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Biomedical subjects

M Hoekstra

Publications and source records attributed to M Hoekstra.

16 recordsLinked to original sources
PubMed2006

A recurring outbreak of Shigella sonnei among traditionally observant Jewish children in New York City: the risks of daycare and household transmission.

Dispersed community outbreaks of Shigella sonnei have occurred cyclically among traditionally observant Jews in the United States. In February 2000, we investigated a S. sonnei outbreak in one Jewish community in New York City. To determine risk factors for introduction of infection into households, we conducted a cohort study of households to compare risk factors for illness among primary subjects within households and age-matched well siblings. Isolates were subtyped by pulsed-field gel electrophoresis (PFGE). We used a random effects model to assess extra-household vs. intra-household transmission in households with multiple ill household members. Daycare or pre-school attendance [matched odds ratio (mOR) 16.1, P<0.001] and age <60 months (mOR 6.3, P<0.001) were independently associated with index subject illness. Outbreak isolates were closely related by PFGE analysis to the strain previously observed in Jewish community outbreaks. The random effects model strongly indicated that multiple illnesses in a single household are due to secondary transmission. Disease containment efforts should focus on reducing Shigella transmission in childcare settings and within homes.

Case-Control Studies↗
PubMed2005

Leflunomide in the treatment of rheumatoid arthritis. An analysis of predictors for treatment continuation.

AIMS: To determine factors predictive for leflunomide drug survival in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: A standard dataset was collected from medical records of consecutive outpatients on leflunomide treatment for rheumatoid arthritis between January 2000 and June 2003. The dataset consisted of patient, disease and treatment characteristics at the start of leflunomide treatment, and data on leflunomide use. RESULTS: Leflunomide was started in 279 patients and 173 patients (62.0%) withdrew from treatment during follow-up. From univariate analysis, concomitant systemic corticosteroid use [hazard ratio (HR) (95% confidence interval) 1.35 (1.00, 1.83)] and an erythrocyte sedimentation rate <35 mm h(-1)[HR 1.38 (1.01, 1.88)] at start of leflunomide were found to be predictive for better leflunomide survival. Furthermore, the attending rheumatologist was correlated with leflunomide drug survival. Hazard ratios varied, depending on the individual rheumatologist, from 0.60 to 2.66. Multivariate analysis suggested attending rheumatologist (HR varying from 0.54 to 2.30 depending on the individual rheumatologist), concomitant systemic corticosteroid use [HR 1.58 (1.14 2.21)] and erythrocyte sedimentation rate <35 mm h(-1)[HR 1.42 (1.03, 1.96)] at start of leflunomide to be associated with leflunomide survival. CONCLUSIONS: Concomitant systemic corticosteroid use, erythrocyte sedimentation rate at the start of treatment and attending rheumatologist were found to be predictive for leflunomide survival. Information on these predictors at the start of leflunomide therapy may offer information on which patients are at an increased risk of withdrawal from leflunomide. Whether this information leads to optimization of leflunomide treatment outcomes remains to be studied.

Aged↗
PubMed2005

Intermittent rises in plasma homocysteine in patients with rheumatoid arthritis treated with higher dose methotrexate.

OBJECTIVES: To investigate the effect of higher weekly maintenance dose methotrexate (MTX) (> or =25 mg/week) on plasma homocysteine concentrations in adults with RA. METHODS: Patients with RA were treated with high doses of MTX with adjuvant folic acid. Plasma homocysteine was determined at baseline and 1, 2, 4, 8, 12, and 48 hours after subcutaneous MTX administration. Maximum homocysteine concentrations after MTX administration were compared with baseline concentrations. RESULTS: Fifteen patients with RA (11 women) were included, with a median age of 61 years (range 31-72) and median disease duration 7 years (range 2-32). Median MTX dose was 30 mg (range 25-40). All patients received folic acid supplementation (5-30 mg/week). Median plasma homocysteine concentration at baseline was 10.1 mumol/l (range 6.6-12.7; normal 6-15). Homocysteine concentrations increased after MTX administration by a median of 2.5 mumol/l (range 0.7-5.1). Median maximum plasma homocysteine was significantly higher than at baseline. Peak homocysteine was reached after 12 hours. No relation between serum folate concentrations and plasma homocysteine concentrations was found. CONCLUSIONS: In patients with RA higher MTX doses with adjuvant folic acid do not increase baseline concentrations of homocysteine. An intermittent significant rise in plasma homocysteine occurs in the 48 hours after MTX administration.

Adult↗
PubMed2004

Pathogen-specific risk factors and protective factors for acute diarrheal illness in children aged 12-59 months in São Paulo, Brazil.

Diarrheal diseases are a leading cause of childhood morbidity and mortality in Latin America. Most studies have focused on infants but not on older children. We enrolled 505 children (age, 12-59 months) with diarrhea and age-matched controls in a case-control study in Sao Paulo, Brazil. Independent risk factors for diarrhea included another household member with diarrhea (matched odds ratio [mOR], 8.1; attributable fraction [AF], 0.17; P<.001) and consumption of homemade juice (mOR, 1.8; AF, 0.10; P=.01); protective factors included boiling of the baby bottle or nipple (mOR, 0.60; AF, 0.19; P=.026), childcare at home (mOR, 0.58; AF, 0.12; P=.004), and piped sewage (mOR, 0.58; AF, 0.05; P=.047). Hand washing by the caretaker after helping the child defecate protected against Shigella infection (mOR, 0.35; P<.05). Preparation of rice, beans, or soup in the morning and serving it to children after noon were associated with enterotoxigenic Escherichia coli infection (mOR, 8.0; P<.05). In these poor households, 28% of cases of diarrhea in 1-4-year-old children was attributable to easily modifiable exposures.

Adenovirus Infections, Human↗
PubMed2003

A multistate outbreak of Salmonella enterica Serotype Newport infection linked to mango consumption: impact of water-dip disinfestation technology.

Fresh produce increasingly is recognized as an important source of salmonellosis in the United States. In December 1999, the Centers for Disease Control and Prevention detected a nationwide increase in Salmonella serotype Newport (SN) infections that had occurred during the previous month. SN isolates recovered from patients in this cluster had indistinguishable pulsed-field gel electrophoresis (PFGE) patterns (which identified the outbreak strain), suggesting a common source. Seventy-eight patients from 13 states were infected with the outbreak strain. Fifteen patients were hospitalized; 2 died. Among 28 patients enrolled in the matched case-control study, 14 (50%) reported they ate mangoes in the 5 days before illness onset, compared with 4 (10%) of the control subjects during the same period (matched odds ratio, 21.6; 95% confidence interval, 3.53- infinity; P=.0001). Traceback of the implicated mangoes led to a single Brazilian farm, where we identified hot water treatment as a possible point of contamination; this is a relatively new process to prevent importation of an agricultural pest, the Mediterranean fruit fly. This is the first reported outbreak of salmonellosis implicating mangoes. PFGE was critical to the timely recognition of this nationwide outbreak. This outbreak highlights the potential global health impact of foodborne diseases and newly implemented food processes.

Adolescent↗
PubMed2003

Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis.

OBJECTIVE: To study factors associated with toxicity, final dose, and efficacy of methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Data were used from a randomised clinical 48 week trial on 411 patients with RA all treated with MTX, comparing folates and placebo. Logistic regression was used to study the relation between baseline variables and various dependent factors, including hepatotoxicity (alanine aminotransferase >/=3 x upper limit of normal), MTX withdrawal, final MTX dose >/=15 mg/week, and MTX efficacy. RESULTS: Addition of folates to MTX treatment was strongly related to the lack of hepatotoxicity. Next to this, high body mass index was related to the occurrence of hepatotoxicity. Prior gastrointestinal (GI) events and younger age were related to the adverse event, diarrhoea. Hepatotoxicity and GI adverse events were the main reason for MTX withdrawal, which in turn was associated with the absence of folate supplementation, body mass index, prior GI events, and female sex. Renal function (creatinine clearance >/=50 ml/min) was not associated with toxicity. Reaching a final dose of MTX of >/=15 mg/week was related to folate supplementation and the absence of prior GI events. Efficacy of MTX treatment was associated with low disease activity at baseline, male sex, use of non-steroidal anti-inflammatory drugs (NSAIDs), and lower creatinine clearance. CONCLUSIONS: MTX toxicity, final dose, and efficacy are influenced by folate supplementation. Baseline characteristics predicting the outcome of MTX treatment are mainly prior GI events, body mass index, sex, use of NSAIDs, and creatinine clearance.

Adult↗
PubMed2002

Transaminase and alkaline phosphatase activity in the serum of burn patients treated with highly purified tannic acid.

The effects of local treatment with highly purified tannic acid (HPTA) on serum transaminase and alkaline phosphatase activity in burn patients were studied, retrospectively. Temporary elevations in the activity of gamma-glutamyl transferase (GGT), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and alkaline phosphatase (AP) were observed in both HPTA-treated patients and their matched controls. No statistically significant difference was found between the two patient-groups with respect to the mean enzyme activities, calculated as the areas under the curve between 5 and 15 days post-burn (PBD). These results seem to indicate that HPTA does not cause hepatotoxicity, at least when applied to a burned area corresponding to approximately 10% of the total body surface. This is in agreement with the widespread and frequent use of HPTA in the food, cosmetic and pharmaceutical industries.

Administration, Topical↗
PubMed1998

Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest.

Chromosome 3q alterations occur frequently in many types of tumours. In a genetic screen for loci present in rhabdomyosarcomas, we identified an isochromosome 3q [i(3q)], which inhibits muscle differentiation when transferred into myoblasts. The i(3q) inhibits MyoD function, resulting in a non-differentiating phenotype. Furthermore, the i(3q) induces a 'cut' phenotype, abnormal centrosome amplification, aneuploidy and loss of G1 arrest following gamma-irradiation. Testing candidate genes within this region reveals that forced expression of ataxia-telangiectasia and rad3-related (ATR) results in a phenocopy of the i(3q). Thus, genetic alteration of ATR leads to loss of differentiation as well as cell-cycle abnormalities.

Aneuploidy↗
PubMed1997

Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage.

BRCA1 localizes to discrete nuclear foci (dots) during S phase. Hydroxyurea-mediated DNA synthesis arrest of S phase MCF7 cells led to a loss of BRCA1 from these structures. Ultraviolet light, mitomycin C, or gamma irradiation produced a similar effect but with no concurrent arrest of DNA synthesis. BARD1 and Rad51, two proteins associated with the BRCA1 dots, behaved similarly. Loss of the BRCA1 foci was accompanied by a specific, dose-dependent change(s) in the state of BRCA1 phosphorylation. Three distinct DNA damaging agents preferentially induced this change in S phase. The S phase BRCA1 phosphorylation response to DNA damage occurred in cells lacking, respectively, two DNA damage-sensing protein kinases, DNA-PK and Atm, implying that neither plays a prime role in this process. Finally, after BRCA1 dot dispersal, BRCA1, BARD1, and Rad51 accumulated, focally, on PCNA+ replication structures, implying an interaction of BRCA1/BARD1/Rad51 containing complexes with damaged, replicating DNA. Taken together, the data imply that the BRCA1 S phase foci are dynamic physiological elements, responsive to DNA damage, and that BRCA1-containing multiprotein complexes participate in a replication checkpoint response.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1997

Role of the casein kinase I isoform, Hrr25, and the cell cycle-regulatory transcription factor, SBF, in the transcriptional response to DNA damage in Saccharomyces cerevisiae.

In the budding yeast, Saccharomyces cerevisiae, DNA damage or ribonucleotide depletion causes the transcriptional induction of an array of genes with known or putative roles in DNA repair. The ATM-like kinase, Mec1, and the serine/threonine protein kinases, Rad53 and Dun1, are required for this transcriptional response. In this paper, we provide evidence suggesting that another kinase, Hrr25, is also involved in the transcriptional response to DNA damage through its interaction with the transcription factor, Swi6. The Swi6 protein interacts with Swi4 to form the SBF complex and with Mbp1 to form the MBF complex. SBF and MBF are required for the G1-specific expression of G1 cyclins and genes required for S-phase. We show that Swi6 associates with and is phosphorylated by Hrr25 in vitro. We find that swi4, swi6, and hrr25 mutants, but not mbp1 mutants, are sensitive to hydroxyurea and the DNA-damaging agent methyl methane-sulfonate and are defective in the transcriptional induction of a subset of DNA damage-inducible genes. Both the sensitivity of swi6 mutants to methyl methanesulfonate and hydroxyurea and the transcriptional defect of hrr25 mutants are rescued by overexpression of SWI4, implicating the SBF complex in the Hrr25/Swi6-dependent response to DNA damage.

Casein Kinase I↗
PubMed1996

The Schizosaccharomyces pombe rad3 checkpoint gene.

The rad3 gene of Schizosaccharomyces pombe is required for checkpoint pathways that respond to DNA damage and replication blocks. We report the complete rad3 gene sequence and show that rad3 is the homologue of Saccharomyces cerevisiae ESR1 (MEC1/SAD3) and Drosophila melanogaster mei-41 checkpoint genes. This establishes Rad3/Mec1 as the only conserved protein which is required for all the DNA structure checkpoints in both yeast model systems. Rad3 is an inessential member of the 'lipid kinase' subclass of kinases which includes the ATM protein defective in ataxia telangiectasia patients. Mutational analysis indicates that the kinase domain is required for Rad3 function, and immunoprecipitation of overexpressed Rad3 demonstrates an associated protein kinase activity. The previous observation that rad3 mutations can be rescued by a truncated clone lacking the kinase domain may be due to intragenic complementation. Consistent with this, biochemical data suggest that Rad3 exists in a complex containing multiple copies of Rad3. We have identified a novel human gene (ATR) whose product is closely related to Rad3/Esr1p/Mei-41. ATR can functionally complement esr1-1 radiation sensitivity in S. cerevisiae. Together, the structural conservation and functional complementation suggest strongly that the mechanisms underlying the DNA structure checkpoints are conserved throughout evolution.

Adenosine Triphosphatases↗
PubMed1994

Structural requirements for bisphosphonate actions in vitro.

We investigated the structural requirements for the binding of bisphosphonates to bone mineral and the relation between their affinity for bone and their effects on bone resorption in vitro. For this we used fetal mouse long bones in culture and bisphosphonates with variable R1 and R2 structures. In addition, we studied the effect of structural differences in the incorporation of calcium into bone. We found that bisphosphonates containing a hydroxyl group in the R1 position have the highest affinity for bone mineral. This was related to their capacity to inhibit the incorporation of calcium into long bones but not to their antiresorptive potency. The latter was primarily determined by R2. Furthermore, the effect of bisphosphonates on calcification, but not on resorption of bone explants, was mainly determined by the mode of addition. The continuous presence of bisphosphonate during culture inhibited calcification even at very low concentrations, but short incubation of the bones with relatively high concentrations had no effect. This is probably a result of differences in the availability of the compound to the process of calcification. Because, in vivo, the more potent bisphosphonates inhibit resorption without adversely affecting mineralization of the skeleton and they disappear rapidly from the circulation after administration, we suggest that cultures of bone explants incubated with bisphosphonates for short times rather than cultures in which the drugs are continuously present provide more accurate information about the in vivo effect of these compounds on both resorption and calcification.

Animals↗
PubMed1986

The biodistribution of 67Ga-labelled N-hydroxyamino acid derivatives in tumour-bearing rats.

The biodistribution of 67Ga-labelled complexes of some mono- and di-N-hydroxyamino acid derivatives and of two siderophores (trihydroxamates) were evaluated in Rhabdomyosarcoma-bearing rats. It was found that the mono- and dihydroxamates could not enhance the tumour-localizing properties of 67Ga-citrate, while the 67Ga-labelled trihydroxamates showed very rapid urinary excretion.

Animals↗
PubMed1982

Relationship between synthesis of ribosomes and RNA polymerase in Bacillus subtilis.

The relationship between RNA polymerase synthesis and ribosome synthesis has been investigated in Bacillus subtilis growing at different rates. The amount of polymerase was determined by quantitation of polymerase subunits on polyacrylamide gels, while ribosome synthesis was estimated from accumulation of total RNA. The ratio of ribosome to RNA polymerase synthesis was 5:1 at slower growth rates and increased with growth rate. Bacillus subtilis was estimated to contain between 10-and 2-fold excess of RNA polymerase depending on its growth rate.

Bacillus subtilis↗
PubMed1980

[Normal values in brain stem electric response audiometry (BERA)].

The normal values in brainstem electric response audiometry (BERA) were studied. A description is given of the latencies and amplitudes of the normal response. The effects of (1) the intensity of the stimulus, (2) the stimulation rate, and (3) the use of a sedative were investigated. It seems that the transmission time P1-P5 is significantly longer (+/- 0.25 msec) in men than in women.

Audiometry↗