The effects of local application of 1% dopamine on intraocular pressure and pupillary diameter

This paper deals with the experimental results of the effect of 1% dopamine on intraocular pressure, pupillary diameter and hemodynamic parameters after its local application in the rabbit eye. Our results show that locally applied dopamine caused an initial increase of intraocular pressure (IOP) (1 h), followed by its decrease that was the most pronounced 3 hours later. Mydriasis was an immediate effect of dopamine, which persisted until the end of the second hour. There were no changes in blood pressure and heart rate. Although the exact mechanism of dopamine effect on IOP is not known yet, our results point out that this is mainly due to the decrease fo aqueous humor formation.     

No association between blood count levels and whole-blood cobalt and chromium levels in 1,900 patients with metal-on-metal hip arthroplasty

Background and purpose — The accelerated wear of poorly functioning metal-on-metal (MoM) hip implants may cause elevated whole-blood cobalt (Co) and chromium (Cr) levels. Hematological and endocrinological changes have been described as the most sensitive adverse effects due to Co exposure. We studied whether there is an association between whole-blood Co/Cr levels and leukocyte, hemoglobin, or platelet levels.Patients and methods — We analyzed whole-blood Co and Cr values and complete blood counts (including leukocytes, hemoglobin, platelets) from 1,900 patients with MoM hips. The mean age at the time of whole-blood metal ion measurements was 67 years (SD 10). The mean time from primary surgery to whole-blood metal ion measurement was 8.2 years (SD 3.0). The mean interval between postoperative blood counts and metal ion measurements was 0.2 months (SD 2.7).Results — The median Co value was 1.9 µg/L (0.2–225), Cr 1.6 µg/L (0.2–125), mean leukocyte count 6.7 × 10⁹/L (SD 1.9), hemoglobin value 143 g/L (SD 13), and platelet count 277 × 10⁹/L (SD 70). We did not observe clinically significant correlations between whole-blood Co/Cr and leukocyte, hemoglobin, or platelet counts.Interpretation — Elevated whole-blood Co and Cr values are unlikely to explain abnormal blood counts in patients with MoM hips and the reason for possible abnormal blood counts should be sought elsewhere.

The abnormal wear of poorly functioning MoM implants may cause elevated whole-blood cobalt (Co) and chromium (Cr) levels (Brodner et al. 2003, Cheung et al. 2016). Soft-tissue reactions termed “pseudotumors” related to poorly functioning MoM hip replacements have been widely described (Boardman et al. 2006, Gruber et al. 2007, Pandit et al. 2008). The use of MoM implants has dramatically decreased but due to their previous popularity there are still a large number of patients with MoM hip replacements under follow-up (Silverman et al. 2016).Even though local reactions have been the most discussed, systemic reactions in patients with high-wearing hip implants have been described. Cardiomyopathy, polyneuropathy, hypothyreosis, and polycythemia have been described in some patients with MoM hip implants and in patients with fractured ceramic-on-ceramic implant revised to metal-on-polyethylene, resulting in abrasive wear of the CoCr head by ceramic fragments (Cheung et al. 2016). Systemic adverse events have been linked mostly to Co, and hematological and thyroid effects have been described as the most sensitive responses to Co in humans (Tvermoes et al. 2014). A case report described polycythemia with hemoglobin 190 g/L due to massive abrasive CoCr head wear when a ceramic-on-ceramic implant had been revised to metal-on-polyethylene after fracture of the ceramic liner (Gilbert et al. 2013). Several studies have suggested that blood lymphocyte counts may be affected by implant metals from MoM hip replacements (Hart et al. 2009, Hailer et al. 2011, Penny et al. 2013, Chen et al. 2014, Briggs et al. 2015, Markel et al. 2018). Although thrombocytopenia has not been linked to implant metals, it has been reported that platelets adhere to and are activated by CoCr (Ollivier et al. 2017).Complete blood count including leukocyte count, hemoglobin, and platelets is among the most used blood tests in the world (Horton et al. 2019) and 10–20% of the measurements include abnormal values (Tefferi et al. 2005). Due to wide media attention to MoM hip replacements, patients with MoM hips are sometimes worried whether their abnormal laboratory findings are related to their hip replacement. We sought to find out whether whole-blood metal ion levels are associated with blood count. Our hypothesis was that if Co or Cr affected leukocytes, hemoglobin, or platelets at concentrations noted in our study group, we would observe an upward or downward trend (depending on variable) when blood Co or Cr concentrations are approaching the highest values.     

Repeated cobalt and chromium ion measurements in patients with large-diameter head metal-on-metal ReCap-M2A-Magnum total hip replacement

Background and purpose — Whole blood (WB) cobalt (Co) and chromium (Cr) ion levels have a major role in the follow-up of metal-on-metal total hip replacement (MoM THR). We investigated, first, if there was a change in WB Co or Cr levels over repeated measurements in patients with ReCap-M2A-Magnum THR, and, second, determined how many patients had WB Co or Cr levels that exceeded the safe upper limits (SUL) in the repeated whole blood metal ion assessment.

Patients and methods — A Recap-M2A-Magnum THR was used in 1,329 operations (1,188 patients) at our institution between 2005 and 2012. We identified all patients (n = 319) with unilateral ReCap-M2A-Magnum implants who had undergone at least 2 repeated metal ion measurements with the first blood sample taken mean 5.5 years (1.8–9.3) after surgery and the second taken mean 2 years (0.5–3) after the first.

Results — The median WB Co and Cr ion levels decreased in repeated measurements from 1.40 (0.40–63) ppb to 1.10 (0.20–68) ppb and from 1.60 (0.60–13.0) ppb to 1.10 (0.30–19.0) ppb, respectively. 7% of the Co ion values exceeded SUL at the initial measurement, and 7% at the control measurement. The proportion of Cr ion values exceeding the safe upper limit (SUL) decreased during the measurement interval from 5% to 4%.

Interpretation — Repeated metal ion measurements in unilateral ReCap-M2A-Magnum patients in a mean 2-year time interval did not show any increase. Long-term ion levels are, however, not yet known.     

Oligomodal metamaterials with multifunctional mechanics

Mechanical metamaterials are artificial composites that exhibit a wide range of advanced functionalities such as negative Poisson’s ratio, shape shifting, topological protection, multistability, extreme strength-to-density ratio, and enhanced energy dissipation. In particular, flexible metamaterials often harness zero-energy deformation modes. To date, such flexible metamaterials have a single property, for example, a single shape change, or are pluripotent, that is, they can have many different responses, but typically require complex actuation protocols. Here, we introduce a class of oligomodal metamaterials that encode a few distinct properties that can be selectively controlled under uniaxial compression. To demonstrate this concept, we introduce a combinatorial design space containing various families of metamaterials. These families include monomodal (i.e., with a single zero-energy deformation mode); oligomodal (i.e., with a constant number of zero-energy deformation modes); and plurimodal (i.e., with many zero-energy deformation modes), whose number increases with system size. We then confirm the multifunctional nature of oligomodal metamaterials using both boundary textures and viscoelasticity. In particular, we realize a metamaterial that has a negative (positive) Poisson’s ratio for low (high) compression rate over a finite range of strains. The ability of our oligomodal metamaterials to host multiple mechanical responses within a single structure paves the way toward multifunctional materials and devices.

Flexible metamaterials use carefully designed arrangements of deformable building blocks to achieve unusual and tunable mechanical functionalities (1). Such mechanical responses rely on on-demand deformation pathways that cost a relatively low amount of elastic energy. A useful and widely applicable paradigm for the design of such pathways leverages the limit in which their elastic energy is zero—these pathways then become mechanisms or zero-energy modes. Flexible metamaterials based on such principle are, so far, either monomodal (Fig. 1A) or plurimodal (Fig. 1C). On one hand, monomodal metamaterials feature a single zero-energy mode and a single functionality (2–8), which is typically robust and easy to control with a simple actuation protocol, that is, a protocol that requires a single actuator, for example, uniaxial compression. On the other hand, plurimodal metamaterials feature a large number of zero-energy modes, which increases with system size (9, 10). The presence of these multiple zero modes offers multiple possible functionalities in principle, but they are hard to control in practice; that is, they require complex actuation protocols—protocols that require more than one actuator—for successful execution (9). The challenge we address here is whether it is possible to find a middle ground between monomodal and plurimodal metamaterials. In other words, can we design and create metamaterials that have more than one zero-energy mode, but not a number that grows with system size? For convenience and clarity, we term such metamaterials oligomodal (Fig. 1B). Could oligomodal metamaterials be actuated in a robust fashion with a simple actuation protocol (Fig. 1B)? Could oligomodal metamaterials host distinct mechanical properties within a single structure?Open in a separate windowFig. 1.Oligomodal materials. (A) Monomodal materials have a single zero-energy mode, hence a single property, that can be obtained via a simple actuation protocol. (B) Oligomodal materials have a small but fixed number of zero-energy modes larger than one, hence a few distinct properties, that can be selected with a simple actuation protocol, for example, uniaxial compression. (C) Plurimodal materials have a large number of zero-energy modes that grows with system size, and hence are kinematically able to host a large number of properties, but they often require complex actuation protocols, for example, multiaxial loading.     

Nitric oxide synthesis is decreased in periodontitis

OBJECTIVES: In order to study the possible role of nitric oxide (NO) in the development of periodontitis, we measured the concentration of its stable metabolite nitrite (NO2-) in the saliva of patients with periodontitis and healthy subjects. MATERIALS AND METHODS: We have analysed salivary NO2- concentrations in 25 subjects with rapidly progressive periodontitis (RPP), 25 with adult periodontitis (AP) and in 25 periodontally-healthy persons. The concentrations of NO2- were determined by the Griess reaction in microtitration plates. Periodontal tissue destruction was determined by measuring the attachment level loss using standard methods. RESULTS: Subjects with periodontitis had significantly less NO2- in saliva than healthy subjects. Subjects with RPP had lower NO2- concentrations than those with AP Parotid gland saliva contained less NO2- than sublingual gland or total saliva. CONCLUSIONS: Local NO production is decreased in patients with periodontitis. This effect is more pronounced in those with severe types of disease.     

Medication Management in Frail Older People: Consensus Principles for Clinical Practice,Research, and Education

Frailty is a geriatric condition associated with increased vulnerability to adverse drug events and medication-related harm. Existing clinical practice guidelines rarely provide medication management recommendations specific to frail older people. This report presents international consensus principles, generated by the Optimizing Geriatric Pharmacotherapy through Pharmacoepidemiology Network, related to medication management in frail older people. This consensus comprises 7 principles for clinical practice, 6 principles for research, and 4 principles for education. Principles for clinical practice include (1) perform medication reconciliation and maintain an up-to-date medication list; (2) assess and plan based on individual's capacity to self-manage medications; (3) ensure appropriate prescribing and deprescribing; (4) simplify medication regimens when appropriate to reduce unnecessary burden; (5) be alert to the contribution of medications to geriatric syndromes; (6) regularly review medication regimens to align with changing goals of care; and (7) facilitate multidisciplinary communication among patients, caregivers, and healthcare teams. Principles for research include (1) include frail older people in randomized controlled trials; (2) consider frailty status as an effect modifier; (3) ensure collection and reporting of outcome measures important in frailty; (4) assess impact of frailty on pharmacokinetics and pharmacodynamics; (5) encourage frailty research in under-researched settings; and (6) utilize routinely collected linked health data. Principles for education include (1) provide undergraduate and postgraduate education on frailty; (2) minimize low-value care related to medication management; (3) improve health and medication literacy; and (4) incorporate evidence in relation to frailty into clinical practice guidelines. These principles for clinical practice, research and education highlight different considerations for optimizing medication management in frail older people. These principles can be used in conjunction with existing best practice guidelines to help achieve optimal health outcomes for this vulnerable population. Implementation of the principles will require multidisciplinary collaboration between healthcare professionals, researchers, educators, organizational leaders, and policymakers.     

Actinomycosis--a multidisciplinary approach to a clinical problem

Actinomycosis is caused by microorganisms of the Actinomyces species, found in the oral cavity, gastrointestinal and genital tract. Infection by Actimomyces species mainly causes chronic supurative disease of the oral, cervico-facial, thoracic, and abdominal regions. Clinical manifestations have been described at every level, but the disease is relatively rarely diagnosed. The causative agent is considered to be an opportunistic pathogen associated with infection, trauma, surgical procedures, or associated with a neoplasm or foreign body. Symptoms include intermittent fever, weight loss, abdominal or thoracic pain, pseudotumor and tumor masses, and local symptoms from the infected area. Pseudotumor and tumor masses are diagnosed by ultrasonography and computerized tomography. The diagnosis is confirmed by the presence of a causative agent in biopsy or surgically acquired samples. The treatment includes the administration of high doses of antibiotics (penicillin, amoxicillin, ceftriaxone) for at least 6-12 months, as well as surgical treatment. Penicillin is a drug of choice. This infection is often polymicrobial, so that antibiotic therapy should include agents that act against the associated pathogens. Treatment outcome and prognosis in these three cases were excellent, despite the prolonged course of the extensive disease.