Muscle-bone interactions during fracture healing.

Although it is generally accepted that the rate and strength of fracture healing is intimately linked to the integrity of surrounding soft tissues, the contribution of muscle has largely been viewed as a vascular supply for oxygen and nutrient exchange. However, more is becoming known about the cellular and paracrine contributions of muscle to the fracture healing process. Research has shown that muscle is capable of supplying osteoprogenitor cells in cases where the periosteum is insufficient, and the muscular osteoprogenitors possess similar osteogenic potential to those derived from the periosteum. Muscle's secrotome includes proteins capable of inhibiting or enhancing osteogenesis and myogenesis following musculoskeletal injury and can be garnered for therapeutic use in patients with traumatic musculoskeletal injuries. In this review, we will highlight the current knowledge on muscle-bone interaction in the context of fracture healing as well as concisely present the current models to study such interactions.

Simple sample processing enhances malaria rapid diagnostic test performance.

Lateral flow immunochromatographic rapid diagnostic tests (RDTs) are the primary form of medical diagnostic used for malaria in underdeveloped nations. Unfortunately, many of these tests do not detect asymptomatic malaria carriers. In order for eradication of the disease to be achieved, this problem must be solved. In this study, we demonstrate enhancement in the performance of six RDT brands when a simple sample-processing step is added to the front of the diagnostic process. Greater than a 4-fold RDT signal enhancement was observed as a result of the sample processing step. This lowered the limit of detection for RDT brands to submicroscopic parasitemias. For the best performing RDTs the limits of detection were found to be as low as 3 parasites per µL. Finally, through individual donor samples, the correlations between donor source, WHO panel detection scores and RDT signal intensities were explored.

Effectiveness of nurse-led services for people with chronic disease in achieving an outcome of continuity of care at the primary-secondary healthcare interface: A quantitative systematic review.

BACKGROUND: Globally, chronic disease is a leading cause of illness, disability and death and an important driver of health system utilization and spending. Continuity of care is a significant component of quality healthcare. However, an association between nurse-led services, interventions, patient outcomes and continuity of care at the primary and secondary interface as an outcome, has not been established for people with chronic disease. OBJECTIVE: To identify the effectiveness of nurse-led services for people with chronic disease in achieving an outcome of continuity of care at the primary-secondary healthcare interface. DESIGN: Quantitative systematic review. DATA SOURCES: Systematic searches of Medline, Cochrane, Embase, Emcare, JBI and Scopus databases were conducted of studies published between 1946 and May 2019 using the search terms "nurse", "continuity of care" and "chronic disease". REVIEW METHODS: Quality of the included studies was assessed using the Cochrane risk of bias tool for randomized controlled trials and Joanna Briggs Institute quality appraisal checklists. A second reviewer screened 10% of full text articles and all articles in critical appraisal. Studies were excluded from the review if they were of poor methodological quality or the description of the effect of the nurse-led service was inadequately reported. RESULTS: Fourteen studies were included in the review (n=4,090 participants). All studies incorporated recognized continuity of care interventions. The nurse-led services were associated with fewer hospitalizations, reduced by 2-8.9% and re-admissions reduced by 14.8-51% (n=886). Reporting of positive patient experiences and improvement in symptoms and lifestyle was also evident. An association of nurse-led services with improved continuity of care between primary and secondary health services as an outcome per se could not be concluded. CONCLUSION: Nurse-led services for adults provide coordinated interventions that support continuity of care for people with chronic disease in both the primary and secondary healthcare settings that are associated with reduced hospitalizations or readmissions and patient satisfaction. However, the limited use of validated continuity of care outcome measurement tools precluded establishing correlations between interventions, patient outcomes and continuity of care as a specific outcome.

Technical note: Digital quantification of eye pigmentation of cattle with white faces.

Cancer of the eye in cattle with white faces occurs less frequently in cattle with pigmented eyelids. Corneoscleral pigmentation is related to eyelid pigmentation and occurrence of lesions that may precede cancer. Objectives of this study were to assess 1) variation in the proportion of eyelid and corneoscleral pigmentation in Hereford, Bos taurus, and Bos indicus crossbreds and 2) the occurrence of lesions with the presence of pigmentation in those areas. Hereford and Bos indicus crosses (Brahman or Nellore with Angus and Hereford and straightbred Brafords) and Bos taurus crosses (Angus-Hereford) were included in the study (n = 1,083). Eyelid pigmentation proportions were estimated by pixel quantification and were evaluated as total proportions and for upper and lower eyelids distinctly for each eye. Fixed effects included breed type, age categories, and sex of the animal. Lesion presence (1) or absence (0) was obtained by visual appraisal of image and was assumed to be binomially distributed. Eyelid pigmentation proportions (overall, upper, and lower eyelids) for Hereford ranged from 0.65 ± 0.03 to 0.68 ± 0.03 and were significantly lower than Bos indicus (range from 0.93 ± 0.02 to 0.95 ± 0.02) or Bos taurus (ranged from 0.88 ± 0.02 to 0.92 ± 0.02) crosses. Corneoscleral pigmentation in Hereford cows (0.17 ± 0.06) did not differ (P = 0.91) from Hereford calves and yearlings (0.16 ± 0.07). Bos indicus and Bos taurus crossbred cows had larger corneoscleral pigmentation (0.38 ± 0.05 and 0.48 ± 0.04 for left eyes and 0.37 ± 0.05 and 0.53 ± 0.04 for right eyes, respectively) than all calves (P < 0.001), and their corneoscleral pigmentations were greater than that of Hereford cows (P < 0.003). Bos indicus and Bos taurus cows had greater proportions of left eye corneoscleral pigmentation (0.38 ± 0.05 and 0.48 ± 0.04, respectively) than Hereford cows (0.17 ± 0.06) and all young animal breed types (P < 0.05). Right eye proportions differed for all cow groups (P < 0.05; 0.53 ± 0.04, 0.37 ± 0.05, and 0.17 ± 0.06). Among calves and yearlings, Hereford had a lower right eye corneoscleral pigmentation proportion (0.16 ± 0.07) than Bos taurus (P = 0.02). The lesion proportion for Hereford (0.08 ± 0.03) was significantly greater than that of either Bos indicus (0.01 ± 0.005) or Bos taurus (0.01 ± 0.003). Crossbreeding with Bos taurus or Bos indicus animals appears to increase eye pigmentation, which may help reduce the occurrence of cancer in eyes of cattle with white faces.

The orthostatic tachycardia syndrome: evaluation of autonomic function and treatment with octreotide and ergot alkaloids.

Orthostatic tachycardia is a poorly understood syndrome in which patients develop dizziness, diaphoresis, or palpitations upon shifting from the supine to the upright posture. The present study was performed to determine whether autonomic neuropathy might be present in these patients, and whether the abnormal hemodynamic response to standing might be the result of failure of reflex vasoconstriction. We measured autonomic function in 9 patients with idiopathic orthostatic tachycardia and 2 patients with orthostatic tachycardia and insulin-dependent diabetes mellitus and compared them to 33 age-matched controls. Although most patients with orthostatic tachycardia had normal vasomotor reflexes and normal surface potential amplitudes, the latency of the autonomic response, a measure of sympathetic nerve conduction velocity, was prolonged in the soles (2.44 +/- 0.08 s in patients with idiopathic orthostatic tachycardia vs. 2.12 +/- 0.04 s in controls; P less than 0.005). In 6 of 9 patients, however, the latencies were within the normal range. Autonomic surface potentials were absent in 1 diabetic patient with orthostatic tachycardia; the latency of the response in the feet was greatly prolonged (2.95 s) in the second patient. We also assessed the response of orthostatic tachycardia patients to octreotide and dihydroergotamine, which are known to have a pressor effect in patients with recognized forms of autonomic neuropathy. These agents, in combination, suppressed orthostatic tachycardia (from 116 +/- 7 to 89 +/- 6 beats/min; P less than 0.001) in patients with this syndrome. In summary, our data indicate that evidence of autonomic dysfunction is present in only a minority of patients with orthostatic tachycardia. Nevertheless, administration of the vasoconstrictor drugs dihydroergotamine and octreotide can prevent the abnormal hemodynamic response to the upright posture shown by patients with this syndrome.

Effects of hospitalists on cost, outcomes, and patient satisfaction in a rural health system.

PURPOSE: Previous studies have examined the effects of hospitalists in urban academic hospitals. We compared the outcomes of patients treated by hospitalists with those of patients treated by internists at a 647-bed rural community hospital. SUBJECTS AND METHODS: The 443 patients in the hospitalists' 10 most common diagnosis-related groups (DRGs) were compared with 1,681 patients in the same DRGs who were cared for by internists in fiscal year 1998. Length of stay, cost of care, patient illness severity, patient satisfaction, 30-day readmission rate, inpatient mortality, discharge status, and resource utilization were compared. RESULTS: The hospitalists' patients had a shorter mean (+/- SD) length of stay (4.1 +/- 3.0 days versus 5.5 +/- 4.9 days, P <0.001) and their cost of care was less than that of the internists' patients ($4,098 +/- $2,455 versus $4,658 +/- $4,084, P <0.001). Analyses that adjusted for patient age, race, sex, insurance status, severity of illness, and specific medical comorbidities confirmed these differences. The differences between hospitalists and internists were most apparent among very ill patients. Mortality rates were similar (4.5% for hospitalists versus 4.9% for internists, P = 0.80), as were the readmission rates (4.5% for hospitalists versus 5.6% for internists, P = 0.41). Patient satisfaction was similar for both groups. The internists used more resources in 8 of 11 categories. CONCLUSIONS: The hospitalists provided cost-effective care, particularly for the sickest patients, with good outcomes and patient satisfaction.

Atrial natriuretic peptide and the development of congestive heart failure in the oldest old: a seven-year prospective study.

BACKGROUND: Atrial natriuretic peptide (ANP) levels are elevated in symptomatic heart failure and correlate with invasively measured left heart pressures. OBJECTIVE: To examine the association between plasma ANP level and the subsequent development of congestive heart failure (CHF) in older subjects with no history of CHF. DESIGN: A 7-year, prospective, blinded, cohort study. SETTING: A life care facility in Boston, Massachusetts. PARTICIPANTS: Two hundred fifty-six frail older subjects (mean age 88 +/- 7) with no history of CHF at study entry. MAIN OUTCOME MEASURE: Clinical episodes of CHF with confirmatory chest roentgenogram findings. Cox proportional hazard analyses were performed to examine the relationship between ANP levels and the development of CHF while controlling for 19 clinical, physical, and laboratory parameters. A Kaplan-Meier estimator (log-rank test) was used to determine if the development of CHF differed by tertile of ANP. RESULTS: During the follow-up period, 32% of the cohort developed CHF. The mean ANP level in the CHF group was 95 pmol/L +/- 11 pmol/L versus 60 pmol/L +/- 5 pmol/L in the no CHF group (two tailed t test P = .005). On multivariate analysis, a high ANP level was found to be associated significantly (P = .01) with the development of CHF. CONCLUSIONS: There is a statistically significant association between ANP level and the subsequent development of CHF in frail older individuals with no history of CHF.

Atrial natriuretic peptide levels in the elderly: differentiating normal aging changes from disease.

BACKGROUND: Atrial natriuretic peptide (ANP) levels increase with advancing age and in patients with cardiac dysfunction. Previous studies have failed to differentiate the elevated ANP levels of normal aging from those of cardiac disease. METHODS: To differentiate the increased ANP levels seen in normal aging from that of disease, fasting supine ANP was measured in healthy young (n = 24), healthy old (n = 90), and clinically stable but cardiovascularly diseased old (n = 269) residents of a life care facility. ANP levels were correlated with physical exam findings, blood chemistries, measures of physical and cognitive function, and medications. RESULTS: ANP levels were almost fourfold higher in the healthy elderly than in the young (11.4 +/- 1.1 (SEM) vs 3 +/- 0.3 pmol/L, p < .01), and two-and-one-half times higher in the cardiovascular-diseased elderly than the healthy elderly (29 +/- 1.9 vs 11.4 +/- 1.1 pmol/L, p < .01). An ANP value of 21 pmol/L has a sensitivity of 83% and specificity of 52% in distinguishing those elders classified as healthy from those classified as having chronic cardiovascular disease. ANP levels had positive univariate correlation with age (even from 70 to 102 years) and systolic blood pressure. ANP rose progressively with increasing numbers of markers of cardiovascular comorbidity. ANP was higher in subjects with jugular venous pressure > 10 cm, presence of a third heart sound, peripheral edema, artificial cardiac pacemaker, atrial arrhythmias, and in those taking digoxin, diuretics, or nitrates. On multivariate analysis independent predictors of ANP levels were, in descending order, nitrates, age, diuretics, and atrial arrhythmias. CONCLUSION: These data suggest that ANP levels greater than 21 pmol/L are associated with cardiovascular comorbidity in a clinically stable elderly cohort.

Are there two types of diabetic foot ulcers?

Neurological function was determined in diabetic patients with peripheral vascular disease and foot ulcers (n = 13). This was compared to that of diabetic patients without foot ulcers with (n = 23) and without (n = 13) symptoms of neuropathy. Diabetic patients with typical neuropathic ulcers (n = 13) and age-matched healthy controls (n = 20) were also studied. The beat-to-beat variation with deep breathing was 6.1 +/- 1.0 beats/min in those with peripheral vascular disease and foot ulcers, less than 50% of that of diabetic patients without foot ulcers (p < 0.01) or normal controls (p < 0.005). Autonomic surface potentials in the soles were greatly diminished or absent in nearly all the patients with peripheral vascular disease and ulcers. Quantitative sensory testing revealed profound abnormalities in small fiber (heat and cold sensation) and large fiber (vibration sensation) function in diabetic patients with peripheral vascular disease and foot ulcers. Our results document the presence of advanced autonomic and somatosensory neuropathy in nearly all diabetic patients with peripheral vascular disease and foot ulcers.

Pharmacokinetics of the acyl coenzyme A:cholesterol acyl transferase inhibitor CP-105,191 in dogs--the effect of food and sesame oil on systemic exposure following oral dosing.

Inhibition of acyl coenzyme A:cholesterol acyl transferase (ACAT) decreases total plasma cholesterol in animals and may be an effective therapy for atherosclerosis in man. The pharmacokinetics of CP-105,191, a potent inhibitor of ACAT, were explored in fed and fasted dogs. Following oral administration of drug, mean apparent plasma half-life ranged from 9 to 16 h. Systemic availability of CP-105,191, as determined by AUC(0-infinity), was approximately 3-4-fold higher in fed dogs than in fasted dogs when 50 mg doses were administered as aqueous suspensions. Tmax was achieved more rapidly and Cmax was lower in fasted dogs. When 50 mg doses, partially dissolved in 20 mL sesame oil, were administered to fed dogs, the availability of CP-105,191 increased by another factor of 2. A 12.5 mg dose of CP-105,191, completely dissolved in sesame oil, was administered to fed and fasted dogs. Plasma AUC's were similar for fed and fasted dogs following the 12.5 mg dose, indicating that the increased availability of drug when administered with food is related to the presence of lipid.

Geriatric depression: physicians' knowledge, perceptions, and diagnostic practices.

An evaluation of physicians' (medical residents) knowledge revealed that whereas they considered detection and treatment of comorbid depression to be important, they knew few of the diagnostic criteria and etiological factors, rarely screened their patients for depression, and viewed current treatments as only marginally efficacious. Implications for graduate training are discussed.

Systemic treatment of cancer in the elderly.

The goal of this review is to provide a readable and exhaustive reference in three major areas of geriatric oncology: complications of chemotherapy and radiotherapy, responsiveness of cancer to systemic treatment, social issues in the care of elderly patients with terminal illnesses. The conclusions of this study are: 1. Progressive deterioration of renal function is the most consistent change of aging. Adjustment of doses of renally excreted drugs to individual creatinine clearance may prevent life-threatening myelotoxicity in the elderly. 2. Intensive chemotherapy regimens (acute leukemia, non Hodgkin's lymphoma) cause more serious and prolonged myelotoxicity in the elderly. Elderly are more susceptible than younger patients to cardiotoxicity and central and peripheral neurotoxicity. Age is a poor predictor of complications in other organs or systems. 3. The prognosis of patients with Hodgkin's disease worsens with aging, possibly due to increased prevalence of mixed cellularity histology. It is controversial whether the prognosis of other neoplasias is poorer. Prognosis is not age-related in multiple myeloma. In general, elderly in good performance status may benefit from systemic cancer treatment to the same extent as younger patients, except for Hodgkin's disease. 4. The Informal Support Network, epitomized by the family, appears the most suitable environment to care for the elderly with cancer.

Brain death: nursing roles and responsibilities.

Nurses working in an intensive care setting must be knowledgeable about the diagnosis of brain death and its ramifications to care competently for the patient and family. The medical community has identified specific physical and diagnostic findings necessary for the determination of brain death. Brain death is an irreversible state, from which recovery has never been reported. The neuroscience nurse's responsibilities include meeting the patient's physical needs and identifying the family's needs and teaching them about brain death. Not fulfilling these responsibilities could result in dysfunctional grieving for the family and loss of a potential organ donor.

Developing a rural primary care practice network.

Establishing and managing a primary care practice in rural communities is particularly challenging. Many rural practices are closing, and relatively few new practices are initiated independently. The integrated health system can provide at least part of the solution to the lack of physicians in the rural setting. The following article describes the objectives, methods, and results of an integrated health system's development of a rural primary care provider network.

Pharmacologic management of depression in the elderly.

Depression, the most common geriatric psychiatric disorder, is a disabling mood disorder that impairs one's well-being and may even threaten a sufferer's life. Severely depressed elderly persons are more likely to kill themselves than individuals in any other age group. However, geriatric depression is, for the most part, a treatable and manageable illness. Antidepressant medication can be very effective in treating major depressive disorder (MDD). Because age-related physical changes in the elderly produce pharmacokinetics that are often different than that experienced by younger adults, different doses are often necessary. This article summarizes recommendations for selecting and initiating appropriate antidepressant therapy in elderly persons suffering from MDD. The benefits and drawbacks of tricyclic antidepressant agents, and other atypical antidepressant agents are discussed. Phases of treatment, drug selection, dosing, and educational tips for pharmacotherapy are presented.

Metal-carbon clusters: the origin of the delayed atomic ion.

Studies of the emission of electrons from excited metal-carbon cluster systems that include the Met-Car (M(8)C(12), where M is Ti, Zr, and V) also have revealed the evolution of a delayed atomic ion. The source of the delayed atomic ion, which involves the emission of ionized atoms on the microsecond time scale, is the focus of this investigation. By studying the delayed ionization of mixed zirconium and titanium carbon complexes produced in a laser vaporization source coupled to a time-of-flight mass spectrometer, for the first time both the zirconium and titanium delayed atomic ions were observed to be emitted in the same experiment. These studies allowed a determination that the source of the delayed atomic ion is an excited metal dicarbide. A plausible mechanism involving the excitation of a high Rydberg state of the metal dicarbide prior to an excited ion pair separation is proposed.

Role of glutamatergic and GABAergic systems in alcoholism.

The pharmacological effects of ethanol are complex and widespread without a well-defined target. Since glutamatergic and GABAergic innervation are both dense and diffuse and account for more than 80% of the neuronal circuitry in the human brain, alterations in glutamatergic and GABAergic function could affect the function of all neurotransmitter systems. Here, we review recent progress in glutamatergic and GABAergic systems with a special focus on their roles in alcohol dependence and alcohol withdrawal-induced seizures. In particular, NMDA-receptors appear to play a central role in alcohol dependence and alcohol-induced neurological disorders. Hence, NMDA receptor antagonists may have multiple functions in treating alcoholism and other addictions and they may become important therapeutics for numerous disorders including epilepsy, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's chorea, anxiety, neurotoxicity, ischemic stroke, and chronic pain. One of the new family of NMDA receptor antagonists, such as DETC-MESO, which regulate the redox site of NMDA receptors, may prove to be the drug of choice for treating alcoholism as well as many neurological diseases.