Obese sedentary patients with dyspnoea on exertion who are at low risk for coronary artery disease by clinical criteria have a very low prevalence of coronary artery disease.

Dyspnoea, a much less specific symptom of ischaemia than chest discomfort, is common among obese patients. Patients with dyspnoea often undergo stress testing as part of their evaluation. We sought to examine the yield of stress testing in non-elderly, obese, sedentary patients with dyspnoea on exertion (DOE) as a chief complaint.We reviewed stress echocardiograms carried out on 203 patients in a stress testing laboratory at a major tertiary care centre. Of these, 81 (40%) fell into a group that was at low risk for coronary artery disease (CAD) by clinical criteria. Ischaemia was detected in two patients in the low-risk group (2.5%), and these results were likely false positives. In the higher risk group, 9.0% of functional tests showed ischaemia; after further testing, 2.5% of the higher risk patients were found to have obstructive coronary lesions. Clinical follow-up was performed for a mean of 815 days. New obstructive coronary disease was detected in 1.6% of all patients, and these patients were from the higher risk group. In obese sedentary patients with DOE but otherwise at low risk of coronary disease stress testing is of very low yield. DOE is generally not an anginal equivalent in this patient population.

A reduction in cardiac arrests and duration of clinical instability after implementation of a paediatric rapid response system.

OBJECTIVE: To determine the effects of a multifaceted paediatric rapid response system on the duration of predefined clinical instability and the subsequent rate of cardiac arrests. METHODS: An interrupted time series study coupled with a retrospective chart review to evaluate the effects of implementing a four component paediatric rapid response system. All patients in a 136-bed university-affiliated paediatric hospital from August 2003 to May 2007 were considered. The main outcome measures included rate of cardiac arrests as indicated by the number of patient days between ward paediatric cardiac arrests and duration of predefined clinical instability before evaluation by critical care personnel. RESULTS: The mean time interval between cardiac arrests increased significantly with the establishment of the rapid response system from a baseline of 2512 to 9418 patient days. The median duration of clinical instability decreased from 9 h 55 min to 4 h 15 min post intervention (p=0.028). CONCLUSIONS: The implementation of a paediatric rapid response system is associated with a significant reduction in the rate of cardiac arrests and duration of clinical instability before evaluation by critical care personnel. This study provides evidence that implementation of a rapid response system brings emergency personnel to deteriorating patients earlier, thus preventing cardiac arrests.

A reduction in cardiac arrests and duration of clinical instability after implementation of a paediatric rapid response system.

OBJECTIVE: To determine the effects of a multifaceted paediatric rapid response system on the duration of predefined clinical instability and the subsequent rate of cardiac arrests. METHODS: An interrupted time series study coupled with a retrospective chart review to evaluate the effects of implementing a four component paediatric rapid response system. All patients in a 136-bed university-affiliated paediatric hospital from August 2003 to May 2007 were considered. The main outcome measures included rate of cardiac arrests as indicated by the number of patient days between ward paediatric cardiac arrests and duration of predefined clinical instability before evaluation by critical care personnel. RESULTS: The mean time interval between cardiac arrests increased significantly with the establishment of the rapid response system from a baseline of 2512 to 9418 patient days. The median duration of clinical instability decreased from 9 h 55 min to 4 h 15 min post intervention (p = 0.028). CONCLUSIONS: The implementation of a paediatric rapid response system is associated with a significant reduction in the rate of cardiac arrests and duration of clinical instability before evaluation by critical care personnel. This study provides evidence that implementation of a rapid response system brings emergency personnel to deteriorating patients earlier, thus preventing cardiac arrests.

Lack of association of matrix metalloproteinase 3 (MMP3) genotypes with ankylosing spondylitis susceptibility and severity.

OBJECTIVE: To study the linkage and association of ankylosing spondylitis (AS) with genotypes for matrix metalloproteinase 3 (MMP3), a gene located at chromosome 11q22.3 and lying within the 101-124 cM region observed in a recent genome-wide scan as a region associated with AS susceptibility. METHODS: MMP3 genotypes were examined in 229 pedigrees with AS, 131 sporadic AS cases and 87 Caucasian controls. Eight single-nucleotide polymorphisms (SNPs) were selected and genotyped using Taqman. Non-parametric linkage (NPL) analysis was conducted between the eight MMP3 SNPs and AS using the NPL-all statistic and two-point parametric linkage analysis using GeneHunter Plus. Unrelated AS cases and controls were compared using chi2 statistics, and family-based controls using the transmission disequilibrium test and pedigree disequilibrium test. RESULTS: None of the eight MMP3 SNPs were significantly associated with AS, either using the 131 sporadic cases alone or in analyses which combined these cases with the 226 unrelated affected AS patients derived from the pedigrees. Analysis of linkage disequilibrium (LD) demonstrated that seven of the eight SNPs studied were in strong LD except for rs626750, which is about 6 kb upstream of the 5' end of the gene. No significant linkage was observed using NPL and LODs in the families. No association was seen of any of the MMP3 SNPs with disease severity (defined by patient functioning), as measured either by the Bath Ankylosing Spondylitis Functional Index or the modified Health Assessment Questionnaire. CONCLUSION: These data suggest that MMP3 genotypes are not involved in AS susceptibility or severity.

[Hormonal "rejuvenation". Warning your patients from false claims!]. / Hormonelle "Verjüngungskuren". Warnen Sie Ihre Patienten vor falschen Versprechungen!

No intervention, including drugs and hormones, has been proven to slow or even reverse aging. Such promises, as well as the term "anti-aging medicine", are misleading. On the other hand, remarkable progress has been made in the prevention and treatment of age-related diseases. The use of hormones constitutes a potentially new option in the prevention and treatment of age-related diseases, but is not an established therapy. The status of scientific evidence for the treatment of seniors with growth hormone, melatonin, DHEA or testosterone is critically reviewed.

High prevalence of osteoporotic vertebral fractures in patients with Crohn's disease.

BACKGROUND AND AIMS: Osteopenia and osteoporosis are frequent in Crohn's disease. However, there are few data on related vertebral fractures. Therefore, we evaluated prospectively the prevalence of osteoporotic vertebral fractures in these patients. METHODS: A total of 293 patients were screened with dual energy x ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur. In 156 patients with lumbar osteopenia or osteoporosis (T score <-1), x ray examinations of the thoracic and lumbar spine were performed. Assessment of fractures included visual reading of x rays and quantitative morphometry of the vertebral bodies (T4-L4), analogous to the criteria of the European Vertebral Osteoporosis Study. RESULTS: In 34 (21.8%; 18 female) of 156 Crohn's disease patients with reduced bone mineral density, 63 osteoporotic vertebral fractures (50 fx. (osteoporotic fracture with visible fracture line running into the vertebral body and/or change of outer shape) and 13 fxd. (osteoporotic fracture with change of outer shape but without visible fracture line)) were found, 50 fx. in 25 (16%, 15 female) patients and 13 fxd. in nine (5.8%, three female) patients. In four patients the fractures were clinically evident and associated with severe back pain. Approximately one third of patients with fractures were younger than 30 years. Lumbar bone mineral density was significantly reduced in patients with fractures compared with those without (T score -2.50 (0.88) v -2.07 (0.66); p<0.025) but not at the hip (-2.0 (1.1) v -1.81 (0.87); p=0.38). In subgroups analyses, no significant differences were observed. CONCLUSIONS: In patients with Crohn's disease and reduced bone mineral density, the prevalence of vertebral fractures-that is, manifest osteoporosis-was strikingly high at 22%, even in those aged less than 30 years, a problem deserving further clinical attention.

Scientific contributions of ankylosing spondylitis patient advocacy groups.

The Spondylitis Association of America has been the driving force behind a major research initiative in the US, having leveraged a substantial amount of money into a $4.5 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The grant last year established the North American Spondylitis Consortium to expedite the search for genes that determine susceptibility to ankylosing spondylitis. The German Ankylosing Spondylitis Society, which has more than 14,000 patient members, initiated in 1996 a professional survey of ankylosing spondylitis patients, with financial support from the German Federal Health Ministry. The results of this survey have recently been published, but only in the German language; a part of it is summarized here in English. Following are some of the important findings. The average age at disease onset does not differ significantly between men and women, but there is a significantly longer delay in disease diagnosis among female patients. The average delay in disease diagnosis is getting shorter; there was an average delay of 15 years for patients with disease onset in the 1950s, and it decreased to 7.5 years for patients with disease onset between 1975 and 1979. There was a relatively greater degree of underdiagnosis of the disease among female than male patients in the past; whereas only 10% of the patients in whom the disease was diagnosed in about 1960 were women, this percentage has progressively increased in the subsequent decades to reach 46% among those in whom the disease was diagnosed since 1990. The speed at which spinal ankylosis progresses is slower in female patients, but women are in a significantly worse situation than men in terms of pain and the need for drug therapy, even though the women in the German Ankylosing Spondylitis Society sample are, on average, younger than the men and have a shorter average disease duration. It is possible that the slower and relatively incomplete progression to spinal ankylosis in female patients impedes the occurrence of a decrease in pain with time, compared with that observed in male patients.

Increase of bone mineral density with sodium fluoride in patients with Crohn's disease.

BACKGROUND AND AIMS: Low bone density with an increased risk of vertebral fractures is a frequent complication in inflammatory bowel disease. Since the aetiology of osteopathia in these patients is different compared to postmenopausal or steroid-induced osteoporosis, no treatment strategy is established. Supplementation of calcium and vitamin D has been shown to prevent further bone loss, but no data are available showing the anabolic effect of sodium fluoride in Crohn's disease. METHODS: We carried out a one-year prospective clinical trial in 33 patients with chronic active Crohn's disease who were randomly assigned to receive either calcium (500 mg b.i.d.) and 1000 IU vitamin D3 only, or retarded-release sodium fluoride (25 mg t.i.d.) additionally. The diagnosis of Crohn's disease had been made at least two years ago, and all patients had received systemic high-dose steroid therapy during the previous year. Eleven of 15 patients who received calcium/vitamin D and 15 of 18 patients who additionally received sodium fluoride completed the study. The primary endpoint of the study was the increase of bone mineral density, measured by dual energy X-ray absorptiometry (DXA) after one year of treatment. Bone-specific alkaline phosphatase and osteocalcin were used as markers for bone turnover. RESULTS: In the calcium/vitamin D only group, bone density was not significantly changed after one year of treatment, whereas in the calcium/vitamin D/fluoride group, bone density of the lumbar spine increased from -1.39+/-0.3 (Z-score, mean +/- SEM) to -0.65+/-0.3 (P<0.05) after one year of treatment. Increase of bone density was positively correlated to the osteoblastic markers bone-specific alkaline phosphatase (r = 0.53) and osteocalcin (r = 0.43). CONCLUSIONS: Sodium fluoride in combination with vitamin D and calcium is an effective, well-tolerated and inexpensive treatment to increase lumbar bone density in patients with chronic active Crohn's disease and osteoporosis.

[Pathological bone density in chronic inflammatory bowel diseases--prevalence and risk factors]. / Pathologische Knochendichte bei chronischentzündlichen Darmerkrankungen--Prävalenz und Risikofaktoren.

INTRODUCTION: Osteopenia and osteoporosis are frequent but often underestimated complications in inflammatory bowel disease. In patients with IBD, several factors could contribute to osteopenia, but the pathogenetic mechanisms are still not completely understood. We carried out a prospective study to evaluate the prevalence and possible etiologic factors for osteopenia and subsequent osteoporosis in IBD-patients. METHODS: 140 patients with inflammatory bowel disease (Crohn's disease n = 125, ulcerative colitis n = 15) underwent clinical and spine radiological assessments. Lumbar bone mineral densities were measured by dual energy X-ray absorptiometry (DXA). Markers of bone formation and resorption and vitamin D were assessed in n = 95 patients. Patients were asked about medication, previous or actual intestinal stenosis, smoking and intestinal resection. A lactose-H2-breath test was undertaken if lactose intolerance was clinically suspected. RESULTS: Compared to age- and sex-matched healthy controls (Z-score), the prevalence of osteopenia (Z < -1) was 62%, while osteoporosis (Z < -2) occurred in 38%. The mean bone density of IBD-patients was osteopenic with no significant differences between Crohn's disease (Z = -1.24) and ulcerative colitis (Z = -1.25). Osteoporotic fractures were seen in three patients (2.1%). Crohn's disease patients with osteoporosis showed a significant lower body mass index (BMI) than patients with normal bone density. 52.9% of patients with manifest osteoporosis underwent systemic steroid treatment in the preceding year, but only 34% of those with normal bone density. Except hemoglobin, none of the biochemical markers showed a significant difference between osteoporosis, osteopenia and patients with normal bone density. CONCLUSION: The results show a high prevalence of osteopenia and osteoporosis in IBD. Since osteoporosis is often associated with low body mass index, multiple intestinal resections and previous systemic steroid treatment, we suggest a bone densitometry in these patients. Since etiology of osteoporosis in IBD is multifactorious and not completely understood, there is still no standard treatment. The effect of osteoanabolic and antiresorptive agents must be evaluated in further studies.

[ABC of osteoporosis therapy. Which drugs for prevention and therapy?]. / Das ABC der Osteoporosetherapie. Welche Medikamente zu Prävention und Therapie?

Medical Prevention and Therapy Fractures in the elderly, in particular of the proximal femur, may give rise to functional impairment with loss of independence and mobility. Apart from falls, the most common cause of fractures is osteoporosis or other impairments of mechanical stability of bone. In addition to the avoidance of falls and their sequelae, and the minimization of risk factors where possible, optimization of the mechanical stability of the bone is an important point of attack for interventional strategies. Current data on medical possibilities of osteoporosis prevention and treatment are presented and evidence for their effectiveness in reducing fractures discussed. Recommendations based on confirmed data are made, and possible future therapeutic approaches discussed.

Prevalence of Helicobacter pylori infection and dyspepsia in young adults in Germany.

Data on the seroprevalence and time of acquisition of Helicobacter pylori (HP) infection in Germany are scarce. We studied the seroprevalence of HP infection and the relationship with gastrointestinal (Gl) symptoms in a group of 168 German medical students in the final year of their practical training and in 260 age-matched blood donors at the University of Ulm. Eight upper Gl symptoms were scored in a questionnaire, and blood samples were taken for the detection of HP lgG antibodies with an Enzyme Immunoassay (Bio-Rad). Values greater than 12.5 U/ml (positive) were detected in 50 medical students (28.8%) and in 96 blood donors (36.9%). At least one occasional Gl symptom was present in 71.4% of medical students and 70.7% of blood donors. When related to the HP status, 27.0% of HP negative and 32.9% of HP positive individuals were completely free of symptoms. Moderate to severe dyspeptic symptoms were reported by 17.4% of HP negative and 14.4% of HP positive individuals. We conclude that the seroprevalence of HP infection in young German adults is presently about 1/3 but that HP infection is not linked to gastrointestinal symptoms in this age class.

[Development and outcome of motivational support during inpatient education of insulin-dependent diabetic patients--a pilot project]. / Entwicklung und Ergebnis einer motivationalen Unterstützung bei der stationären Schulung von insulinabhängigen Diabetikern--ein Pilotprojekt.

At the Ulm University Hospital 43 type-1-diabetes patients took part in a structured in-patient diabetes education program during a 12-day hospitalization period. 27 of the patients received an additional motivational support program which addressed psychological and social impediments related to the topics of the structured diabetes education program. 16 patients underwent the structured diabetes education program only. Motivational support aimed at reducing the specifically addressed sociopsychological barriers. Thus, the effects of the structured diabetes education program should be stabilized and an optimal outcome insured. All patients were asked to complete a questionnaire before, right after and 3 months after the program. Glycosylated hemoglobin (HbAlc) was evaluated before and 3 months after the program. Patients who underwent the motivational support program still felt 3 months after completion of the program that metabolic control was important, whereas patients without motivational support did not. Metabolic control--as indicated by measurement of glycosylated hemoglobin--could be maintained in the patient group with motivational support. Although their blood glucose levels had been in the normal range to start with. These encouraging results suggest implementation of a motivational support program into standard diabetes education programs for type-I-diabetes patients.

Cephalic phase of pancreatic polypeptide release: a valid test of autonomic neuropathy in diabetics?

We investigated pancreatic polypeptide (PP) release by chew and spit sham feeding as a test of autonomic function in 33 patients with diabetes mellitus (DM) and 24 age-matched healthy controls. Plasma samples were taken at nine 5-min time intervals, and PP plasma levels were determined by radioimmunoassay. Autonomic neuropathy (AN) was diagnosed and staged according to four standardized tests of cardiovascular autonomic function. The integrated PP response during sham feeding was decreased in DM patients (1067 + or - 397 vs. 2670 + or - 394 pg/ml/30 min; P < 0.05). The maximum increase of PP plasma levels was significantly different between the DM subgroups with AN (36 + or - 19 pg/ml; n = 13) and without AN (132 + or - 36 pg/ml; n = 20) but varied widely in healthy controls (219 + or - 29 pg/ml; range 20-460 pg/ml). A cutoff of maximum PP increase < 20 pg/ml (specificity 100%) resulted in only 46% sensitivity, while a cutoff < 160 pg/ml (sensitivity 100%) yielded 38% specificity for diagnosis of AN. The diagnostic value of the PP test for identifying individual patients against the variable reference range is therefore limited. Maximum PP increase < 20 pg/ml indicates AN, while maximum PP increase > 160 pg/ml excludes AN in diabetic patients.

Progress in practical endocrinology. The Glucosensor Unitec Ulm--a portable monitor for continuous blood glucose measurement.

The Glucosensor Unitec Ulm is the first portable glucose sensor for continuous glucose monitoring in blood. The Glucosensor weighs 850 g and has a size of 15 x 19 x 7 cm. Over a 24 hr period 15-25 ml of blood are withdrawn for continuous measurement, depending on the pumping velocity. Its storing capacity for data of blood glucose readings amounts to 32 KB. With the Glucosensor "long-term glucograms" under near-normal conditions can be registered. The glucograms enable the physician to recognize the different deteriorations of glucose met- abolism eg. periods of silent hypoglycemia during the night as well as postprandial hyperglycemia. The degree of glycemic control of diabetic patients can be analyzed and the effect of blood glucose lowering therapeutics can be realistically assessed.

["Glucosensor Unitec Ulm". A portable, continuously measuring glucose sensor and monitor]. / "Glucosensor Unitec Ulm". Ein tragbarer, kontinuierlich messender Glukosesensor und Monitor.

The "Glucosensor Unitec Ulm" is the first commercially available, portable glucose monitor that permits continuous measurement in venous blood under ambulatory conditions for up to 256 hours. The device weights 850 g, and measures 15 x 19 x 7 cm. Depending on the flow rate of the pump, the blood requirement is 15-25 ml/24 h. The size of the built-in-memory is 32 kByte, enough to store 3180-15,900 glucose values. The "24 hour glucogram" obtained under day to day living conditions permits the detection of disturbances of carbohydrate metabolism. Thus, early abnormalities of type II diabetes can be detected as well the degree of blood glucose normalization in patients suffering from severe insulin-dependent diabetes. Moreover, the effects of glucose-lowering drugs can be analyzed objectively. Finally, this portable glucose monitor permits the recognition of hypoglycemia induced by insulin administration or endogenous insulin overproduction due to tumors.

In vivo measurement of subcutaneous glucose concentrations with an enzymatic glucose sensor and a wick method.

An amperometric enzyme electrode and a wick technique were used for measurement of glucose in sc. tissue of sheep. When wicks were left implanted long enough to equilibrate with interstitial fluid, sc. glucose could have been reproducibly determined with the necessary accuracy. It was demonstrated that sc. tissue glucose concentrations in sheep are about 30% higher than in whole blood and are on the level of plasma glucose. This allows interpretation of sc. glucose sensor currents since results of in vitro-calibrations cannot be transferred to in vivo conditions. When an enzymatic sensor was implanted in the sc. compartment, the sensor signals were closely related to changes of blood glucose. These in vivo experiments indicate that short term glucose-monitoring with an subcutaneously implantable glucose sensor is feasible and so may provide a possible access to glycemic control. Further experiments will have to show, if glucose-controlled insulin infusions based on the output of a sc. glucose sensor will be able to maintain stable normoglycemia.

Similar effects of pulsatile and constant intravenous insulin delivery.

Effects of constant and pulsatile i.v. insulin delivery were examined in seven healthy subjects by means of euglycemic clamp technique. Each subject received constant insulin infusion (0.175 mU/kg.min) or insulin pulses at 12-min intervals (2.1 mU/kg) in randomized order for 8-h periods (08.00-16.00 h). Endogenous secretion of insulin was inhibited by concomitant administration of somatostatin (300 micrograms/h). Serum insulin concentrations during constant infusion (12 +/- 1 microU/ml) did not differ from basal values (11 +/- 1 microU/ml). Pulsatile insulin delivery resulted in oscillations of mean concentrations between values of about 10 and 20 microU/ml. Mean blood glucose concentrations during experiments were kept at 80 +/- 1 mg/dl, irrespective of the mode of insulin administration. Moreover, dextrose requirements for maintenance of these glucose concentrations did not differ over the hole periods of examination. We conclude that effects of constant and pulsatile delivery of basal amounts of insulin are not different. This at least applies to peripheral, short-term insulin administration in somatostatin-treated normal man, during an euglycemic clamp.