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Biomedical subjects

A Pan

Publications and source records attributed to A Pan.

At least 19 recordsLinked to original sources
PubMed2005

An RNAi system in Physcomitrella patens with an internal marker for silencing allows for rapid identification of loss of function phenotypes.

RNAi is a powerful method for generating loss of function mutants, especially for targeting genes belonging to large gene families. We have recently shown that RNAi functions in the moss Physcomitrella patens. We obtained stable lines that show constitutive silencing of a nuclearly localized GFP:GUS fusion protein (NLS:GFP:GUS). However, lines that display silencing of the protein do not necessarily have reduced transcript levels. Therefore, a system has been developed that silences the NLS:GFP:GUS reporter construct at the same time as it silences a gene of interest. Gateway (Invitrogen) recombination cassettes were incorporated into these vectors to facilitate cloning of many different cDNA sequences. In addition, vectors were generated that contain genomic moss DNA sequence information to increase the production of stable moss lines. Transformation with these constructs results in strong silencing within 24 h and is stable for at least a month after transformation. FtsZ2-1, whose loss of function phenotype is known, was incorporated as a test case for analyzing phenotypes. One hundred per cent of regenerating colonies that have silenced GFP exhibit a loss of function FtsZ2-1 phenotype, validating the use of this system to assay phenotypes for plant genes of unknown function.

Blotting, Northern↗
PubMed2005

Risk factors for myocardial infarction in HIV-positive patients.

We describe the clinical characteristics of 12 HIV-infected patients who suffered from myocardial infarction (MI) in our clinical cohort. They were compared with a control group matched (1:2) for factors related to cardiovascular risk (age, gender, smoking habit, risk factor for HIV acquisition, hypertension, family history for relevant cardiovascular events, and body mass index) by conditional (fixed-effect) logistic regression analysis. Among patients with MI, 6/12 had never used protease inhibitors (PIs) or were antiretroviral therapy naive. The only variables marginally associated with MI were nadir CD4+ T-cell count <50/mm(3) (odds ratio (OR): 7.2; 95% confidence interval (CI) 0.81-64.2; P: 0.077) and zenith >100,000 HIV RNA copies/mL (OR: 7; 95% CI 0.81-60.2; P: 0.076) at univariate analysis. Moreover, the use of PIs did not result in being associated with the risk of MI. Our data show that in HIV-infected patients, PI use does not seem to have any negative impact on MI while the possible impact of advanced HIV infection itself needs further investigations.

Adult↗
PubMed2004

Acute ophthalmoparesis in the anti-GQ1b antibody syndrome: electrophysiological evidence of neuromuscular transmission defect in the orbicularis oculi.

OBJECTIVE: To prospectively study anti-GQ1b antibody positive cases of acute ophthalmoparesis (AO) clinically and electrophysiologically. METHODS: Nine consecutive cases presenting with predominantly acute ophthalmoplegia were assessed clinically and had stimulated single fibre electromyography (SFEMG) of the orbicularis oculi at presentation. All had magnetic resonance imaging brain scans and anti-GQ1b antibody titres determined. RESULTS: Four cases had elevated anti-GQ1b antibody titres and abnormal SFEMG studies, which improved in tandem with clinical recovery over three months. Five other anti-GQ1b antibody negative cases were diagnosed as diabetic related cranial neuropathy, idiopathic cranial neuropathy, ocular myasthenia gravis, and Tolosa-Hunt syndrome. All five cases showed complete recovery over a three month period. CONCLUSIONS: This study demonstrated electrophysiologically the dynamic improvement of neuromuscular transmission of anti-GQ1b antibody positive cases of AO, in tandem with clinical recovery. SFEMG is of value in differentiating weakness due to neuromuscular transmission defect from neuropathy in these clinical situations.

Acute Disease↗
PubMed2004

Case reports of two biopsy-proven patients with Creutzfeldt-Jakob disease in Singapore.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is the most common transmissible human subacute spongiform encephalopathy. There is limited literature on CJD in Southeast Asia. We describe the clinical course and diagnostic evaluation of 2 Singapore patients with biopsy-proven CJD. CLINICAL PICTURE: Two patients presented with non-specific symptoms such as withdrawal, forgetfulness, asthenia, giddiness and insomnia. Both patients had spontaneous myoclonic jerks and impairment of multiple neurologic systems (visual, pyramidal, cerebellar and neurocognitive systems). Magnetic resonance imaging and electroencephalography provided helpful supportive evidence. Diagnosis of CJD was established on brain biopsy. Histological features included spongioform degeneration, neuronal cell loss and astrocytosis. TREATMENT/OUTCOME: Treatment remains palliative. Deterioration in their clinical condition was relentless, progressing to a totally dependent state within 10 to 12 months. CONCLUSION: The early features of CJD can be varied and non-specific. It is important for physicians from different specialties to be cognisant of the clinical manifestations of CJD and the appearance of supportive and definitive investigations.

Biopsy, Needle↗
PubMed2002

Assessment of atherosclerosis using carotid ultrasonography in a cohort of HIV-positive patients treated with protease inhibitors.

OBJECTIVE: Lipid disorders associated with the use of protease inhibitors (PI) may be a risk factor for premature atherosclerosis development. The aim of this study is to evaluate the extent of carotid intima media thickness (IMT) among HIV-positive patients treated with PI containing regimens compared to PI-naïve and HIV-negative subjects. METHODS: We analysed plasma lipid levels and carotid IMT in 28 HIV-positive patients treated with protease inhibitors (PIs) for a mean of 28.7 months (range 18-43) and in two control groups constituted, respectively, by 15 HIV-positive naïve patients and 16 HIV-negative subjects, that were matched for age, risk factors for HIV infection, cigarette smoke use and CD4+ cell count. RESULTS: PI-treated patients had higher triglyceride, HDL and apo B levels than controls. Carotid IMT was significantly increased in PI-treated patients compared to naïve or HIV-negative subjects. A correlation between cholesterol HDL, triglyceride and ApoB levels and IMT was observed among the entire cohort. CONCLUSIONS: Plasma lipid alterations were associated with an increased IMT and intima media thickening was more pronounced in PI-treated patients than in the two control groups. Periodical evaluation of blood lipid profile and, if required, the use of lipid-lowering agents is advisable. Moreover, physicians should address concurrent risk factor for atherosclerosis that can be modified, including smoking, hypertension, obesity and sedentary life-style.

Adult↗
PubMed2001

The shorter zinc finger protein ZNF230 gene message is transcribed in fertile male testes and may be related to human spermatogenesis.

The zinc finger gene family represents one of the largest in the mammalian genome, with several of these genes reported to be involved in spermatogenesis. A newly discovered gene has been identified that is expressed abundantly in the testicular tissue of fertile men as determined by mRNA differential display. The gene encodes a C(3)HC(4)-type zinc finger protein motif (ring finger motif) consistent with a role in pre-meiotic or post-meiotic sperm development. The gene was named ZNF230 and mapped to the short arm of chromosome 11 (11p15). ZNF230 has two transcripts, of 1 kb and 4.4 kb in length. The shorter 1 kb transcript was only detected in testicular tissue whereas the longer 4.4 kb transcript was not detected in testis but was found in several other tissues. The lack of detectable ZNF230 expression in azoospermic patients by reverse transcriptase-mediated PCR analysis is interpreted to mean that this gene is involved in maintaining normal human male fertility.

Amino Acid Sequence↗
PubMed2001

Acquired Robertsonian translocations in two leukemia patients.

Robertsonian translocations were observed in two leukemia patients. The first case was a patient with chronic lymphocytic leukemia, who was found to have a rare Robertsonian translocation der(14;15)(q10;q10). The second case, a patient with acute myeloid leukemia, had multiple Robertsonian translocations: der(15)t(13;15)(q11.1;p11.1), der(14;22)(q10;q10), and dic(21;22)(p11.1;p11.1). Acquired multiple Robertsonian translocations have not been reported previously in leukemia.

Acute Disease↗
PubMed2001

Higher levels of HIV DNA in memory and naive CD4(+) T cell subsets of viremic compared to non-viremic patients after 18 and 24 months of HAART.

The degree of infection of memory and naive CD4(+) T cells in patients treated with HAART and with durable undetectable or detectable viral load in plasma was evaluated. The following two groups of patients were analyzed cross-sectionally: (i) patients with undetectable HIV RNA plasma levels during follow-up (responders); (ii) patients with no reduction or with rebound in HIV RNA levels during treatment (non-responders). Patients were examined following 6, 12, 18 and 24 months of HAART, respectively, by quantifying: (i) plasma HIV RNA load; (ii) CD4(+) T cells; (iii) memory and naive CD4(+) T cells; (iv) HIV DNA levels in memory and naive CD4(+) T cells. HIV RNA plasma levels were significantly higher in non-responders vs responders at each time point (P<0.02), while CD4(+) T cell counts as well as memory and naive CD4(+) T cell levels were comparable in both viremic and non-viremic patients. However, higher HIV DNA values were observed in both memory and naive CD4(+) T cells of non-responders vs responders after 18 and 24 months of HAART (P<0.02), suggesting an increased amount of HIV-infected naive CD4(+) T cells and a sustained high degree of infection of memory CD4(+) T cells. Immunological reconstitution following HAART might potentially be hampered in viremic patients despite the absolute increase in CD4(+) T cell counts.

Anti-HIV Agents↗
PubMed2001

Deep brain stimulation in epilepsy.

Since the pioneering studies of Cooper et al. to influence epilepsy by cerebellar stimulation, numerous attempts have been made to reduce seizure frequency by stimulation of deep brain structures. Evidence from experimental animal studies suggests the existence of a nigral control of the epilepsy system. It is hypothesized that the dorsal midbrain anticonvulsant zone in the superior colliculi is under inhibitory control of efferents from the substantia nigra pars reticulata. Inhibition of the subthalamic nucleus (STN) could release the inhibitory effect of the substantia nigra pars reticulata on the dorsal midbrain anticonvulsant zone and thus activate the latter, raising the seizure threshold. Modulation of the seizure threshold by stimulation of deep brain structures-in particular, of the STN-is a promising future treatment option for patients with pharmacologically intractable epilepsy. Experimental studies supporting the existence of the nigral control of epilepsy system and preliminary results of STN stimulation in animals and humans are reviewed, and alternative mechanisms of seizure suppression by STN stimulation are discussed.

Animals↗
PubMed2001

Virological and immunological responses to a once-a-day antiretroviral regimen with didanosine, lamivudine and efavirenz.

Current antiretroviral drugs cannot eradicate HIV infections, and persons living with HIV are often faced with very demanding daily therapeutic schedules that can induce poor adherence. More conveniently dosed and patient-friendly regimens are needed. We investigated, in this 48-week pilot study, a once-a-day highly active antiretroviral therapy regimen of didanosine, lamivudine and efavirenz. Seventy-five consecutive antiretroviral-naive subjects were enrolled. Over the 48-week period, plasma HIV-RNA levels declined sharply, with a median decrease at the end of the observation time >3.4 log copies/ml. The proportion of patients achieving a plasma HIV-RNA level below the limit of detection (50 copies/ml) was 77% (intention to treat analysis) at the end of the study period. The mean CD4 cell count increased steadily over time from 251 to 459 cells/microl. Antiviral efficacy was similar in patients with a baseline HIV-RNA level above or below 100,000 copies/ml. However, patients with a baseline CD4 cell count <200 cells/microl showed a significantly worse virological response than that observed in patients with higher baseline CD4 counts. Overall 15 patients interrupted therapy. In four cases treatment interruption was due to lack of treatment response; three additional patients were lost to follow-up or withdrew informed consent. Eight patients stopped therapy because of adverse events. The once-daily combination of didanosine, lamivudine and efavirenz resulted in sustained viral suppression and was well-accepted by patients. This regimen may offer advantages in selected difficult-to-treat populations, allows directly observed therapy and can be a safe and effective alternative in antiretroviral-naive patients. These encouraging pilot results need to be confirmed in a comparative clinical trial.

Adult↗
PubMed2001

[Evaluation of the efficacy of a program to control nosocomial spread of methicillin-resistant Staphylococcus aureus].

OBJECTIVE: To evaluate the efficacy of a program to control nosocomial spread of methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Analysis of the incidence of infection and contamination due to MRSA in patients admitted to the hospital of Cremona 6 months before and 3 years after the introduction of the guidelines (July 1997). RESULTS: During the 42 months of the study period, on 80705 admissions, 511 cases of MRSA contamination/infection were identified, the incidence being 0.57 cases per 100 admissions. The infection rate dropped from 0.34 (IC95%: 0.25-0.45) in the first 6 months of the study, before the introduction of guidelines, to 0.17 (IC95%: 0.14-0.20) in the following 3 years (p=0.01). Severe infection decreased from 0.18 to 0.1 per 100 admissions, with a 44% decrease (p=0.058), while mild infections diminished from 0.16 to 0.07 per 100 admissions (p=0.045). Methicillin resistance among nosocomial isolates of Staphylococcus aureus was reduced from 53 % to 35 % (p<0.0001). CONCLUSIONS: The introduction of a program to control the nosocomial spread of MRSA proved effective in reducing both the incidence of infection and the methicillin-resistance of Staphylococcus aureus isolates. The cost effectiveness of the program seems very favourable.

Body Fluids↗
PubMed2000

Scaling of the conductivity spectra in ionic glasses: dependence on the structure

A scaling approach in the conductivity formalism is applied to lithium tellurite glasses of different compositions. We observe that the hopping frequency can be used as the scaling frequency in the absence of well-defined dielectric loss peaks, and a universality of the scaling of the conductivity can be obtained for compositions with a similar structure. Further, the reasons behind the inapplicability of the scaling approach reported recently are elucidated in terms of structure of the glasses.

Journal Article↗
PubMed2000

Different immunologic profiles characterize HIV infection in highly active antiretroviral therapy-treated and antiretroviral-naïve patients with undetectable viraemia. The Master Group.

BACKGROUND: Suppression of human immunodeficiency virus (HIV) replication can be obtained in chronically infected individuals by highly active antiretroviral therapy (HAART) and can also be observed in antiretroviral-naïve patients. The immunological correlates of these two situations were examined. DESIGN AND METHODS: Cross-sectional study involving 32 HIV-infected patients with undetectable HIV plasma viraemia (< 500 copies/ml) and either antiretroviral-naive (n = 14) or undergoing HAART therapy with two nucleoside reverse transcriptase inhibitors (NRTI) plus one (n = 13) or two (n = 5) protease inhibitors (PI). CD4 counts, disease duration, and CDC clinical stage were comparable between the two groups of individuals. Immune parameters (antigen- and mitogen-stimulated proliferation and cytokine production; cytokine mRNA; beta chemokine production; HIV coreceptors mRNA) were analysed in all patients. RESULTS: Results showed immune profiles to be profoundly different in antiretroviral-naive in comparison with HAART-treated patients. Thus: (1) T-cell proliferation to HIV-specific and HIV-unrelated antigens is potent in antiretroviral-naive but suppressed in HAART-treated individuals; (2) interleukin-(IL)2, IL-12 and interferon gamma (IFNgamma) production is robust in naive patients; and (3) a high CCR5/low CXCR4 pattern of HIV coreceptors-specific mRNA is observed in naive but not in HAART-treated patients. In contrast with these observations, no clear differences were detected when beta chemokine production by either peripheral blood mononuclear cells or purified CD8+ T-cells was analysed. Results from HAART-treated patients undergoing therapy with one PI and two NRTI or two PI and two NRTI were in very close agreement. CONCLUSIONS: These data suggest that control over HIV replication can be independently achieved by pharmacological or immunologic means. HAART is associated with weaker HIV-specific and -non-specific immune responses.

CD8-Positive T-Lymphocytes↗
PubMed2000

Higher short-term virologic efficacy of three-class versus two-class highly active antiretroviral salvage therapy in HIV-infected patients.

The efficacy of two-class versus three-class antiretroviral salvage treatment was analyzed retrospectively in 63 HIV-infected patients in whom highly active antiretroviral therapy failed. Twenty-eight patients (group A) received two-class therapy, and 35 patients (group B) received three-class therapy. After 3 months of treatment, a significantly greater proportion of patients in group B (23/35, 65.7%) than in group A (8/28, 28.5%) showed a > or = 1 log10 decrease in the plasma HIV RNA level (P = 0.0034). However, after 9-12 months, 12 of 23 (52.1%) group B responders showed viral load rebound. The results were partially explained by the finding that, at baseline, the great majority (21/27, 77.7%) of group A patients showed mutations conferring resistance to all drugs administered, whereas in group B patients' susceptibility to at least two drug classes was retained. However, after 9-12 months of therapy, most (18/20, 90%) of the short-term responders in group B showed emergence of additional mutations that hampered long-term response.

Anti-HIV Agents↗
PubMed2000

Quantification of the impact of HIV-1 reverse transcriptase and protease mutations on the efficacy of rescue HAART.

The reduction in the efficacy of rescue treatment (administered on a clinical basis) due to drug resistance was retrospectively quantified in 55 human immunodeficiency virus type 1 (HIV-1)-infected patients failing highly active antiretroviral therapy (HAART) by using a novel score calculation system based upon HIV-1 reverse transcriptase (RT) and protease (PR) mutations. Patients were all naive for nelfinavir (NFV) and efavirenz (EFV) and were assigned to one of the following rescue therapy schedules: (i) 17 patients received NFV + EFV + stavudine (d4T) (group A); (ii) 14 patients received NFV + saquinavir (SQV) + lamivudine (3TC) + d4T/zidovudine (AZT) (group B); (iii) 19 patients received NFV + d4T + didanosine (ddI)/3TC/zalcitabine (ddC) (group C); (iv) five patients received miscellaneous treatments including NFV (group D). Responders were considered patients showing a drop in HIV-1 RNA level > 0.5 log10 after 3 months of therapy. Forty-eight (28 responders and 20 non-responders) out of 55 patients completed the first 3 months of rescue therapy and reduction in HIV-1 viral load was found to be significantly higher in group A compared to groups B and C (81.2% responders vs. 38.5 and 40.0%, respectively). At baseline, no patient carried EFV- or d4T-resistant HIV-1 strains, despite prolonged administration of d4T, while 41/48 (87.2%) patients had mutations conferring resistance to NFV in the absence of previous treatment with this drug. A significant inverse correlation between reduction in viral load and reduction in therapy efficacy due to drug resistance, as determined by the score calculation system, was found (r = 0.62). A cut-off value of 36% reduction in therapy efficacy showed a positive predictive value (capacity to detect failure of rescue treatment) of 81.2% and a negative predictive value (ability to detect successful treatment) of 75.8%. In addition, 45 out of 48 patients completed also the 9-12 month period of rescue therapy and 10/28 responders had a rebound in HIV-1 viral load level detected after the first 3 months of rescue therapy. Of these, 5/7 (71.4%) showed a further reduction in rescue therapy efficacy due to the emergence of new mutations.

Anti-HIV Agents↗
PubMed2000

Clinical pharmacokinetics of nelfinavir combined with efavirenz and stavudine during rescue treatment of heavily pretreated HIV-infected patients.

Nelfinavir is a novel protease inhibitor that exhibits good inhibitory activity against human immunodeficiency virus type 1 (HIV-1) and is currently used in combination with reverse transcriptase inhibitors for the management of HIV infection. In this study we analysed the pharmacokinetic profile of nelfinavir after multiple oral doses in 18 HIV-infected patients during a combination regimen of nelfinavir plus efavirenz and stavudine. Patients who received the study drug for >/=4 weeks were considered for pharmacokinetic evaluation. Blood samples were obtained at the following times: 0 (before nelfinavir administration), 1, 2, 3, 4, 6 and 8 h after administration. Nelfinavir plasma concentrations were analysed by a specific and validated HPLC assay with ultraviolet detection. Nelfinavir concentration-time data were analysed by compartmental and non-compartmental techniques and the pharmacokinetic parameters of nelfinavir were determined according to a one-compartment model. We found a high variability between individuals in nelfinavir plasma concentrations. The mean average drug plasma concentration was 2.22 +/- 1.25 mg/L and the mean AUC during the dosing interval was 17.7 +/- 10.0 mg*h/L. The mean nelfinavir trough plasma concentration was 1.58 +/- 1.0 mg/L. A good relationship was found between AUC(0-8h) and the plasma concentrations measured at 6 h, and the trough plasma concentrations made total body exposure for nelfinavir less predictable. Alternatively, a 2 h abbreviated AUC provides a good estimate of the full AUC(0-8h). Comparing the pharmacokinetic parameters obtained in our patients with those reported for patients receiving nelfinavir monotherapy or nelfinavir combined with nucleoside analogues, one observes substantial overlap with nelfinavir concentrations achieved without efavirenz.

Adult↗