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Biomedical subjects

H Melander

Publications and source records attributed to H Melander.

13 recordsLinked to original sources
PubMed2001

Incorrect use and limited weight reduction of orlistat (Xenical) in clinical practice. A cohort study.

OBJECTIVE: To study the prescribing of the antiobesity drug orlistat in relation to the approved indication and its weight-reducing effect in clinical practice during the first 3 months of treatment. METHODS: Anonymous postal questionnaire survey to prescribers of orlistat concerning a random sample of 1000 of 20,000 prescriptions. PARTICIPANTS: Useful information was obtained for 789 patients. SETTING: Primary and secondary care in Sweden. MAIN OUTCOME MEASURES: Beginning and continued treatment according to the approved indication. Dropout from treatment. Weight loss during treatment. RESULTS: Four percent of the patients were prescribed orlistat despite having a body mass index (BMI) less than 28 kg/m2. Only 24% of the patients had a diet period with a weight loss of 2.5 kg or greater before the start of therapy. Half of the patients with a weight loss of less than 5% after 3 months continued the treatment. Ten percent gained weight or had no weight loss at all while 43% lost less than 5% in weight. At least one-quarter of the patients stopped the treatment within the observation period. CONCLUSION: Orlistat was not prescribed according to the approved indication in the majority of cases. The dropout rate was high and most patients had minor gain from the treatment.

Adult↗
PubMed1997

Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: We wanted to study the effects of amphetamine on symptoms of attention-deficit hyperactivity disorder (ADHD) over a longer period than has been reported in previous studies of central stimulants in this condition. METHODS: Sixty-two children, aged 6 to 11 years, meeting DSM-III-R symptom criteria for ADHD participated in a parallel-group design, randomized, double-blind, placebo-controlled study of amphetamine treatment. Treatment was not restricted to children with "pure" ADHD, ie, some had comorbid diagnoses. In the amphetamine group, children received active treatment for 15 months. RESULTS: Amphetamine was clearly superior to placebo in reducing inattention, hyperactivity, and other disruptive behavior problems and tended to lead to improved results on the Wechsler Intelligence Scale for Children--Revised. Treatment failure rate was considerably lower and time to treatment failure was longer in the amphetamine group. Adverse effects were few and relatively mild. CONCLUSION: The results of this long-term, placebo-controlled study of the central stimulant amphetamine in the treatment of ADHD indicate that there are remaining positive effects of the drug 15 months after starting treatment.

Abdominal Pain↗
PubMed1997

Early discontinuation of treatment in children with uncomplicated epilepsy: a prospective study with a model for prediction of outcome.

PURPOSE: The main purpose of the present study was to identify predictor variables with significant influence on seizure outcome after discontinuation of treatment in children with uncomplicated epilepsy and to analyze whether these variables, included in a prognostic model could identify children in whom 1-year treatment would be sufficient. METHODS: Before initiation of treatment in children aged 2-16 years with uncomplicated epilepsy, the duration of treatment was randomized to 1 year (group I) or 3 years (group II). At the end of the allotted period, treatment was discontinued in 161 children who had been seizure fre during the previous 6 months. The mean follow-up period after treatment was 5.8 years. Twenty-three predictor variables were analyzed by survival methods regarding their influences on the outcome. RESULTS: At the latest follow-up check, 60 children (37%) had relapsed. The following predictor variables were selected by multiple regression analysis and constituted a model with a simple scoring system: age at seizure onset; seizure type; generalized, irregular spike-wave activity on EEG after 1 year of treatment; and persistent 3-Hz spike-wave activity after 6 months of treatment in children with absence epilepsy. In group I, the remission rate was 73% in children with high prognostic scores, 10% in children with low scores, and 40% in those with intermediate scores (log-rank test, p = 0.0001). CONCLUSIONS: After 1 year of treatment, our prognostic model identified children in whom treatment could be withdrawn at that time. Our model should be easily applicable in clinical practices and may be of clinical importance in determining the duration of treatment in children with uncomplicated epilepsy.

Adolescent↗
PubMed1997

Alternating treatment with didanosine and zidovudine versus either drug alone for the treatment of advanced HIV infection. The Alter Study. Nordic HIV Therapy Group.

The efficacy and safety of an alternating regime with zidovudine and didanosine versus treatment with either drug alone were investigated in a randomized, open, controlled trial, 552 patients with advanced HIV infection, 47% of whom had received prior treatment with zidovudine, were enrolled. The patients were randomly assigned to zidovudine 600 mg/day, didanosine 400 mg/day or 4-week alternations with the 2 drugs in the same dose. The study had a median length of follow-up of 88 weeks. In the overall analyses, time to death (p = 0.48) and time to death or new AIDA event (0.80) were equally distributed between the 3 treatment groups. In the subgroup of patients with a CD4 count < 100 x 10(6)/l the survival was longer in the alternating arm (p < 0.005) primarily because of differences among zidovudine naive patients. The alternating regime was better tolerated than the 2 monotherapies, with a longer time to dose reduction or withdrawal owing to side effects (p < 0.001).

Adult↗
PubMed1996

Comparison between one and three years of treatment in uncomplicated childhood epilepsy: a prospective study. I. Outcome in different seizure types.

PURPOSE: The main purpose of this prospective study was to analyze whether 1 year of treatment was as effective as 3 years with respect to remission rate in children with idiopathic epilepsy. METHODS: Treatment for epileptic seizures was started in 207 children aged 2-16 years. They were randomized to treatment for 1 or 3 years. At the end of the predetermined treatment period, 161 children had been seizure-free for 6 months and the treatment could be gradually withdrawn. RESULTS: The overall remission rate in our group of patients was significantly higher (71%) in the group treated for 3 years than in the group treated for 1 year (53%). However, comparison of remission rates between patients with different seizure types showed statistically significant differences in outcome depending on duration of treatment only in children with complex partial seizures (CPS). CONCLUSIONS: Our results show that 1 year of treatment can be recommended in children with benign partial epilepsy with rolandic spikes (BECT) and in children with simple partial seizures (SPS) but is clearly insufficient in children with CPS. A proper seizure classification is one important tool, although not sufficient, in offering recommendations concerning the duration of treatment in children with idiopathic epilepsy.

Adolescent↗
PubMed1995

G2/M transition requires multisite phosphorylation of oncoprotein 18 by two distinct protein kinase systems.

Oncoprotein 18 (Op18) is a conserved cytosolic protein that is a target for both cell cycle and cell surface receptor-regulated phosphorylation events. The four residues Ser16, Ser25, Ser38, and Ser63 are all subject to cell cycle-regulated phosphorylation. Ser25 and Ser38 are targets for cyclin dependent kinases (CDKs), while Ser16 and Ser63 are phosphorylated by an unidentified protein kinase. We have recently shown that induced expression of a CDK target site-deficient mutant, Op18-S25A,S38A, blocks human cell lines during G2/M transition. In the present report we show that mitosis is associated with complete phosphorylation of the two Op18 CDK target sites Ser25 and Ser38 and that Ser16 and Ser63 are also phosphorylated to a high stoichiometry. To evaluate the function of multisite phosphorylation of Op18, we expressed and analyzed the cell cycle phenotype of different kinase target site-deficient mutants. The data showed that induced expression of the S16A,S63A, S25A,S38A, and S16A,S25A,S38A,S63A mutants all resulted in an indistinguishable phenotype, i.e. immediate G2/M block and subsequent endoreduplication, a given fraction of G2 versus M-phase blocked cells, and a characteristic nuclear morphology of M-blocked cells. This result was unexpected; however, a likely explanation was provided by analysis of Op18 phosphoisomers, which revealed that mutations of the CDK sites interfere with phosphorylation of Ser16 and Ser63. The simplest interpretation of our results is that phosphorylation of Ser16 and Ser63 is essential during G2/M transition and that the phenotype of the S25A,S38A mutant is mediated by the observed block of Ser16/Ser63 phosphorylation.

Amino Acid Sequence↗
PubMed1994

The phenotype of a "Cdc2 kinase target site-deficient" mutant of oncoprotein 18 reveals a role of this protein in cell cycle control.

Oncoprotein 18 (Op18) is a cytosolic protein that is expressed in all proliferating cells. This phosphoprotein is up-regulated in a variety of human neoplasm, and phosphorylation of its two Cdc2 kinase target sites, Ser-25 and Ser-38, fluctuates dramatically during the cell cycle. We have investigated the potential role of the Cdc2 kinase-mediated phosphorylation of these two sites by expressing a "Cdc2 kinase target site-deficient" mutant of Op18 (Op18-S25,38A), and analyzed the phenotype on the level of cell cycle regulation. The result shows that induced expression of Op18-S25,38A results in rapid accumulation of cells in the G2 phase of the cell cycle. The block in G2 seems transient, since prolonged incubation was found to result in a large fraction of the transfected cells entering S phase in the absence of mitosis, i.e. endoreduplication. In addition, a fraction (30%) of the transfected cells was blocked in mitosis. Whereas the morphology of the G2 arrested cells appeared normal, expression of Op18-S25,38A caused a serious defect during mitotic chromosome segregation. Analyses of the mechanism behind the phenotype of Op18-S25,38A suggest an essential role for Op18 during cell division and that the mutant interferes with the function of the endogenous gene product.

Amino Acid Sequence↗
PubMed1992

Body growth in relation to tonsillar enlargement and tonsillectomy.

Severe airway obstruction caused by tonsillar enlargement can result in disturbances in body growth. The effect of this interference and of tonsillectomy in the child with only moderate symptoms have been less satisfactoril evaluated. In this study, 122 children with symptoms and signs of tonsillar obstruction were investigated concerning the height and weight before and after tonsillectomy. None of the individuals demonstrated cardiopulmonary complications of tonsillar obstruction. Altogether 10% of the children exhibited abnormalities in body weight and/or length prior to surgery. Especially during the first postoperative year, the weight and height gain exceeded the expected in 75% of the patients. The accelerated weight gain increased with tonsil size, but there was no relation to the extent of difficulties in swallowing or sleeping disruptions. The results support the hypothesis that tonsillar hypertrophy frequently is associated with disturbances in body growth and that this is seldom demonstrable prior to tonsillectomy.

Adolescent↗
PubMed1991

Time-dependent variation in the cardiac conduction system assessed in young healthy individuals at weeks' interval: implications for clinical trials.

The time-dependent physiologic variations of the cardiac conduction system were evaluated at repeated invasive studies in 10 healthy individuals. Their mean age was 28 years (range 22 to 34) and they volunteered to undergo two electrophysiologic studies at intervals of 14 to 63 days (mean 25). The coefficients of variation, repeatability and reproducibility, which should be the preferred statistics when assessing the reproducibility of continuous variables, were calculated. The mean sinus cycle length had a high reproducibility, with coefficients of variation between 2% and 6%. The mean and maximal sinus node recovery times, however, varied considerably. The reproducibility was very high for ventricular depolarization and repolarization (QRS, JT, QT), with coefficients of variation between 2% and 6%. The coefficients of variation were below the acceptable 10% value for intraatrial conduction, atrioventricular (AV) node conduction, His-Purkinje conduction as well as the Wenckebach point; for the effective refractory period of the AV node, it was 12%. Repeat invasive electrophysiologic testing is a safe and reproducible method for evaluating and comparing cardioactive drug effects in healthy subjects. The same statistical analyses were applied to previously published studies on continuous electrophysiologic variables, which allowed comparisons among different groups of healthy and sick persons, as well as among different electrophysiologic variables and procedures. Furthermore, the minimal actual treatment differences that can be detected with a reasonable (80%) probability at a predetermined (5%) significance level using a crossover design were estimated for different electrophysiologic variables. These data will assist in the calculation of the necessary sample size for clinical trials and related purposes.

Adult↗