Effectiveness and safety of newgeneration antihistamines in allergenic rhinitis and urticaria

Allergic diseases are on the increase, affecting 30-40% of the population. Histamine remains the most important mediator of clinical reactions in allergic diseases such as rhinitis, urticaria, and food and drug allergies. The need for more effective and safe antihistamines is critical and intensive drug development has become more demanding and competitive. Although the old “first generation” antihistamines were effective, major limitations included their strong potential for sedation and their anti-cholinergic side effects. Not only could patients not function well in their normal daily activities, but these medications posed an important risk for safety, particularly for motor vehicle drivers and machine and precision instrument operators. Unacceptable side effects were a particular problem in the elderly. In May 2001, CONGA, an international consensus group, convened to formulate guidelines for the development of new antihistamines. Several important areas were reviewed and a document of recommendations was published, focusing specifically on the safety and efficacy aspects of antihistamines. South African Family Practice Vol. 47(7) 2005: 24-2

Editorial: Latex allergy- time to adopt a powder-free policy nationwide

No Abstrac

Socio-epidemiological aspects of respiratory allergic diseases in Southern Africa

The prevalence of respiratory allergic diseases has been increasing in Southern Africa both in urban and in rural environments. Various factors may contribute toward this situation, namely, exposure to aeroallergens, such as grass pollens and house dust mites. However, other irritant environmental triggers, such as exposure to tobacco smoke and certain indoor and outdoor fumes, may also play a relevant part. Furthermore, certain parasitic and mycobacterial infections may act as allergic disease risk modifiers, although such an influence should be confirmed. Finally, certain cultural and socioeconomic factors may also influence accessibility to healthcare and adherence to treatment of these diseases

Allergenicity and crossreactivity of buffalo grass (Stenotaphrum secundatum)

Background. In the subtropical climate of South Africa, grasses of the subfamily Panicoideae are predominant. Bermuda grass has previously been shown to be an important local allergen, and immunoglobulin E (IgE) epitopes of Bermuda grass extracts are known to be distinct from those of the Pooid pollen extracts. Following our demonstration of sensitivity in 43% of patients grass-allergic to the Panicoid, Kikuyu grass, we have studied the closely related buffalo grass, Stenotaphrurn secundaturn, indigenous to the Western Cape region, the east coast of Africa and the oceanic islands such as Mauritius; and Eragrostis, another common indigenous grass with a wide distribution.Objective. To partially characterise the allergens of buffalo pollen, and examine its immunological relationships with local common grasses such as Eragrostis and Kikuyu.Methods. Grass-allergic patients were evaluated clinically, and skin prick tests (SPTs) and radio-allergosorbent tests (RASTs) to Bermuda and grass mix were performed. Sera of timothy grass-sensitive patients from Belgium were also included in this study. Pollen extract from buffalo grass was characterised by specific IgE binding by means of immunoblotting and enzyme-linked immunosorbent assay (ELISA). Crossreactivity between the grasses was studied by means of inhibition of IgE binding.Results. More than 90% of grass-sensitive patients were found to have IgE antibodies to Buffalo and Eragrostis pollen. Inhibition of ELISA and immunoblots revealed that extracts of these grass pollens could significant inhibit IgE binding to the local grass pollens, Kikuyu, buffalo, Eragrostis and Bermuda on solid phase, but 100% inhibition was never achieved, indicating that cross-reactive but also unique epitopes are present. We also identified a subset of patients with negative RASTs to Bermuda, and minimal inhibition by Bermuda pollen extract.Conclusion. Buffalo and Eragrostis are important aeroallergens in the Cape, dispersed during the long dry, windy summer. Our data suggest that the local grasses are major  sensitisers, and that South African diagnostic panels should include extracts of buffalo and Eragrostis grasses

Complement component C6 deficiency and susceptibility to Neisseria Meningitidis infection

Meningococcal disease remains one of the most serious bacterial infections in both Western and developing countries. Despite recent advances in treatment the mortality rate remains at about 12%.1 There is a group of South Africans who are particularly vulnerable to this disease. They are individuals with genetically determined deficiencies of individual terminal complement proteins, in particular of the sixth component of complement (C6).2 The human complement system forms part of the humeral immune system and consists of a series of proteins.3 The interaction of antigen (such as components of bacterial outer membranes) and antibody leads to activation of the first component C1q, and consequent activation of part or all of the complement cascade. This has a number of biological effects including the formation on the membrane of the membrane attack complex (MAC) from components C5b, C6, C7, C8 and C9. The MAC is able to mediate lysis of some mammalian cells such as red blood cells, as well as lysis of bacteria and certain viruses. This action of complement has been recognised for many years as playing a major role in defence against infection.4 In addition, MAC action is often sublytic on nucleated host cells, and this interaction can sometimes stimulate cellular biosynthesis and act in a pro-inflammatory manner.5 Many other complement proteins, and products of complement activation, also interact with the cellular immune system and the inflammatory system. If activation is caused by pathological processes such as ischaemia, complement can be an important contributor to host tissue necrosis.6 The effects of complement activation are very complex and can be detrimental as well as beneficial

Socio-epidemiological Aspects of Respiratory Allergic Diseases in Southern Africa

The prevalence of respiratory allergic diseases has been increasing in Southern Africa both in urban and in rural environments. Various factors may contribute toward this situation, namely, exposure to aeroallergens, such as grass pollens and house dust mites. However, other irritant environmental triggers, such as exposure to tobacco smoke and certain indoor and outdoor fumes, may also play a relevant part. Furthermore, certain parasitic and mycobacterial infections may act as allergic disease risk modifiers, although such an influence should be confirmed. Finally, certain cultural and socioeconomic factors may also influence accessibility to healthcare and adherence to treatment of these diseases

Quantifying microsatellite mutation rates from intestinal stem cell dynamics in Msh2-deficient murine epithelium

Microsatellite sequences have an enhanced susceptibility to mutation and can act as sentinels indicating elevated mutation rates and increased risk of cancer. The probability of mutant fixation within the intestinal epithelium is dictated by a combination of stem cell dynamics and mutation rate. Here we exploit this relationship to infer microsatellite mutation rates. First a sensitive, multiplexed and quantitative method for detecting somatic changes in microsatellite length was developed that allowed the parallel detection of mutant [CA]n sequences from hundreds of low-input tissue samples at up to 14 loci. The method was applied to colonic crypts in Mus musculus and enabled detection of mutant subclones down to 20% of the cellularity of the crypt (around 50 of 250 cells). By quantifying age-related increases in clone frequencies for multiple loci, microsatellite mutation rates in wild-type and Msh2- deficient epithelium were established. An average 388-fold increase in mutation per mitosis rate was observed in Msh2-deficient epithelium (2.4 x10-2) compared to wild- type epithelium (6.2 x10-5)

The Mississippian Section at Paddys Bluff, Crittenden County, Kentucky

Paddys Bluff (Figs. 1-3) is located on the south side of the Illinois Basin on the Cumberland River, 1.7 miles downstream from Dycusburg in Crittenden County, Ky., in Carter coordinate section 23-I-16 and ecoregion 71f of the Western Highland Rim of Kentucky (Woods and others, 2002). This bluff is on a right-descending bend 18 liver miles above its junction with the Ohio River at Smithland, Livingston County. The bluff (Figs. 4A, B) is locally famous as the location for a scene from the classic 1962 film, How the West Was Won,\u27 a winner of three Academy Awards, starling James Stewart, John Wayne, and others. We observed Paddys Bluff from the starboard Texas deck of the steamboat Della Queen one rainy morning in October 2005; the thick, persistent white bed midway in the bluff especially attracted our attention (Fig. 4). Paddys Bluff is the best natural exposure of Mississippian limestone between Barkley Dam and the Ohio River, a distance of 31 river miles. The bluff, some 1,700 feet long (Fig. 4), rises 160 feet above the Cumberland River and deflects it about 16° into a long westward reach, the river removing all talus at the base of the bluff. The bluff lies in a graben between two inferred faults st liking N40 to 45°E (Amos and Hayes, 1974). Readily seen in the limestones along the river at the base of the bluff is a prominent joint set parallel to these faults. This bluff is mapped on the Dycusburg geologic quadrangle map (Table 1) as the combined Salem and St. Louis Limestones (Amos and Hayes, 1974) and is capped by at least 15 feet of poorly exposed gravel of the Cretaceous Tuscaloosa Formation (Olive, 1980). Across the river less than 2 miles distant are scattered continental deposits of reddish brown Lafayette-type, sandy cobble-gravel (Olive, 1980), below which are outliers of the Cretaceous Tuscaloosa Formation; both cap hilltops of the same underlying Mississippian limestones. Why is Paddys Bluff of interest? There are at least six reasons to study it. First, can the Salem and St. Louis Limestones be individually identified at the bluff? If, in fact, they can be separated, the upper boundary of sequence S4 recognized in the Lake Cumberland area of south-central Kentucky by Khetani and Read (2002, Fig. 12) extends much farther west. Still another challenge is the enigmatic, massive, fine-grained, whitish-weathering carbonate mudstone bed, unit C of our section, high in the bluff. What does it represent? How widespread is it? Why do beds below rt have a strong petroliferous odor and not those above it? Why are some of the coral heads (Fig. 5) at Paddys Bluff overturned and others not? The last challenge is the bluff itself: Why is it there and how long has it been there