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J J Nauta

Publications and source records attributed to J J Nauta.

At least 19 recordsLinked to original sources
PubMed1998

No interaction between ciprofloxacin and an oral contraceptive.

Several antibiotics have been reported to lessen the ovarian suppression produced by oral contraceptive agents, as a result of drug interactions. The present investigation was designed to study the likelihood of the occurrence of any such interaction between the fluoroquinolone antibiotic ciprofloxacin (Ciproxin) at a dosage of 500 mg twice a day and the "low-dose" oral contraceptive Marvelon (30 microgram of ethinyl estradiol [EE] plus 150 microgram of desogestrel). Twenty-four healthy female volunteers were studied in a double-blind, placebo-controlled, randomized crossover trial. There were no significant differences between measurements of the area under the concentration-time curve of EE up to 24 h after oral contraceptive intake during placebo and ciprofloxacin administration on days 11 and 16 of the cycles, indicating the absence of pharmacokinetic interaction. Similarly, no clinically significant differences in the levels of sex hormone binding globulin were found between the placebo and ciprofloxacin cycles, indicating no major variation in EE levels during ciprofloxacin and placebo treatment. Ten subjects in each of the placebo and ciprofloxacin groups had early-follicular-phase levels of 17-beta estradiol (<184 ng/liter) at one or more points during their cycles, but none had values above the early-follicular-phase range, indicating no significant ovarian activity. In addition, all subjects had progesterone levels of <2 ng/ml, indicating the absence of ovulation. Only two subjects, who received the placebo, had evidence of sustained follicular growth to a potentially ovulatory follicle ( approximately 18 mm). We conclude that ciprofloxacin does not interfere with the ovarian suppression produced by the low-dose oral contraceptive Marvelon.

Adult↗
PubMed1997

Nocturnal waking and morning dip of peak expiratory flow in clinically stable asthma patients during treatment. Occurrence and patient characteristics.

The occurrence of nocturnal waking due to asthma and morning dip of the peak expiratory flow (PEF), and the associated patient characteristics were investigated in 103 clinically stable asthmatic patients from a pulmonary outpatient clinic. Analysis of a 1 week diary showed a mean week morning PEF dip (i.e. morning/daytime highest PEF) of 12%. A mean dip of > or = 20% was found in 20% of the patients. Three groups were distinguished: 10% were 'nocturnal-waking patients' (waking up > or = 2 nights a week with a PEF dip of > or = 20%); 19% 'morning-dipping patients' (patients with > or = 3 dips a week of > or = 20% but with waking up on < 2 nights a week) leaving 71% 'remaining patients'. 28% of all patients showed morning PEF dips. In a questionnaire, waking every night was reported by 9%, at least once a week by 42% and once a month by 72%. In 'nocturnal-waking patients' FEV1 and morning and evening PEFs were lower than in 'remaining patients'; complaints during the night and on rising were more severe. The morning PEF dip was the same in 'nocturnal-waking patients' and 'morning-dipping patients'. The occurrence of waking was the same in 'morning-dipping patients' and in the 'remaining patients'. There were no differences in other clinical parameters among the three groups. We conclude that a subset of clinically stable asthma patients presents morning dips and nocturnal waking. They do not differ substantially from the remaining patients in other clinical characteristics.

Activity Cycles↗
PubMed1997

Specific power calculations for magnetic resonance imaging (MRI) in monitoring active relapsing-remitting multiple sclerosis (MS): implications for phase II therapeutic trials.

Inhomogeneous patient samples have been used in previous studies to determine the power of magnetic resonance imaging (MRI) for trial monitoring in multiple sclerosis (MS). These power-calculations might not be applicable to the active relapsing-remitting patient who is preferably included in trials. In order to reevaluate the power-calculations for MRI in the monitoring of treatment in strictly relapsing-remitting MS and to compare the power of different trial designs we studied 12 relapsing-remitting MS patients prospectively for a median period of 12 months using monthly clinical assessments and gadolinium-enhanced MRI. A median number of two clinical relapses/patient occurred of which a median of one was treated with steroids. A median of 1.59 new lesions/scan/patient was detected (range 0-8). The total number of new active lesions correlated significantly with study period relapses (SRCC = 0.72, P = 0.023). Computer simulations using the bootstrap technique yielded mostly lower power values for a parallel groups design than in previous studies except for short follow-periods in larger samples. In this-sample the open cross-over design was found to be between 20 and 40% more powerful. Results of power-calculations are clearly sample dependent implying that for treatment trial monitoring using MRI in relapsing-remitting MS conservative sample size estimates are to be used. In an active patient group open cross-over trial designs could be a very powerful alternative to parallel groups design.

Adult↗
PubMed1996

Miglitol (Bay m 1099) has no extraintestinal effects on glucose control in healthy volunteers.

In this double-blind, cross-over, placebo-controlled, randomized study, possible extraintestinal effects of miglitol, an absorbable alpha-glucosidase inhibitor, were investigated. Sixteen healthy male volunteers underwent two 75 g oral glucose tolerance tests with concomitant administration of miglitol or placebo. Peak and post-peak areas under the curve values for blood glucose, serum insulin and serum C-peptide after miglitol were not different from those found after placebo. The post-peak AUC-ratio (AUC (peak, 180 min) on miglitol/AUC (peak, 180 min) on placebo) was for glucose 1.15 (CI 0.94-1.40, P = 0.16), for insulin 1.12 (CI 0.95-1.33, P = 0.17) and for C-peptide 0.98 (CI 0.81-1.18, P = 0.82). It is concluded that miglitol exerts no clinically relevant extraintestinal effects on glucose control.

1-Deoxynojirimycin↗
PubMed1996

Treatment of nocturnal asthma by addition of oral slow-release albuterol to standard treatment in stable asthma patients.

Nocturnal and early-morning complaints in asthma patients are sometimes difficult to treat. We investigated the efficacy of an oral osmotically controlled release (OR) formulation of albuterol 8 mg in 35 patients with stable asthma and nocturnal complaints and/or morning dipping of the peak expiratory flow (PEF). The mean age was 45 years (range 22-70), the FEV(1) was 61 +/- 20% of predicted, and inhaled steroids were used by 32 patients. Albuterol OR was added to their usual treatment. The use of theophyllines and oral adrenergics was not allowed. Twice-daily (b.i.d.) dosing was compared to one dose at night and to placebo. The three-period crossover study was double-blind placebo-controlled with treatment periods of 2 weeks. Responses have been analyzed by means of multiple regression analysis at a significance level of 5%. There was no significant difference of the FEV(1) or the weekly means of PEFs between the periods. During the b.i.d. treatment, the daytime and nocturnal symptom scores, used rescue medication, subjective sleep quality, and nocturnal waking tended to be better. Mental fitness was improved, but significantly only in the morning. We concluded that additional treatment with albuterol 8 mg OR once or twice daily did not lead to an overall clinical improvement in this group of patients with nocturnal asthma during standard treatment. In view of the tendency to improvement, it may be worth trying this treatment in individual patients.

Administration, Oral↗
PubMed1995

[Glucose intolerance in elderly persons in The Netherlands; the Twello Study].

OBJECTIVE: To determine the prevalence of grades of glucose intolerance in subjects over 64 years of age. DESIGN: Point prevalence study. SETTING: Twello, a rural village in the Netherlands. METHODS: Of a total of 696 persons aged over 64 years recruited from a general practice, 460 subjects had an oral glucose tolerance test (OGTT) in 1985, 56 were known with non-insulin-dependent diabetes mellitus. Glucose estimations were done in capillary whole blood with a Glucometer. OGTT results were classified according to WHO 1985 recommended cut-off points and combination rules. RESULTS: The prevalence of normal glucose tolerance was 42%, of impaired glucose tolerance 27% and of diabetes mellitus 31%. The estimated prevalence in the source population were 45% (44.4-44.6), 28% (28.3-28.5) and 27% (95% CI: 27.1-27.2) respectively, adjusted for age and gender by standardization to the Dutch population of 1985. Re-evaluation of the earlier diagnoses of 'diabetes mellitus' according to the new WHO guidelines revealed that 55% of earlier diabetic with diet as the only therapy were no longer classified as diabetics. The prevalence of diabetes mellitus in persons over 64 was 10% before the investigation took place, and 30% afterwards. CONCLUSIONS: Te prevalence of diabetes mellitus as well as of impaired glucose tolerance from the Twello study rank among the higher rates reported in Caucasian populations. Case finding of glucose intolerance in those at risk over 64 years of age is recommended.

Aged↗
PubMed1995

Role of genetic factors in the etiology of squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine the role of genetic predisposition in the etiology of head and neck squamous cell carcinoma. DESIGN: Retrospective study. SETTING: The outpatient clinics of the departments of otorhinolaryngology and maxillofacial surgery. PATIENTS: First-degree relatives of patients with new head and neck cancer, with first-degree relatives of the patients' spouses as controls. MAIN OUTCOME MEASURE: Occurrence of cancer of the respiratory and upper digestive tract in relatives of patients with head and neck cancer and controls. RESULTS: First-degree relatives (n = 617) of 105 patients with head and neck cancer had 31 cases of cancer of the respiratory and upper digestive tract vs 10 cases in the control group (n = 618) (relative risk, 3.5; P = .0002). This higher rate of cancer was even larger in siblings (16 vs 2, relative risk, 14.6; P = .0001). CONCLUSIONS: Genetic predisposition is an important risk factor for squamous cell carcinoma of the head and neck.

Carcinoma, Squamous Cell↗
PubMed1995

Subjective sleep quality and mental fitness in asthmatic patients.

Asthmatic patients from our outpatient pulmonary clinic were asked to fill out a questionnaire about their sleep and daytime fitness. Seventy-eight responded. Sixty-five healthy persons served as a control group. Patients reported decreased sleep quality, decreased daytime mental fitness, and increased daytime somnolence. There was no relation between these features and lung function, bronchial hyperreactivity, or nocturnal asthma. We conclude that these asthmatic patients reported more sleep disturbances and daytime somnolence than healthy control persons.

Adolescent↗
PubMed1994

Increased mutagen sensitivity in head-and-neck squamous-cell carcinoma patients, particularly those with multiple primary tumors.

Mutagen sensitivity is a constitutional factor which may be used to identify head-and-neck squamous-cell carcinoma (HNSCC) patients at high risk for the development of multiple primary tumors (MPT). In this retrospective study, mutagen sensitivity was measured in HNSCC patients with a single primary tumor (SPT), HNSCC patients who have already developed MPT and control subjects with no tumor history. In vitro, lymphocytes were challenged with bleomycin and chromosomal damage was quantified by scoring chromatid breaks of 100 cells. A significant difference in the mean number of breaks per cell (b/c) was found between SPT patients and controls. Patients with MPT showed a significantly higher mean b/c value than SPT patients. This increase in mutagen sensitivity in HNSCC patients was not related to well-known cancer risk factors such as age, or life-style factors such as smoking and alcohol drinking habits. In addition, tumor site but not tumor stage was found to be related to mutagen sensitivity. On the basis of our findings, we propose that mutagen sensitivity is not an independent risk factor but a constitutional factor which reflects the way in which genotoxic compounds are dealt with and is thereby directly related to cancer risk.

Aged↗
PubMed1994

Clinical efficacy and morbidity associated with continuous cyclic compared with continuous ambulatory peritoneal dialysis.

OBJECTIVE: To assess the clinical efficacy and morbidity of continuous cyclic peritoneal dialysis compared with continuous ambulatory peritoneal dialysis with a Y-connector as renal replacement therapy. DESIGN: Prospective, randomized study. SETTING: University hospital. PATIENTS: All new patients with end-stage renal failure consecutively entering the dialysis program from January 1988 through July 1991 were randomly assigned to receive continuous ambulatory peritoneal dialysis with a Y-connector or continuous cyclic peritoneal dialysis and were followed prospectively. MEASUREMENTS: Patient and technique survival, dialysis adequacy, and (infectious) morbidity. RESULTS: Forty-one patients (median age, 56 years; range, 18 to 86 years) started continuous ambulatory peritoneal dialysis with a Y-connector (follow-up, 688 patient-months), and 41 patients (median age, 54 years; range 21 to 76 years) started continuous cyclic peritoneal dialysis (follow-up, 723 patient-months). The two groups showed no significant differences in adequacy of dialysis (as assessed by blood pressure control and laboratory and neurologic variables) and patient or technique survival. Renal transplant was the primary reason for discontinuing the assigned dialysis technique in both groups. The average number of hospitalizations per patient-year was 1.0 using continuous ambulatory peritoneal dialysis with a Y-connector and 0.6 per patient-year using continuous cyclic peritoneal dialysis (P = 0.02), with a mean duration of 10.8 and 9.6 days per admission, respectively (not significant). Peritonitis occurred significantly less often in those receiving continuous cyclic peritoneal dialysis (0.94 compared with 0.51 episodes per patient-year; P = 0.03). No difference in causative pathogens was observed. Exit site infection rate was 0.38 episodes per patient-year in both groups. CONCLUSION: In an unselected patient group, continuous cyclic peritoneal dialysis was accompanied by significantly lower rates of peritonitis and dialysis-related hospital admission, whereas it was as effective as continuous ambulatory peritoneal dialysis with a Y-connector for patient and technique survival.

Adolescent↗
PubMed1994

Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor.

BACKGROUND: Biologic aggressiveness of head and neck carcinoma is reflected in its capability to metastasize to regional lymph nodes and its propensity to recur after treatment. METHODS: The authors report on 244 patients treated at the Department of Otolaryngology-Head and Neck Surgery of the Free University Hospital, Amsterdam, The Netherlands, with excision of primary tumor with incontinuity neck dissection with or without postoperative radiation therapy between January 1973 and July 1986. All patients had surgical margins free of tumor. RESULTS: The overall recurrence rate was 12.3%. Stages T3-4 and the presence of more than three positive nodes on histopathologic examination were associated with a 16.2% and 26.2% incidence in recurrence at the primary site, respectively. No prognostic influence arose from primary tumor localization, three or fewer positive nodes, extranodal spread, and postoperative radiation therapy. CONCLUSIONS: Patients with T3-4 disease and those with more than three positive lymph nodes may benefit from novel adjuvant treatment modalities.

Adult↗
PubMed1994

Limited duration of the effect of methylprednisolone on changes on MRI in multiple sclerosis.

Treatment with methylprednisolone reduces the duration and severity of clinical relapses in multiple sclerosis (MS), while reducing the number of gadolinium-enhancing lesions on T1-weighted MRI. We performed serial MRI imaging after methylprednisolone treatment to see whether suppression of enhancement persists and whether related abnormalities on T2-weighted images disappear at follow-up. Thirteen patients with definite MS received a total of 31 courses of methylprednisolone over an average period of 50 weeks. Gadolinium-enhanced MRI was obtained before and after treatment, then at monthly intervals, using a standardised repositioning and imaging protocol. Two experienced readers in conference defined the number of active (gadolinium-enhancing and new or enlarging nonenhancing) lesions. We detected 609 active lesions on 195 examinations. Directly after treatment the reduction in the number of enhancing lesions was 78%, indicating restoration of the BBB and suppression of inflammation. It was uncommon for a lesion which stopped enhancing to show enhancement on a subsequent examination. No beneficial effect was observed on the rate of disappearance of related abnormalities on T2-weighted images, indicating persistent change such as oedema, cellular infiltration or demyelination. Moreover, in 89% of cases, an increase in the number of active lesions was observed before new clinical activity, if any, was observed (on average 52% earlier). MRI enabled us to demonstrate that the duration of the effect of methylprednisolone treatment is temporary (on average 9.7 weeks).

Adult↗
PubMed1994

Magnetic resonance imaging in monitoring the treatment of multiple sclerosis patients: statistical power of parallel-groups and crossover designs.

Serial brain magnetic resonance (MR) imaging detects active lesions 5-10 times more frequently than the occurrence of clinical changes in patients with early relapsing-remitting and secondary progressive multiple sclerosis (MS). Based on monthly unenhanced and gadolinium enhanced MR findings in 23 unselected and untreated patients, the power of an MS treatment trial was calculated, using MR imaging activity as the primary measure of outcome. It was shown that a 80% reduction in the number of active lesions (i.e. an efficacy of 80%) should be detected using a placebo-controlled parallel-groups design with a power of 80%, if either 2 x 20 patients are scanned monthly for 4 months, or 2 x 30 patients monthly for 2 months. Short to medium term studies of new experimental treatments in MS, using MR imaging as the primary outcome measure, provide considerable statistical power in small patient populations studied over a short period of time.

Adult↗
PubMed1994

Determinants of insulin sensitivity and consequences for lipoproteins and blood pressure in subjects with non-insulin-dependent diabetes mellitus.

The aim of the present study was to investigate the possible determinants of insulin sensitivity and the relationships of these determinants and insulin sensitivity to lipoprotein levels and blood pressure in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied 46 patients with NIDDM (26 women, 20 men) treated either with diet alone or in combination with sulfonylureas. Insulin sensitivity was assessed as the insulin-mediated glucose uptake rate (M value) with the hyperinsulinemic euglycemic clamp technique. In a multiple regression model, only percent body fat, waist to hip ratio (WHR), and resting energy expenditure (REE) emerged as significant independent determinants of the M value, with a multiple R2 for the model of 44%, whereas age, hemoglobin A1c (HbA1c) level, thyroid function, fitness level, smoking status, alcohol consumption, and dietary habits did not contribute significantly. The M value was independently and negatively associated with the concentrations of triglyceride (TG) and very-low-density lipoprotein (VLDL) cholesterol and positively associated with high-density lipoprotein (HDL) cholesterol subfractions and apolipoprotein A1. In our predominantly normotensive subjects, we found no association between the M value and blood pressure. Moreover, fasting insulin contributed directly, ie, independent of the M value, to the variation of TG, but not to the other lipoproteins and not to blood pressure. The results suggest that in NIDDM (1) insulin sensitivity is determined mainly by percentage body fat and REE, (2) the insulin level determines the TG level directly, whereas the lipoproteins are influenced indirectly as a reflection of the degree of insulin resistance, and (3) insulin sensitivity is not related to blood pressure in a normotensive population.

Aged↗
PubMed1994

Peripheral blood progenitors mobilised by G-CSF (filgrastim) and reinfused as unprocessed autologous whole blood shorten the pancytopenic period following high-dose melphalan in multiple myeloma.

Growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) is effective at progenitor release into the peripheral blood. After high-dose chemotherapy haematopoietic reconstitution occurs after reinfusion of these peripheral blood progenitor cells (PBPC). However, the collection by leukapheresis and further processing of PBPC are very time consuming and expensive. We have studied the transplantation potential of a small volume of unprocessed autologous whole blood after G-CSF mobilisation. Six patients with plasma cell disorders received G-CSF 10 micrograms/kg sc during 6 days. Subsequently 11 of whole blood was collected by phlebotomy, kept unprocessed at room temperature and reinfused 24 h after high-dose melphalan 140 mg/m2. CFU-GM content was 845 per ml blood (median, range 320-3472) and CD34+ cells rose to a median percentage of 0.9 (range 0.4-2.0). Haematological recovery was significantly faster in the study group compared with the control group of 20 patients who received the same dose of melphalan without reinfusion of PBPC. The neutrophil count reached 0.5 x 10(9)/l at a median of 12.5 days after infusion of PBPC vs 38 days in the control group (p = 0.0003). The platelet count reached 20 x 10(9)/l after a median of 23.5 days vs 38 days (p = 0.0218). The shortened recovery was reflected by less transfusions, less antibiotic use and shortening of hospital stay (19 days vs 43 days, p = 0.0003). We conclude that this easy technique of mobilisation and collection of PBPC is very effective for hastening haematologic recovery after high-dose chemotherapy.

Adult↗
PubMed1993

Association between bleomycin genotoxicity and non-constitutional risk factors for head and neck cancer.

Sensitivity of phytohaemagglutinin-stimulated lymphocytes to bleomycin clastogenicity is increased in patients with tumours in organs and tissues that are in direct contact with the external environment, such as the mucosa of the head and neck. Sensitivity to bleomycin may reflect a genetically determined hypersensitivity to certain genotoxicants and therefore may be important in the carcinogenic process. In this study the applicability of bleomycin genotoxicity was investigated in cultured lymphocytes of forty individuals without a tumour history. No correlations were observed with increasing age or the well-known head and neck cancer risk factors alcohol and tobacco consumption. Since inter-individual variation in sensitivity greatly exceeded intra-individual variation, our results suggest that an elevated bleomycin clastogenicity score may identify individuals who have a constitutional hypersensitivity towards certain genotoxicants and may show an increased cancer susceptibility.

Alcohol Drinking↗
PubMed1993

A panel of biomarkers of carcinogenesis of the upper aerodigestive tract as potential intermediate endpoints in chemoprevention trials.

BACKGROUND: Patients with squamous cell carcinoma of the head and neck have a 10-30% risk of developing a second primary tumor. The concept of "field cancerization" assumes that the whole upper aerodigestive tract is affected and prone to malignant transformation. This study was undertaken to investigate the value of a panel of monoclonal antibodies to identify biomarkers in oral mucosa associated with cancer risk. Such biomarkers may be suitable candidates to serve as intermediate endpoints in cancer chemoprevention trials. METHODS: As a model, the expression of antigens was assessed in cytologic preparations obtained from macroscopically normal oral mucosa of patients with tongue carcinoma and of controls. The panel consisted of antibodies against cytokeratin 8, 10, 13, and 19 and the monoclonal antibodies designated K931, K984, E48, Ki-67, and UM-A9. RESULTS: Oral mucosa of cancer patients had a more than threefold increased expression of cytokeratin 19 as compared with controls (36.0 versus 11.3%; P < 0.01). CONCLUSION: Cytokeratin 19 is a potential intermediate endpoint in head and neck cancer chemopreventive trials.

Adult↗