Epidemiology of Diagnosed Age-related Macular Degeneration in Germany: An Evaluation of the Prevalence Using AOK PLUS Claims Data.

INTRODUCTION: Epidemiologic data on age-related macular degeneration (AMD) are mainly based on cohort studies, including both diagnosed and undiagnosed cases. Using health claims data allows estimating epidemiological data of diagnosed subjects with AMD within the health care system using diagnosis codes from a regional claims database (AOK PLUS) to estimate the prevalence and incidence of non-exudative and exudative AMD in Germany. METHODS: Patients with AMD were identified among AOK PLUS insured patients based on at least two outpatient, ophthalmologic or one inpatient H35.3 diagnoses for the years 2012 to 2021. Patients without continuous observation in a calendar year were excluded. Prevalence was assessed, and 1-year cumulative incidence was determined by the number of newly diagnosed patients divided by the number of individuals at risk. For 2020 and 2021, the AMD stage was assessed by diagnostic subcodes for non-exudative and exudative AMD, respectively. For 2012 to 2019, patient numbers were estimated based on the average proportions of non-exudative AMD and exudative AMD, respectively, in 2020 and 2021. Incidence and prevalence numbers were then extrapolated to Germany. RESULTS: Between 2012 to 2021, the prevalence of diagnosed AMD cases remained relatively stable among approximately 3.27 million AOK PLUS insured persons, ranging from 0.96% (minimum in 2021) to 1.31% (maximum in 2014) for non-exudative AMD, about twice as high as for exudative AMD (min-max: 0.53-0.72%). The age- and sex-adjusted projections amounted to 644,153 diagnosed non-exudative and 367,086 diagnosed German patients with exudative AMDs in 2021. The 1-year cumulative incidence for non-exudative and exudative AMD, respectively, ranged from 122,427-142,932 to 46,092-86,785 newly diagnosed cases. CONCLUSION: The number of diagnosed cases with AMD in Germany has increased slightly over the past decade. For the first time, patient counts with non-exudative and exudative AMD were approximated for Germany based on a representative, large-scale database study.

[Diagnosis and Management of Late-Onset Pompe Disease]. / Diagnostik, Therapie und psychosoziale Aspekte bei late-onset Morbus Pompe.

Pompe disease is a lysosomal storage disorder, with onset between the first weeks after birth and adulthood, depending on its phenotype. It can affect multiple organ systems and presents itself with a wide variety of symptoms. Thus, recognizing Pompe disease is difficult. Especially since enzyme replacement therapy for Pompe disease was introduced (in Germany in 2006), early diagnosis by means of enzyme activity determination from dried blood spot analysis and genetic verification has become important for outcome and quality of life. When facing an obscure muscular disorder, it is crucial to consider Pompe disease. This article provides an overview about Pompe disease and focuses on the diagnosis of the late onset type. The most important aspects of interdiciplinary care for patients with Pompe disease are presented. Additionally, it contains a section focusing on psychosocial challenges for children with Pompe disease and their families, which may include mental disorders and social retreat, and gives advice on how to support parents of affected children.

Systematic review of oral and craniofacial findings in patients with Fabry disease or Pompe disease.

Fabry disease and Pompe disease are rare lysosomal storage disorders that belong to a heterogeneous group of more than 200 distinct inborn metabolic diseases. Mutations followed by loss of function of enzymes or transporters that are localised in the acidic environment of the lysosome may result in degradation of many substrates, such as glycosaminoglycans, glycosphingolipids, glycogen, cholesterol, oligosaccharides, glycoproteins, and peptides, or the excretion of the products degraded by the lysosome. Our aim was to identify the oral signs and symptoms of Fabry disease and Pompe disease from a systematic review made using MEDLINE/PubMed, and a hand search for relevant articles, following the PRISMA guidelines. Both diseases show various craniofacial and oral changes, including supernumerary teeth, dental agenesis, angiokeratoma, and telangiectases in Fabry disease; and macroglossia, teeth fusion, and taurodontism in Pompe disease. Common clinical signs of Fabry disease include hyposalivation, hypohidrosis, and xerophthalmia, and a generally reduced physical resilience was apparent in patients with Pompe disease. Oral and craniofacial changes in patients with both diseases extend over their entire lifetime and can be detected even in an infant. Lysosomal storage diseases should be taken into consideration in the differential diagnosis of relevant diverse symptoms, because treatment, when available, is most effective when started early. The main therapeutic concepts are enzymatic replacement for Pompe disease, whereas patients with Fabry disease require additional oral chaperone treatment or enzyme replacement.

Numerical simulation of micro-particle rotation by the acoustic viscous torque.

We present the first numerical simulation setup for the calculation of the acoustic viscous torque on arbitrarily shaped micro-particles inside general acoustic fields. Under typical experimental conditions, the particle deformation plays a minor role. Therefore, the particle is modeled as a rigid body which is free to perform any time-harmonic and time-averaged translation and rotation. Applying a perturbation approach, the viscoacoustic field around the particle is resolved to obtain the time-averaged driving forces for a subsequent acoustic streaming simulation. For some acoustic fields, the near-boundary streaming around the fluid-suspended particle induces surface forces on the nonrotating particle that integrate into a non-zero acoustic viscous torque. In the equilibrium state, this torque is compensated by an equal and opposite drag torque due to the particle rotation. The rotation-induced flow field is superimposed on the acoustic streaming field to obtain the total fluid motion around the rotating particle. In this work, we only consider cases within the Rayleigh limit even though the presented numerical model is not strictly limited to this regime. After a validation by analytical solutions, the numerical model is applied to challenging experimental cases. For an arbitrary particle density, we consider particle sizes that can be comparable to the viscous boundary layer thickness. This important regime has not been studied before because it lies beyond the validity limits of the available analytical solutions. The detailed numerical analysis in this work predicts nonintuitive phenomena, including an inversion of the rotation direction. Our numerical model opens the door to explore a wide range of experimentally relevant cases, including non-spherical particle rotation. As a step toward application fields such as micro-robotics, the rotation of a prolate ellipsoid is studied.

Acoustophoresis of disk-shaped microparticles: A numerical and experimental study of acoustic radiation forces and torques.

Disk-shaped microparticles experience an acoustic radiation force and torque in an ultrasonic standing wave. Hence, they are translated by the acoustic field, an effect called acoustophoresis, and rotated. The torque effect is also known from the "Rayleigh disk" which is described in literature for sound intensity measurements. In this paper, inviscid numerical simulations of acoustic radiation forces and torques for disks with radius ≪ wavelength in water are developed in good agreement with former analytical solutions, and the dependence on disk geometry, density, and orientation is discussed. Experiments with alumina disks (diameter 7.5 µm), suspended in an aqueous liquid in a silicon microchannel, confirm the theoretical results qualitatively at the microscale and ultrasonic frequencies around 2 MHz. These results can potentially be applied for the synthesis of disk-reinforced composite materials. The insights are also relevant for the acoustic handling of various disk-shaped particles, such as red blood cells.

Numerical simulation of acoustofluidic manipulation by radiation forces and acoustic streaming for complex particles.

The numerical prediction of acoustofluidic particle motion is of great help for the design, the analysis, and the physical understanding of acoustofluidic devices as it allows for a simple and direct comparison with experimental observations. However, such a numerical setup requires detailed modeling of the acoustofluidic device with all its components and thorough understanding of the acoustofluidic forces inducing the particle motion. In this work, we present a 3D trajectory simulation setup that covers the full spectrum, comprising a time-harmonic device model, an acoustic streaming model of the fluid cavity, a radiation force simulation, and the calculation of the hydrodynamic drag. In order to make quantitatively accurate predictions of the device vibration and the acoustic field, we include the viscous boundary layer damping. Using a semi-analytical method based on Nyborg's calculations, the boundary-driven acoustic streaming is derived directly from the device simulation and takes into account cavity wall vibrations which have often been neglected in the literature. The acoustic radiation forces and the hydrodynamic drag are calculated numerically to handle particles of arbitrary shape, structure, and size. In this way, complex 3D particle translation and rotation inside experimental microdevices can be predicted. We simulate the rotation of a microfiber in an amplitude-modulated 2D field and analyze the results with respect to experimental observations. For a quantitative verification, the motion of an alumina microdisk is compared to a simple experiment. Demonstrating the potential of the simulation setup, we compute the trajectory of a red blood cell inside a realistic microdevice under the simultaneous effects of acoustic streaming and radiation forces.

Modeling and optimization of acoustofluidic micro-devices.

We investigate how the combination of numerical simulation tools and optimization routines can be used to design micro-devices. Experimental devices that are designed in this way can only provide optimal performance if the simulation model, used in the optimization procedure, reflects the real device characteristics accurately. Owing to this fact, the modeling of acoustofluidic devices is summarized. The mathematical formulation of the optimization problem, the parameterization of the device design and the implementation of the optimization loop is addressed alongside with practical recommendations for the chosen genetic algorithm optimization. In order to validate the implementation, an optimized planar resonator is compared with the optimal geometry given in the literature. The optimization of a typical 3D micro-device shows that devices can be designed to generate any desired acoustic mode shape at maximum pressure amplitude. The presented automatic design approach is of great practical relevance for the development of highly optimized micro-devices and it can speed up and facilitate the design-process in the growing field of acoustofluidics.

Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial.

BACKGROUND: Gemcitabine plus a platinum-based agent (eg, cisplatin or oxaliplatin) is the standard of care for advanced biliary cancers. We investigated the addition of cetuximab to chemotherapy in patients with advanced biliary cancers. METHODS: In this non-comparative, open-label, randomised phase 2 trial, we recruited patients with locally advanced (non-resectable) or metastatic cholangiocarcinoma, gallbladder carcinoma, or ampullary carcinoma and a WHO performance status of 0 or 1 from 18 hospitals across France and Germany. Eligible patients were randomly assigned (1:1) centrally with a minimisation procedure to first-line treatment with gemcitabine (1000 mg/m(2)) and oxaliplatin (100 mg/m(2)) with or without cetuximab (500 mg/m(2)), repeated every 2 weeks until disease progression or unacceptable toxicity. Randomisation was stratified by centre, primary site of disease, disease stage, and previous treatment with curative intent or adjuvant therapy. Investigators who assessed treatment response were not masked to group assignment. The primary endpoint was the proportion of patients who were progression-free at 4 months, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00552149. FINDINGS: Between Oct 10, 2007, and Dec 18, 2009, 76 patients were assigned to chemotherapy plus cetuximab and 74 to chemotherapy alone. 48 (63%; 95% CI 52-74) patients assigned to chemotherapy plus cetuximab and 40 (54%; 43-65) assigned to chemotherapy alone were progression-free at 4 months. Median progression-free survival was 6·1 months (95% CI 5·1-7·6) in the chemotherapy plus cetuximab group and 5·5 months (3·7-6·6) in the chemotherapy alone group. Median overall survival was 11·0 months (9·1-13·7) in the chemotherapy plus cetuximab group and 12·4 months (8·6-16·0) in the chemotherapy alone group. The most common grade 3-4 adverse events were peripheral neuropathy (in 18 [24%] of 76 patients who received chemotherapy plus cetuximab vs ten [15%] of 68 who received chemotherapy alone), neutropenia (17 [22%] vs 11 [16%]), and increased aminotransferase concentrations (17 [22%] vs ten [15%]). 70 serious adverse events were reported in 39 (51%) of 76 patients who received chemotherapy plus cetuximab (34 events in 19 [25%] patients were treatment-related), whereas 41 serious adverse events were reported in 25 (35%) of 71 patients who received chemotherapy alone (20 events in 12 [17%] patients were treatment-related). One patient died of atypical pneumonia related to treatment in the chemotherapy alone group. INTERPRETATION: The addition of cetuximab to gemcitabine and oxaliplatin did not seem to enhance the activity of chemotherapy in patients with advanced biliary cancer, although it was well tolerated. Gemcitabine and platinum-based combination should remain the standard treatment option. FUNDING: Institut National du Cancer, Merck Serono.

Acoustofluidics 19: ultrasonic microrobotics in cavities: devices and numerical simulation.

Acoustic radiation forces are increasingly used for the handling of micron sized particles (cells, functionalized beads, etc.) suspended in a fluid in the chamber of a manipulation device. The primary radiation forces arise as a nonlinear effect when an acoustic wave interacts with a particle. For specific robotic applications, precise control of the acoustic field in the cavity is important, which is excited, for example, by piezoelectric transducers attached to the device. Based on Gor'kov's potential the relevant forces on spherical particles can be computed. The field can be controlled by varying the excitation parameters: chamber and electrode configuration, as well as frequency, amplitude and phase of the excitation and their modulation. In the first part of the present tutorial, a number of examples are described: displacement and rotation of particles in micro machined chambers and macroscopic transport of particles in a larger chamber. In the second part, numerical tools (Finite Volume Method, COMSOL) are used to model the interaction of the acoustic field with a particle beyond a Gor'kov potential: viscosity, effects of walls near particles and acoustic radiation torque to rotate the particle. Excellent agreement between the various methods has been found.

Acoustofluidics 6: Experimental characterization of ultrasonic particle manipulation devices.

Because of uncertainties in material and geometrical parameters in ultrasonic devices, experimental characterization is an indispensable part in their successful application for the manipulation of particles or cells. Its miniaturized size precludes the use of many of the usual tools used for macroscopic systems. Also, a further challenge is the fact that the resulting motion due to the electromechanical actuation has both high frequency and small amplitudes. Contactless methods like laser interferometry are therefore promising methods. In addition, as long as there is strong electromechanical coupling between the transducer and the device also electrical measurements like admittance curves give insight into the frequencies at which the devices might work best. This is the case for example for piezoelectric transducers working at one of their resonance frequencies. Because the devices usually are used in resonant modes, narrow frequency detection methods like lock in amplifiers help to improve the signal to noise ratio. Also many analysis tools have been established in the context of modal analysis, which is based on frequency domain methods. Special emphasis is placed here on the determination of the quality factor Q of the resonator, as Q determines the efficiency of a device.

Proximal contact tightness between direct-composite additions in the posterior dentition: an in vitro investigation.

PURPOSE: The aim of the study was to test whether a novel three-step matrix technique for posterior direct-composite additions creates sufficiently strong proximal contacts. MATERIALS AND METHODS: Contact tightness was measured between direct-composite additions and between original teeth on a model. Therefore, the frictional forces required to remove a straight, 0.05-mm-thick, metal matrix band inserted between adjacent teeth and held by a universal testing machine (Zwicki, Zwick GmbH, Ulm, Germany) were recorded. Measurements were taken at three time points to carry out reference analysis: at baseline, after removal of the maxillary right second premolar (tooth #15) to simulate a diastema, and after closure of the diastema by inserting two direct-composite additions with the three-step matrix technique on the maxillary right first premolar (tooth #14) and first molar (tooth #16). Measurements were performed in the maxillary right (first) and left (second) quadrants to document sagittal displacement. RESULTS: The original contact tightness values were between 1.65 ± 0.88 N and 3.05 ± 0.60 N in the first quadrant and between 1.23 ± 0.51 N and 2.18 ± 0.43 N in the second quadrant. After removal of tooth 15, values decreased significantly in the first quadrant and insignificantly in the second. After reconstruction, the contact tightness between teeth 14 and 16 was significantly stronger (tighter) (3.20 ± 0.80 N) than the originally measured contact tightness between teeth 14 and 15 (2.86 ± 0.64 N) and teeth 15 and 16 (1.65 ± 0.88 N) (p=0.006 and 0.001, respectively). CONCLUSIONS: Within the limitations of an in vitro investigation, this study has shown that by using a novel, three-step matrix technique, direct posterior composite additions can form sufficiently tight proximal contacts.

Clinical utility of anti-glycan antibodies in pediatric Crohn's disease in comparison with an adult cohort.

BACKGROUND: We tested a panel of serological anti-glycan antibodies including the novel anti-laminarin (Anti-L) and anti-chitin (Anti-C) antibodies in pediatric Crohn's disease (CD) patients for diagnosis of CD and association with complicated CD behavior. In addition, we compared this panel in pediatric CD with adult CD patients for possible changes in accuracy over time. METHODS: Anti-L, Anti-C, anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA), and anti-Saccaromyces cervisiae (gASCA) antibodies were tested in serum samples of 131 pediatric participants (59 CD, 27 ulcerative colitis [UC], and 45 noninflammatory bowel disease [IBD] controls) with enzyme-linked immunosorbent assay (ELISA). The results were compared to an adult cohort of 728 participants (355 CD, 129 UC, and 244 non-IBD controls). RESULTS: In all, 78% of the pediatric CD patients were positive for at least one of the anti-glycan antibodies. gASCA was most accurate for the diagnosis of CD, but combined use of the antibodies improved differentiation of CD from UC. gASCA, AMCA, ALCA, or Anti-L and an increasing antibody level were independently linked to complicated CD behavior, CD-related surgery, and ileal disease location (odds ratio 3.9-8.7). Considering the age at sample procurement the accuracy of the markers compared to an adult cohort remained stable for the differentiation of CD versus UC as well as for the association with complications, CD-related surgery, and ileal disease involvement. CONCLUSIONS: A panel of anti-glycan antibodies including the novel Anti-L and Anti-C may aid in the differentiation of pediatric CD from UC and is associated with complicated CD behavior. The marker accuracy remained constant over time.

Low hemoglobin is associated with poor functional outcome after non-traumatic, supratentorial intracerebral hemorrhage.

INTRODUCTION: The impact of anemia on functional outcome and mortality in patients suffering from non-traumatic intracerebral hemorrhage (ICH) has not been investigated. Here, we assessed the relationship between hemoglobin (HB) levels and clinical outcome after ICH. METHODS: One hundred and ninety six patients suffering from supratentorial, non-traumatic ICH were extracted from our local stroke database (June 2004 to June 2006). Clinical and radiologic computed tomography data, HB levels on admission, mean HB values and nadir during hospital stay were recorded. Outcome was assessed at discharge and 3 months using the modified Rankin score (mRS). RESULTS: Forty six (23.5%) patients achieved a favorable functional outcome (mRS

Papillary thyroid cancer associated with syndrome of inappropriate antidiuresis: a case report.

INTRODUCTION: The syndrome of inappropriate antidiuresis is the most common cause of euvolemic hypo-osmolality. This syndrome is associated with a wide variety of diseases. However, its most frequent causes are related to malignancies, especially lung cancer. In this case report, we describe an unknown association of the syndrome of inappropriate antidiuresis with papillary thyroid cancer. CASE PRESENTATION: We present the case of a 71-year-old Caucasian, German woman with marked hyponatremia and neurological symptoms. After a detailed clinical investigation, the common causes of syndrome of inappropriate antidiuresis and other malignancies were ruled out. A thyroid nodule was detected by ultrasound and magnetic resonance imaging. Although fine needle aspiration cytology showed negative results, our patient underwent surgery. Papillary thyroid cancer was later diagnosed. After total thyroidectomy, a complete remission of the clinical symptoms occurred and our patient subsequently had iodine-131 radioactive therapy. Hyponatremia was no longer observed during the follow-up investigations. CONCLUSION: This is the first reported case of paraneoplastic syndrome of inappropriate antidiuresis caused by papillary thyroid carcinoma. Since its symptoms occurred before the development of local symptoms, total thyroidectomy may provide a timely and efficient treatment for the underlying malignancy.

C-reactive-protein levels associated with infection predict short- and long-term outcome after supratentorial intracerebral hemorrhage.

BACKGROUND: The aim of the current study was to assess the occurrence of infection and its impact on the short- and long-term outcome of patients with supratentorial intracerebral hemorrhage (ICH). METHODS: 247 patients suffering from supratentorial ICH were extracted from our local stroke database. Complete data sets including long-term functional outcome measured by the modified Rankin Scale (mRS), and baseline computed tomography data could be obtained in 113. The charts of these patients were screened for the presence and cause of infection, and baseline and maximal C-reactive protein (CRP) levels were recorded. RESULTS: We identified 52 patients (50.5%) with infection during their hospital stay. Patients with infection, had significantly larger hemorrhages (28.7 vs. 11.9 ml; p = 0.002), a poorer admission status (National Institutes of Health Stroke Scale, NIHSS, score 14 vs. 6; p = 0.002) and more frequently intraventricular hemorrhage extension (46.2 vs. 23.5%; p = 0.016) than those without infection. In a multivariate logistic regression model, baseline NIHSS score (odds ratio, OR, 1.2, 95% confidence interval, CI, 1.1-1.31, p < 0.001), age (OR 1.1, 95% CI 1.03-1.16, p = 0.002) and maximal CRP levels (OR 1.72, 95% CI 1.12-2.64, p = 0.013) were independent predictors of poor long-term functional outcome (mRS >2). CONCLUSION: Infections were frequent complications in our cohort of ICH patients and occurred significantly more often in patients with poor functional outcome. Maximal CRP levels were an independent predictor of poor outcome in a multivariate model.

Common RAPD pattern of Pseudomonas aeruginosa from patients and tap water in a medical intensive care unit.

The epidemiology of Pseudomonas aeruginosa infections and colonizations was studied prospectively on a 12-bed medical intensive care unit. Patients were monitored for P. aeruginosa colonization by performing throat swabs or tracheal aspirates on admission and weekly thereafter over a period of 6 months. Cultures of possibly infected sites were taken as clinically indicated. Water samples from all patient care-related tap water outlets were collected in 2-weekly intervals and examined for the presence of P. aeruginosa. Strains isolated from patients and water samples were analysed by serotyping and random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) typing. During the 6-month period, 60 of 143 (42%) water samples contained P. aeruginosa at various levels ranging from 1 to >100 colony-forming units per 100ml sample. Genotypically, water samples contained 8 different clonotypes. Nine patients had infections due to P. aeruginosa and 7 patients were colonized. Isolates from patients showed a similar distribution of genotypes as did tap water isolates, and strains of identical genotype as patient strains had been isolated previously from tap water outlets in 8 out of 16 (50%) infection or colonization episodes. However, patients also harboured strains not previously isolated from tap water. Thus, in addition to tap water, other environmental or unknown reservoirs appeared to play a role for the epidemiology of P. aeruginosa infections on this ward. However, because tap water played a significant role for strain transmissions, we conclude that intensified water site care is justified.

Serum antibody positivity for distinct Helicobacter pylori antigens in benign and malignant gastroduodenal disease.

Infection with Helicobacter pylori may be associated with a variety of gastroduodenal diseases. Although H. pylori infection is common, peptic ulcer disease and gastric cancer occur in only a small minority of infected persons. This work was intended to correlate the pathological findings with the serological response to certain H. pylori antigens. Serum samples were taken from 285 patients who underwent gastroscopy. H. pylori infection was diagnosed by histology, culture or rapid urease test (RUT). Serum IgG reactivity against H. pylori-specific antigens was studied by Western blot. There was a significant association between the diagnosis of gastric cancer and the presence of IgG antibodies against the 19.5, 33 and 136 kDa (CagA) antigens. Comparing all H. pylori-positive patients with the gastric cancer group for the presence of the 19.5, 33 and 136 kDa (CagA) antigens, the results were as follows: chi2: 17.482, p < 0.001, power P = 0.994, odds ratio (OR) for the presence of gastric cancer: 19.5 (95% confidence interval (CI): 4.11-92.56). Antibodies against CagA alone or other bands (except 33 and 19.5 kDa antigens), as well as the age of patients were not related to a diagnosis of gastric cancer. Male patients were more likely to develop duodenal ulcer. IgG antibodies against the 19.5, 33 and 136 kDa (CagA) antigens could be helpful to identify patients at enhanced risk for the development of gastric cancer.

The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism.

BACKGROUND: Aging has been associated with various alterations of immune functions, the musculoskeletal system and a decline of sex hormone levels. Estradiol has a central role in the regulation of bone turnover and also modulates the production of cytokines such as interleukin-1 and -6 and tumor necrosis factor-alpha. We therefore studied the effect of age and gender on cytokine production by mononuclear cells and markers of bone metabolism. METHODS: Peripheral blood mononuclear cells were isolated from young and elderly subjects; intracellular detection of cytokine production after stimulation with ionomycine and PMA (T cells) or LPS (monocytes) was performed by four color flow cytometry. Sex hormone levels and markers of bone metabolism were measured by RIA or ELISA: RESULTS: When we compared elderly to young women we found an increased proportion of T cells that were positive for interferon-gamma, interleukin-2, -4, -10 and -13. Also the percentage of cells producing interleukin-4 or interferon-gamma within the CD8(+) population was higher in the group of elderly women. In contrast, proportionally fewer monocytes of elderly women were positive for tumor necrosis factor-alpha or interleukin-6 than those of young women. In elderly men a higher percentage of T cells produced interleukin-2, -4 and -13. In the group of aged men we found a higher frequency of cells that produced interleukin-4 within the CD4(+) or CD8(+) population. Moreover, within monocytes of elderly men we found an increased percentage of cells positive for both interleukin-1beta and tumor necrosis factor-alpha. The data on markers of bone metabolism indicated an increase of bone turnover in old age. CONCLUSION: Our data demonstrate that aging is associated with significant alterations of bone metabolism and cytokine production by T cells and monocytes. For particular cytokines (interferon-gamma and interleukin-10 in T cells, interleukin-6 and tumor necrosis factor-alpha in monocytes) these changes are gender specific.