Primary hyperoxaluria type I is a rare genetic disorder of glyoxylate metabolism in which patient... more Primary hyperoxaluria type I is a rare genetic disorder of glyoxylate metabolism in which patients usually present during the first decade of life with recurrent calcium oxalate nephrolithiasis (see Williams and Smith, 1983). Although it was long believed that hyperoxaluria type I is associated with a deficiency of the cytosolic form of 2-oxoglutarate: glyoxylate carboligase, it is now clear that the primary defect in hyperoxaluria type I is at the level of a deficient alanine: glyoxylate aminotransferase activity as first shown by Danpure and Jennings (1986). Although most hyperoxaluria type I patients die before 20 years of age from progressive renal insufficiency, several patients have been described suffering from a milder, pyridoxine responsive form of hyperoxaluria type I (see Williams and Smith, 1983). In these patients the urinary excretion of oxalate and glycolate, the two characteristic metabolites in blood and urine from hyperoxaluria type I patients, can be reduced upon administration of pyridoxine. In the present report we determined the activity of alanine glyoxylate aminotransferase (AGT) in liver needle specimens from one patient who died from pyridoxine-resistant hyperoxaluria type I and three patients with the pyridoxine-responsive form of the disease using an improved sensitive enzyme assay.
We have studied the characteristics of human liver alanine-glyoxylate aminotransferase, which is ... more We have studied the characteristics of human liver alanine-glyoxylate aminotransferase, which is deficient in hyperoxaluria type I, an inherited disorder of glyoxylate metabolism. The enzyme was optimally active at pH 8.0 showing apparent Km values for L-alanine and glyoxylate of 8.3 and 1.3 mmol/l, respectively. Activity was found to proceed linearly for up to 4 h. Measurements under these optimal conditions enabled the biochemical diagnosis of hyperoxaluria type I to be made via enzyme activity measurements in percutaneous needle biopsy specimens of liver tissue.
BackgroundEthnic minorities have higher rates of SARS-CoV-2 diagnoses, but little is known about ... more BackgroundEthnic minorities have higher rates of SARS-CoV-2 diagnoses, but little is known about ethnic differences in past exposure. We aimed to determine whether prevalence and determinants of SARS-CoV-2 exposure varied between six ethnic groups in Amsterdam, the Netherlands.MethodsParticipants aged 25-79 years enrolled in a population-based prospective cohort were randomly selected within ethnic groups and invited to test for SARS-CoV-2-specific antibodies and answer COVID-19 related questions. We estimated prevalence and determinants of SARS-CoV-2 exposure within ethnic groups using survey-weighted logistic regression adjusting for age, sex and calendar time.ResultsBetween June 24-October 9, 2020, we included 2497 participants. Adjusted SARS-CoV-2 seroprevalence was comparable between ethnic-Dutch (25/498; 5.5%, 95%CI=3.2-7.9), South-Asian Surinamese (22/451; 4.8%, 95%CI=2.1-7.5), African Surinamese (22/400; 8.2%, 95%CI=3.0-13.4), Turkish (30/408; 7.8%, 95%CI=4.3-11.2) and Moroc...
New HIV diagnoses among men having sex with men (MSM) have not decreased appreciably in most coun... more New HIV diagnoses among men having sex with men (MSM) have not decreased appreciably in most countries, even though care and prevention services have been scaled up substantially in the past 20 years. To maximize the impact of prevention strategies, it is crucial to quantify the sources of transmission at the population level. We used viral sequence and clinical patient data from one of Europe's nationwide cohort studies to estimate probable sources of transmission for 617 recently infected MSM. Seventy-one percent of transmissions were from undiagnosed men, 6% from men who had initiated antiretroviral therapy (ART), 1% from men with no contact to care for at least 18 months, and 43% from those in their first year of infection. The lack of substantial reductions in incidence among Dutch MSM is not a result of ineffective ART provision or inadequate retention in care. In counterfactual modeling scenarios, 19% of these past cases could have been averted with current annual testing...
Nederlands tijdschrift voor geneeskunde, Jan 18, 2001
To evaluate the effect of treatment of HIV-1 infection with combination therapy consisting of sin... more To evaluate the effect of treatment of HIV-1 infection with combination therapy consisting of since 1996 in the Netherlands available protease and reverse transcriptase inhibitors. Prospective cohort study. In an observational clinical cohort of HIV-1-infected individuals, the short-term successful treatment end point of antiviral therapy including at least one antiretroviral drug licensed in the Netherlands since July 1, 1996 (protease inhibitors and reverse transcriptase inhibitors), was HIV-1 RNA plasma levels < or = 500 copies/ml (virological success). Cox proportional hazard models were used to identify prognostic markers for therapy success. The study included 2,148 infected individuals with a median follow-up of 135 weeks of treatment; 1,049 had been pre-treated with antiretroviral drugs before starting their new regimen and 1,099 were treatment naive. Plasma HIV-1 RNA levels < or = 500 copies/ml at 24 weeks of treatment were seen in 61% of all patients. The chance of t...
Nederlands tijdschrift voor geneeskunde, Jan 29, 1999
Two patients, men aged 39 and 52 years, are described with a mononucleosis-like syndrome, due to ... more Two patients, men aged 39 and 52 years, are described with a mononucleosis-like syndrome, due to a primary HIV infection. Both patient developed dermatological manifestations. One patient presented with an encephalitis with an inversed CD4/CD8 cell ratio in the cerebrospinal fluid. Primary HIV infection is often missed as a clinical diagnosis. The possible preservation of a strong cellular immune response against HIV itself in case of early start of treatment argues for an immediate intervention with a combination of antiretroviral drugs in this syndrome.
Nederlands tijdschrift voor geneeskunde, Jan 18, 1997
To gain insight into the spread of HIV strains with different sensitivities to antiretroviral dru... more To gain insight into the spread of HIV strains with different sensitivities to antiretroviral drugs prescribed in the Netherlands. Prospective cohort study in intravenous drug users and homosexual men. Amsterdam, the Netherlands. HIV negative participants in the Amsterdam cohort studies among homosexual men and intravenous drug users are tested two to three times a year for HIV antibodies. The first positive serum sample of those who seroconverted was used to determine, on the basis of the nucleotide sequence of the reverse transcriptase gene of HIV, if viruses were present with a reduced sensitivity to reverse transcriptase inhibitors. In 1996, 17 new HIV infections occurred (8 in homosexual men and 9 in intravenous drug users). In two new infections in homosexual men HIV strains with reduced sensitivity to zidovudine were present.
The objective of this study was to assess the benefit of temporary combination antiretroviral the... more The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1∶1∶1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1∶1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count < 350 cells/mm(3) or symptomatic HIV diseas...
Starting standard antiretroviral therapy within 10 days after the onset of a primary HIV-1 infect... more Starting standard antiretroviral therapy within 10 days after the onset of a primary HIV-1 infection cannot prevent the establishment of a reservoir of HIV-1-infected memory CD4 T cells. Here we studied the reservoir of HIV-1-infected memory CD4 T cells in four patients who started a triple class, five-drug regimen during primary HIV-1 infection. There was a strong correlation between the proportion of productively infected CD4 HLA-DR- T lymphocytes and plasma HIV-1 RNA levels (r=0.852; P<0.001) during the first 24 weeks of therapy. Within 45 weeks of treatment, in three of the four patients the proportion of productively infected CD4 HLA-DR- T lymphocytes was reduced below the level of quantification. In the fourth patient the cellular reservoir remained quantifiable. In two patients who stopped therapy 44 weeks after initiation an immediate rebound of the plasma HIV-1 RNA level and the proportion of productively infected CD4 HLA-DR– T lymphocytes occurred. In conclusion, initia...
During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication... more During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication-competent HIV-1 can still be recovered from resting memory CD4 T cells. In an attempt to accelerate the clearance of this pool of infected CD4 T cells, eight antiretroviral therapy-naive HIV-1-infected patients were treated with a five-drug regimen. While plasma HIV-1 RNA levels generally remained below the level of detection (<5 copies/ml), replication competent HIV-1 was isolated from HLA-DR- CD4 T cells from all patients on multiple occasions throughout treatment. Decay slopes of infected CD4 T cells ranged from -0.061/week (half-life=2.6 months) to +0.003/week (half-life=infinite). Virus was still detectable at the last time point analysed (80–173 weeks) in all patients. Although more intensive treatment results in improved suppression of plasma viraemia compared with standard drug regimens, it does not result in clearance of the viral reservoir in this timeframe. Strategies othe...
Primary hyperoxaluria type I is a rare genetic disorder of glyoxylate metabolism in which patient... more Primary hyperoxaluria type I is a rare genetic disorder of glyoxylate metabolism in which patients usually present during the first decade of life with recurrent calcium oxalate nephrolithiasis (see Williams and Smith, 1983). Although it was long believed that hyperoxaluria type I is associated with a deficiency of the cytosolic form of 2-oxoglutarate: glyoxylate carboligase, it is now clear that the primary defect in hyperoxaluria type I is at the level of a deficient alanine: glyoxylate aminotransferase activity as first shown by Danpure and Jennings (1986). Although most hyperoxaluria type I patients die before 20 years of age from progressive renal insufficiency, several patients have been described suffering from a milder, pyridoxine responsive form of hyperoxaluria type I (see Williams and Smith, 1983). In these patients the urinary excretion of oxalate and glycolate, the two characteristic metabolites in blood and urine from hyperoxaluria type I patients, can be reduced upon administration of pyridoxine. In the present report we determined the activity of alanine glyoxylate aminotransferase (AGT) in liver needle specimens from one patient who died from pyridoxine-resistant hyperoxaluria type I and three patients with the pyridoxine-responsive form of the disease using an improved sensitive enzyme assay.
We have studied the characteristics of human liver alanine-glyoxylate aminotransferase, which is ... more We have studied the characteristics of human liver alanine-glyoxylate aminotransferase, which is deficient in hyperoxaluria type I, an inherited disorder of glyoxylate metabolism. The enzyme was optimally active at pH 8.0 showing apparent Km values for L-alanine and glyoxylate of 8.3 and 1.3 mmol/l, respectively. Activity was found to proceed linearly for up to 4 h. Measurements under these optimal conditions enabled the biochemical diagnosis of hyperoxaluria type I to be made via enzyme activity measurements in percutaneous needle biopsy specimens of liver tissue.
BackgroundEthnic minorities have higher rates of SARS-CoV-2 diagnoses, but little is known about ... more BackgroundEthnic minorities have higher rates of SARS-CoV-2 diagnoses, but little is known about ethnic differences in past exposure. We aimed to determine whether prevalence and determinants of SARS-CoV-2 exposure varied between six ethnic groups in Amsterdam, the Netherlands.MethodsParticipants aged 25-79 years enrolled in a population-based prospective cohort were randomly selected within ethnic groups and invited to test for SARS-CoV-2-specific antibodies and answer COVID-19 related questions. We estimated prevalence and determinants of SARS-CoV-2 exposure within ethnic groups using survey-weighted logistic regression adjusting for age, sex and calendar time.ResultsBetween June 24-October 9, 2020, we included 2497 participants. Adjusted SARS-CoV-2 seroprevalence was comparable between ethnic-Dutch (25/498; 5.5%, 95%CI=3.2-7.9), South-Asian Surinamese (22/451; 4.8%, 95%CI=2.1-7.5), African Surinamese (22/400; 8.2%, 95%CI=3.0-13.4), Turkish (30/408; 7.8%, 95%CI=4.3-11.2) and Moroc...
New HIV diagnoses among men having sex with men (MSM) have not decreased appreciably in most coun... more New HIV diagnoses among men having sex with men (MSM) have not decreased appreciably in most countries, even though care and prevention services have been scaled up substantially in the past 20 years. To maximize the impact of prevention strategies, it is crucial to quantify the sources of transmission at the population level. We used viral sequence and clinical patient data from one of Europe's nationwide cohort studies to estimate probable sources of transmission for 617 recently infected MSM. Seventy-one percent of transmissions were from undiagnosed men, 6% from men who had initiated antiretroviral therapy (ART), 1% from men with no contact to care for at least 18 months, and 43% from those in their first year of infection. The lack of substantial reductions in incidence among Dutch MSM is not a result of ineffective ART provision or inadequate retention in care. In counterfactual modeling scenarios, 19% of these past cases could have been averted with current annual testing...
Nederlands tijdschrift voor geneeskunde, Jan 18, 2001
To evaluate the effect of treatment of HIV-1 infection with combination therapy consisting of sin... more To evaluate the effect of treatment of HIV-1 infection with combination therapy consisting of since 1996 in the Netherlands available protease and reverse transcriptase inhibitors. Prospective cohort study. In an observational clinical cohort of HIV-1-infected individuals, the short-term successful treatment end point of antiviral therapy including at least one antiretroviral drug licensed in the Netherlands since July 1, 1996 (protease inhibitors and reverse transcriptase inhibitors), was HIV-1 RNA plasma levels < or = 500 copies/ml (virological success). Cox proportional hazard models were used to identify prognostic markers for therapy success. The study included 2,148 infected individuals with a median follow-up of 135 weeks of treatment; 1,049 had been pre-treated with antiretroviral drugs before starting their new regimen and 1,099 were treatment naive. Plasma HIV-1 RNA levels < or = 500 copies/ml at 24 weeks of treatment were seen in 61% of all patients. The chance of t...
Nederlands tijdschrift voor geneeskunde, Jan 29, 1999
Two patients, men aged 39 and 52 years, are described with a mononucleosis-like syndrome, due to ... more Two patients, men aged 39 and 52 years, are described with a mononucleosis-like syndrome, due to a primary HIV infection. Both patient developed dermatological manifestations. One patient presented with an encephalitis with an inversed CD4/CD8 cell ratio in the cerebrospinal fluid. Primary HIV infection is often missed as a clinical diagnosis. The possible preservation of a strong cellular immune response against HIV itself in case of early start of treatment argues for an immediate intervention with a combination of antiretroviral drugs in this syndrome.
Nederlands tijdschrift voor geneeskunde, Jan 18, 1997
To gain insight into the spread of HIV strains with different sensitivities to antiretroviral dru... more To gain insight into the spread of HIV strains with different sensitivities to antiretroviral drugs prescribed in the Netherlands. Prospective cohort study in intravenous drug users and homosexual men. Amsterdam, the Netherlands. HIV negative participants in the Amsterdam cohort studies among homosexual men and intravenous drug users are tested two to three times a year for HIV antibodies. The first positive serum sample of those who seroconverted was used to determine, on the basis of the nucleotide sequence of the reverse transcriptase gene of HIV, if viruses were present with a reduced sensitivity to reverse transcriptase inhibitors. In 1996, 17 new HIV infections occurred (8 in homosexual men and 9 in intravenous drug users). In two new infections in homosexual men HIV strains with reduced sensitivity to zidovudine were present.
The objective of this study was to assess the benefit of temporary combination antiretroviral the... more The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1∶1∶1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1∶1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count < 350 cells/mm(3) or symptomatic HIV diseas...
Starting standard antiretroviral therapy within 10 days after the onset of a primary HIV-1 infect... more Starting standard antiretroviral therapy within 10 days after the onset of a primary HIV-1 infection cannot prevent the establishment of a reservoir of HIV-1-infected memory CD4 T cells. Here we studied the reservoir of HIV-1-infected memory CD4 T cells in four patients who started a triple class, five-drug regimen during primary HIV-1 infection. There was a strong correlation between the proportion of productively infected CD4 HLA-DR- T lymphocytes and plasma HIV-1 RNA levels (r=0.852; P<0.001) during the first 24 weeks of therapy. Within 45 weeks of treatment, in three of the four patients the proportion of productively infected CD4 HLA-DR- T lymphocytes was reduced below the level of quantification. In the fourth patient the cellular reservoir remained quantifiable. In two patients who stopped therapy 44 weeks after initiation an immediate rebound of the plasma HIV-1 RNA level and the proportion of productively infected CD4 HLA-DR– T lymphocytes occurred. In conclusion, initia...
During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication... more During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication-competent HIV-1 can still be recovered from resting memory CD4 T cells. In an attempt to accelerate the clearance of this pool of infected CD4 T cells, eight antiretroviral therapy-naive HIV-1-infected patients were treated with a five-drug regimen. While plasma HIV-1 RNA levels generally remained below the level of detection (<5 copies/ml), replication competent HIV-1 was isolated from HLA-DR- CD4 T cells from all patients on multiple occasions throughout treatment. Decay slopes of infected CD4 T cells ranged from -0.061/week (half-life=2.6 months) to +0.003/week (half-life=infinite). Virus was still detectable at the last time point analysed (80–173 weeks) in all patients. Although more intensive treatment results in improved suppression of plasma viraemia compared with standard drug regimens, it does not result in clearance of the viral reservoir in this timeframe. Strategies othe...
Uploads