Acute sinusitis: Finnish clinical practice guidelines

These clinical practice guidelines aim at providing assistance mainly to primary health care physicians for the diagnosis and management of acute sinusitis. Despite the huge impact of upper respiratory infections, criteria for diagnoses are often vague, and physicians are often uncertain of their diagnoses. This is not surprising, as the sole definition of acute sinusitis is somewhat confusing, not to mention the existing discrepancies between treatments, even among specialists. The Finnish Society of Otorhinolaryngology has set up a committee to evaluate existing data on acute sinusitis and to formulate these guidelines. The committee comprised Finnish experts in adult and paediatric otorhinolaryngology, clinical microbiology, radiology, paediatrics, and epidemiology. Recommendations given are based on the principles of evidence-based medicine, with the level of evidence presented.     

Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.     

Ocular side-effects in breast cancer patients treated with tamoxifen and toremifene: a randomized follow-up study

PURPOSE: 3Tamoxifen and toremifene are non-steroidal anti-oestrogens widely used in the treatment of advanced breast cancer and as adjuvant therapy following surgery in early stage disease. Tamoxifene has also been approved for use in reducing the incidence of breast cancer amongst high risk women. However, certain well documented adverse effects, mainly involving the reproductive organs, have been reported amongst users of both drugs. The aim of this study was to monitor the ocular side-effects of both of these commonly used anti-oestrogens. METHODS: Sixty postmenopausal (age range 50-79 years) breast cancer patients were randomized into adjuvant tamoxifen or toremifene therapy groups for 3 years. Prior to commencement of medication, a thorough ocular examination was undertaken. The first follow-up visit took place after 6 months and the remaining three at 12-month intervals thereafter. RESULTS: Sixteen patients had cataract at the first visit (seven in the tamoxifen group and nine in the toremifene group). Ten patients developed cataract during the study period (five in each group), giving annual cataract rates of 6.8% and 6.2% in the tamoxifen and toremifene groups, respectively. Three patients had macular crystals at the first visit (one in the tamoxifen group and two in the toremifene group). The crystals remained stable throughout the follow-up. Macular drusen were diagnosed in five patients at the first ophthalmological check-up (two in the tamoxifen and three in the toremifene group). Two patients in the toremifene group developed drusen maculopathy during follow-up visits. Yellowish spots in the macular area were found in one tamoxifen-treated patient at the second visit. At the final visit after 3.5 years' follow-up the spots had disappeared. No abnormal corneal findings or keratopathy were documented during the follow-up. CONCLUSION: We observed no serious ocular side-effects among the 60 breast cancer patients treated with tamoxifen or toremifene over a 3.5-year period.     

Familial hypercholesterolaemia in Finland: common, rare and mild mutations of the LDL receptor and their clinical consequences. Finnish FH-group

Familial hypercholesterolaemia (FH) is an autosomal co-dominantly inherited condition resulting from mutations of the low-density lipoprotein (LDL) receptor which occur in heterozygous form in approximately one in 500 individuals. Clinically, FH is characterized by 2-3-fold elevation of serum LDL cholesterol levels, accelerated development of atherosclerotic vascular disease, and, if untreated, shortened lifespan. The Finnish population, which represents a genetic isolate, offers exceptional possibilities for genetic-epidemiological studies on FH, as a handful of founder gene mutations account for the majority of FH cases in Finland. This review summarizes data from our FH studies carried out since 1985. We wish to emphasize the continuum of genotype-phenotype relationships, the importance of molecular diagnosis, the detection of novel risk factors of vascular disease, and innovations inhibiting cholesterol absorption for the modern treatment of FH.     

Detection and molecular genetics of extended-spectrum beta-lactamases among cefuroxime-resistant Escherichia coli and Klebsiella spp. isolates from Finland, 2002-2004

Extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella spp. isolates are spreading and becoming an increasing problem concerning treatment, diagnostics and hospital hygiene. We wanted to discover which genotypes are occurring in Finland and to assess the CLSI screening method. The isolates were collected from 26 laboratories during a 3-y period from 2002 to 2004. We studied the zone diameters by disk diffusion according to CLSI recommendations. ESBL genes were detected by PCR and the TEM and SHV genes were sequenced traditionally, while the CTX-M isolates were analysed with pyrosequencing. Of the 402 isolates included in the study, 269 (67%) were confirmed to be ESBL producers according to the CLSI criteria. The CTX-M genes were the most prevalent, especially the combination of a CTX-M-1-group and a TEM-1 gene. In our material there were few isolates that had an ESBL gene but were negative in the CLSI ESBL confirmatory test. During recent y especially the CTX-M producing isolates have increased in Europe and now they are also found in Finland with increasing prevalence.     

Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes

Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.     

Physical activity, diet, and incident diabetes in relation to an ADRA2B polymorphism

PURPOSE: The 12Glu9 polymorphism of the alpha2B-adrenergic receptor gene may impair insulin secretion and modify the effects of a lifestyle intervention on the risk of type 2 diabetes, but the interaction with specific lifestyle components is unknown. We assessed the associations of leisure-time physical activity (LTPA), dietary changes, and weight loss on the risk of type 2 diabetes according to the 12Glu9 polymorphism in 481 participants of the Finnish Diabetes Prevention Study. METHODS AND RESULTS: The lifestyle intervention decreased the risk of diabetes in 9Glu carriers (9Glu9, intervention vs control, relative risk (RR) = 0.23, 95% confidence interval (CI) 0.09-0.62), but not in 12Glu12 homozygotes. In the combined intervention and control groups, increased total LTPA as estimated with a questionnaire decreased the risk of diabetes in 12Glu carriers (12Glu12, upper vs lower third, RR = 0.12, 95% CI 0.03-0.53) but not in 9Glu9 homozygotes (P for the interaction 0.033). In contrast, favorable dietary changes, estimated using a dietary score, reduced the risk of diabetes in those with the 9Glu9 genotype (upper vs lower third, RR = 0.21, 95% CI 0.06-0.75) but not in those with the 12Glu allele. Weight loss significantly decreased the risk of diabetes only in 12Glu carriers. CONCLUSION: Increased LTPA decreased the risk of type 2 diabetes more in those with the 12Glu allele of the ADRA2B gene, whereas dietary changes may have mediated the greater risk reduction of the lifestyle intervention in 9Glu homozygotes.     

Antimicrobial resistance of invasive pneumococci in Finland in 1999-2000

The resistance patterns and macrolide resistance mechanisms of 910 Finnish invasive pneumococci isolated during 1999 and 2000 were studied. Macrolide resistance was detected in 6.9% of isolates. Penicillin resistance was detected in 1.5% of isolates, and penicillin intermediate resistance was detected in 4.0% of isolates. Active macrolide efflux, mediated by the mef(A) gene, was the most common macrolide resistance mechanism. Four macrolide-resistant isolates had mutations in rRNA or ribosomal protein L22.     

Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance

BACKGROUND: Ghrelin is a gut-brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study. METHODS: The Finnish Diabetes Prevention Study was a longitudinal study where 522 subjects with impaired glucose tolerance were randomized into either an intervention or control group. DNA was available from 507 subjects (mean body mass index [BMI] 31.2+/-4.5 kg/m2, age 55+/-7 years). All six SNPs were screened by the restriction fragment length polymorphism method. RESULTS: Subjects with the most common genotype combination of the following four SNPs, -604G/A, -501A/C, Leu72Met, and Gln90Leu, had the lowest systolic (131+/-11 v 137+/-13 mm Hg, P=.003) and diastolic BP levels (79+/-7 v 83+/-7 mm Hg, P=.004) at the baseline of the study and during 3 years of follow-up compared to all other genotypes. Adjustments for age, gender, antihypertensive medication, BMI, waist circumference, and alcohol intake did not change this association. CONCLUSIONS: Several ghrelin gene variations were associated with BP levels in subjects with impaired glucose tolerance.