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Biomedical subjects

L Perrin

Publications and source records attributed to L Perrin.

At least 37 records · Page 2Linked to original sources
PubMed2001

The significance of psammoma bodies on cervical cytology smears.

OBJECTIVE: The association between psammoma bodies on cervical smear (PBCS) and the presence of gynecological malignancy has been documented previously. The aim of this study was to determine the incidence of malignancy where psammoma bodies were detected on smear, to identify features that may be predictive of associated malignancy, and to make recommendations about management. METHODS: The databases of two large private pathology laboratories were accessed to obtain details of all patients reported to have PBCS between April 1992 and May 2000. A retrospective review was then undertaken to determine if any patients were found to have gynecological malignancies. The appearances of the background cells on the cervical smear and details of clinical management were recorded and evaluated. RESULTS: Twenty-two patients were found to have PBCS. Five patients were found to have a gynecological malignancy. These five patients were significantly older than the remaining patients. When these results were combined with all cases reported in the world literature, it became apparent that patients with coexisting malignancy were statistically significantly older than those not found to have malignancy (P < 0.0001). The cytological appearance of cells on the background smear was highly predictive of the presence or absence of malignancy. CONCLUSIONS: There is an association between PBCS and genital tract malignancy. This association is much stronger for postmenopausal women. The background cytology is highly predictive of the presence of associated malignancy. There is a strong argument that all women with psammoma bodies on cervical smear should undergo smear review, pelvic ultrasonography, hysteroscopy and biopsy, and laparoscopy to exclude the presence of a gynecological malignancy. For younger reproductive-aged women, a negative workup is reassuring.

Adult↗
PubMed2001

Diagnosis and management of urinary incontinence in the older patient.

OBJECTIVES: To review the various causes of urinary incontinence (UI) in elderly patients and to outline a therapeutic approach to the clinical management of UI. DATA SOURCES: Online search of MEDLINE and additional references selected from the articles found during the search. STUDY SELECTION: All peer-reviewed articles and review articles listed on MEDLINE published between 1966 and 1999. Key search terms included urinary incontinence, geriatric, aging, pelvic floor rehabilitation, and indwelling catheter. DATA EXTRACTION: Articles with clinical relevance to the geriatric population were selected based on the robustness of the studies and reviews. If applicable, data from studies of healthier or younger populations was extrapolated to the elderly population examined in this review. DATA SYNTHESIS: UI is a common occurrence among older adults treated in rehabilitation settings. The causes of UI in the elderly vary, including transient causes, established pathologic states of the urinary tract, and systemic multifactorial influences. Both behavioral and pharmacologic management strategies can successfully be implemented for UI, even in the frail elderly. CONCLUSION: UI can be effectively investigated and treated by rehabilitation practitioners by following a simple, stepwise approach.

Aged↗
PubMed2001

Primary Bartholin gland carcinoma: a report of seven cases.

This study reviews our experience with 7 patients with primary Bartholin gland cancer (BGC) treated at the Queensland Gynaecological Cancer Centre (QCGC) and compares this with previously published data. A retrospective clinicopathologic review of all patients with primary BGC treated at QCGC from 1988 to 2000 was performed. Of the 7 patients treated, all underwent primary surgery and 5 of the 7 patients received radiotherapy postoperatively. All patients presented with a local swelling or a lump. Two had associated discharge and 2 had associated pain. Of the 7 patients, 2, 3 and 2 respectively were classified as having Stage IB, II or III disease. Five of the 7 patients had squamous cell carcinoma (SCC), one had adenoid-cystic carcinoma and 1 had a small-cell neuroendocrine cancer of the Bartholin gland. None of the patients with SCC developed recurrent disease. The patient with adenoid-cystic carcinoma experienced local recurrences at 4 years and again at 5 years and 3 months. Nine years after primary treatment she was diagnosed with pulmonary metastases. The patient with small-cell neuroendocrine cancer of the Bartholin gland was considered tumour-free after operation. Thorough imaging, including a CT scan of her chest, abdomen and pelvis showed no evidence of disease. She died 1 year and three months after diagnosis from disseminated pulmonary disease. We present the first report of small cell neuroendocrine cancer of the Bartholin gland. Therapeutic principles in the management of vulval cancer at other sites appear to be appropriate for management of BGC.

Adult↗
PubMed2001

Resistance to nucleoside analog reverse transcriptase inhibitors mediated by human immunodeficiency virus type 1 p6 protein.

Resistance of human immunodeficiency virus type 1 (HIV-1) to antiretroviral agents results from target gene mutation within the pol gene, which encodes the viral protease, reverse transcriptase (RT), and integrase. We speculated that mutations in genes other that the drug target could lead to drug resistance. For this purpose, the p1-p6(gag)-p6(pol) region of HIV-1, placed immediately upstream of pol, was analyzed. This region has the potential to alter Pol through frameshift regulation (p1), through improved packaging of viral enzymes (p6(Gag)), or by changes in activation of the viral protease (p6(Pol)). Duplication of the proline-rich p6(Gag) PTAP motif, necessary for late viral cycle activities, was identified in plasma virus from 47 of 222 (21.2%) patients treated with nucleoside analog RT inhibitor (NRTI) antiretroviral therapy but was identified very rarely from drug-naïve individuals. Molecular clones carrying a 3-amino-acid duplication, APPAPP (transframe duplication SPTSPT in p6(Pol)), displayed a delay in protein maturation; however, they packaged a 34% excess of RT and exhibited a marked competitive growth advantage in the presence of NRTIs. This phenotype is reminiscent of the inoculum effect described in bacteriology, where a larger input, or a greater infectivity of an organism with a wild-type antimicrobial target, leads to escape from drug pressure and a higher MIC in vitro. Though the mechanism by which the PTAP region participates in viral maturation is not known, duplication of this proline-rich motif could improve assembly and packaging at membrane locations, resulting in the observed phenotype of increased infectivity and drug resistance.

Amino Acid Sequence↗
PubMed2001

The Drosophila tumor suppressor gene lethal(2)giant larvae is required for the emission of the Decapentaplegic signal.

The Drosophila tumor suppressor gene lethal(2) giant larvae (lgl) encodes a cytoskeletal protein required for the change in shape and polarity acquisition of epithelial cells, and also for asymmetric division of neuroblasts. We show here that lgl participates in the emission of Decapentaplegic (Dpp), a member of the transforming growth factor beta (TGFbeta) family, in various developmental processes. During embryogenesis, lgl is required for the dpp-dependent transcriptional activation of zipper (zip), which encodes the non-muscle myosin heavy chain (NMHC), in the dorsalmost ectodermal cells - the leading edge cells. The embryonic expression of known targets of the dpp signaling pathway, such as labial or tinman was abolished or strongly reduced in lgl mutants. lgl mutant cuticles exhibited phenotypes resembling those observed in mutated partners of the dpp signaling pathway. In addition, lgl was required downstream of dpp and upstream of its receptor Thickveins (Tkv) for the dorsoventral patterning of the ectoderm. During larval development, the expression of spalt, a dpp target, was abolished in mutant wing discs, while it was restored by a constitutively activated form of Tkv (Tkv(Q253D)). Taking into account that the activation of dpp expression was unaffected in the mutant, this suggests that lgl function is not required downstream of the Dpp receptor. Finally, the function of lgl responsible for the activation of Spalt expression appeared to be required only in the cells that produce Dpp, and lgl mutant somatic clones behaved non autonomously. We therefore position the activity of lgl in the cells that produce Dpp, and not in those that respond to the Dpp signal. These results are consistent with a same role for lgl in exocytosis and secretion as that proposed for its yeast ortholog sro7/77 and lgl might function in parallel or independently of its well-documented role in the control of epithelial cell polarity.

Animals↗
PubMed2001

Drug resistance mutations in HIV-1-infected subjects during protease inhibitor-containing highly active antiretroviral therapy with nelfinavir or indinavir.

OBJECTIVES: The aim of this retrospective study was to evaluate treatment outcome and characterize the pattern of genotype mutations in subjects with treatment failure on highly active antiretroviral therapy (HAART) containing nelfinavir or indinavir. STUDY DESIGN AND METHODS: The database of the Swiss HIV Cohort Study was screened for all subjects naive to protease inhibitor (PI) treatment who started HAART with nelfinavir or indinavir, responded initially (HIV-RNA <400 copies/ml) and received >24 weeks of treatment. Responders with subsequent treatment failure (HIV-RNA >1000 copies/ml, bordered by HIV-RNA >400 copies/ml) were selected for genotypic analysis. RESULTS: Initial treatment response, maintenance of response and subsequent virological failure were observed at a comparable frequency in 1143 nelfinavir and 1555 indinavir subjects. Of the treatment-naive patients, 13% who took nelfinavir and 16% who took indinavir had HIV-RNA >1000 copies/ml at least once. These values increased to 24 and 27%, respectively, for reverse transcriptase inhibitor-experienced subjects. Genotypic analysis in a subset of subjects with virological failure identified 30N as the only primary mutation in the nelfinavir subjects (8 out of 21, 38%) whereas isolated or combined 82A/T and 461/L mutations were detected in the indinavir subjects (9 out of 20, 45%). CONCLUSIONS: In this population of previously PI-naive subjects, the rate of virological failure and the frequency of resistance mutations at the time of virological failure were comparable in subjects receiving nelfinavir- or indinavir-containing HAART. In nelfinavir subjects, 30N was the only primary mutation whereas isolated or combined 82A/T and 461/L mutations were detected in indinavir subjects.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Decay of cell-associated HIV-1 DNA correlates with residual replication in patients treated during acute HIV-1 infection.

OBJECTIVES: To evaluate the decay rate of cell-associated HIV-1 RNA and DNA and to identify factors associated with residual viral load in patients treated at the time of primary HIV-1 infection. PATIENTS: A group of 15 patients adherent to highly active antiretroviral therapy (HAART) with sustained undetectable HIV-1 viremia for at least 24 months. METHODS: Viremia, cell-associated HIV-1 RNA and DNA in blood and lymph node mononuclear cells were measured using ultrasensitive assays. RESULTS: Viremia decreased rapidly in all patients; HIV RNA remained < 3 copies/ml in nine patients and fluctuated between 3 and 50 copies/ml in five patients and between 50 and 200 copies/ml in one patient. Decay rates of cell-associated RNA and DNA presented an inflexion point at 1 and 3 months, respectively: first-phase mean half-lives were 0.15 and 0.84 months, respectively, and second-phase mean half-lives were 13.7 and 6.6 months, respectively (95% confidence interval 4.4-13.8). The second phase decay rates were markedly slower, with a DNA decay rate that was highly associated with the mean levels of cell-associated RNA measured in blood from 6 to 33 months (P= 0.001) and in lymph nodes collected at 14 months (P= 0.02). CONCLUSIONS: The clearance of HIV-1 infected cells is correlated with the extent of viral replication as measured by cell-associated RNA levels in both blood and lymph nodes. Quantification of cell-associated RNA and DNA further defines treatment efficacy in 'aviremic' patients.

Adult↗
PubMed2000

Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent among HIV-1-infected individuals, but its contribution to the morbidity and mortality of coinfected patients who receive potent antiretroviral therapy is controversial. We used data from the ongoing Swiss HIV Cohort Study to analyse clinical progression of HIV-1, and the virological and immunological response to potent antiretroviral therapy in HIV-1-infected patients with or without concurrent HCV infection. METHODS: We analysed prospective data on survival, clinical disease progression, suppression of HIV-1 replication, CD4-cell recovery, and frequency of changes in antiretroviral therapy according to HCV status in 3111 patients starting potent antiretroviral therapy. RESULTS: 1157 patients (37.2%) were coinfected with HCV, 1015 of whom (87.7%) had a history of intravenous drug use. In multivariate Cox's regression, the probability of progression to a new AIDS-defining clinical event or to death was independently associated with HCV seropositivity (hazard ratio 1.7 [95% CI 1.26-2.30]), and with active intravenous drug use (1.38 [1.02-1.88]). Virological response to antiretroviral therapy and the probability of treatment change were not associated with HCV serostatus. In contrast, HCV seropositivity was associated with a smaller CD4-cell recovery (hazard ratio for a CD4-cell count increase of at least 50 cells/microL=0.79 [0.72-0.87]). INTERPRETATION: HCV and active intravenous drug use could be important factors in the morbidity and mortality among HIV-1-infected patients, possibly through impaired CD4-cell recovery in HCV seropositive patients receiving potent antiretroviral therapy. These findings are relevant for decisions about optimum timing for HCV treatment in the setting of HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed2000

Long-term hydroxyurea in combination with didanosine and stavudine for the treatment of HIV-1 infection. Swiss HIV Cohort Study.

OBJECTIVE AND METHODS: In 1998 we reported on a randomized comparison between stavudine plus didanosine plus placebo versus stavudine plus didanosine plus hydroxyurea (HU), in patients with a CD4 count of 200-500 x 10(6) cells/l. After 3 months, the HU group had a higher proportion of patients with viral load < 200 x 10 cells/l. At the end of the 3 months blinded period, patients in the placebo group had the option to add HU if their viral load remained > 200 x 10(6) cells/l. We report results after 24 months. RESULTS: Seventy-two patients were randomized to the HU arm, and a further 30 elected to add HU after 12 weeks. Twenty-four months after the start of the trial, only 25% of the 72 patients originally randomized to HU, and 20% of the 30 who added HU after week 12, were still taking it. The reasons for stopping HU were: lack of efficacy (45%), adverse events (37%) and patient or physician preference (18%). Side effects were more frequent in the didanosine/stavudine/HU group than in the didanosine/stavudine group: neuropathy (35 versus 15%, P< 0.02), fatigue (22 versus 7%, P< 0.01), and nausea or vomiting (26 versus 9%, P< 0.01). Of those who had discontinued HU, 73% were taking three drugs including a protease inhibitor. Patients who had started HU were compared with similar patients who had started protease inhibitors in the Swiss cohort. The probability of stopping HU was higher than the probability of stopping nelfinavir or indinavir, and similar to the probability of stopping ritonavir. CONCLUSION: HU increased the antiviral effect of stavudine plus didanosine. However, side effects were more frequent, and after 24 months the majority of patients had switched to protease inhibitor regimens.

Anti-HIV Agents↗
PubMed2000

Immunological and virological responses in HIV-1-infected adults at early stage of established infection treated with highly active antiretroviral therapy.

OBJECTIVE: To evaluate the immunological and virological responses to highly active antiretroviral therapy (HAART) in blood and lymphoid compartments of HIV-1-infected patients at an early stage of infection. DESIGN: An open-label, observational, non-randomized, prospective trial of outpatients attending the Centre of Clinical Investigation in Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. SUBJECTS: Forty-one antiretroviral-naive HIV-1-infected adults with 400 CD4 T cells/microl or greater and 5000 plasma HIV-1-RNA copies/ml or greater were enrolled, and 32 finished the study. Forty-nine HIV-negative individuals were included as controls. All subjects gave written informed consent. INTERVENTIONS: All patients received abacavir 300 mg by mouth every 12 h and amprenavir 1200 mg by mouth every 12 h for 72 weeks. MAIN OUTCOME MEASURES: The extent of immune reconstitution in blood and lymph nodes after 72 weeks of HAART was evaluated, and compared with immunological measures of 49 HIV-negative subjects. RESULTS: Virus replication was effectively suppressed (-3.5 log10 at week 72). Substantial increments of CD4 T cell count in blood and percentage in lymph nodes were observed over time, and these measures were comparable to HIV-negative subjects by week 24 in blood and by week 48 in lymph nodes. The increase was equally distributed between naive and memory CD4 T cells. Recovery of HIV-specific CD4 responses occurred in 40% of patients. CONCLUSION: The initiation of HAART at an early stage of established HIV infection induces systemic quantitative normalization of CD4 T cells, a partial recovery of HIV-specific CD4 cell responses, and effective and durable suppression of virus replication.

Adolescent↗
PubMed2000

Virological and immunological effects of combination antiretroviral therapy with zidovudine, lamivudine, and indinavir during primary human immunodeficiency virus type 1 infection.

Forty-seven patients presenting with primary human immunodeficiency virus (HIV) infection were treated with zidovudine 200 mg 3 times a day, lamivudine 150 mg 2 times a day, and indinavir 800 mg 3 times a day for 1 year. From a mean pretreatment viral RNA level of 4.93 log(10) copies/mL, the proportions of patients having <500 copies/mL at 24 and 52 weeks were 92.0% and 89.2%, respectively. For the 35 patients with data available at 24 and 52 weeks, the corresponding proportions for the <50 copies/mL analysis were 86.6% and 79.3%, respectively. The change in virus load was -2.19 and -2.41 log(10) copies/mL at weeks 8 and 52, respectively. CD4 cell counts increased, from a mean of 546 cells/mm(3), by 142 cells/mm(3) at week 24 and by 210 cells/mm(3) at week 52. Three patients discontinued the study because of drug-related toxicity. Six (12.8%) patients had adverse experiences associated with nephrolithiasis. Combination therapy with zidovudine, lamivudine, and indinavir during primary HIV infection results in a profound and sustained reduction in virus load with concurrent recovery of the CD4 cell population.

Adult↗
PubMed2000

Incubation time of acute human immunodeficiency virus (HIV) infection and duration of acute HIV infection are independent prognostic factors of progression to AIDS.

The severity and the duration of acute human immunodeficiency virus (HIV) infection (AHI) are associated with a faster rate of progression to AIDS, but the prognostic value of the length of incubation time of AHI (IncAHI), defined as the time between HIV infection and AHI, on progression to AIDS has not been assessed. We explored this issue prospectively in 70 individuals with documented AHI and a known date of HIV infection. The median IncAHI was 21.5 days (range, 5-70 days), and the median duration of AHI was 15.5 days (range, 3-67 days). The adjusted relative hazard of progression to AIDS or to a CD4(+) count <200x103/mL was 4.23 (95% confidence interval [CI], 1.40-12.73; P=.01) for the patients with an IncAHI <21.5 days, compared with those with longer IncAHI, and was 3.53 (95% CI, 1.09-11.36; P=.03) for the patients with a duration of AHI >15.5 days, compared with those with shorter duration. Both IncAHI and duration of AHI were independent predictors of progression. This suggests that early pathogenic events before the onset of AHI influence the rate of HIV disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Comparison of clinical features, CD4 and CD8 responses among patients with acute HIV-1 infection from Geneva, Seattle and Sydney.

OBJECTIVE: To compare the clinical features and T-cell subsets among 160 patients with acute HIV-1 infection not treated with antiretroviral agents from three different locations (Geneva, Seattle and Sydney). DESIGN: Patients with documented acute HIV-1 infection were enrolled in four prospective studies: one randomized placebo controlled trial (RCT) and three observational cohort studies. SETTING: All patients were diagnosed and followed in three university affiliated tertiary clinical care centers. METHODS: The chi-square test was used for comparing proportions and one way analysis of variance (ANOVA) for comparing continuous variables among these groups. Multiple regression analysis was used to identify the variables independently associated with the duration of acute HIV-1 infection. The differences in mean CD4 and CD8 load between centers were assessed using the random-effect models for the longitudinal data. RESULTS: Minor differences were noted in the frequency of symptoms among subjects enrolled at different locations. RCT patients reported a longer duration of symptoms (31 days) compared with that for observational patients (15 days; P < 0.0001). For the most common symptoms such as fever, skin rash, arthralgia, myalgia, and headaches, a longer duration was observed in the RCT group compared with that for observational patients (P range, 0.001 to < 0.0001). T-cells subsets within 100 days of seroconversion did not statistically differ by centre or by mode of recruitment. CONCLUSIONS: These results suggest a selection bias toward patients with longer symptomatic acute HIV-1 infection enrolled in the RCT. Data collected from RCT are not comparable to that collected in observational studies. However, data from collaborative international studies can be combined.

CD4 Lymphocyte Count↗
PubMed2000

Time of initiation of antiretroviral therapy: impact on HIV-1 viraemia. The Swiss HIV Cohort Study.

OBJECTIVE: The current recommendation that patients infected with HIV-1 be treated early is based on little evidence. We examined whether the early initiation of antiretroviral treatment affects residual HIV-1 viraemia. METHODS: Viraemia was measured using an assay with a detection limit of 3 HIV-1 RNA copies/ml in drug-naive patients who started antiretroviral therapy at the time of primary HIV-1 infection (PHI) (n = 10), during chronic infection without immune suppression (CD4 cell counts > or = 500/mm3; median 577) (n = 10), or after immune suppression developed (CD4 cell counts < 500/mm3; median 113) (n = 21). RESULTS: In 249 samples collected 24 to 120 weeks after treatment initiation, the mean proportion of samples with HIV-1 RNA levels of less than 3 copies/ml was 75% for PHI patients compared with 32 and 8% for immunocompetent and immunosuppressed chronically infected patients, respectively. Fifty per cent of PHI patients, but none of the chronically infected patients, had persistently fewer than 3 HIV-1 RNA copies/mL. PHI patients had lower residual HIV-1 RNA levels than chronically infected patients, and immunocompetent patients had lower residual HIV-1 RNA levels than immunosuppressed patients (all pairwise, P< 0.001). The mean residual HIV-1 RNA level was independently associated with the initiation of therapy during PHI and baseline CD4 cell counts (P < 0.001 for both associations). CONCLUSION: Viraemia levels are associated with clinical progression and predict virological treatment failure. The initiation of antiretroviral therapy at the time of PHI and while CD4 cell counts are high results in lower residual viraemia. These results support early antiretroviral therapy in HIV-1-infected patients.

Anti-HIV Agents↗
PubMed2000

Cognitive bias in eating disorders: interpretation of ambiguous body-related information.

Three groups of women: eating disorder, body dysphoric controls, and nonsymptomatic controls, participated in an experiment testing hypotheses derived from cognitive-behavioral theories of eating disorders. In phase 1, participants encoded ambiguous information via instructions to imagine themselves in a variety of ambiguous situations that involved two types of information: body-related or health-related. On a subsequent memory task, participants in the eating disorder group and the body dysphoric control group recalled imagery of the body-related situations with a fatness interpretation and participants in the nonsymptomatic control group recalled imagery with a thinness interpretation. The three groups did not differ in their interpretation of the health-related situations. In phase 2, participants were instructed to imagine themselves in each body-related situation, but were explicitly instructed to imagine the scenes with either a positive or negative interpretation. Results indicated that the eating disorder and body dysphoric groups were able to change their interpretation of body-related information when instructed to do so.

Adult↗