Preventing HIV-1: lessons from Mwanza and Rakai.
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Biomedical subjects
Publications and source records attributed to A M Johnson.
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PURPOSE: To evaluate function and assess incidence of complications relating to upper extremity implanted venous access devices placed in oncology patients primarily for chemotherapy. MATERIALS AND METHODS: The authors retrospectively evaluated the clinical course of 205 upper extremity implanted venous access devices placed with fluoroscopic and sonographic guidance in 204 patients during a 2-year period. All patients had a diagnosis of malignancy for which chemotherapy was planned. Follow-up data were collected by patient examination, direct evaluation of device function, as well as chart review and review of relevant imaging procedures. A modified technique for device placement is described. RESULTS: The devices were placed successfully on the initial attempt in all cases. Clinical follow-up was obtained for 195 devices (95.1%) for a total device service period of 33,619 days (mean service interval = 169 days). Seventy-eight devices (40%) had service intervals greater than 180 days. Thirty-seven devices (19% of total devices) led to 39 complications (0.116 event/100 days). No immediate procedural complications were incurred. Eight complications occurred after 180 days of port service. Nineteen devices (9.7% of total devices followed) required removal as a result of complication. Common complications included port malfunction requiring urokinase to clear (n = 10; 0.030 event/100 days), ipsilateral upper extremity deep venous thrombosis (n = 9; 0.027), and local infection (n = 7, 0.021). A comparison of these results relative to other published series of similar devices placed for mixed indications is presented. CONCLUSIONS: Implanted venous access devices are an effective means of long-term venous access in oncology patients. Complication rates in this large series compared favorably to other published radiologic and surgical series. Analysis of complications in a subgroup of extended use implanted venous access devices (greater than 180 days follow-up) showed no statistically significant (P < .05) difference from the larger group of devices.
The aim of this study was to compare cancer incidence in a cohort of HIV-infected patients with the incidence rates in the population of South East England. Data collected for a retrospective cohort study of 2048 HIV-infected patients were analysed to examine the incidence of cancer. Cases of cancer occurring in South East England from 1985-1995 were obtained from the Thames Cancer Registry. Standardized incidence ratios were calculated by comparison of the observed number of cases for each cancer type in HIV-infected non-Africans with the numbers expected, calculated from the age and sex specific registration rates for the South East England population using person-years of observation. The crude incidence rates of cancer were calculated for HIV-infected Africans. The incidence of non-AIDS defining cancers such as Hodgkin's disease (standardized incidence ratio 22; 95% CI: 3-80) and anal cancer (standardized incidence ratio 125; 95% CI: 3-697) were significantly increased for non-African males with HIV disease. Anal cancer was also significantly increased for non-African females (standardized incidence ratio 1667; 95% CI: 43-9287). Kaposi's sarcoma (KS) was the commonest cancer among HIV-infected Africans and males had an incidence which was nearly 3 times that of females. There is evidence to suggest that the risks for other non-AIDS defining cancers were significantly increased in persons with HIV disease which may have implications for HIV/AIDS surveillance.
Levels of several plasma proteins, including albumin, transferrin, and transthyretin (prealbumin), have been proposed as markers for protein energy malnutrition. However, many other factors, especially inflammatory disease and drug or hormone therapy, affect levels of these proteins. These factors probably account for the majority of low levels of transthyretin. Levels of albumin and other proteins may be helpful in determining increased risk of morbidity and mortality, but better markers are needed for diagnosis of protein energy malnutrition per se.
OBJECTIVE: To identify risk factors for the acquired immune-deficiency syndrome (AIDS) associated with tuberculosis, in patients with AIDS attending 11 of the largest human immunodeficiency virus (HIV)/AIDS Units in London. DESIGN: Case-control study nested in a retrospective cohort of 2048 HIV-1 positive patients. Cases were defined as patients with a definitive diagnosis of tuberculosis, and controls as patients with AIDS and without tuberculosis during follow-up. RESULTS: Of 627 patients diagnosed with AIDS, 121 had a definitive diagnosis of tuberculosis. Significant risk factors for tuberculosis in the univariate analysis were sex, ethnicity, age, HIV exposure category and hospital attended, and in the multiple regression analysis ethnicity, age and hospital attended. African ethnicity was the strongest risk factor for tuberculosis (adjusted odds ratio [AOR] 5.9, 95% confidence interval 3.4-10.2). The risk of tuberculosis was higher in the younger age groups (test for trend P < 0.001). The hospital-associated risk of tuberculosis was more heterogeneous in the non-African group, and non-Africans attending Hospital 1 had an increased risk of tuberculosis which was statistically significant. CONCLUSIONS: The risk factors for AIDS-associated tuberculosis in London are sub-Saharan African origin, younger age group, and, among the non-Africans only, attending one hospital in east London. Different transmission patterns and mechanisms for the development of tuberculosis may operate in different settings depending on the background risk of tuberculous infection. Screening for tuberculosis infection and disease among HIV-positive individuals in London is important for the provision of preventive or curative therapy, and prophylaxis policies need to be designed in accordance with the transmission patterns and mechanisms of disease.
OBJECTIVE: To characterize the antinuclear antibody (ANA) titer distributions and patterns in normal subjects, segregated by age and sex. METHODS: Sera were obtained from 183 blood donors (130 females, 53 males) aged 20-63 years, from 200 schoolchildren (100 females, 100 males) aged 10-19 years, and from 237 children (102 females, 135 males) aged 3 months to 9 years whose sera were received for unrelated clinical testing. ANA was assayed by indirect immunofluorescence using HEp-2 cells as substrate. RESULTS: In adults, ANA titers were slightly higher in females than in males (p=0.053); there was no sex effect in subjects aged <20 years. ANA titer increased significantly with age only among females (p<0.01). Homogeneous staining was associated with lower titers than speckled or nucleolar staining (p=0.058), at least in part because of antigen density in the test substrate itself. The frequency of cytoskeletal staining decreased (p<0.01) with age, while that of nucleolar staining increased (p<0.01). CONCLUSION: Reference ranges for ANA vary by age, sex, and immunofluorescence pattern. Therefore, all these variables must be considered in the interpretation of ANA results.
The gene encoding the catalytic subunit of the Toxoplasma gondii DNA polymerase alpha enzyme has been isolated. The coding region is 6487 bp in length, containing three introns, and specifies a protein of 1690 aa. The seven conserved regions which characterize the polalpha polypeptide, as well as four of the five polalpha-specific aa domains, were found in the T. gondii gene. The absence of one of these domains, as well as the presence of a unique cysteine cluster between domains IV and B in the T. gondii polalpha, may result in a slight difference in the secondary or even tertiary structure compared with the human homologue and thus may be suitable for designing anti-Toxoplasma drugs. A number of amino acid differences within the seven conserved regions between the human and T. gondii polalpha, as well as variations in the spacings of these regions, were also observed.
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OBJECTIVE: To examine differences in progression to AIDS and death between HIV-1-positive Africans (most infected in sub-Saharan Africa and therefore with non-B subtypes) and HIV-1-positive non-Africans in London. DESIGN: Retrospective cohort study of 2048 HIV-1-positive individuals. SETTING: HIV-1-infected individuals attending 11 of the largest HIV/AIDS units in London. PATIENTS: Subjects were 1056 Africans and 992 non-Africans seen between 1982-1995. RESULTS: There were no differences in crude survival from presentation to death between Africans and non-Africans (median 82 and 78 months, respectively; P = 0.22). Africans progressed more rapidly to AIDS [hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.02-1.45] but after adjustment for age, sex, Centers for Disease Control and Prevention category B symptoms and CD4+ lymphocyte count at presentation, year of HIV diagnosis and hospital attended, this difference was no longer significant (adjusted HR, 1.15; 95% CI, 0.93-1.43). Africans with AIDS had a reduced risk of death compared with non-Africans (HR, 0.78; 95% CI, 0.63-0.96) but not after adjustment for age, CD4+ lymphocyte count at AIDS, initial AIDS-defining conditions (ADC) and hospital attended (HR, 0.98; 95% CI, 0.76-1.27). Tuberculosis as the first ADC was associated with a 64% reduction in the risk of death. CD4+ lymphocyte decline was not significantly different between Africans and non-Africans (P = 0.18). CONCLUSIONS: Differences in progression to AIDS and death and CD4+ lymphocyte decline between HIV-1-infected Africans and non-Africans in London could not be attributed to ethnicity or different viral subtypes. Age and the clinical and immunological stage at presentation, or AIDS, were the major determinants of outcome. Compared with other diagnoses, tuberculosis as the initial ADC was associated with increased survival. Lack of access to health care and exposure to environmental pathogens are the most likely causes of reduced survival with AIDS in Africa, rather than inherently different rates of progression of immune deficiency due to racial differences or viral subtypes.
OBJECTIVE: To assess the impact of specific AIDS-defining conditions on survival in HIV-infected persons, with emphasis on the effect of tuberculosis. METHODS: A retrospective cohort analysis of HIV-infected Africans and non-Africans attending 11 specialist HIV/AIDS units in London enrolled for a comparison of the natural history of HIV/AIDS in different ethnic groups. RESULTS: A total of 2048 patients were studied of whom 627 (31%) developed 1306 different AIDS indicator diseases. Pneumocystis carinii pneumonia accounted for 159 (25%) of initial AIDS episodes and tuberculosis for 103 (16%). In patients with HIV disease, tuberculosis had the lowest risk [relative risk (RR), 1.11; 95% confidence interval (CI), 0.75-1.63], and high-grade lymphoma had the highest risk (RR, 20.56; 95% CI, 2.70-156.54) for death. For patients with a prior AIDS-defining illness, the development of subsequent AIDS indicator diseases such as Pneumocystis carinii pneumonia (RR, 1.18; 95% CI, 0.77-1.83) and tuberculosis (RR, 1.36; 95% CI, 0.76-2.47) had the best survival, and non-Hodgkin's lymphoma had the worst survival (RR, 9.67; 95% CI, 1.26-74.33). Patients with tuberculosis had a lower incidence of subsequent AIDS-defining conditions than persons with other initial AIDS diagnoses (rate ratio, 0.47; 95% CI, 0.37-0.59). CONCLUSIONS: Considerable variation exists in the relative risk of death following different AIDS-defining conditions. The development of any subsequent AIDS-defining condition is associated with an increased risk of death that differs between diseases, and this risk should be considered when evaluating the impact of specific conditions. Like other AIDS-defining conditions, incident tuberculosis was associated with adverse outcome compared with the absence of an AIDS-defining event, but we found no evidence of major acceleration of HIV disease attributable to tuberculosis.
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OBJECTIVE: To evaluate the feasibility and effectiveness of a standardized HIV partner notification programme within genitourinary medicine clinics in England. DESIGN: A prospective survey of HIV partner notification activity over a 12-month period. SETTING: Nineteen genitourinary medicine clinics in England. PATIENTS AND PARTICIPANTS: A total of 501 eligible HIV-positive patients (either newly diagnosed or with whom partner notification had not been undertaken previously) seen during the study period. MAIN OUTCOME MEASURES: The numbers of partners named by patients, and the number of contacts notified, counselled and HIV-tested. RESULTS: Information on overall partner notification activity was obtained by reviewing available medical records of 471 patients; 353 (75%) had discussed partner notification with a health-care worker during the study period and 197 (42%) had undertaken partner notification. Detailed information on outcomes was obtained for only 70 patients who named 158 contacts as being at risk of acquiring HIV. Although 71 (45%) contacts were eventually notified, only 28 were subsequently seen in participating clinics. Almost all contacts (n = 27) requested HIV counselling and testing, and five were diagnosed HIV-positive. Patient referral was the most popular notification method chosen. CONCLUSIONS: This study illustrates some of the practical difficulties that limit HIV partner notification within genitourinary medicine clinics. These include health-care workers' misgivings about undertaking partner notification, insufficient locating information to identify contacts, and migration of newly diagnosed patients, which prevents continuity and completion of notification. Nevertheless, HIV partner notification uncovered previously undiagnosed HIV infections. Further work needs to be undertaken in staff training and policy implementation if higher rates of partner notification and outcome measurements are to be achieved.
A retrospective serological and genetic study of hantaviruses responsible for hemorrhagic fever with renal syndrome (HFRS) in Greece during the last 17 years is presented. Fifty-one serum samples taken from 30 HFRS cases previously diagnosed by immunofluorescence assay were tested by ELISA for IgG (Hantaan, Dobrava, and Puumala) and IgM antibodies (Hantaan and Puumala). Results were compatible with the majority of infections being related to hantaviruses carried by rodents of the subfamily Murinae. RNA was extracted from 26 selected samples and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using primers specifically designed for the detection of hanta-viruses associated with murine (MS-N-specific, MM-G1-specific primers) or arvicoline rodents (PPT-N-specific primers). In addition, primers previously designed for the detection of the G2 coding region of the Murine-associated hanta-viruses were also used. Sequencing of the PCR products was then performed, followed by phylogenetic analysis of nucleotide sequence differences. Eleven out of the 26 serum samples tested were found to be positive by PCR with the MS-N primers, whereas four were positive with the MM-G1 primers, and only two with the G2 primers. None of the samples was found positive with the PPT primers. The sequence analysis showed that the virus that was responsible for these 11 HFRS cases was the Dobrava virus, which is endemic throughout the Balkans.
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The IC intron, found within the DNA polymerase alpha gene of Toxoplasma gondii, was used to evaluate the genetic relationship among 10 strains of T. gondii. Sequence comparison detected polymorphisms within this 652 bp intron which correlated with murine virulence. The results reported here suggest that T. gondii contains two lineages, corresponding with their virulence, evolving independently following their separation. The extensive homology of the IC sequences within the virulent and avirulent groups affirms the close relationship of the strains within the group, as reflected by the identical nucleotide substitutions and dinucleotide insertions/deletions observed. In addition, the presence of the Nde I restriction enzyme site within the IC intron of avirulent strains allows definition of a T. gondii strain as murine virulent or avirulent without needing to test it in vivo.
This study compared the genes encoding cytoplasmic 70 kDa heat shock protein in virulent and avirulent strains of Toxoplasma gondii, to determine whether differences may contribute to the variation in protein expression levels previously reported for this protozoan parasite. A T. gondii PCR probe with homology to Eimeria acervulina cytoplasmic 70 kDa heat shock protein was used to screen a genomic DNA mini-library and isolate the gene from the virulent RH strain. The entire coding region was subsequently amplified from the avirulent ME49 strain by PCR. Alignment of the gene sequences revealed that the virulent RH strain had four copies of a seven-aa repeat unit (GGMPGGM) at the 3'- end of the gene compared with five copies in the avirulent ME49 strain. Comparison of this region among other virulent and avirulent strains revealed that this difference was consistent with virulence. Copy number estimation revealed that this gene is single-copy in both the RH and the ME49 strains. Analysis of mRNA expression revealed a 1.5- to 2-fold increase in transcription of this gene in virulent strains when compared with avirulent strains. For each strain, mRNA was observed at similar levels whether grown in vivo or in vitro. Also, heat-shock treatment of tachyzoites prior to harvest did increase mRNA levels in vitro. This suggests that post-transcriptional regulation of cytoplasmic 70 kDa heat shock protein may occur in T. gondii. Differences in cytoplasmic 70 kDa heat shock protein have been demonstrated at genomic and transcriptional levels in virulent strains compared with avirulent strains, suggesting that this 70 kDa heat shock protein may play an important role in the virulence of T. gondii.
In plant and algal cells, inhibition of the enzyme protoporphyrinogen oxidase (Protox) by the N-phenyl heterocyclic herbicide S-23142 causes massive protoporphyrin IX accumulation, resulting in membrane deterioration and cell lethality in the light. We have identified a 40.4 kb genomic fragment encoding S-23142 resistance by using transformation to screen an indexed cosmid library made from nuclear DNA of the dominant rs-3 mutant of Chlamydomonas reinhardtii. A 10.0 kb HindIII subclone (Hind10) of this insert yields a high frequency of herbicide-resistant transformants, consistent with frequent non-homologous integration of the complete RS-3 gene. A 3.4 kb XhoI subfragment (Xho3.4) yields rare herbicide-resistant transformants, suggestive of homologous integration of a portion of the coding sequence containing the mutation. Molecular and genetic analysis of the transformants localized the rs-3 mutation conferring S-23142 resistance to the Xho3.4 fragment, which was found to contain five putative exons encoding a protein with identity to the C-terminus of the A rabidopsis Protox enzyme. A cDNA clone containing a 1698 bp ORF that encodes a 563 amino acid peptide with 51% and 53% identity to Arabidopsis and tobacco Protox I, respectively, was isolated from a wild-type C. reinhardtii library. Comparison of the wild-type cDNA sequence with the putative exon sequences present in the mutant Xho3.4 fragment revealed a G-->A change at 291 in the first putative exon, resulting in a Val-->Met substitution at a conserved position equivalent to Val-389 of the wild-type C. reinhardtii cDNA. A sequence comparison of genomic Hind10 fragments from C. reinhardtii rs-3 and its wild-type progenitor CC-407 showed this G-->A change at the equivalent position (5751) within exon 10.
We developed a disease-specific 9-item Acne Quality of Life scale that is sensitive to changes in patient-rated indices of acne severity and the psychological morbidity that is associated with acne. Seventy patients with mild to moderate acne vulgaris completed a 12-item scale that was developed to assess both the social and vocational impacts of acne. Factor analysis revealed the presence of two dimensions underlying the quality of life construct. The first dimension consisted of 9 items and addressed the social impact of acne, while the second dimension consisted of 3 items and addressed the vocational impact of acne. Only the first dimension correlated with indices of acne severity, such as pustules and scarring, and all 3 scales correlated with a wide range of psychopathologic measures. The 9-item scale had a very high degree of internal consistency and test-retest reliability. This 9-item scale may be used to evaluate the relation between acne severity and quality of life, especially among mildly to moderately affected patients for whom quality of life issues are often a major consideration in deciding whether or not to institute therapies for the acne.