Reduced insulin binding to human fat cells following beta-adrenergic stimulation — experimental evidence and studies in patients with a phaeochromocytoma

Summary The effect of -adrenergic stimulation on insulin binding was studied in human fat cells in vitro. Isoproterenol rapidly ( 5 min) reduced insulin binding through a -adrenergic and dose-dependent mechanism. The reduced binding was enhanced by the addition of adenosine deaminase and was also elicited by the addition of dibutyryl cAMP. This effect was due to a decreased number of binding sites. The reduction was rapidly reversed by propranolol (t1/2 10 min) and other -adrenoreceptor blocking agents. Insulin binding was also measured in fat cells from 6 patients with a phaeochromocytoma. A significant negative correlation between tracer binding and the log value of total urinary catecholamine excretion was found (r=–0.821,p<0.05). Mean tracer insulin binding was reduced about 30% as compared to cells from 16 carefully matched control subjects. Decreased insulin binding was again mainly attributable to a decreased number of binding sites. Thus, -adrenergic stimulation, both in vitro and in vivo, leads to a decreased number of binding sites for insulin in human fat cells.     

Advances in modern electrocardiographic equipment for long-term ambulatory monitoring

Electrocardiographic ambulatory Holter monitoring (AECG) is an essential tool inthe diagnostic evaluation of patients with cardiac arrhythmias. Recent advances in digital Holter technologyhave improved the quality of the ECG signals and new dedicated algorithms have expanded the clinical applicationof software-based AECG analysis systems. Due to the availability of inexpensive large storage capacities, verylong-term (weeks to months) continuous high-quality AECG monitoring will soon be available, togetherwith devices for long-term long-distance telemetric surveillance for high-risk cardiac patients, utilizingtrans-telephonic transmission of ECG data.New digital recorders will also have the capability for multichannel simultaneous recordings (currentlyfrom 3 to 8 simultaneous leads). Multichannel digital recordings will allow the recording of differentbiological signals by appropriate sensors, such as respiratory frequency, peripheral oxygen tension, arterialpulse pressure, EEG, and others. This will transform conventional AECG in ambulatory policardiography, allowingthe comprehensive evaluation of patients with complex disorders, such as heart failure or sleep apneasyndromes.By this global approach, Holter analysis becomes a real noninvasive electrophysiologicaltest, to identify potential risk factors for life-threatening cardiac arrhythmias.     

Flatus-related colorectal and anal motor events

Although complaints of excessive gas symptoms are frequently encountered in clinical practice, the physiologic and pathophysiologic grounds of flatus events are poorly understood, partly because of the social taboos associated with the topic and partly because of technical difficulties in measuring flatus. For these reasons, we studied the colorectal and anal motor events occurring during artificially evoked flatus events and compared them to those that occurred spontaneously. Five healthy male volunteers were studied by multilumen probes placed in the left colon and rectum and across the anal canal, to observe the flatus-related motor events that occurred after instillation of air into the colon. Flatus-related spontaneously occurring motor events were also checked in 24-hr motility tracings obtained in three patients with functional bowel disorders. Analysis of the tracings showed that both artificially induced and spontaneously occurring flatus-related motor phenomena were characterized by colonic propagated contractions associated with a rise in rectal pressure and early relaxation of the anal sphincter, in a sequence resembling that observed following swallowing. Spontaneous flatus events were associated with colonic waves of lesser amplitude than those following insufflation of air into the colon.     

Impaired cytokine production in whole blood cell cultures of patients with urological carcinomas

The production of the cytokines interferon (IFN ), interleukin-1 (IL-1 ) and tumor necrosis factor (TNF ) was investigated in the mitogen-stimulated whole blood cell culture media from 51 patients with urinary bladder carcinomas, 52 patients with renal carcinomas, 31 patients with prostatic carcinomas and 360 healthy controls. The cytokines were measured 4 days after induction by a sensitive enzymo-immunological assay. In the blood cell culture supernatants of the patients with urinary bladder carcinomas significancy lower levels of IFN (P0.001), IL-2 (P0.001) and TNF (P0.05) were found as compared to the controls. Blood cells of patients with renal carcinomas had lower production of IFN (P0.01), IL-2 (P0.001) and IL-1 (P0.01), whereas the values of the total group of patients with prostatic carcinomas were not significantly different from those of the controls. Lymphocyte and monocyte counts were almost identical in the control and all tumor patient groups. When the patients with renal carcinomas and prostatic carcinomas were analyzed according to their different clinical stages we could show a gradual depression of the IFN- levels, which was related to tumor burden.Abbreviations PHA phytohemagglutinin - PWM pokeweed mitogen - ELISA enzyme-linked immunoassay - IL interleukin - IFN interferon - TNF tumor necrosis factor, mAb, monoclonal antibody     

Effects of catecholamines,nicotine, acetylcholine and potassium on the mechanical activity of the colonic muscularis mucosae in the cat

Conclusions Our conclusions on cat colonic muscularis mucosae can be summarized as follows: The smooth muscle contains-excitatory and-inhibitory receptors. Both adrenergic and nonadrenergic inhibitory nervous structures, which can be excited through nicotinic and muscarinic receptors, are present. The possible role of 5-HT in permitting nonadrenergic inhibitory responses is suggested. In the colonic muscularis mucosae, the apparent lack of cholinergic motor neurones has been demonstrated.Supported by CNR Grant No. 115-123-1357.     

Duration of Anticoagulation for Venous Thromboembolism

The duration of oral anticoagulant therapy for venous thromboembolism (VTE) depends on the risk of recurrence if treatment is stopped and the risk of bleeding if treatment is continued. If the risk of recurrence is low (e.g., thrombosis provoked by a major reversible risk factor such as surgery), 3 months of treatment is usually adequate. If the risk of recurrence is high (unprovoked idiopathic VTE or associated with a non-reversible risk factor such as active cancer), 6 months or indefinite anticoagulant therapy is indicated. The presence of malignancy, an antiphospholipid antibody, and other selected thrombophilic states suggests more prolonged therapy, whereas isolated distal deep vein thrombosis, high risk of bleeding, and patient preference suggest a shorter course of treatment.     

Plasma lysosomal enzyme levels in patients with motor neuron disease

Summary -Hexosaminidase and acid--mannosidase were estimated in 17 adult patients with motor neuron disease. Normal plasma levels of -hexosaminidase ((A+B) and A) were found in all patients studied. Plasma acid -mannosidase levels were normal in all but two patients with the spinal muscular atrophy type of the disorder. In addition, altered biochemical properties of acid -mannosidase (i.e.K _m, thermal stability) were found in the low-activity cases.     

Presence of Two Signaling TGF-β Receptors in Human Pancreatic Cancer Correlates with Advanced Tumor Stage

Transforming growth factor- (TGF-)signal transduction is mediated via specific cellsurface signaling TGF- receptors, most notably thetype I ALK5 (TR-I_ALK5)and the type II(TR-II). We evaluated TR-I_ALK5 andTR-II expression in 41 human pancreatic cancertissue samples and correlated these findings withclinical data of the patients. Northern blot analysisindicated that, in comparison with the normal pancreas,pancreatic adenocarcinomas exhibited 8.0-fold and4.5-fold increases (P < 0.01), respectively, in mRNAlevels encoding TR-I_ALK5 andTR-II. In situ hybridization showed that both TR-I_ALK5 mRNAwere highly expressed in the majority of pancreaticcancer cells. Immunohistochemical analysis ofTR-I_ALK5 and TR-II revealedpositive immunostaining in 73% and 56% of the tumors, respectively. Both receptorswere concomitantly present in 54% of the pancreaticcancer samples. The presence ofTR-I_ALK5 or TR-II and theconcomitant presence of TR-I_ALK5 and TR-II in the cancer cells was associatedwith advanced tumor stage (P < 0.01). These findingsshow that in many human pancreatic cancers, increasedlevels of the two signaling TRs are present. The presence of the signaling TRs inadvanced tumor stages indicates a role in diseaseprogression.     

Der Patient als Keimquelle in der Intensivpflegestation

Zusammenfassung 133 Patienten einer Intensivpflegestation, die bei der Aufnahme keine Symptome bakterieller Infektion zeigten und noch keine Antibiotika erhalten hatten, wurden nach dem Zufallsprinzip zwei Gruppen zugeordnet. Eine Gruppe (+Pat.) erhielt eine Antibiotikaprophylaxe mit Penicillinen oder Cephalosporinen, die zweite Gruppe (–Pat.) erhielt keine Antibiotika. Staph. aureus war bei –Pat. im Trachealsekret und in der Umgebung der häufigste potentiell pathogene Keim. Staph. aureus war im Trachealsekret und in der Umgebung der –Pat. signifikant häufiger als bei +Pat.. Klebsiella spp. standen im Trachealsekret und in der Umgebung von +Pat. an erster Stelle. Sie waren im Trachealsekret von +Pat. signifikant häufiger als bei –Pat.. In der ersten Woche des Stationsaufenthaltes traten bei +Pat. starke Veränderungen in der Keimflora der Trachealsekrete auf: die Besiedelung mit gramnegativen Keimen stieg auf fast 100% an, gleichzeitig ging die Frequenz von Staph. aureus zurück. In den Abklatschuntersuchungen aus der Patientenumgebung traten gramnegative Stäbchen bei +Pat. in signifikant höheren Koloniezahlen auf als bei –Pat.. Die paarweisen Vergleiche von Bakterienstämmen aus den Trachealsekreten und aus der Patientenumgebung ergaben, daß +Pat. gramnegative Keime und –Pat. Staph. aureus signifikant häufiger an die Umgebung abgaben. Auf die Kontamination der Patientenumgebung mit Staph. aureus wirkte sich der Faktor der trachealen Intubation nicht aus. Gramnegative Keime waren im Trachealsekret von intubierten Patienten signifikant häufiger als bei nicht intubierten. Derselbe Trend zeigte sich auch in der Patientenumgebung. Die Antibiotikaprophylaxe konnte, wie die klinischen Ergebnisse der Studie zeigten, die Patienten nicht im erwarteten Ausmaß vor Infektionen schützen. Patienten, insbesondere tracheal-intubierte, die Antibiotika erhalten, sind als Streuquellen für hochresistente gramnegative Keime anzusehen.

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The patient as a source of bacteria in intensive care units: Influence of antibiotics and tracheal intubation

Summary 133 patients in an intensive care unit, who prior to admission had not shown any signs of bacterial infection and had not received antibiotic treatment, were assigned to two groups at random. One group received antibiotic prophylaxis with penicillins or cephalosporins (+Pat.), the other group did not receive antibiotics (–Pat.). Staph. aureus was the most frequent facultative pathogen in tracheal secretions and in the environment of –Pat.. This organism was significantly more frequent in –Pat. than in +Pat. in both the tracheal secretions and the enviroment. Klebsiella spp. outnumbered all other species in +Pat.. They were significantly more frequent in tracheal secretions of +Pat. than of –Pat.. In the first week of hospitalisation marked changes were seen in bacterial flora of tracheal secretions of +Pat.. Colonization with gramnegative bacteria rose to nearly 100%, the frequency of Staph. aureus diminishing at the same time. Monitoring by contact cultures revealed that gramnegative rods were significantly more numerous in the environment of +Pat. than of –Pat.. Matching bacterial strains cultured from tracheal secretions and from the environment of the patients proved that +Pat. spread significantly higher numbers of their gramnegative bacteria into the environment. The same is true of –Pat. for Staph. aureus. Intubation had no noticeable effect on the degree of contamination of the surroundings with Staph. aureus. Gramnegative rods were significantly more frequent in tracheal secretions of patients with intubation than in patients without. The same trend was observed for environmental contamination. As the clinical results of this study have shown, antibiotic prophylaxis does not protect patients from infections to the extent expected. Patients, and particularly intubated patients, receiving antibiotic treatment have to be considered as sources of highly resistant gramnegative organisms.

     

Quantitative Transplantationsversuche mit dem Yoshida-Ascitessarkom der Ratte

Ohne ZusammenfassungHerrn Prof. Dr. Reinhard Mecke, Freiburg i. Br., zum 60. Geburtstag gewidmet. — Die Untersuchungen wurden durch die Deutsche Forschungsgemeinschaft ermöglicht.Mit 4 Textabbildungen.     

Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes

Summary Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration (diffuse, cluster, and large) were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was diffuse in 18, cluster in 48, and large in 40 cases. RAEB-t patients accounted for about half of the large cases, and none had a diffuse pattern (p<0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by cluster blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of large cases (p<0.001) and in none of the cluster cases with severe BM fibrosis (p<0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with cluster BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy.     

Serum concentrations of resistin-like molecules β and γ are elevated in high-fat-fed and obese db/db mice, with increased production in the intestinal tract and bone marrow

Aims/hypothesis Resistin and the resistin-like molecules (RELMs) comprise a novel class of cysteine-rich proteins. Among the RELMs, RELM and RELM are produced in non-adipocyte tissues, but the regulation of their expression and their physiological roles are largely unknown. We investigated in mice the tissue distribution and dimer formation of RELM and RELM and then examined whether their serum concentrations and tissue expression levels are related to insulin resistance.Methods Specific antibodies against RELM and RELM were generated. Dimer formation was examined using COS cells and the colon. RELM and RELM tissue localisation and expression levels were analysed by an RNase protection assay, immunoblotting and immunohistochemical study. Serum concentrations in high-fat-fed and db/db mice were also measured using the specific antibodies.Results The intestinal tract produces RELM and RELM, and colonic epithelial cells in particular express both RELM and RELM. In addition, RELM and RELM were shown to form a homodimer and a heterodimer with each other, in an overexpression system using cultured cells, and in mouse colon and serum. Serum RELM and RELM levels in high-fat-fed mice were markedly higher than those in mice fed normal chow. Serum RELM and RELM concentrations were also clearly higher in db/db mice than in lean littermates. Tissue expression levels revealed that elevated serum concentrations of RELM and RELM are attributable to increased production in the colon and bone marrow.Conclusions/interpretation RELM and RELM form homo/heterodimers, which are secreted into the circulation. Serum concentrations of RELM and RELM may be a novel intestinal-tract-mediating regulator of insulin sensitivity, possibly involved in insulin resistance induced by obesity and a high-fat diet.     

Smooth muscle sphincteroplasty in colostomy

PURPOSE The present work elaborated on Schmidts idea of an effective smooth muscle sphincteroplasty. The aim of the study was to analyze the effects on the patients with a lower quadrant colostomy constructed after abdominoperineal extirpation of a modified smooth muscle sphincteroplasty combined with colon irrigations.METHODS Seventy-two rectal cancer patients (39 men and 33 women, median age, 54.5 years) with smooth muscle sphincteroplasty and 20 controls with conventional colostomy using colon irrigations (11 men and 9 women, median age, 63.2 years) were examined. A modified smooth muscle wrap of the colostomy with a free graft of a 4-cm-long colon segment without mucosa was applied. In this precolostomy segment a high intraluminal pressure was achieved. The functional capacity and anatomic integrity of the transplanted smooth muscle graft were examined manometrically, electromyographically, and histomorphologically. The functional activity of the colostomy was assessed by periodic recording of the number of spontaneous and directed defecations.RESULTS In the patients with smooth muscle sphincteroplasty, the basal intraluminal pressure of the precolostomy segment two years after operation measured 29.7 mmHg. After dilatation of the transplant, these pressures reached up to 43 mmHg (P < 0.001). The weekly spontaneous stools were 3 to 5 times less frequent than in the controls (P < 0.001).CONCLUSIONS The modified smooth muscle sphincteroplasty offers operative-technical opportunities for increasing intraluminal pressure in the precolostomy colon segment. Its combination with colonic irrigations facilitates control of the evacuatory rhythm and spontaneous stools in colostomy patients, thus improving their quality of life.     

Insulin and growth hormone responses to glucose loading in treated acromegalics

Summary The insulin and growth hormone responses to oral glucose load (100 g) in 23 acronaegalic patients, previously treated by external irradiation, are described. Based on current clinical findings, sixteen acromegalics were considered inactive and seven patients active. Two of the latter were treated diabetics. Thirteen healthy, non-obese subjects formed the control group. Five inactive acromegalics had blood glucose values exceeding the upper limits of normal after the glucose load. Both the inactive and active acromegalics had hyperinsulinemia in the fasting state and after glucose load. The observation of an exaggerated serum insulin response to glucose load in clinically inactive acromegalics suggested that chronically elevated levels of circulating growth hormone may have led to permanent changes in the responsiveness of the pancreatic islets to glucose stimulation. The mean fasting value of serum growth hormone was about the same in the controls and the inactive acromegalics; the latter did not show suppression in serum growth hormone levels after glucose load.Research Fellow, Medical Research Council of Canada     

The treatment of hypertension: New lamps for old?

Summary Meta-analysis of clinical trials does not help the clinician to treat individual patients. A general conclusion that the reduction of high blood pressure is beneficial has to be matched by specific information about the level of blood pressure that is acceptable and about the effect of particular doses of specific drugs. Results obtained from trials of old-fashioned antihypertensive drugs cannot confidently be extrapolated to modern agents. Sufficient data do not exist to encourage universal drug treatment for patients with mild hypertension.     

Immunoglobulin production and secretion in bence jones protein myeloma and “nonsecretory” myeloma

Summary Using our electron microscopic method for polysome analysis and an immunofluorescent technique we studied Ig production and secretion by tumor cells in seven BJP myeloma patients and seven nonsecretory myeloma patients.In BJP myeloma Ig production and secretion is of three types: Type 1, only L-chains are synthesized and secreted; Type 2, the myeloma cells show fluorescence for H-chains, but upon polysome analysis there is no peak at polysomes corresponding to H-chain production; Type 3, the myeloma cells show fluorescence for H-chains, and polysome analysis shows two peaks corresponding to L- and H-chain production.Polysome analysis of nonsecretory myelomas show the presence of only very few membrane-bound polysomes and their distribution curves are entirely different from those of ordinary myeloma. Furthermore, the distribution patterns vary among seven cases. Results obtained by polysome analysis and immunofluorescent technique suggest that the nonsecretory myeloma could be divided into several subtypes.Supported in part by grants-in-aid for scientific Research (748103, 867050, 167092, 267108, 777124) from the Ministry of Education, Science and Culture of Japan     

Experimentelle Untersuchungen zur Syncarcinogenese

Zusammenfassung Hauttropfungen bei C 57 black-Mäusen mit Urethan (Einzeldosis: 11,2 mg; Gesamtdosis: 1560 mg/Tier) führten vorwiegend (84%) zu Blutcysten in der Leber und bei einem tier (2%) zu einem Plattenepithelcarcinom lokal an der Applikationsstelle.Hauttropfungen mit 9,10-Dimethyl-1,2-benzanthracen (Einzeldosis: 0,0018 mg; Gesamtdosis: 0,0504 mg/Tier) ergaben in 9,5% der Fälle lokale Hautcarcinome.Wurden beide Substanzen in der gleichen Dosierung kombiniert auf die Haut aufgebracht, dann erhöhte sich die Tumorausbeute nicht. Es liegt also keine Syncarcinogenese vor.

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Summary Droplet application of urethan to the skin of C 57 black mice (single dose: 11.2 mg; total dosage: 1560 mg/animal) led chiefly (84%) to hepatic blood cysts, and in one animal (2%) to a squamous cell carcinoma locally at the site of application. The cutaneous droplet application of 9,10-dimethyl-1,2-benzanthracene (single dose: 0.0018 mg; total dosage: 0.0504 mg/animal) caused skin carcinomas in 9.5% of the animals. When both substances were applied together to the skin in the same dosage as above, the number of tumors induced was not increased. No syncarcinogenesis existed.

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Herrn Prof. Dr. Hamperl, Bonn, zum 65. Geburtstag gewidmet.

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Mis Unterstützung der Deutschen Forschungsgemeinschft.     

Localization of transforming growth factor-β 1 precursor and latent TGF-β 1 binding protein in colorectal adenomas

Transforming growth factor- ₁ (TGF- ₁) is a multifunctional cytokine and is thought to be involved in colorectal tumorigenesis as a regulator of cell growth and differentiation. This role is mainly supported byin vitro studies while its rolein vivo remains unclear. The aim of the present study was to investigate whether the TGF- ₁ precursor ( ₁-LAP) and the latent TGF- ₁ binding protein (LTBP) are expressed in colorectal adenomas, the presumed precursors of most of colorectal adenocarcinomas. TGF- ₁ precursor and LTBP were examined in 35 adenomas and 10 normal colonic mucosa specimens by immunohistochemistry, using specific polyclonal antibodies. In normal colonic mucosa, ₁-LAP was moderately expressed in epithelial crypt cells and in the stromal cells in the lamina propria. In adenomas, ₁-LAP was localized in epithelial cells with an heterogeneous pattern and was also present in stromal cells around the adenomatous glands. LTBP was not detected in epithelial cells but was observed in stromal cells and in the extracellular matrix (ECM). ₁-LAP expression in epithelial cells did not correlate with the grade of dysplasia, while LTBP localized in stromal cells and ECM appeared to be closely associated with areas of higher grade of dysplasia. This study is the first demonstration of both ₁-LAP and LTBP in colorectal adenomas with different dysplasia grades. Our results suggest that TGF- ₁ might be involved in the mechanisms controllingin vivo colorectal tumorigenesis and support a role for the stromal-associated TGF- ₁.J.-L. Van Laethem is supported by a grant of the Fondation Erasme (Brussels, Belgium).     

Compound heterozygosity for a β∘-thalassemia (frameshift codons 38/39; -C) and a nondeletional swiss type of HPFH (A→C at NT -110, Gγ) in a Czechoslovakian family

Summary We have analyzed the levels and composition of the fetal hemoglobin (Hb F) in several members of a Czechoslovakian family with a heterozygosity for a newly discovered -thalassemia (codons 38/39; -C), or for a newly detected nondeletional hereditary persistence of fetal hemoglobin (a form of Swiss-HPFH with an AC mutation at nucleotide –100 5 to the Cap site of G), or with a compound heterozygosity for these two conditions. The Hb F level in the -thalassemia heterozygotes averaged 0.3% with low G values ( 28%) and relatively high AT values ( 50%), that in the two Swiss-HPFH heterozygotes averaged 0.8% with 95% G, while that of the compound heterozygote was 3.1% with 95% G. The low Hb F levels were determined with a recently published cation exchange high-performance liquid chromatography (HPLC) procedure that is accurate at the 0.1%–0.2% Hb F level [3]. This method, together with a reversed-phase HPLC procedure, made it possible to detect this unusual type of nondeletional G-HPFH and provided the data indicating that the increased Hb F in the compound heterozygote was derived mainly from the chromosome with the HPFH determinant.This study was supported in part by USPHS Research Grant HLB-41544     

Burden of musculoskeletal pain in Japan

Based on the prevalence of musculoskeletal pain in the context of interference with daily activities (IDA) and treatment for musculoskeletal disorders in the study population (n = 3188), we estimated the prevalence and years lived with disability (YLD) of musculoskeletal pain in Japan. The total of 42287 thousand (41.2%) of Japanese adult people was estimated to suffer from musculoskeletal pain. Among them, 9127 thousand was estimated to interfere with daily activities due to the pain. Overall YLD for musculoskeletal pain in Japan were estimated at 1297843.7 (1263.6 per 100000). The YLD for Pain without IDA were 33159.3 (32.3 per 100000) and the YLD for Pain with IDA were 1264684.4 (1231.3 per 100000). One-way sensitivity analysis showed that the YLD of musculoskeletal pain might increase to 4421844.0 (4305.2 per 100000) with the increased disability weight for Pain without IDA of 0.1, while they might inversely decrease to 1018875.0 (992.0 per 100000) with the increased treatment rate in Pain with IDA of 100%. Musculoskeletal pain imposes a substantial burden on the Japanese adult population. To allow the population to keep their health-related quality of life, health professionals should pay more attention to musculoskeletal pain and make positive efforts to improve prevention and control of musculoskeletal pain.