Identification of novel genetic variants in the mutational hotspot region 14 kb upstream of the LCT gene in a Mexican population.

Several polymorphic loci linked to lactase persistence (LP) have been described, all located in a small mutational hotspot region far upstream (∼14 kb) of the lactase (LCT) gene. One is typically found in Europeans, LCT -13910C > T, several others are found in East Africans and Arabs, e.g. LCT -13907C > G and LCT -13915T > G. The possibility of similar loci, specific to populations in South and Central America, has not received much attention so far. To identify possible novel polymorphisms in the mutational hotspot region, we sampled 158 subjects from a rural area in South-Central Mexico. DNA was isolated from serum, and Sanger sequencing of a 501 bp region spanning the LCT -13910C > T hotspot was successfully performed in 150 samples. The frequency of the European-type LCT -13910 T-allele was q = 0.202, and 35% of the population was thus lactase-persistent (CT or TT). Sixteen novel genetic variants were found amongst 11 of the subjects, all were heterozygotes: seven of the subjects were also carriers of at least one LCT -13910 T-allele. Thus, the mutational hotspot region is also a hotspot in the rural Mexican population: 11/150 subjects carried a total of 16 previously unknown private mutations but no novel polymorphism was found. The relationship between such novel genetic variants in Mexicans and lactase persistence is worthy of more investigation.

Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?

BACKGROUND: According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist. AIM: To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test. METHODS: A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274). RESULTS: Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups. CONCLUSIONS: Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance.

Influence of combined resistance training and healthy diet on muscle mass in healthy elderly women: a randomized controlled trial.

The delivery of efficient nonpharmacological treatment to prevent the loss of muscle mass in older adults is a major challenge, and information on the combined effects of training and diet is particularly important. Here we aimed to evaluate the effects of 24 wk of resistance training combined with a healthy dietary approach (n-6/n-3 ratio < 2) in a population of healthy and physically active older women (65-70 years). The three-armed randomized controlled trial included a resistance training + healthy diet group (RT-HD), a resistance training group (RT), and controls (CON). All subjects included in the study were physically active and had low levels of serum inflammatory markers. In accordance with the dietary goals, the n-6/n-3 ratio dietary intake significantly decreased only in RT-HD by 42%. An increase in 1 repetition maximum in leg extension occurred in RT (+20.4%) and RT-HD (+20.8%), but not in CON. Interestingly, leg lean mass significantly increased only in RT-HD (+1.8%). While there were no changes in serum C-reactive protein and IL-6 levels, a significant decrease in serum level of the pro-inflammatory precursor arachidonic acid (-5.3 ± 9.4%) together with an increase in serum n-3 docosahexaenoic acid (+8.3%) occurred only in RT-HD. Altogether, this study demonstrates that the effects of resistance training on muscle mass in healthy older adults can be optimized by the adoption of a healthy diet.

Interventions for lifestyle changes to promote weight reduction, a randomized controlled trial in primary health care.

BACKGROUND: Overweight and obesity are growing public health problems in high income countries and is now growing at a dramatic pace in low and middle income countries, particularly in urban settings. The aim of this trial was to examine the effects of a weight reduction program in adults and to determine whether or not a more extensive intervention was superior to ordinary care. METHODS: Patients seeking advice for overweight/obesity or illness related to overweight/obesity at eight primary health care centers in Sweden were randomized either to intervention or control care groups with both groups given dietary advice and individualized information on increased regular physical activity. In the intervention group advice was more extensive and follow-up more frequent than in the control group during the study period of two years. Main outcome measure was reduction in body weight of five percent or more from study start. RESULTS: From October 2004 to April 2006, 133 patients, 67 in the intervention group and 66 in the control group, were randomized over a period of 18 months. Target weight was achieved at 12 months by 26.7% of the patients in the intervention group compared with 18.4% in the control group (p = 0.335). There was an average absolute weight loss of 2.5 kg in the intervention group and 0.8 kg in the control group at 12 months as compared with the weight at study entry. There were no significant differences between the groups in quality of life, blood glucose and lipids. At 24 months target weight was achieved in 21.9% versus 15.6%, with an average weight reduction of 1.9 kg and 1.2 kg in the two groups, respectively. CONCLUSIONS: Promotion of a diet with limited energy intake, appropriate composition of food and increased physical activity had limited effects on body weight in a Swedish primary care setting. More extensive advice and more frequent visits made no significant difference to the outcome. TRIAL REGISTRATION: ClinicalTrial.gov: NCT01606917.

Drug treatment in the elderly: an intervention in primary care to enhance prescription quality and quality of life.

OBJECTIVE: The aim of the study was to assess the effect on prescription quality and quality of life after intervention with prescription reviews and promotion of patient participation in primary care. DESIGN: A randomized controlled study with three groups: (A) controls, (B) prescription review sent to physician, and (C) as in B and with a current comprehensive medication record sent to the patient. SETTING: The municipality of Örebro, Sweden (130 000 inhabitants). INTERVENTION: The study focused on the easiest possible intervention to increase prescription quality and thereby increase quality of life. The intervention should be cost-efficient, focus on colleague-to-colleague advice, and be possible to perform in the primary health care centre without additional resources such as a pharmacist. SUBJECTS: 150 patients recently discharged from hospital. Inclusion criteria were: ≥ 75 years, ≥ five drugs and living in ordinary homes. MAIN OUTCOME MEASURES: Quality of life (EQ-5D index, EQ VAS) and quality of prescriptions. RESULTS: Extreme polypharmacy was common and persistent in all three groups and this was accompanied by an unchanged frequency of drug-risk indicators. There was a low EQ-5D index and EQ VAS in all three groups throughout the study. No statistically significant differences were found anywhere between the groups. CONCLUSION: The intervention seems to have had no effect on quality of prescriptions or quality of life. This underlines the major challenge of finding new strategies for improving prescription quality to improve patient outcome measures such as quality of life and reduce the known risks of polypharmacy for the elderly.

Medication quality and quality of life in the elderly, a cohort study.

BACKGROUND: Modern drugs have made large contributions to better health and quality of life. Increasing proportions of negative side effects due to extensive pharmacological treatment are however observed especially among elderly patients who have multiple health problems. The aim of our study was to see if there is an association between medication quality and quality of life. METHODS: 150 patients discharged from hospital. Inclusion criteria were: living in ordinary homes, ≥ 75 years and ≥ 5 drugs. Home visits were performed to all, including prescription reviews and calculation of medication appropriateness index. The patients were divided into three groups depending on index score and followed for 12 months. The validated and recognized EQ-5D and EQ VAS instruments were used to assess quality of life. RESULTS: A lower medication quality was associated with a lower quality of life. EQ-5D index was statistically significantly different (declining for each group) among the groups (p = 0.001 at study start, p = 0.001 at 6 months and p = 0.013 at 12 months) as was EQ VAS (p = 0.026 at study start, p = 0.003 at 6 months and p = 0.007 at 12 months). CONCLUSIONS: This study has shown the validity of the basic principle in prescribing: the more appropriate medication the better quality of life. Since drug quality is related to the patients' quality of life, there is immense reason to continuously evaluate every prescription and treatment. The evaluation and if possible deprescribing should be done as a process where both the patient and physician are involved.

Lactase persistence and milk consumption are associated with body height in Swedish preadolescents and adolescents.

BACKGROUND: Body height is a classic polygenic trait. About 80%-90% of height is inherited and 10%-20% owed to environmental factors, of which the most important ones are nutrition and diseases in preadolescents and adolescents. OBJECTIVE: The aim of this study was to explore potential relations between the LCT (lactase) C>T-13910 polymorphism, milk consumption, and body height in a sample of Swedish preadolescents and adolescents. DESIGN: In a cross-sectional study, using a random sample of preadolescents and adolescents (n = 597), dietary intakes were determined. Anthropometric measurements including sexual maturity (Tanner stage) and birth weight were assessed. Parental body height and socio-economic status (SES) were obtained by questionnaires. Genotyping for the LCT C>T-13910 polymorphism that renders individuals lactase persistent (LP) or lactase non-persistent (LNP) was performed by DNA sequencing. Stepwise backward multivariate linear regression was used. RESULTS: Milk consumption was significantly and positively associated with body height (ß = 0.45; 95% CI: 0.040, 0.87, p = 0.032). Adjustments were performed for sex, parental height, birth weight, body mass index (BMI), SES, and Tanner stage. This model explains 90% of the observed variance of body height (adjusted R(2) = 0.89). The presence of the -13910 T allele was positively associated with body height (ß = 2.05; 95% CI: 0.18, 3.92, p = 0.032). CONCLUSIONS: Milk consumption is positively associated with body height in preadolescents and adolescents. We show for the first time that a nutrigenetic variant might be able to explain in part phenotypic variation of body height in preadolescents and adolescents. Due to the small sample size further studies are needed.

"We feel rejected": experiences of women with hirsutism consulting physicians.

The aim of the study was to describe how women with hirsutism experience their relationship with health care. Data were collected by tape-recorded individual interviews, which were analyzed by means of qualitative content analysis. The results showed that the relationship with health care, from the perspective of patients with hirsutism, is suboptimal.

Nurse-led multidisciplinary programme for patients with COPD in primary health care: a controlled trial.

AIM: To investigate the effects of a nurse-led multidisciplinary programme (NMP) of pulmonary rehabilitation in primary health care with regard to functional capacity, quality of life (QoL), and exacerbations among patients with chronic obstructive pulmonary disease (COPD). METHOD: A 1-year longitudinal study with a quasi-experimental design was undertaken in patients with COPD, 49 in the intervention group and 54 in the control group. Functional capacity was assessed using the 6-minute walking test, and quality of life (QoL) was assessed using the Clinical COPD Questionnaire. Exacerbations were calculated by examination of patient records. RESULTS: No significant differences were found between the groups in functional capacity and QoL after 1 year. The exacerbations decreased in the intervention group (n = -0.2) and increased in the control group (n = 0.3) during the year after NMP. The mean difference of change in exacerbation frequency between the groups was statistically significant after one year (p=0.009). CONCLUSIONS: The NMP in primary care produced a significant reduction in exacerbation frequency, but functional capacity and QoL were unchanged. More and larger studies are needed to evaluate potential benefits in functional capacity and QoL.

Peritonsillar abscess and cellulitis and their relation to a positive antigen detection test for streptococcal infection.

The microbiological cause of peritonsillar abscess and the role of group A ß-haemolytic Streptococcus (GAS) are unclear. We performed a retrospective study at the ear, nose and throat clinic (ENT) of Orebro University Hospital, Sweden, and included 376 events of peritonsillitis between 2002 and 2004. We determined if the patients had visited a primary healthcare centre (PHCC) within 30 days prior to inclusion. The results of the rapid antigen detection test for GAS (Strep A) taken at the PHCC were compared with the occurrence of peritonsillar abscess (PTA) and peritonsillar cellulitis (PTC). A Strep A test was performed in 61% (229/376) of the events studied. Strep A was positive in 22% of PTA events and in 35% of PTC events (p = 0.036). Of 48,000 Strep A tests taken in primary healthcare, mainly for sore throat, 22% were positive. We examined the relationship between age, the incidence of PTA, and positive Strep A tests. We also determined if there was a monthly correlation between number of positive Strep A tests and number of PTA events. We found no significant correlations. In conclusion, our findings indicate that GAS does not play a major role in the development of PTA/PTC.

Body fat and dairy product intake in lactase persistent and non-persistent children and adolescents.

BACKGROUND: Lactase non-persistent (LNP) individuals may be lactose intolerant and therefore on a more restricted diet concerning milk and milk products compared to lactase persistent (LP) individuals. This may have an impact on body fat mass. OBJECTIVE: This study examines if LP and LNP children and adolescents, defined by genotyping for the LCT-13910 C > T polymorphism, differ from each other with regard to milk and milk product intake, and measures of body fat mass. DESIGN: Children (n=298, mean age 9.6 years) and adolescents (n=386, mean age 15.6 years), belonging to the Swedish part of the European Youth Heart Study, were genotyped for the LCT-13910 C > T polymorphism. Dietary intakes of reduced and full-fat dairy varieties were determined. RESULTS: LNP (CC genotype) subjects consumed less milk, soured milk and yoghurt compared to LP (CT/TT genotype) subjects (p<0.001). Subsequent partitioning for age group attenuated this observation (p=0.002 for children and p=0.023 in adolescents). Six subjects were reported by parents to be 'lactose intolerant', none of whom were LNP. LNP children and adolescents consumed significantly less reduced fat milk and milk products than LP children and adolescents (p=0.009 for children and p=0.001 for adolescents). CONCLUSIONS: We conclude that LP is linked to an overall higher milk and dairy intake, but is not linked to higher body fat mass in children and adolescents.

Associations between lactase persistence and the metabolic syndrome in a cross-sectional study in the Canary Islands.

BACKGROUND: The single nucleotide polymorphism (SNP) LCT -13910 C>T, associated with genetically determined phenotypes of lactase persistence (LP) or non-persistence (LNP), was studied in relation to the metabolic syndrome (MS). AIM OF THE STUDY: The aim was to determine if milk intake and MS are associated. We applied Mendelian randomization (MR). The SNP, LCT -13910 C>T, with the genotypes LP (TT/CT) and LNP (CC), was taken as a proxy for milk consumption. METHODS: A representative sample of adults belonging to the Canary Islands Nutrition Survey (ENCA) in Spain aged 18-75 years (n = 551) was genotyped for the LCT -13910 C>T polymorphism. We used the International Diabetes Federation (IDF) criteria to define MS. RESULTS: 60% of the population was LP and 40% LNP. One hundred seven LP subjects (35.0%) and 53 LNP subjects (25.6%) showed MS (chi (2) = 5.04, p = 0.025). LP subjects showed a significantly higher odds ratio (OR) for MS than LNP subjects computed for the whole population: both the crude OR (1.56; 95% CI 1.06-2.31) and adjusted OR for sex, age, daily energy intake, physical activity and educational level (1.57; 95% CI 1.02-2.43). Adjusted OR for women with LP was 1.93; 95% CI 1.06-3.52. CONCLUSIONS: The T allele of the SNP might constitute a nutrigenetic factor increasing the susceptibility of LP subjects, especially women, to develop MS in the Canary Islands.

Patient focused drug surveillance of elderly patients in nursing homes.

PURPOSE: To examine whether patient focused drug surveillance was associated with a higher quality of drug treatment at nursing homes. METHODS: An intervention study in four nursing homes in Sweden and four other nursing homes served as controls. At the intervention nursing homes physicians focused on patients' health status as a baseline for further ongoing medication. The outcomes were mortality, health care consumption, and number of drugs, health status and evaluations as parameters for "quality of drug treatment". RESULTS: There were no significant differences in mortality rates. Health care consumption and polypharmacy were extensive in both groups. There was a significant reduction of number of drugs used per patient at the intervention homes during the study (p < 0.05). Monitoring and evaluation of the effects of medications were significantly more frequent at the intervention homes (p < 0.01). CONCLUSIONS: The intervention resulted in significant positive results in relation to "quality of drug treatment", a shift in health care utilization with concomitant use of fewer drugs. The study showed an extreme shortage of monitoring of health status and surveillance of the effects of drugs in the elderly.

Incidence of peritonsillar abscess and relationship to age and gender: retrospective study.

The incidence of peritonsillitis is not very well known. A retrospective study was performed at the Ear, Nose and Throat clinic (ENT) at the University Hospital of Orebro Sweden. We studied every case from 2002 to 2004 and related it to a well-defined catchment area of 179,200 inhabitants. We identified 283 events of peritonsillitis, of which 85 were defined as peritonsillar cellulitis (PTC). Peritonsillar abscess (PTA) was found in 198 events in patients between 7 and 82 y of age. 13 patients had 2 episodes of PTA during the study period. The overall incidence was 37/100,000/y. The highest incidence was found between 14 and 21 y of age, with 124/100,000/y. The male: female ratio was 1: 1. Affected females were younger than males (p=0.04), and the peak incidence was earlier for females. This may be due to differences in immunological response, owing to hormonal maturation. The annual incidence of PTA was higher in this study than found in previous studies, which is probably attributable to the fact that our study identified almost all cases in the population.

Increasing CSF phospho-tau levels during cognitive decline and progression to dementia.

BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. OBJECTIVE: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline. METHODS: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). RESULTS: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up. CONCLUSION: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.

Prevalence and trends in adult-type hypolactasia in different age cohorts in Central Sweden diagnosed by genotyping for the adult-type hypolactasia-linked LCT -13910C > T mutation.

OBJECTIVE: Adult-type hypolactasia (AtH) can be diagnosed by genotyping in addition to functional tests or intestinal biopsy. The aims of this study were to estimate the prevalence of AtH by genotyping and to investigate whether AtH prevalence has changed in Sweden during the 20th century. MATERIAL AND METHODS: Schoolchildren (n=690) born in 1983 and 1989, and elderly individuals (n=392) born between 1920 and 1932 were genotyped for AtH using Pyrosequencing technology. RESULTS: The overall prevalence of AtH among children was 14.1%. The majority of children (92%, n=635) were Caucasians with genotype prevalences: CC, 61 (10%); CT, 259 (41%); TT, 307 (49%). The frequency of the mutated allele q was 0.300 in this cohort. The prevalence of AtH estimated from the Hardy-Weinberg equilibrium (HWE) (q 2), was 9.0% (95% CI: 6.7-11.2%). Eight percent (n=55) of the children were non-Caucasian; genotype prevalences were CC, 36 (66%); CT, 15 (27%); TT, 4 (7%). The prevalence of AtH in these children estimated from HWE was 62.5% (95% CI: 49.7-75.3%). The elderly subjects were all Caucasians. Their genotype prevalences were: CC, 20 (5%); CT, 166 (42%); TT, 206 (53%); the frequency of the mutated allele q was 0.262 and their AtH prevalence estimated from HWE was 6.8% (95% CI: 4.3-9.2%). CONCLUSIONS: The overall prevalence of AtH in children (14%) was higher than previously thought. Among Caucasians, higher figures were seen in children than in the elderly (9% versus 6.8%). The prevalence thus seems to be increasing and this may be due to the immigration of both non-Caucasian and Caucasian groups with a higher prevalence of AtH.

Differential CSF biomarker levels in APOE-epsilon4-positive and -negative patients with memory impairment.

OBJECTIVES: To investigate the relationships between episodic memory, APOE genotype, CSF markers (total tau, T-tau; phospho-tau, P-tau; beta-amyloid, Abeta42) and longitudinal cognitive decline. METHODS: 124 memory clinic patients were retrospectively divided into 6 groups based on (i) episodic memory function (Rey Auditory Verbal Learning Test, RAVLT): severe, moderate or no impairment (SIM, MIM or NIM), and (ii) APOE genotype (epsilon4+ or epsilon4-). CSF marker levels and cognitive decline were compared across groups. RESULTS: Episodic memory function, according to RAVLT scores, was significantly correlated with CSF marker levels only among epsilon4+ subjects and not among epsilon4- subjects. When comparing the 6 subgroups, SIM epsilon4+ and MIM epsilon4+ groups showed significantly lower Abeta42 levels than the other groups. T-tau and P-tau levels were significantly increased in SIM epsilon4+ when compared to all the other groups, including the SIM epsilon4- group. However, both SIM epsilon4+ and SIM epsilon4- declined cognitively during the follow-up. CONCLUSION: It remains to be determined whether APOE genotype affects the expression of biomarkers in CSF, or whether the different biomarker patterns reflect different types of disease processes in patients with progressive cognitive dysfunction.

C-reactive protein in diagnosis of community-acquired pneumonia in adult patients in primary care.

The usefulness of non-specific inflammatory parameters for the diagnosis of community- acquired pneumonia (CAP) in primary care is not settled. The aim of this study was to assess the value of serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) for this purpose. These inflammatory parameters, as well as the aetiological agents, were studied in 82 patients with radiologically confirmed CAP. CRP was elevated (>5 mg/l) in 76 patients, with a median value of 65 mg/l. 25 patients had a value of over 100 mg/l. In 32 patients the CRP levels were <50 mg/l and in 17 patients they were <20 mg/l. ESR varied from 5 to 100 mm/h, with a median value of 53 mm/h; in 21 patients the value was <30 mm/h. WBC varied from 4.4 to 21.4x10(9)/l, with a median value of 9.8x10(9)/l. No associations between the levels of the inflammatory parameters and the various aetiologies were found. It is concluded that the examined inflammatory parameters did not contribute notably in the routine diagnosis of CAP established by clinical measures.