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Biomedical subjects

P Mustajoki

Publications and source records attributed to P Mustajoki.

At least 37 records · Page 2Linked to original sources
PubMed1998

A nurse-managed weight reduction programme for obstructive sleep apnoea syndrome.

OBJECTIVES: This longitudinal, clinical intervention study was designed to investigate whether pulmonary departments can set up a cost-effective weight and lifestyle programme as primary treatment of obstructive sleep apnoea syndrome (OSAS). SETTING: A weight reduction programme (1 year) in a pulmonary department for outpatients in Helsinki University Central Hospital. SUBJECTS: A total of 24 (23 men) moderately obese (body mass index [BMI], 30-40 kg m(-2)) patients with newly diagnosed OSAS. Interventions. The first 6 weeks consisted of a very low-calorie diet (VLCD, 500 kcal day(-1)) and thereafter normal food low in calories. There were altogether 12 group meetings for behavioural management. MAIN OUTCOME MEASURES: Daytime somnolence, BMI and oxygen desaturation index of 4% (ODI4) were measured prior to the programme, at the end of the VLCD phase and at 1 year. RESULTS: The programme was easy to administer without any serious side-effects. At 1 year, patients had lost a mean of 33% of their overweight (mean weight at baseline 110 kg, after 99 kg) and their ODI4 indexes improved significantly (P < 0.005). There was no correlation between the amount of weight loss and improvement in ODI4 indexes. The cost per patient was about half the cost of treatment with nCPAP (nasal continuous positive airway pressure) for 1 year at our hospital. CONCLUSIONS: A nurse-managed programme with VLCD and behavioural management is safe and effective on an outpatient basis. Weight loss should be encouraged in OSAS in patients with moderate overweight. The amount of weight loss needed for improvement of OSAS is unique to each individual.

Adult↗
PubMed1998

Acute porphyria: treatment with heme.

The characterization of porphyrias as disorders of heme biosynthesis leading to hepatic heme deficiency and raised formation and secretion of heme precursors laid the basis for heme treatment. Although mild attacks sometimes respond to glucose administration, severe attacks or symptoms that are likely to progress should be treated with heme. The heme compounds used in treatment are hematin and heme arginate. In our opinion, heme arginate is preferable to hematin in the treatment of acute porphyrias because of its better stability, fewer side effects, and better documentation of its benefits.

Acute Disease↗
PubMed1997

Comparison of behavior therapy with and without very-low-energy diet in the treatment of morbid obesity. A 5-year outcome.

BACKGROUND: Very-low-energy diets (VLEDs) together with behavior therapy (BT) are widely used in the treatment of morbid obesity, but there is no evidence of their long-term effectiveness as compared with behavior therapy alone. METHODS: Fifty-nine morbidly obese patients (25 men and 34 women; mean weight, 132.8 +/- 20.7 kg; mean age, 43.1 +/- 9.2 years) were treated with combined therapy of VLED and BT or BT alone. No maintenance program was used. Eighty-seven percent of eligible patients were contacted 4.8 to 6.2 years after the program. RESULTS: During treatment, 56% of patients dropped out of the VLED + BT group and 28% from the BT group (P = .03). High scores on the Symptom Checklist-90R before treatment predicted dropout from the VLED+BT group, but not from BT. At the end of therapy, mean weight change was -22.9 kg in the VLED+BT group and -8.9 kg in the BT group (P < .001). The overall weight change from pretreatment to the 5-year follow-up was greater in the VLED+BT group than in the BT group (-16.9 kg vs -4.9 kg, respectively; P = .03). Men succeeded better in the VLED+BT group than in BT. Among the dropouts, the mean weight change from baseline was +5.2 kg in the VLED+BT group and +13.0 kg in the BT group. CONCLUSIONS: Our data suggest that in the treatment of morbid obesity, VLED combined with BT may produce a better 5-year maintenance than BT alone, especially among men. A satisfactory weight loss can be achieved without a maintenance program.

Adult↗
PubMed1997

Diagnostic strategy, genetic diagnosis and identification of new mutations in intermittent porphyria by denaturing gradient gel electrophoresis.

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease of heme metabolism caused by mutations in the hydroxymethylbilane synthase gene. Diagnosing AIP during an acute attack using traditional biochemical markers is unproblematic, but it can be difficult to obtain a definite diagnosis in asymptomatic carriers. These limitations may, however, be solved through a genetic approach for diagnosing AIP carrier status. A mutation screening assay based on the denaturing gradient gel electrophoresis (DGGE) principle was established in a setup that allows within 24 hr to pinpoint which of the 15 exons of the hydroxymethylbilane synthase gene carries the underlying mutation, and thereby reduces subsequent sequencing, needed to determine the specific mutation, to this particular gene region. To evaluate sensitivity and specificity of the DGGE assay, samples from 22 AIP patients with known mutations and six healthy controls were examined in a blinded design. Following unblinding, it was revealed that in all 22 AIP samples the correct mutation carrying region had been pointed out. In two samples containing a previously undescribed polymorphism, this additional region was also pointed out. All controls were correctly characterized as normal in the DGGE assay. Subsequently, to evaluate the assay in the clinical setting, samples from six previously uncharacterized Danish AIP probands were examined and the underlying mutation detected in all six. In conclusion, a simple and sensitive mutation screening assay based on the DGGE principle allows genetic diagnosis of AIP in a routine setting and may be used as an additional tool in genetic counseling of AIP families.

DNA Mutational Analysis↗
PubMed1997

Use of very low-calorie diet in preoperative weight loss: efficacy and safety.

We report the efficacy of a very low-calorie diet (VLCD)-based weight reduction program in patients with morbid obesity whose elective surgery had been postponed because of being overweight. The safety of weight loss on the immune system will also be evaluated. Thirty patients (mean age, 50 years; weight, 125 kg; BMI, 44 kg/m2) were treated. The program consisted of a 7-week to 24-week VLCD period, supported by individual sessions with a therapist, and of a refeeding period of 1 month before surgery. Two patients discontinued, and the mean weight loss of the remaining 28 patients was 19.6 kg (15% of initial weight). In 23 patients, weight loss was 10% or more of the initial weight. After weight loss, 15 patients underwent surgery, 4 patients did not need an operation, and the remaining 9 patients were not operated on for various reasons. The numbers of circulating leukocytes, neutrophils, basophils, monocytes, CD3+, CD4+, CD8+, and natural killer cells did not change significantly by the ninth week on VLCD or by the end of the program. However, there was a significant (p < 0.05) decrease in the immunoglobulinM serum concentration during the program. In conclusion, a VLCD program is suitable for preoperative weight reduction in morbid obesity and seems not to compromise the immune system.

Adolescent↗
PubMed1997

Markers for the gene ob and serum leptin levels in human morbid obesity.

Leptin, the product of the ob gene, reduces body fat in genetically obese animals and circulates in elevated concentrations in the blood of obese patients. Polymorphic markers situated in the proximity of the human ob gene have recently been suggested to be linked to morbid obesity. We have studied the possible association between the microsatellite markers near the ob gene and morbid obesity in 252 morbidly obese patients with a mean body mass index (BMI) of 43 +/- 7 kg/m2, and 151 lean controls with a mean BMI of 22 +/- 2 kg/m2, and searched for linkage of these gene markers to obesity in 76 affected sib-pairs (BMI > or = 32). No significant association was observed between any of the eight microsatellite markers and morbid obesity, and affected-sib-pair analysis failed to show linkage of three selected ob gene markers to obesity in the sibships. There was a strong positive correlation between serum leptin levels and BMI in morbidly obese patients; a carrier status for either of the two most prevalent alleles of the microsatellite marker D7S530 in the vicinity of the ob gene was associated with serum leptin levels in the obese subjects. Two of the markers (D7S2519, D7S649) showed a significant relation to the weight-losing response to a 16-week very-low-calorie dietary intervention. We have thus been able to confirm a tight relationship between serum leptin and body mass but have found no evidence for genetic linkage of the ob gene markers to morbid obesity in a population considered to represent a genetic isolate and to be an ideal model for studies of complex disorders.

Adult↗
PubMed1997

Novel polymorphism of the human ob gene promoter in lean and morbidly obese subjects.

OBJECTIVE: Leptin, the circulating product of the human ob gene, may play role in control of appetite and metabolic rate. We screened the proximal promoter area of the ob gene for mutations and common polymorphisms in order to find out whether genetic variation in the regulatory area of this gene plays a role in human obesity. DESIGN: The technique of single-strand-conformation polymorphism (SSCP) was applied to screen for the promoter area of the ob gene for genetic alterations in morbidly obese patients. SUBJECTS: A total of 249 morbidity obese (present or past body mass index [BMI] > or = 40 kg/m2) and 141 lean (BMI < or = 25 kg/m2) subjects. MEASUREMENTS: DNA analysis was carried out using a single-strand conformation polymorphism (SSCP) technique and PCR followed by digestion with the restriction enzyme BssHll. Leptin was determined by radioimmunoassay in obese subjects. Serum lipids, glucose and insulin concentrations in the obese subjects were also determined. RESULTS: A new polymorphism C(-188)A was identified in the promoter region of the ob gene. This polymorphism was detected with allelic frequencies of 0.06 in morbidly obese subjects and 0.09 in lean controls (P = 0.28). Initial studies failed to show an association of this polymorphism with serum leptin, response to treatment for obesity, history and extent of weight gain, or serum insulin, glucose of lipid concentrations. CONCLUSIONS: We have identified a common polymorphism in the promoter area of the human ob gene which appears to be very useful for genetic association and linkage studies. Further studies are needed to elucidate its potential role in the regulation of the human ob gene and in human metabolic disorders.

Adolescent↗
PubMed1997

Steady-state transcript levels of the porphobilinogen deaminase gene in patients with acute intermittent porphyria.

PCR-based solid-phase minisequencing method was used to analyze the steady-state mRNA levels of the porphobilinogen deaminase gene in eight patients with acute intermittent porphyria. The patients had the earlier characterized mutations 517C --> T (R173W), 518G --> A (R173Q), 673C --> G (R225G), 673C --> T (R225X), 713T --> G (L278P), and 1073delA (frame shift). All mutations, except the missense mutation 517C --> T in exon 10, affected the steady-state transcript levels of the mutant allele. The mutant mRNA levels in lymphocytes varied from 5% to 95% of the corresponding wild-type allele levels. In contrast to the CRIM-negative mutation 517C --> T, the CRIM-positive mutation in the same codon 518G --> A resulted in reduction of the steady-state transcript level of the mutant allele to 65% of that of the normal allele. The two mutations, 673C --> G or T, affecting the same nucleotide in exon 12 also differed considerably in their effect on mRNA levels: The transcript level of the allele with a missense mutation was decreased to 80% of that of the normal allele, whereas a nonsense mutation at the same position resulted in a dramatic decrease (fivefold) in the levels of the mutant transcript. Our data showed large variations between the levels of mutant transcript in AIP patients and these variations did not correlate either to CRIM class, to the location of the disease causing mutation in the PBGD gene, or to the clinical phenotype of AIP.

Alleles↗
PubMed1996

Four novel mutations in the ferrochelatase gene among erythropoietic protoporphyria patients.

A novel mutation was identified by direct sequencing of genomic polymerase chain reaction products in each of four Finnish erythropoietic protoporphyria families. All four mutations, including two deletions (751delGAGAA and the first de novo mutation, 1122delT) and two point mutations (286C-->T and 343C-->T), resulted in a dramatically decreased steady-state level of the allelic transcript, since none of the mutations could be demonstrated by direct sequencing of the amplified cDNAs synthesized from total RNA extracted from patients' lymphoblast cell lines. Because the assays of the ferrochelatase activity and erythrocyte protoporphyrin identify asymptomatic patients poorly, the DNA-based demonstration of a mutation is the only reliable way to screen individuals for the disease-associated mutation.

Base Sequence↗
PubMed1996

Improved gas exchange during exercise after weight loss in morbid obesity.

The aim of this study was to determine the effect of weight loss induced by 6 weeks very-low-calorie-diet (VLCD) and behavioural intervention on pulmonary gas exchange during exercise in non-smoking morbid obese (BMI>40 kg/m2) otherwise healthy patients. Seven obese patients underwent a maximal bicycle ergometer test with continuous analysis of expired air and arterial blood sampling before and after a mean weight loss of 18% (25.7 kg, range: 10-50 kg). Body mass index (BMI) decreased with weight loss from 46.6 (6.3) kg/m2 to 38.0 (4.7) kg/m2 (P<0.01). Oxygen consumption (VO2) at low and submaximal exercise levels decreased after weight reduction, but the change was not statistically significant. The peak oxygen consumption related to body weight (VO2/kg) increased 22% from the initial 16.2 (3.6) ml/min/kg to 19.8 (3.1) ml/min/kg (P<0.05). Decrease in VCO2 was significant at submaximal exercise level. Ventilatory equivalent for CO2 increased significantly after weight reduction (P<0.05). Standing up and light exercise resulted in a significant increase in the mean arterial oxygen tension (PaO2) (P<0.05) and a significant decrease in the mean alveolar-arterial difference P(A-a)O2 (P<0.05) when compared to supine values. The mean increase in PaO2 with weight loss was not significant. The peak P(A-a)O2 decreased significantly after weight reduction. In conclusion, weight reduction induced by VLCD and behavioural intervention without exercise therapy can improve gas exchange during exercise in morbid obesity. Increased wasted ventilation, and a tendency to alveolar hyperventilation, after weight loss may reflect a delay in the adaptation of regulation of breathing to rapid weight loss.

Adult↗
PubMed1996

Two year maintenance of weight loss after a VLCD and behavioural therapy for obesity: correlation to the scores of questionnaires measuring eating behaviour.

OBJECTIVE: To investigate changes in weight, Three Factor Eating Questionnaire and Binge eating scores during a two-year period from the start of a VLCD (Nutrilett) and behavioural modification therapy for obesity. DESIGN: Prospective study of a 17-weeks weight loss programme with one- and two-year follow-up visits. SUBJECTS: 62 healthy, overweight subjects without previous eating disorders. The mean (+/- SD) age 41 +/- 8 years and BMI 36.4 +/- 2.6 kg/m2. MAIN OUTCOME MEASURES: Weight loss, Binge eating scale, Bulimic Investigatory Test and Three Factor Eating Questionnaire before and after therapy and at 1 and 2 year control visits. RESULTS: The mean weight loss (+/- SD) at the end of the treatment was 14.9 +/- 4.6 kg (n = 59) and at the two-year control 5.8 +/- 7.6 kg (n = 57). After two years 20 (32%) patients had a weight loss of more than 10% (good result), 24 patients a weight loss of 0-10% of their initial weight (partial result) and 13 patients weighed more than before therapy (poor result). The mean binge eating, disinhibition and hunger scores decreased in all patients by the end of the therapy. At the end of two years these improvements in the scores were maintained in patients with a good result but the scores returned to the pretreatment levels in the patients with partial or poor result. The mean restraint scores increased in all patients after treatment and were maintained in those with a good or partial result. CONCLUSIONS: VLCD combined with behaviour modification is a useful mode of therapy for obesity with low drop-out rate and majority (71%) of patients below pretreatment weight at the two-year control. One third of the patients succeeded to maintain positive changes in the scores measuring eating behaviour which was associated with sustained weight loss.

Adult↗
PubMed1996

Polymorphism of the beta 3-adrenergic receptor gene in morbid obesity.

OBJECTIVE: The Trp64-->Arg allele of the beta 3-adrenergic receptor gene was recently proposed to be associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), features of insulin resistance and a tendency to gain weight. We investigated whether the Arg64 allele predisposes to severe obesity. DESIGN AND SUBJECTS: A genetic association study of 254 subjects with morbid obesity [body-mass index (BMI) > or = 40; mean 42.8 +/- 7.0] and 151 lean healthy control subjects [BMI < or = 25; mean BMI 22.3 +/- 1.9]. MEASUREMENTS: beta 3-adrenergic receptor genotyping was carried out with a solid-phase minisequencing technique. Serum lipids, glucose and insulin levels in the obese subjects were also determined. RESULTS: The frequency of the Arg64 did not significantly differ in the morbidly obese patients (9.1%) and lean controls (8.9%), nor was there any statistically significant association between the mean BMI values and the beta 3-adrenergic receptor genotype. However, obese subjects carrying the Arg64 allele developed obesity more often before the age of 15 y than those without it (P < 0.05, adjusted for multiple comparisons). The frequency of the Arg64 allele was similar in nondiabetic and diabetic patients; the mean age at the onset of NIDDM did not differ according to the beta 3-adrenergic receptor genotype. There was no significant association between the receptor genotype and the level of the serum cholesterol, HDL-cholesterol, triglyceride, glucose or insulin, nor was this polymorphism associated with the behavioural or psychopathological characteristics of the morbidly obese subjects. Response to a 16 w treatment program including a very-low calorie diet (VLCD) regimen, dietary and exercise counseling, as well as behavioural modifications, did not differ according to the genotype. CONCLUSION: Our data do not support a significant role for the codon 64 polymorphism of the beta 3-adrenergic receptor as a genetic marker of morbid obesity. Although there was an association between the Arg64 allele and an earlier onset of obesity in individuals subsequently developing morbid obesity, this allele was not associated with the actual BMI gained or response to weight-loss therapy on a hypocaloric diet.

Adult↗
PubMed1995

Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene.

The sensitivity of single-strand conformation polymorphism (SSCP) analysis for the detection of mutations in the porphobilinogen deaminase (PBGD) gene among Finnish patients with acute intermittent porphyria (AIP) was studied. 13 novel mutations including one de novo event, and six previously characterized mutations were identified among AIP patients. The 19 mutations reported here for 28 families cover 72% of all the AIP families in the Finnish population of five million. When compared to direct sequencing, SSCP-analysis detected 17 (89%) of the 19 mutations when a combination of various electrophoretic conditions were used. The most informative electrophoretic condition was a gel run without glycerol in the coldroom (11/18 mutations). 86% of mutations were identified from amplified fragments greater than 300 bp and detection was dependent on both the amount of glycerol in the gel and the running temperature, but seemed to be independent of the size of the analyzed fragment or the type of mutation. The diagnostic efficiency of biochemical assays versus mutation screening in the PBGD gene was studied in three large AIP families, each representing different CRIM subtypes of AIP. The results demonstrated that using assays of erythrocyte PBGD activity, the majority (82%) of family members (n = 51) were diagnosed correctly. Of a total of 81 family members, 30 of whom had deficiency of PBGD confined to non-erythroid tissues, diagnosis at the asymptomatic stage of disease in 11 individuals (14%) required the application of mutation screening.

Alleles↗
PubMed1995

Effect of weight loss and body position on pulmonary function and gas exchange abnormalities in morbid obesity.

OBJECTIVE: To determine, whether behavioral management of obesity including very-low-calorie-diet would produce weight loss enough to improve pulmonary mechanics and gas exchange in morbid obesity. DESIGN: Pulmonary function and arterial oxygenation were studied before and after weight loss in 11 patients attending a group therapy with the program of VLCD for 6 weeks and 16 weeks' behavioral intervention. MEASUREMENTS: Spirometry, diffusing capacity, body plethysmograph, closing volume and arterial blood gas analyses. RESULTS: The mean initial BMI was 45.4 kg/m2 (range 39.8-58.7 kg/m2) and decreased to 39.4 kg/m2 (range 31-49.8 kg/m2) (P < 0.01). Expiratory reserve volume (ERV) and functional residual capacity (FRC) improved significantly with weight loss. Closing capacity (CC) exceeded FRC in 10 cases of 11 at the initial stage, but after weight loss only in three patients. The mean arterial oxygen tension with the patients in supine position did not change after weight loss, but standing up improved PaO2 significantly before and after weight loss. CONCLUSION: The dietary treatment of morbid obesity was sufficient to induce improvement in lung volumes, but not enough to improve arterial oxygenation, although ventilatory mechanics was improved significantly and the tendency to early small airway closure was decreased. Hypoxemia was significantly relieved by standing up both before and after weight loss.

Adult↗