Symptoms of respiratory tract infection and associated care-seeking in subjects with and without obstructive lung disease; The Tromso Study: Tromso 6

ABSTRACT: BACKGROUND: Respiratory tract infections (RTIs) may be more severe in those with asthma or COPD and these patients are more frequently in need of health care. The aim of the study was to describe the frequency of RTI symptoms in a general adult population and how care-seeking is associated with the presence of obstructive lung disease. METHODS: Cross-sectional data including spirometry and self-reported chronic diseases were collected among middle-aged and elderly subjects in the Tromso population survey (Tromso 6). Self- reported RTI symptoms, consultations and antibiotic use were the main outcome variables. Possible predictors of RTI symptoms were evaluated by multivariable logistic regression. RESULTS: Of the 6414 subjects included, 798 (12.4 %) reported RTI symptoms in the previous week. RTI symptoms were reported less frequently by subjects aged 75 years or above, than by those younger than 55 years (OR 0.5). Winter season (OR 1.28), current smoking (OR 1.60), low self-rated health (OR 1.26) and moderate to severe bronchial obstruction (OR 1.51), were also statistically significant independent predictors of RTI symptoms, but these variables did not predict RTI symptoms that had started within the previous seven days. Among subjects with RTI symptoms, 5.1 % also reported a consultation with a doctor. In those with bronchial obstruction by spirometry, who did not report asthma or COPD, this frequency was 2.4 %. Antibiotic treatment was reported by 7.4 % of the participants, among whom one third had consulted a doctor. Antibiotics were taken more frequently when asthma or COPD was reported (13.7 %), but not in subjects with bronchial obstruction who did not report these diseases (7.2 %). CONCLUSIONS: RTI symptoms seldom led to consultation with a doctor and not even in subjects with obstructive lung disease. This was in particular the case in subject who did not know about their obstructive lung disease. Strategies for early diagnosis of COPD and providing health care to subjects with such disease cannot rely on their doctor visits due to respiratory symptoms.     

Investigation of the Effect of Deprivation on the Burden and Management of Venous Leg Ulcers: A Cohort Study Using the THIN Database

Background

There has been limited examination of the contribution of socio-economic factors to the development of leg ulcers, despite the social patterning of many underlying risk factors. No previous studies were found that examined social patterns in the quality of treatment received by patients with leg ulcers.

Methods

Using The Health Improvement Network (THIN) database we identified a cohort of over 14000 patients with a diagnosis of venous leg ulceration, prospectively recorded between the years 2001 and 2006, with linked area-level socio-economic information (Townsend deprivation quintile). We assessed socio-economic differences in the incidence and prevalence of leg ulcers using negative binomial regression. Socio-economic differences in two key areas of guideline recommended leg ulcer management, arterial Doppler assessment and compression bandaging, were assessed using multilevel regression.

Results

The risk of incident venous leg ulceration increased for patients living in areas of higher deprivation, even after adjustment for known risk factors age and gender. Overall reported rates of Doppler assessment and provision of compression therapy were low, with less than sixteen per cent of patients having a database record of receiving these recommended diagnostic and treatment options. Patients diagnosed with incident venous leg ulcers living in the most deprived areas were less likely to receive the recommended Doppler-aided assessment for peripheral vascular disease than patients living in the least deprived areas (odds ratio 0.43, 95% confidence interval 0.24–0.78). Documented provision of compression therapy did not vary with deprivation.

Conclusions

A socio-economic gradient in venous leg ulcer disease was observed. The overall rates of people with venous leg ulcers who were documented as receiving guideline recommended care (2001–2006) were low. Reported use of Doppler ultrasound assessment was negatively associated with socio-economic status. These findings suggest that the inequalities experienced by leg ulcer patients may be exacerbated by reduced access to guideline-based management.     

Chloroquine use improves dengue-related symptoms

Dengue is the most important arboviral disease in the world. As chloroquine, an antimalarial agent, has shown some antiviral effects, this study evaluated its effect in patients with dengue. A randomised, double-blind study was performed by administering chloroquine or placebo for three days to 129 patients with dengue-related symptoms. Of these patients, 37 were confirmed as having dengue and completed the study; in total, 19 dengue patients received chloroquine and 18 received placebo. There was no significant difference in the duration of the disease or the degree and days of fever. However, 12 patients (63%) with confirmed dengue reported a substantial decrease in pain intensity and a great improvement in their ability to perform daily activities (p = 0.0004) while on the medication and the symptoms returned immediately after these patients stopped taking the medication. The same effect was not observed in patients with diseases other than dengue. Therefore, this study shows that patients with dengue treated with chloroquine had an improvement in their quality of life and were able to resume their daily activities. However, as chloroquine did not alter the duration of the disease or the intensity and days of fever, further studies are necessary to confirm the clinical effects and to assess the side effects of chloroquine in dengue patients.     

Meta-analysis of efficacy of quinine for treatment of nocturnal leg cramps in elderly people.

OBJECTIVE--To assess quantitatively the efficacy of quinine (as quinine sulphate) compared with placebo in the treatment of nocturnal leg cramps. DESIGN--A meta-analysis of six randomised, double blind, crossover trials. SETTING--Randomised trials that were available as of April 1994. SUBJECTS--A total of 107 general ambulatory patients who suffered from regular nocturnal leg cramps from six clinical trials. RESULTS--Data from individual patients were used to calculate point estimates and 95% confidence intervals for each of the outcome measures reported by these studies. Treatment with quinine resulted in a significant reduction in the number of cramps for a four week period compared with placebo (8.83 fewer cramps; 95% confidence interval 4.16 to 13.49). Treatment with quinine reduced the number of nights with cramps by 27.4% (24.0% to 30.8%) compared with placebo. Treatment did not produce a significant change in the severity or duration of individual nocturnal leg cramps. Side effects were uncommon. CONCLUSIONS--The results indicate that quinine can prevent nocturnal leg cramps in general ambulatory populations. Given the possible serious side effects of treatment with quinine, the benefits and risks in patients taking this drug should be closely monitored.     

E1Lymphocytopenia in pseudo-lupus-erythmetaosus syndrome]

Seven female patients with pseudo-lupus erythematosus (LE)-syndrome had markedly reduced lymphocyte counts in their peripheral blood during the active phase of the disease. One patient, we were able to study during the active phase of her disease, had a diminuation of spontaneous rosettes-forming (T-)lymphocytes, using neuraminidase-treated sheep red blood cells for the test. In this case the percentage of surface-immunoglobulin-bearing (B-)lymphocytes determined by an indirect immunofluorescence technique was augmented. In comparison with 20 normal controls 6 other patients did not show any alterations in the relation of B- and T-lymphocytes in the peripheral blood. 5 patients had circulating lymphocytotoxic antibodies in their serum. A specificity of these antibodies for T-lymphocytes could not be realized.     

Factors Contributing to the Delay in Diagnosis and Continued Transmission of Leprosy in Brazil – An Explorative,Quantitative, Questionnaire Based Study

BackgroundLeprosy is a leading cause of preventable disability worldwide. Delay in diagnosis of patients augments the transmission of infection, and allows progression of disease and more severe disability. Delays in diagnosis greater than ten years have been reported in Brazil. To reduce this delay, it is important to identify factors that hinder patients from presenting to doctors, and those that delay doctors from diagnosing patients once they have presented. This study aimed to explore factors associated with the delayed diagnosis of leprosy in Brazil.

Methodology/ Principal Findings

This is an exploratory study using a self-constructed questionnaire delivered to patients attending three leprosy referral clinics across three states in Brazil. Data were analysed to determine associations between variables and the time taken for participants to present to the health-service, and between variables and the time taken for doctors to diagnose participants once they had presented. Participants who suspected they had leprosy but feared community isolation were 10 times more likely to wait longer before consulting a doctor for their symptoms (OR 10.37, 95% CI 2.18–49.45, p = 0.003). Participants who thought their symptoms were not serious had a threefold greater chance of waiting longer before consulting than those who did (OR 3.114, 95% CI 1.235–7.856, p = 0.016). Forty-two point six per cent of participants reported initially receiving a diagnosis besides leprosy. These had a three times greater chance of receiving a later diagnosis of leprosy compared to those not misdiagnosed or not given a diagnosis (OR 2.867, 95% CI 1.288–6.384, p = 0.010).

Conclusions/ Significance

This study implies a need for patient education regarding leprosy symptoms and the reduction of stigma to encourage patients to present. The high rate of misdiagnosis reported suggests a need to increase clinician suspicion of leprosy. Further education regarding disease symptoms in medical school curriculums may be advisable.     

Merocyanine 540 recognizes membrane abnormalities of erythrocytes in chronic myelogenous leukemia

Merocyanine 540 is a fluorescent dye which stains erythrocytes that have lost their normal membrane phospholipid asymmetry. Because erythrocytes from patients with chronic myelogenous leukemia have been reported to display this abnormal phenotype, peripheral blood erythrocytes from such patients were examined for their ability to stain with the dye. Erythrocytes from all patients with active disease states stained, whereas neither erythrocytes from normal, healthy individuals nor from a patient whose disease symptoms were eliminated by chemotherapy stained. These results suggest that merocyanine 540 may have utility in the clinical evaluation of chronic myelogenous leukemia.     

Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome

Previous investigations have allowed for stratification of patients with postural tachycardia syndrome (POTS) on the basis of peripheral blood flow. One such subset, comprising "normal-flow POTS" patients, is characterized by normal peripheral resistance and blood volume in the supine position but thoracic hypovolemia and splanchnic blood pooling in the upright position. We studied 32 consecutive 14- to 22-yr-old POTS patients comprising 13 with low-flow POTS, 14 with normal-flow POTS, and 5 with high-flow POTS and 12 comparably aged healthy volunteers. We measured changes in impedance plethysmographic (IPG) indexes of blood volume and blood flow within thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations in the supine posture and during incremental tilt to 20 degrees, 35 degrees, and 70 degrees. We validated IPG measures of thoracic and splanchnic blood flow against indocyanine green dye-dilution measurements. We validated IPG leg blood flow against venous occlusion plethysmography. Control subjects developed progressive vasoconstriction with incremental tilt. Splanchnic blood flow was increased in the supine position in normal-flow POTS, despite marked peripheral vasoconstriction, and did not change during incremental tilt, producing progressive splanchnic hypervolemia. Absolute hypovolemia was present in low-flow POTS, all supine flows and volumes were reduced, there was no vasoconstriction with tilt in all segments, and segmental volumes tended to increase uniformly throughout tilt. Lower body (pelvic and leg) flows were increased in high-flow POTS at all angles, with consequent lower body hypervolemia during tilt. Our main finding is selective and maintained orthostatic splanchnic vasodilation in normal-flow POTS, despite marked peripheral vasoconstriction in these same patients. Local splanchnic vasoregulatory factors may counteract vasoconstriction and venoconstriction in these patients. Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels.     

Familial thrombosis: inherited deficiency of antithrombin III.

Several members of a family living on the west coast of Scotland and on one of the islands off the coast had serious thrombotic disease. The plasma antithrombin III (ATIII) concentrations were measured by both functional and immunological assay in all available members of the family. Concentrations were 25% to 66% of normal in 12 people, including all seven with thrombotic disease. The inheritance pattern was characteristic of an autosomal dominant disorder. Thrombotic disease generally affected the leg, mesenteric, and axillary veins, although one man who had died before the study began had had severe arterial atheroma. In women the first thrombotic symptoms usually occurred during pregnancy. None of these patients have developed thrombotic symptoms until they were at least 18, so four younger members of the family who have ATIII deficiency but no thrombotic disease may eventually develop symptoms.     

Motor Neuron Disease in the Rocky Mountain Region

We saw 166 patients with motor neuron disease over a ten-year period, 116 with amyotrophic lateral sclerosis–111 sporadic and 5 familial–and 50 with progressive muscular atrophy. The age at onset varied widely, with the youngest mean onset occurring in the familial group. The most common presenting symptoms were leg or arm weakness and difficulty speaking or swallowing; fewer patients reported cramping, fasciculation, or fatigue. Mean survival time was less in familial cases, women, older patients, and in those with difficulty speaking and swallowing. A total of 50% of all patients were alive after four years; 13% were alive after ten years. Previous reports on the natural history of motor neuron disease may be overly pessimistic in suggesting that survival time rarely exceeds two years.     

Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2).

We undertook clinical evaluation (32 cases) and molecular evaluation (31 cases) of unrelated patients affected with Smith-Magenis syndrome (SMS) associated with an interstitial deletion of band p11.2 of chromosome 17. Patients were evaluated both clinically and electrophysiologically for peripheral neuropathy, since markers showing close linkage to one form of Charcot-Marie-Tooth disease (CMT1A) map to this chromosomal region. The common clinical findings were broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, and hoarse, deep voice. Fifty-five percent of the patients showed clinical signs (e.g., decreased or absent deep tendon reflexes, pes planus or pes cavus, decreased sensitivity to pain, and decreased leg muscle mass) suggestive of peripheral neuropathy. However, unlike patients with CMT1A, these patients demonstrated normal nerve conduction velocities. Self-destructive behaviors, primarily onychotillomania and polyembolokoilamania, were observed in 67% of the patients, and significant symptoms of sleep disturbance were observed in 62%. The absence of REM sleep was demonstrated by polysomnography in two patients. Southern analysis indicated that most patients were deleted for five 17p11.2 markers--FG1 (D17S446), 1516 (D17S258), pYNM67-R5 (D17S29), pA10-41 (D17S71), and pS6.1-HB2 (D17S445)--thus defining a region which appears to be critical to SMS. The deletion was determined to be of paternal origin in nine patients and of maternal origin in six patients. The apparent random parental origin of deletion documented in 15 patients suggests that genomic imprinting does not play a role in the expression of the SMS clinical phenotype. Our findings suggest that SMS is likely a contiguous-gene deletion syndrome which comprises characteristic clinical features, developmental delay, clinical signs of peripheral neuropathy, abnormal sleep function, and specific behavioral anomalies.     

Exercise testing and training in patients with peripheral vascular disease and lower extremity amputation.

Patients with peripheral vascular disease have a high risk of coronary artery disease. The risk is even greater when the peripheral vascular disease leads to lower extremity amputation. Exercise testing using lower extremity exercise has been the "gold standard" for screening for coronary artery disease, but many patients with peripheral vascular disease and those with amputations have difficulty doing this type of exercise. Arm exercise ergometry has been shown to be a safe and effective alternative for the detection of coronary artery disease in patients who cannot do leg exercise. This test has also been used to determine safe exercise levels and may be able to predict the ultimate level of prosthetic use in amputees. Exercise training with arm ergometry also improves cardiovascular efficiency and upper body strength in poorly conditioned patients. Studies are needed to appreciate fully the role of exercise testing and training in the recovery of these patients after amputation.     

Prediction of restenosis based on hemodynamical markers in revascularized femoro-popliteal arteries during leg flexion

Endovascular therapy in patients suffering from peripheral arterial disease shows high rates of restenosis. The poor clinical outcomes are commonly explained by the demanding mechanical environment due to leg movements, but the mechanisms responsible for restenosis remain unknown. In this study, we hypothesized that restenosis following revascularization is associated with hemodynamical markers derived from blood flow during leg flexion. Therefore, we performed personalized computational fluid dynamics (CFD) analyses of 20 patients, who underwent routine endovascular femoro-popliteal interventions. The CFD analyses were conducted using 3D models of the arterial geometry in straight and flexed positions, which were reconstructed from 2D angiographic images. Based on restenosis rates reported at 6-month follow-up, logistic regression analyses were performed to predict restenosis from hemodynamical parameters. Results showed that severe arterial deformations, such as kinking, induced by leg flexion in stented arteries led to adverse hemodynamic conditions that may trigger restenosis. A logistic regression analysis based solely on hemodynamical markers had an accuracy of 75%, which showed that flow parameters are sufficient to predict restenosis (p = 0.031). However, better predictions were achieved by adding the treatment method in the model. This suggests that a more accurate image acquisition technique is required to capture the localized modifications of blood flow following intervention, especially around the stented artery. This approach, based on the immediate postoperative configuration of the artery, has the potential to identify patients at increased risk of restenosis. Based on this information, clinicians could take preventive measures and more closely follow these patients to avoid complications.

     

Pathogenicity ofAeromonas hydrophila in red leg disease in frogs

Endotoxin and hemolysin fromAeromonas hydrophila A₃ were studied to understand the pathogenicity of the organism. Neither the endotoxin nor the hemolysin alone produced typical red leg disease symptoms or death in frogs, even at a very high dosage of 8,000 μg; however, endotoxin and hemolysin together did. Further, histamine-stressed frogs died from hemolysin but not endotoxin. Hemolytic activity of hemolysin increased in cells that were preincubated with endotoxin. Results point to the conclusion that red leg disease in frogs represents a complex interaction between endotoxin and hemolysin and that stress-producing factors other than the endotoxin might trigger disease production.     

Is the postphlebitic leg always postphlebitic? Relation between phlebographic appearances of deep-vein thrombosis and late sequelae.

One hundred and thirty legs of 67 patients were examined 5-10 years after the patient had suffered a phlebographically proved deep-vein thrombosis. Forty-seven of the limbs were normal at the time of the phlebogram, 83 contained thrombus. There was little correlation between the phlebographic severity of the thrombus and the late symptoms and signs: 32% of the legs with no thrombosis had symptoms, while 33% of the legs which had suffered severe thrombosis had no symptoms. Postphlebitic symptoms were more common in legs with aging thrombus at the time of phlebography, but upper limit of the thrombus, the age of the patient, and preexisting symptoms did not affect the incidence of late sequelae. The development of a "postphlebitic leg" does not depend solely on the extent of the initial thrombosis and can apparently develop in the absence of thrombosis.     

Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease.

Patients with peripheral arterial disease (PAD) have abnormalities of carnitine metabolism that may contribute to their functional impairment. To test the hypothesis that muscle acylcarnitine generation (intermediates in oxidative metabolism) in patients with PAD provides a marker of the muscle dysfunction, 10 patients with unilateral PAD and 6 age-matched control subjects were studied at rest, and the patients were studied during exercise. At rest, biopsies of the gastrocnemius muscle in the patients' nonsymptomatic leg revealed a normal carnitine pool and lactate content compared with control subjects. In contrast, the patients' diseased leg had higher contents of lactate and long-chain acylcarnitines than controls. The muscle short-chain acylcarnitine content in the patients' diseased leg at rest was inversely correlated with peak exercise performance (r = -0.75, P less than 0.05). With graded treadmill exercise, only patients who exceeded their individual lactate threshold had an increase in muscle short-chain acylcarnitine content in the nonsymptomatic leg, which was identical to the muscle carnitine response in normal subjects. In the patients' diseased leg, muscle short-chain acylcarnitine content increased with exercise from 440 +/- 130 to 900 +/- 200 (SE) nmol/g (P less than 0.05). In contrast to the nonsymptomatic leg, there was no increase in muscle lactate content in the diseased leg with exercise, and the change in muscle carnitine metabolism was correlated with exercise duration (r = 0.82, P less than 0.01) and not with the lactate threshold. We conclude that energy metabolism in ischemic muscle of patients with PAD is characterized by the accumulation of acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis and reconstruction of the human temporomandibular joint after trauma or internal derangement

This study reviewed the standardized records of 1100 patients with the symptoms of temporomandibular joint syndrome. Of these patients, only 4.5 percent required surgical intervention. The remaining patients were found to have masticatory muscle spasm and were treated by conservative dental methods. Over half the surgical patients had significant macrotrauma to the jaws in their past history. In addition, electromyographic measurement of the masseteric silent period duration in these patients did not reveal muscle spasm. These factors further serve to differentiate the surgical patient from the patient with myofascial pain dysfunction. The patients selected for surgery demonstrated moderate to severe joint disease and required arthroplasty with partial meniscectomy. A surgical technique is presented demonstrating the reconstruction of the meniscus with silicone implant. This same surgical technique is studied in 10 monkeys, and their joints are examined histologically. The results of surgery reveal that 87 percent of the patients reported improvement 1 year after surgery. In all patients complaining of temporomandibular joint clicking or crepitus, surgery produced complete alleviation of these symptoms. The results of surgery were also associated with a 62 percent increase of jaw opening. Histologic evaluation of the human meniscal resections revealed that in addition to an anatomic displacement of the meniscus, there are also significant cellular changes. These changes consisted of calcification, a decrease in cellularity, hyperemia, and a decrease in elastin content.     

Leg vasoconstriction during head-up tilt in patients with autonomic failure is not abolished

Maintaining blood pressure during orthostatic challenges is primarily achieved by baroreceptor-mediated activation of the sympathetic nervous system, which can be divided into preganglionic and postganglionic parts. Despite their preganglionic autonomic failure, spinal cord-injured individuals demonstrate a preserved peripheral vasoconstriction during orthostatic challenges. Whether this also applies to patients with postganglionic autonomic failure is unknown. Therefore, we assessed leg vasoconstriction during 60° head-up tilt in five patients with pure autonomic failure (PAF) and two patients with autonomic failure due to dopamine-β-hydroxylase (DBH) deficiency. Ten healthy subjects served as controls. Leg blood flow was measured using duplex ultrasound in the right superficial femoral artery. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. DBH-deficient patients were tested off and on the norepinephrine pro-drug l-threo-dihydroxyphenylserine (l-DOPS). During 60° head-up tilt, leg vascular resistance increased significantly in PAF patients [0.40 ± 0.38 (+30%) mmHg·ml(-1)·min(-1)]. The increase in leg vascular resistance was not significantly different from controls [0.88 ± 1.04 (+72%) mmHg·ml(-1)·min(-1)]. In DBH-deficient patients, leg vascular resistance increased by 0.49 ± 0.01 (+153%) and 1.52 ± 1.47 (+234%) mmHg·ml(-1)·min(-1) off and on l-DOPS, respectively. Despite the increase in leg vascular resistance, orthostatic hypotension was present in PAF and DBH-deficient patients. Our results demonstrate that leg vasoconstriction during orthostatic challenges in patients with PAF or DBH deficiency is not abolished. This indicates that the sympathetic nervous system is not the sole or pivotal mechanism inducing leg vasoconstriction during orthostatic challenges. Additional vasoconstrictor mechanisms may compensate for the loss in sympathetic nervous system control.     

How well do older persons tolerate moderate altitude?

We studied the physiologic and clinical responses to moderate altitude in 97 older men and women (aged 59 to 83 years) over 5 days in Vail, Colorado, at an elevation of 2,500 m (8,200 ft). The incidence of acute mountain sickness was 16%, which is slightly lower than that reported for younger persons. The occurrence of symptoms of acute mountain sickness did not parallel arterial oxygen saturation or spirometric or blood pressure measurements. Chronic diseases were present in percentages typical for ambulatory elderly persons: 19 (20%) had coronary artery disease, 33 (34%) had hypertension, and 9 (9%) had lung disease. Despite this, no adverse signs or symptoms occurred in our subjects during their stay at this altitude. Our findings suggest that persons with preexisting, generally asymptomatic, cardiovascular or pulmonary disease can safely visit moderate altitudes.