How much protection is enough?

The debate on preventive HIV vaccines at the International AIDS Conference made global economic differences visible. The typical cost of $15,000 per year to treat AIDS patients is beyond the reach of 90 percent of the world's HIV population, most of whom live in Africa and Asia. However, no vaccine developed to date has been worthy of wide-scale testing, but about 25 vaccines are in phase-1 safety testing worldwide. There are many ethical concerns with testing HIV viruses because it is likely that volunteers will be infected in the testing process.     

How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma?

PURPOSE OF REVIEW: The purpose of this review is to describe the scientific evidence that specific immunotherapy can prevent the development of asthma in patients suffering from rhinoconjunctivitis as well as reduce the number of new allergies developing. RECENT FINDINGS: Proposed strategies for the prevention of the development of allergic rhinoconjunctivitis and asthma include allergen avoidance, pharmacological treatment (antihistamines and steroids) and specific immunotherapy. Long-term follow-up on immunotherapy studies demonstrates that specific immunotherapy for 3 years shows persistent long-term effects on clinical symptoms after termination of treatment and long-term, preventive effects on later development of asthma in children with seasonal rhinoconjunctivitis. It is so far the only treatment for allergic diseases that has been shown to be able to prevent worsening of disease and development of asthma. Also, specific immunotherapy seems to reduce the development of new allergic sensitivities as measured by the skin prick test as well as specific IgE measurements. SUMMARY: Specific immunotherapy is the only treatment that interferes with the basic pathophysiological mechanisms of the allergic disease and thereby carries the potential for changes in the long-term prognosis of respiratory allergy. Specific immunotherapy should be recognized not only as first-line therapeutic treatment for allergic rhinoconjunctivitis, but also as secondary preventive treatment for respiratory allergic diseases.     

How modality specific is processing of auditory and visual rhythms?

The present study used ERPs to test the extent to which temporal processing is modality specific or modality general. Participants were presented with auditory and visual temporal patterns that consisted of initial two‐ or three‐event beginning patterns. This delineated a constant standard time interval, followed by a two‐event ending pattern delineating a variable test interval. Participants judged whether they perceived the pattern as a whole to be speeding up or slowing down. The contingent negative variation (CNV), a negative potential reflecting temporal expectancy, showed a larger amplitude for the auditory modality compared to the visual modality but a high degree of similarity in scalp voltage patterns across modalities, suggesting that the CNV arises from modality‐general processes. A late, memory‐dependent positive component (P3) also showed similar patterns across modalities.     

How much tissue is present in archival paraffin blocks and slides?

In order to inform the debate about tissue blocks and slides introduced by the Retained Organs Commission, a study is undertaken to determine the percentage weight of tissue present in the surgical archive in the cellular pathology department of a district general hospital. When original, unprocessed tissue weight is expressed as a percentage, based on the weight of 100 archival paraffin blocks, values range from 0.2% to 41.5%. When the corresponding archival slides are also included, the values fall as low as 0.1% (i.e. up to 99.9% of the stored archival material for a piece of processed tissue could be non-human material). The results are used to make a case for including archival histological material as part of the patient's clinical record, although it is accepted that this study was performed only on surgical tissue.     

Bacterial identification in the diagnostic laboratory: How much is enough?

The major impetus for bacterial identification came after the advent of solid culture media. Morphological appearance of bacterial colonies was often sufficient for their identification in the laboratory. Even in modern times, preliminary identification of most cultivable bacteria is based on such morphological characters. Advances have been made media for the presumptive identification of common organisms encountered in clinical samples. Phenotypic characterisation of bacteria with, physiological tests with a battery of biochemical tests differentiate related bacterial genera as well as confirm their identity. . Each laboratory can select its own method(s) of identification, provided they are based on scientific / epidemiological evidence; clinical laboratory and standards institute (CLSI) is a widely accepted organization and laboratories in many parts of the world follow its recommendations for bacterial identification. Some of the latest advances in identification include Matrix Assisted Laser Desorption Ionization - Time of Flight Mass Spectroscopy (MALDI-TOF) is a state of art facility used for fast and reliable species-specific identification of bacteria including Mycobacteria and fungi including yeasts. However the single most important factor that decides the method of bacterial identification in any laboratory is the cost involved. In the final analysis, selection of tests for bacterial identification should be based on their standardization with proper scientific basis. Considering the cost and lack of easy availability of commercial kits, we have put forward a simplified and rapid method of identification for most commonly encountered bacterial pathogens causing human infection in India.     

How much formalin is enough to fix tissues?

A total of sixty samples from human breast, uterus, liver, skin and abdominal fat were fixed for 8; 24 and 48 hours at a room temperature of 20 to 22°C with neutral buffered formalin (NBF) with volume to tissue ratios of 1:1; 2:1; 5:1 and 10:1 and manually processed with isopropyl alcohol and mineral oil mixtures. All the slides prepared were evaluated as suitable for diagnostic purposes by nine pathologists from three different Russian histopathology institutions. The microtomy quality differences between the samples was not statistically significant for the different fixation volume ratios tested, but the differences between fixation periods and tissues types were, with 48 hours being the optimum fixation period, with skin and fat the most difficult to infiltrate. Neither the time and volume ratio combinations affected the pH of NBF or the immunostaining for vimentin in uterus or the histochemical periodic acid reaction or reticular demonstration fibers in liver. Fixing tissues with a ratio of NBF volume to tissue volume of 2:1 for 48 hours at 20-22°C was enough to assure a proper fixation and infiltration of the tested tissues and there is no objective reason to expect that other tissues will not behave similarly. It is suggested that in order to obtain good fixation and paraffin wax infiltration in around 10 hours, the fixation with NBF at 2:1 should be at 45°C with pressure and agitation.     

What is the genetic relationship between anxiety and depression?

Anxiety and depression share a long, close history in psychiatric nosology and treatment. The anxiety disorders, individually and as a group, exhibit remarkably high rates of comorbidity with each other and with major depression. Analyses done in large-scale epidemiologic surveys have identified major patterns of phenomenological overlap between these conditions. Researchers have tested hypotheses of shared genetic etiologies as a potential basis of this relationship. In general, available family studies have found mixed evidence for co-aggregation of anxiety and depressive disorders, while twin studies more definitively indicate that shared genetic risk factors largely account for this comorbidity. Some of this appears to be accounted for by genetic variation in personality traits that broadly predispose to anxiety and depression. Molecular genetic studies of these conditions, though too early to draw firm conclusions, thus far provide tentative support for specific genetic loci that may generally influence susceptibility across the anxiety-depressive spectrum.     

Alcohol--how much is too much?

The aims of this study were to examine perceptions of what a sample of students and graduates consider an excessive alcohol intake to be and it's effect on their health. 115 University College Cork (UCC) students and 133 UCC graduates were questioned about their opinions of an acceptable weekly intake of alcohol. The results reveal dramatic changes in drinking habits over recent decades. Students began drinking earlier than graduates and are far more accepting of greater amounts of alcohol being consumed. The student's average opinion of what constituted an excessive weekly alcohol intake was 26.5 units of alcohol/week whereas the graduates felt over 18 units/week was too much. We concluded that even amongst these highly educated cohorts there is a low level of awareness of safe limits of alcohol consumption.     

How accurate and safe is the diagnosis of hazelnut allergy by means of commercial skin prick test reagents?

BACKGROUND: Allergy to tree nuts, like hazelnuts, ranks among the most frequently observed food allergies. These allergies can start at early childhood and are, in contrast to other food allergies, not always outgrown by the patient. Tree nut allergy is frequently associated with severe reactions. Diagnosis partially relies on in vivo testing by means of a skin prick test (SPT) using commercially available SPT reagents. METHODS: Protein and allergen composition of nine commercial SPT solutions was evaluated using standard protein detection methods and specific immunoassays for measurement of five individual allergens. Diagnostic performance was assessed by SPT in 30 hazelnut-allergic subjects, of which 15 were provocation proven. RESULTS: Protein concentrations ranged from 0.2-14 mg/ml. SDS-PAGE/silver staining revealed clear differences in protein composition. The major allergen Cor a 1 was present in all extracts but concentrations differed up to a factor 50. An allergen associated with severe symptoms, Cor a 8 (lipid transfer protein), was not detected on immunoblot in three products, and concentrations varied by more than a factor 100 as was shown by RAST inhibition. Similar observations were made for profilin, thaumatin-like protein and a not fully characterized 38-kD allergen. Ratios of individual allergens were variable among the nine extracts. SPT showed significant difference, and 6/30 patients displayed false-negative results using 3/9 products. CONCLUSION: Variability in the composition of products for the diagnosis of hazelnut allergy is extreme. Sometimes, allergens implicated in severe anaphylaxis are not detected by immunoblotting. These shortcomings in standardisation and quality control can potentially cause a false-negative diagnosis in subjects at risk of severe reactions to hazelnuts.     

How much is too much? Phenotypic consequences of Rai1 overexpression in mice

The retinoic acid induced 1 (RAI1) gene when deleted or mutated results in Smith-Magenis syndrome (SMS), while duplication of 17p11.2, including RAI1, results in the dup(17)(p11.2) syndrome characterized by mental retardation, growth and developmental delays, and hyperactivity. Mouse models for these human syndromes may help define critical roles for RAI1 in mammalian development and homeostasis that otherwise cannot be deduced from patient studies. A mouse model for duplication, Dp(11)17+, involving Rai1 has been reported. However, this mutant was engineered on a mixed genetic background confounding phenotypic effects due to possible modifier genes. We have therefore created and evaluated mice with a graded series of four (hemizygous) and six (homozygous) copies of Rai1, and overexpressing Rai1>1.5-fold and >2-fold, respectively. Data show that Rai1-transgenic mice have growth retardation, increased locomotor activity, and abnormal anxiety-related behavior compared to wild-type littermates. Rai1-transgenic mice also have an altered gait with short strides and long sways, impaired ability on a cage-top hang test, decreased forelimb grip strength, and a dominant social behavior. Further, analyses of homozygous transgenic mice revealed a dosage-dependent exacerbation of the phenotype, including extreme growth retardation, severe neurological deficits, and increased hyperactivity. Our results show that Rai1 dosage has major consequences on molecular processes involved in growth, development, and neurological and behavioral functions, thus providing evidence for several dosage-thresholds for phenotypic manifestations causing dup(17)(p11.2) syndrome or SMS in humans.