Appetite stimulation with cannabis-based medicine and methods for assessment of glomerular filtration in older patients with medical illness: A study protocol.

BACKGROUND AND AIM: Malnutrition in older patients is linked to poor appetite. Cannabis-based medicine may have orexigenic properties in older patients, but this has to our knowledge never been investigated. In older patients, uncertainty applies to the accuracy of estimated glomerular filtration rate (eGFR) based on creatinine, which is crucial for medication prescribing. In older patients with poor appetite, the study aims (1) to assess the efficacy of Sativex® (8.1-mg delta-9-tetrahydrocannabinol [THC] and 7.5-mg cannabidiol [CBD]) to stimulate appetite and (2) to compare the performance of various GFR-estimates and measured-GFR (mGFR) for determining gentamicin clearance utilizing population pharmacokinetic (popPK) modelling methods. METHODS AND OBJECTIVES: This study is composed of two substudies. Substudy 1 is an investigator-initiated single-center, double-blinded, randomized, placebo-controlled, superiority, cross-over study. Substudy 1 will recruit 17 older patients with poor appetite, who will also be invited to substudy 2. Substudy 2 is a single-dose pharmacokinetics study and will recruit 55 patients. Participants will receive Sativex® and placebo in substudy 1 and gentamicin with simultaneous measurements of GFR in substudy 2. The primary endpoints are as follows: Substudy 1-the difference in energy intake between Sativex® and placebo conditions; substudy 2- the accuracy of different eGFR equations compared to mGFR. The secondary endpoints include safety parameters, changes in the appetite hormones, total ghrelin and GLP-1 and subjective appetite sensations, and the creation of popPK models of THC, CBD, and gentamicin.

Low back pain scores correlate with the cytokine mRNA level in lumbar disc biopsies: a study of inflammatory markers in patients undergoing lumbar spinal fusion.

PURPOSE: The molecular mechanism behind pain in degenerative disc disease (DDD) and chronic low back pain (LBP) patients is largely unknown. This present study examines the association of LBP and disability to mediators of the inflammatory cascade, as indexed by mRNA gene expression of pro-inflammatory cytokine markers in the intervertebral disc (IVD). METHODS: Biopsies of the annulus fibrosus (AF) and the nucleus pulposes (NP) from patients with DDD undergoing 1-2 level fusion surgery at L4/L5 or L5/S1 were obtained from total of 34 patients [9 M, 25 F] with average age of 53 [32-63]. The mRNA expression of TNF-α, IL-1ß, and IL-6 in the AF and NP was analyzed using quantitative real-time polymerase chain reaction (RT-qPCR), and the expression level of these markers was correlated to the visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores (0-100) for pain and disability. RESULTS: We report a statistically significant positive correlation between pain intensity (VAS score) and the expression of TNF-α in both the AF (r = 0.54, p = 0.001) and NP (r = 0.40, p = 0.02), similarly with IL-1ß in AF (r = 0.37, p = 0.02) and IL-6 in NP (r = 0.40, p = 0.02). In addition, we found significant positive correlation observed between disability score (ODI) and expression of IL-6 in both AF (r = 0.36, p = 0.03) and NP (r = 0.41, p = 0.01). CONCLUSION: We conclude that the intensity of LBP and disability is associated with the level of inflammation in the disc.

MEP recruitment curves in multiple sclerosis and hereditary spastic paraplegia.

OBJECTIVE: Axons remodel at multiple levels after a single inflammatory lesion in the spinal cord, which can contribute to recovery. The primary aim of this study was to investigate whether the MEP response as function of the excitatory strength, here called recruitment curves, may be used in discriminating demyelination from compensated axonal loss. Multiple sclerosis (MS) represents both demyelination and axonal degeneration. Hereditary Spastic Paraplegia (HSP) was included as a model of pure axonal loss. METHODS: To investigate both spinal and cortical recruitment, the methods used for gradual recruitment were two different test paradigms of voluntary pre-activation and stimulus intensity. The MEP-recruitment curves were obtained by means of transcranial magnetic stimulation (TMS) in 29 MS patients, 9 patients with HSP and in 30 healthy controls. RESULTS: Saturated recruitment curves were obtained in all subject groups, muscles and paradigms and were generally found to be identical. The two groups of patients had clinical signs, CMCT changes and reduced MEP amplitude reflecting relevant cortico-spinal disorder. CONCLUSIONS: We conclude that both demyelination and axonal degeneration in the CNS leads to diminished MEP amplitudes and CMCT changes. The recruitment curves of MS and HSP was identical to controls and may not be used for diagnostic or monitoring purposes.

Assessment of habitual energy and macronutrient intake in adults: comparison of a seven day food record with a dietary history interview.

OBJECTIVE: To examine the quantitative agreement between a 7 day food record and a diet history interview when these are conducted under the same conditions and to evaluate whether the two methods assess habitual diet intake differently among subgroups of age and body mass index (BMI). DESIGN: Cross-sectional study. SETTING: Population study, Denmark. SUBJECTS: A total of 175 men and 173 women aged 30-60 y, selected randomly from a larger population sample of Danish adults. INTERVENTIONS: All subjects had habitual diet intake assessed by a diet history interview and completed a 7 day food record within 3 weeks following the interview. The diet history interview and coding of records were performed by the same trained dietician. MAIN OUTCOME MEASURE: Median between-method difference in assessment of total energy intake, absolute intake of macronutrients, and nutrient energy percentages. Difference between reported energy intake from both methods and estimated energy expenditure in different subgroups. RESULTS: Energy and macronutrient intake was assessed slightly higher by the 7 day food record than by the diet history interview, but in absolute terms the differences were negligible. The between-method difference in assessment of total energy intake appeared to be stable over the range of age and BMI in both sexes. As compared to estimated total energy expenditure, both diet assessment methods underestimated energy intake by approximately 20%. For both methods the under-reporting increased by BMI in both sexes and by age in men. CONCLUSIONS: Energy and macronutrient intake data collected under even conditions by either a 7 day food record or a diet history interview may be collapsed and analysed independent of the underlying diet method. Both diet methods, however, appear to underestimate energy intake dependent on age and BMI. SPONSORSHIP: Danish Medical Research Council, the FREJA programme.

[Screening for thyroid disease. Occurrence of hypothyroidism and hyperthyroidism in patients admitted to a geriatric department]. / Screening for thyroideasygdom. Undersøgelse af forekomsten af hypo- og hypertyreose hos patienter indlagt på geriatrisk afdeling.

INTRODUCTION: The aim of this study was to evaluate whether screening of all geriatric patients for thyroid disorders should be recommended and to assess the prevalence of thyroid dysfunction in a geriatric population. MATERIAL AND METHODS: From 1 April 1997 to 31 March 1998, all patients above 60 years of age admitted to the ward of geriatric medicine at Copenhagen University Hospital, Glostrup were screened for thyroid disease with a sensitive TSH assay. RESULTS: Of 480 patients with no former history of thyroid disease, three (0.6%) were found to have hypothyroidism (elevated TSH and free T4 below normal) and started treatment with Eltroxin. Twenty-three patients (4.8%) had elevated TSH with normal values of T3 and free T4 (subclinical hypothyroidism). Forty-nine patients (10.2%) had TSH values below normal with normal T3 and free T4 (subclinical hyperthyroidism). Four patients (0.8%) had TSH values below normal and elevated T3 and/or free T4 and isotope uptake studies showed multinodular goitre. None of these patients was treated. Of the 34 patients (6.2%) with known thyroid dysfunction ten patients had their treatment adjusted and two patients started treatment. DISCUSSION: We found that less than 1% of the patients had an unrecognised thyroid disease that required treatment. The total prevalence of thyroid dysfunction was 7.2%. One third of the patients with a known thyroid disease needed their treatment adjusted. We would not recommend screening for thyroid dysfunction of all geriatric patients, but we would advocate better monitoring of patients already in treatment.

High-dose estrogen treatment in postmenopausal breast cancer patients heavily exposed to endocrine therapy.

Estrogens administered in high doses were commonly used for therapy of advanced breast cancer before the introduction of contemporary endocrine therapy. While the mechanism of the antitumor effect is unknown, in vitro investigations have shown estrogens in high concentrations to be toxic to cell growth. Further, it has been shown that exposure of MCF-7 cells to estrogens in low concentrations may enhance the sensitivity and also lower the toxicity threshold to estrogens. This study was designed to evaluate treatment with diethylstilbestrol (DES) in postmenopausal women with advanced breast cancer becoming resistant to estrogen deprivation. Thirty-two patients with advanced breast cancer previously exposed to multiple endocrine treatment regimens (median 4, range 2-10) were enrolled. Their tumor should have revealed evidence of endocrine sensitivity (previous partial response or at least stable disease for > or = 6 months to therapy). Each patient received DES 5 mg t.i.d. Four patients terminated therapy after < or = 2 weeks on therapy due to side effects; another two patients terminated therapy before progression for similar reasons (one patient after SD for 15 weeks and one with a PR after 39 weeks). Four patients obtained CR and six patients PR. In addition, two patients had SD for > or = 6 months duration. Five patients had an objective response and one patient a SD lasting for > or = 1 year. Our results reveal estrogens administered in high doses may have antitumor effects in breast cancer patients heavily pretreated with endocrine therapy. Such treatment represents a valuable alternative to chemotherapy in selected patients.

Food intake patterns, self rated health and mortality in Danish men and women. A prospective observational study.

OBJECTIVE: To examine whether self rated health confounds or modifies the relation between a prudent food intake pattern and mortality and to study whether the prudent food intake pattern predicts subsequent changes in self rated health. DESIGN: A prospective cohort study with follow up of total mortality and changes in self rated health. Food intake patterns were identified by principal component analysis from a 28 item food frequency questionnaire, collected at baseline. SETTING: MONICA surveys, Copenhagen County, Denmark. PARTICIPANTS: A random sample of 3698 men and 3618 women aged 30-70 years were followed up from 1982 to 1998 (median 15 years). MAIN RESULTS: Among participants with complete information on all variables 18% had rated their health as poor (average or bad) at the baseline examination. Poor self rated health was related to a low score on the prudent food intake pattern, which was characterised by a frequent intake of wholemeal bread, fruit and vegetables. Three hundred and seventy six men and 210 women died during follow up. Poor self rated health and a low prudent food score were associated with increased mortality in both men and women. Self rated health did not modify the relation between diet and mortality. Of the 1098 men and 1048 women with good self rated health at baseline, 243 men and 297 women reported poor health during follow up. Low prudent food score, smoking, and high BMI increased the risk of developing poor health in both men and women, but in multivariate analysis the associations attenuated and were only significant for BMI. CONCLUSION: Both prudent food intake pattern and self reported health are independent predictors of mortality. Self rated health does not seem to modify the relation between diet and mortality.

Dietary patterns and mortality in Danish men and women: a prospective observational study.

The analysis of dietary patterns emerged recently as a possible approach to examining diet-disease relation. We analysed the risk of all-cause and cardiovascular mortality associated with dietary patterns in men and women, while taking a number of potential confounding variables into account. Data were from a prospective cohort study with follow-up of total and cause-specific mortality. A random sample of 3698 men and 3618 women aged 30-70 years and living in Copenhagen County, Denmark, were followed from 1982 to 1998 (median 15 years). Three dietary patterns were identified from a twenty-eight item food frequency questionnaire, collected at baseline: (1) a predefined healthy food index, which reflected daily intakes of fruits, vegetables and wholemeal bread, (2) a prudent and (3) a Western dietary pattern derived by principal component analysis. The prudent pattern was positively associated with frequent intake of wholemeal bread, fruits and vegetables, whereas the Western was characterized by frequent intakes of meat products, potatoes, white bread, butter and lard. Among participants with complete information on all variables, 398 men and 231 women died during follow-up. The healthy food index was associated with reduced all-cause mortality in both men and women, but the relations were attenuated after adjustment for smoking, physical activity, educational level, BMI, and alcohol intake. The prudent pattern was inversely associated with all-cause and cardiovascular mortality after controlling for confounding variables. The Western pattern was not significantly associated with mortality. This study partly supports the assumption that overall dietary patterns can predict mortality, and that the dietary pattern associated with the lowest risk is the one which is in accordance with the current recommendations for a prudent diet.

"RAI"--an international system for assessment of nursing home residents. / "RAI"--et internationalt system til vurdering af beboere på plejehjem.

The Resident Assessment Instrument (RAI) is described. The RAI consists of three basic components: 1) the Minimum Data Set (MDS) is a collection of items covering all the areas one would expect when assessing the needs of elderly people and developing a care plan, 2) the Resident Assessment Protocols are a series of protocols which guide the assessor through the best practice of care planning for the common problems faced by the elderly and 3) the Resource Utilization Groups is a classification system based on MDS to predict resource use at the level of the individual resident. The goal of RAI is to improve the quality of care. It also enables national and international comparisons between long term care residents. RAI was used at 65 nursing homes in Copenhagen in 1992-93 and 3451 residents were examined. The reproducibility and validity of the instrument was tested and found to be good. Results from the use of RAI in Denmark is presented. We conclude that RAI is useful in assessing residents at nursing homes, because the collected data triggers actions that improve the quality of care.

[The influence of dietary factors on weight change estimated by the use of multivariate graphical models]. / Kostfaktorers indflydelse på vaegtaendringer vurderet ved hjaelp af multivariate grafiske modeller.

The aim of the present study was to analyse the influence of dietary factors on weight change in a multifactorial context by use of graphical models. A random sample of 2304 Danish men and women, aged 30, 40, 50, and 60 years, living in Copenhagen County underwent a general health examination, and their BMI was calculated. They all completed questionnaires regarding education, life conditions, life habits, and dietary intake at entry. At follow-up five years later BMI was also calculated. BMI at entry depended on family predisposition to obesity, and for women, on cohabitation as well. At follow-up five years later BMI in the male group was only related to former BMI, whereas in the female group it was influenced by parity as well: No association was found between total energy intake, percentage of energy from fat or from alcohol and weight changes. No influence of other putative determining factors was found for either gender. We conclude, that although the graphical model detected several relations between diet, habits, and social factors, no influence of dietary factors on weight changes were found by use of multifactorial graphical models.

Influence of dietary factors on weight change assessed by multivariate graphical models.

OBJECTIVE: To analyse the influence of dietary factors on weight changes in a multifactorial context by use of graphical models. DESIGN: Two age-stratified cohorts of Danish men and women were examined twice with five years interval. SETTING: The Glostrup Population Studies in the Copenhagen County, Denmark. SUBJECTS: A random population sample of 2009 men and women, aged 30, 40, 50, and 60 years. METHODS: At baseline all underwent a general health examination including measurement of height and weight, and they completed questionnaires regarding familial predisposition, cohabitation, school education, vocational training, social class, smoking habits, physical activity during work and leisure time, and parity. Dietary intake was evaluated by 7-day food records, allowing estimation of total energy intake and intake of fat and alcohol. At the follow-up examination height and weight were measured again and at each examination BMI was calculated. The statistical analysis was performed by graphical models based on multidimensional contingency tables defined by independence graphs, these may include several categorial or ordinal scale variables and include the assumed temporal relationship between the variables. RESULTS: BMI at entry depended on familial predisposition to obesity, and for women on cohabitation as well. At follow-up 5 years later, BMI in the male group was only related to former BMI, whereas in the female group it was influenced by parity as well. There were several significant associations between the dietary factors, other life style habits and social factors. However, no significant associations were found between total energy intake, percentage of energy from fat or from alcohol and weight changes. For neither gender was there any significant influence of other putative determining factors. CONCLUSION: No influence of dietary factors on weight changes were found when assessed in the context of many other putative determinants of weight change.

Who completes seven-day food records?

This study is an attempt to characterize a group of people who volunteered to complete 7-day food record forms. The group was an age- and sex-stratified random sample, comprising 4807 men and women, born in 1922, 1932, 1942 and 1952, drawn from the Civil Registration System. They all received an invitation to the Glostrup Population Studies in 1982-1984. A total of 49.2% completed a 7-day record form. The percentage of respondents was highest in the older age groups. Women were more willing to participate. There was no difference between the groups regarding body mass index. Marital status had some influence, but school education and vocational training had minor importance. A higher percentage of participants, who had never smoked or had quit smoking, completed the records. The male respondents had a lower weekly consumption of beer. No significant differences could be found between the dietary values of the respondents' and non-respondents' food consumption according to a food frequency questionnaire.

Reproducibility and validity of 7-day food records.

The reproducibility of the 7-day food record method, as used in The Glostrup Population Studies, has been tested by 40 adult volunteers, mainly hospital staff, recording their dietary intakes in two 7-day periods. To validate the calculated protein intake a 24-h urine specimen was collected from all participants in period II, but for various reasons urine specimens were only obtained from 31 in period I. There were significant differences in the intakes of energy, protein and some vitamins and minerals between the two periods, but the nutrient densities, except for vitamin A, were equal. The mean energy distributions in the diet showed no significant differences between the two periods. The weekly variance ratio (S2within/S2between) was between 0.25 and 0.80 for most nutrients. The only ratios above 1.0 were found for vitamin A, vitamin C, vitamin D, vitamin B12 and chromium, selenium and sodium. The weekly coefficients of variance (CV) were for most nutrients less than 30%. In period II the mean protein intake estimated from the urine samples was 74.7 (+/- 15.9 SD) g/day, whereas the protein intake calculated from the diet records was 70.6 (+/- 18.4) g/day. The average estimated protein intake for the 31 people who collected urine in period I was 72.1 (+/- 18.3) g/day, whereas the calculated intake was 78.0 (+/- 22.7) g/day. In neither period were the mean differences significant.

[Incidence and diagnosis of pneumococcal pneumonias requiring admission to hospital]. / Incidens og diagnostik af indlaeggelseskraevende pneumonier forårsaget af pneumokokker.

A prospective investigation of patients admitted to the local hospital during a period of one year was undertaken. A total of 107 patients participated. 50% of the cases of pneumonia were found by Streptococcus pneumoniae. The diagnosis was established partly by demonstration of antigens and increase in antibody titre and also employing the traditional methods: Blood culture, microscopic examination and culture of the expectorate or tracheal secretion. 70% of the patients were over the age of 60 years. The mortality was found to be 17%. The difficulties in etiological investigations of infections in the lower respiratory tract are discussed.

Gallstones and diet in a Danish population.

A cross-sectional study of gallstone disease, ascertained by ultrasonography, comprised 4581 men and women of Danish origin, aged 30, 40, 50, and 60 years, of whom 3608 (79%) took part in the investigation. The prevalence was assessed in relation to alcohol intake and number of daily meals. A randomly chosen subgroup of 593 persons was interviewed about their dietary habits. Both in the univariate and the multivariate analysis, gallstone disease was significantly related to abstinence from alcohol but not to number of meals. There was a trend towards positive association between gallstones and intake of refined sugars and total fat, whereas a negative trend was found between gallstones and intake of fibres and polyunsaturated to saturated fat ratio. None of the associations were significant. The same relations were observed when gallstones less than 10 mm were used in the analysis. The problem of assessing diet in relation to gallstone prevalence is stressed.

Pancytopenia--a rare manifestation of folic acid deficiency.

In the western world folic acid deficiency is a relatively rare cause of anaemia in the elderly population. A 79-year-old woman presented with pancytopenia (haemoglobin 3.4 mmol l-1, leucocytes 1.2.10(9)l-1, thrombocytes 22.10(9)l-1) due to folic acid deficiency. The deficiency was caused by an extremely low dietary intake. The case was complicated with infection and haemorrhagic manifestations. Administration of folic acid increased the number of erythrocytes, leucocytes and thrombocytes markedly. Beside vitamin B12 deficiency folic acid deficiency must be borne in mind in megaloblastic anaemias complicated with leucopenia and/or thrombocytopenia. Since the body stores of folic acid are low, rapid diagnosis and treatment are important.

Ultrastructural and cytochemical studies on the cytodifferentiation of duodenal endocrine cells.

The development of cytodifferentiation of endocrine cells that produce the gastrointestinal hormones gastrin, cholecystokinin and secretin have been studied by a combined fluorescence-cytochemical, immunocytochemical and ultrastructural approach. The results show that, during development, several ultrastructurally distinct cell types exhibit COOH-terminal gastrin and cholecystokinin immunoreactivity. Furthermore, some cells simultaneously contain both gastrin- and cholecystokinin-specific antigenic determinants. Studies on the time course of development of gastrin and cholecystokinin cells, together with the above-mentioned data, suggest that gastrin cells may be converted into cholecystokinin cells in development. During this period, gastrin, cholecystokinin and secretin cells store the biogenic monoamine, 5-hydroxytryptamine a feature not displayed by the adult counter-parts of these cells. In the adult duodenum, characteristic enterochromaffin (EC) cells store 5-hydroxytryptamin for which, evidence for a possible hormonal role has been presented. Taken together, our data indicate that the differentiation of duodenal endocrine cells occurs in distinct steps, each involving a restriction in the biosynthetic repertoire of the cell.