a pneumonic illness following an episode of treated Pneumocystis carinii pneumonia (PCP). He had a rise in his CD4 count from 4 to 125 cells/microL on antiretroviral therapy prior to the onset of the second respiratory event. Bronchoalveolar lavage (BAL) revealed no pathogen, although a CD4 lymphocytosis in addition to a highly unusual population of rapidly proliferating CD8 cells was demonstrated. Following 2 weeks of steroid and anti-pneumocystis therapy, a repeat bronchoscopy demonstrated that the expression of these markers had returned to low values. This second respiratory illness, which may have arisen as a consequence of the regenerating immune response reacting to residual P. carinii antigen in the lung, is apparently not rare. When we reviewed our case notes, five further individuals were identified that had started antiretroviral therapy following an episode of PCP and subsequently developed a self-limiting pneumonitis for which no pathogen was identified on bronchoscopy.

AIDS-Related Opportunistic Infections↗

PubMed2002

Acute demyelinating encephalomyelitis (ADEM) in a patient with HIV infection.

A case of acute demyelinating encephalomyelitis (ADEM) in a patient with HIV infection is reported. Although the diagnosis of ADEM is based on clinical and radiological findings, the potential for full recovery, with appropriate treatment, is highlighted by this case. A concise review of the subject is given in the discussion.

Acute Disease↗

PubMed2002

Osteonecrosis of the knee in a patient receiving antiretroviral therapy.

A case of avascular osteonecrosis of the right knee is described in a patient with HIV infection. The patient had been receiving highly active antiretroviral therapy for two years prior to presentation. Osteonecrosis is an uncommon albeit serious complication of HIV infection and is associated with use of antiretroviral agents.

Adult↗