An updated model of cell-mediated immunity--listeriosis: clinical and research aspects.

Listeria monocytogenes causes sepsis and meningitis in immunocompromised hosts and a devastating maternal/fetal infection in pregnant women. In recent years a more benign gastroenteritis in normal hosts has been described. Listeria has been increasingly identified as a food-borne pathogen, and large-scale contamination of processed foods with resulting outbreaks has occurred in recent years, possibly as a result of consolidation of the food industry. Experimental listeriosis in mice has proven to be an extraordinarily useful model for analyzing cell-mediated immune host defenses. Contrary to original concepts, we found that neutrophils, not macrophages, are the prime effectors during early infection. CD8+ T cells are then responsible for lysing infected hepatocytes through perforin-related (early primary and secondary infection) or Fas-L/Fas mechanism (late primary). Of interest, non-classical MHC class Ib restricted recognition mechanisms exist early, whereas MHC class Ia mechanisms can be detected throughout infection.     

Geriatrics. An updated bibliography

This is the author's fourth revision of a geriatrics bibliography. Approximately one-third of the previous references have been replaced by more current or more detailed articles. Because the literature pertinent to geriatrics has continued to grow ever more rapidly, it has been necessary to omit many informative articles from the bibliography. Preference is given to recent publications; almost all of the references date from the past four years. Some articles were selected to highlight current controversies or changes in viewpoint. An occasional unreferred article is cited to amplify geriatric aspects of common diseases. Most of the references deal specifically with an elderly patient population, though few use a multidisciplinary approach. Studies of the elderly are confounded by concomitants of aging frequent but not universal in our society: inactivity, obesity, malnutrition, and psychosocial trauma. The articles cited concern primarily medical ailments of the elderly but legal, ethical, and sociologic topics are also covered. The references are divided into categories. The first set deals with some possible causes of aging, the second with physiologic decline accompanying aging, the third with the atypical and nonspecific characteristics of illness among geriatric patients, the fourth with the elderly and society, and the fifth with care options. The remainder of the references are cited by pertinent medical specialty. Within each category, references are divided by disease process. Articles are further subgrouped by aspects of those diseases such as evaluation or therapy.     

Role of sublingual immunotherapy in the treatment of asthma: An updated systematic review

Background

The purpose of the systematic review is to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of allergic asthma.

Methods

PubMed, Embase, and CENTRAL databases were searched, updating an earlier review (January 1, 2005 through May 8, 2017). Randomized, controlled studies (RCTs) were included, which reported one of the prespecified outcomes: asthma symptoms measured by control composite scores; quality of life; medication use; pulmonary physiology; and health‐care utilization. For safety outcomes, RCTs and observational studies were included. Two independent reviewers extracted data, assessed risk of bias, and graded strength of evidence (SOE) for each outcome.

Results

Fourteen RCTs (n = 2585) assessed the efficacy of SLIT for asthma. The RCTs utilized house dust mite (HDM), birch, or grass allergen. SLIT improved asthma symptoms (high SOE), decreased use of long‐term control medication, and improved forced expiratory volume in 1 second (FEV₁) (moderate SOE). SLIT may decrease quick‐relief medication use, and improve disease‐specific quality of life (low SOE). For safety, 20 RCTs and 10 observational studies (n = 3621) were identified. Local (risk differences ranged from ?0.03 to +0.765) and systemic allergic reactions (risk differences ranged from ?0.03 to +0.06) were a common occurrence in SLIT and control groups. Life‐threatening reactions were uncommon, with 3 cases of anaphylaxis and no deaths reported.

Conclusion

There is moderate‐to‐high strength evidence that SLIT improves allergic asthma symptoms, reduces long‐term control medication use, and improves FEV₁ based on studies of HDM, birch, and grass. SLIT rarely is associated with life‐threatening adverse events.

     

Diagnosis of bronchial asthma by clinical evaluation. An unreliable method

To determine the predictive value of wheeze compared to methacholine inhalation challenge (MIC) in diagnosing asthma, we prospectively evaluated 34 patients considered to be difficult diagnostic problems, referred with a history of wheeze. On the basis of MIC results, 12 patients had hyperreactive airways consistent with asthma, while 22 had airways that were no more reactive than those of normal controls. Compared to MIC, a history of wheeze was predictive of hyperreactive airways 35 percent of the time, a prior clinical diagnosis of asthma 62 percent, and scattered monophonic expiratory wheeze 43 percent. We conclude that: (1) a history of wheeze, a prior clinical diagnosis of asthma, and expiratory wheezing on physical examination are much less reliable than MIC in predicting the presence or absence of asthma; (2) these parameters cannot be used as reliable epidemiologic markers for asthma; and (3) the clinical suspicion of asthma should be confirmed by bronchoprovocation challenge or the demonstration by spirometry of reversible expiratory airflow obstruction.     

Role of long-acting beta2-adrenergic agonists in asthma management based on updated asthma guidelines

PURPOSE OF REVIEW: This review examines the role of long-acting beta2-adrenergic agonists in the management of asthma, particularly focusing on recommendations in the newly revised Global Initiative for Asthma (GINA) and National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines. RECENT FINDINGS: GINA guidelines recommend increasing inhaled corticosteroid doses in all children with asthma not controlled on low-dose inhaled corticosteroids before adding a long-acting beta2-adrenergic agonist, whereas NHLBI guidelines have different age-based recommendations for children. In patients younger than 5 years, NHLBI guidelines recommend increasing the inhaled corticosteroid dose before adding a long-acting beta2-adrenergic agonist; in children aged 5-11 years, equal weight is given to increasing the inhaled corticosteroid dose or including add-on therapy to low-dose inhaled corticosteroids. In adults and adolescents aged 12 years and older, GINA recommends adding long-acting beta2-adrenergic agonists to low-dose inhaled corticosteroids over increasing the inhaled corticosteroid dose. NHLBI guidelines give equal weight to these choices, with alternative, although not preferred, therapies including the addition of theophylline, zileuton, or leukotriene receptor antagonists to low-dose inhaled corticosteroids. SUMMARY: In the recently updated GINA and NHLBI asthma guidelines, long-acting beta2-adrenergic agonists are an important class of agents for the management of persistent asthma in patients whose asthma is not well controlled with inhaled corticosteroid monotherapy.     

Encainide—An updated safety profile

The safety of encainide has been evaluated using retrospective analyses of the Bristol-Myers Supraventricular and Ventricular Arrhythmias data base and of the Post-Marketing Adverse Experience Report data and prospective analyses of the Cardiac Arrhythmia Suppression Trial (CAST), the Cardiac Arrhythmia Pilot Study (CAPS), and the Ventricular Tachycardia/Heart Disease and Boston studies. CAST, a randomized, placebo-controlled study in patients with a history of myocardial infarction with asymptomatic or minimally symptomatic ventricular arrhythmias, showed that sudden death or nonfatal cardiac arrest occurred more frequently on encainide (24/418, 5.7%) than on placebo (7/416, 1.7%). The highest sudden death/cardiac arrest rates were found in patients with a left ventricular ejection fraction of less than 0.30, those with a ventricular premature beat count of more than 50/hr and those with a myocardial infarction of more than 90 days. Similar sudden death/cardiac arrest rates were seen in the flecainide-treated group of the study but not in the moricizine-treated group. A retrospective analysis of the data collected from a similar cohort of patients in the Bristol-Myers data base showed a 1-year cumulative incidence of 10.2% in patients with a history of myocardial infarction. A retrospective analysis of mortality data in patients with supraventricular arrhythmias (301 patients) showed this to be slightly lower than in a matched sample of the general U.S. population. The sudden death mortality in the Ventricular Tachycardia/Heart Disease and Boston studies were similar to those reported with other antiarrhythmic agents. Abnormal laboratory findings caused four patients to be discontinued prematurely, but there have been no reported cases of any blood dyscrasias. Thus, there are currently no data showing that patients with symptomatic reentry supraventricular and life-threatening ventricular arrhythmias are at increased risk with encainide therapy. Encainide should be reserved for those patients who are refractory or intolerant to other antiarrhythmic agents. Encainide is not indicated in patients with symptomatic ventricular arrhythmias and structural heart disease. In patients without structural heart disease and symptomatic ventricular arrhythmias, the benefit and risks of encainide therapy should be carefully considered before it is prescribed.     

An Internet survey of asthma treatment.

The aim of this investigation was to study pharmacological treatment in relation to asthma severity among patients visiting an asthma web site on the Internet. The study comprised 650 subjects from 30 countries with self-reported asthma that participated in an Internet based patient survey. The survey was posted on the web site Asthma Information Centre (www.mdnet.de). Moderate or severe night cough or wheezing was reported by 43% and activity limitation by 55% of the asthmatics. Short-acting beta-agonists were used by 67% and inhaled steroids by 59%. The use of short-acting beta-agonists decreased with age, whereas the use of inhaled steroids, long-acting beta-agonists and antileukotrienes was lowest in the youngest (0-20 years) and highest age groups (> 60 years). The use of short-acting beta-agonists increased, and the use of inhaled steroids decreased with the severity of nocturnal symptoms (p < 0.01). Side effects were most often reported for oral beta-agonists (42%) and least often for antileukotrienes (9%). We conclude that despite problems with selection and external validity, an online asthma survey produces results that agree highly with more resource-demanding surveys. We find that many asthmatics have a low level of asthma control, and the survey indicates that underuse of inhaled steroids is one of the reasons why the goals set up in asthma guidelines so far have not been reached.     

Epidemiology of atherosclerosis: An updated overview

Ongoing epidemiologic research continues to provide new Insight Into the muttifactorial etiology of atherosclerosis and coronary artery disease (CAD). Cigarette smoking remains a primary risk factor; low tar and nicotine cigarettes have apparently not contributed to a reduced Incidence of CAD and cardiovascular death. The stepwise risk of increasing levels of diastolic blood pressure to cardiovascular death is well known; however, elevated systolic blood pressure may be a more potent risk factor. The benefits of treating diastolic blood pressure ≥ 115 mm Hg are indisputable; the benefits of treating milder hypertension, Le., diastolic blood pressure between 90 and 114 mm Hg, probably outweigh the risks, but controversy persists. Low-density lipoprotein cholesterol, which comprises approximately 70% of total cholesterol, Is strongly associated with CAD. Studies continue to relate hypercholesterolemia and CAD, showing approximately a 2 % reduction in disease for each 1 % reduction in total cholesterol. The Influences of diabetes mellitus, thrombosis and psychosocial factors in the genesis of CAD are reviewed, as well as the evidence supporting the synergistic hazard presented by risk-factor clusters.High-density lipoprotein cholesterol bears an inverse, protective relation to CAD. Factors affecting high-density lipoprotein levels, e.g., obesity/exercise, cigarette smoking, alcohol consumption and postmenopausal use of estrogen in women, are also reviewed in light of recent findings. Additional investigation is necessary to clarify the benefits and risks associated with the treatment or modification of known risk factors and to identify others.     

Dual-phase response model for bronchial asthma.

The authors have successfully developed an animal model of dual-phase bronchial responses and very high IgG titer by sensitizing Hartley-strain male guinea pigs. Specific airway resistance, which was determined in a two-chamber body plethysmograph, was elevated to sevenfold during immediate response, followed by a late phase response with a smaller but marked elevation in resistance. Furthermore, hematological and histological examinations revealed that the total cell count increased in BAL obtained during both immediate and late bronchial responses as compared to pre-OVA challenges. A significant increase in BAL eosinophils was present only for the late bronchial samples, and this finding was supported by histological examination.     

Bone scintiscanning updated.

Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.     

An updated review on Cryptosporidium and Giardia

Cryptosporidium and Giardia are two of the most commonly occurring enteric protozoans. They are responsible for diarrheal diseases that may lead to nutritional deficiencies and significant morbidity and mortality, especially among children in developing countries and patients who have immune defects. Both are difficult to diagnose with microscopic techniques. This article provides an updated review of the epidemiology, pathogenesis, clinical manifestations, and treatment of Cryptosporidium and Giardia.     

Human monkeypox virus: An updated review

The human monkeypox is an emerging zoonotic orthopoxvirus with a clinical presentation similar to that of smallpox. It is difficult to differentiate monkeypox from other orthopedic infections, and laboratory diagnosis is the primary component of disease identification and monitoring. However, current diagnostics are time-consuming, and new tests are needed for rapid and precise diagnosis. Most cases have been reported in Central Africa; however, an increasing number of cases have been reported in Europe, the United States of America (USA), Australia, and the United Arab Emirates. Although investigation of the current global outbreak is still ongoing, viral transmission seems to have occurred during crowded events in Spain and Belgium. New therapeutics and vaccines are being deployed for the treatment and prevention of monkeypox, and more research on the epidemiology, biology, and ecology of the virus in endemic areas is required to understand and prevent further global outbreaks.     

Multiple symmetric lipomatosis: an updated clinical report

A systematic survey of 19 male patients with multiple symmetric lipomatosis (MSL) gives evidence for newly delineated and clinically relevant features of the disease. Signs and symptoms of a hitherto unrecognized severe peripheral and autonomic neuropathy were observed in all patients. A mediastinal location of lipomatous tissue was identified by computed tomography in five patients, with clinical evidence of a space-occupying syndrome in four of them. A further deep location of lipomatous tissue below the trapezius muscle, independent of the involvement of the overlying subcutaneous adipose tissue, was demonstrated in seven patients. Alcohol-related abnormalities in liver function tests were present in 10 of 19 patients. The disease is characterized by peculiar metabolic abnormalities, such as marked increase in adipose tissue lipoprotein lipase activity, a plasma hyperalphalipoproteinemia and a specific defect of the adrenergic-stimulated lipolysis in lipomatous tissue. Finally, a red blood cell macrocytosis or overt macrocytic anemia and abnormalities in liver function tests were found in MSL patients, related to elevated alcohol intake. An 8-year follow-up of nine MSL patients demonstrated that peripheral neuropathies and space-occupying mediastinal syndromes represent the most incapacitating, sometimes rapidly progressive, complication of MSL.     

Dyspnoea perception during clinical remission of atopic asthma.

Symptoms of atopic asthma often disappear around puberty. The authors recently demonstrated that this clinical remission is accompanied with ongoing airways inflammation in most subjects. The discrepancy between lack of symptoms and persistent airway inflammation suggests that perception of the symptoms is unclear. In the present study, young adults in clinical remission of atopic asthma assigned themselves a modified Borg score during methacholine and adenosine-5'-monophosphate induced bronchoconstriction. Borg scores of subjects in clinical remission were compared with those of symptomatic asthmatic subjects. A marked variation in the Borg scores at a 20% fall in the forced expiratory volume in one second was found. Significant differences in Borg scores between remission patients and asthmatics could not be detected. It was concluded that perception of dyspnoea, induced with methacholine and adenosine challenge, is similar in young adults in clinical remission of atopic asthma compared to that of patients with symptomatic asthma. Hence, an unclear perception seems to be an unlikely explanation for the discrepancy between lack of symptoms and ongoing inflammation. Other factors, including both physical and psychological ones, may play a role in the apparent absence of symptoms, thereby potentially leading to undertreatment.