Compliance with antibiotic prophylaxis in urinary tract infection

Compliance with antibiotic prophylaxis after urinary tract infection was assessed in 32 children, using a parent questionnaire, and a urine test for antibacterial substances. In 31 (97%) cases, parents reported giving the antibiotics every day but only 22 (69%) of urine tests were positive. Failure to understand the reasons for prophylaxis and non-compliance were significantly associated.     

The value of one hour daytime sleep recording in the diagnosis of the sleep apnoea syndrome

In this study we investigated whether the diagnosis of sleep apnoea syndrome (SAS), based on night-time polysomnography (NPSG), can be predicted or excluded by a one-hour daytime polysomnography (DPSG). The results of 306 NPSGs were compared with DPSGs, which were performed the day before. Treated patients were excluded. In the 89 patients with SAS (Apnoea index (AI)>/=5) 59 showed apnoeas during the DPSG and 30 did not. In the 217 without SAS 25 showed apnoeas daring DPSG and 192 did not. Sensitivity for detecting SAS was 66%, the specificity was 88%, the positive predictive value (PPV) 70% and the negative predictive value (NPV) 86%. For relevant SAS (AI>/=10) the NPV would be 95%. We conclude that the one-hour DPSG is not sufficient for diagnosing or excluding SAS with certainty. It can be used to make the presence of relevant SAS unlikely.     

Metaflammasome components in the human brain: a role in dementia with Alzheimer's pathology?

Epidemiological and genetic studies have identified metabolic disorders and inflammation as risk factors for Alzheimer's disease (AD). Evidence in obesity and type‐2 diabetes suggests a role for a metabolic inflammasome (“metaflammasome”) in mediating chronic inflammation in peripheral organs implicating IKKβ (inhibitor of nuclear factor kappa‐B kinase subunit beta), IRS1 (insulin receptor substrate 1), JNK (c‐jun N‐terminal kinase), and PKR (double‐stranded RNA protein kinase). We hypothesized that these proteins are expressed in the brain in response to metabolic risk factors in AD. Neocortex from 299 participants from the MRC Cognitive Function and Ageing Studies was analysed by immunohistochemistry for the expression of the phosphorylated (active) form of IKKβ [pSer^176/180], IRS1 [pS³¹²], JNK [pThr¹⁸³/Tyr¹⁸⁵] and PKR [pT⁴⁵¹]. The data were analyzed to investigate whether the proteins were expressed together and in relation with metabolic disorders, dementia, Alzheimer's pathology and APOE genotype. We observed a change from a positive to a negative association between the proteins and hypertension according to the dementia status. Type‐2 diabetes was negatively related with the proteins among participants without dementia; whereas participants with dementia and AD pathology showed a positive association with JNK. A significant association between IKKβ and JNK in participants with dementia and AD pathology was observed, but not in those without dementia. Otherwise, weak to moderate associations were observed among the protein loads. The presence of dementia was significantly associated with JNK and negatively associated with IKKβ and IRS1. Cognitive scores showed a significant positive relationship with IKKβ and a negative with IRS1, JNK and PKR. The proteins were significantly associated with pathology in Alzheimer's participants with the relationship being inverse or not significant in participants without dementia. Expression of the proteins was not related to APOE genotype. These findings highlight a role for these proteins in AD pathophysiology but not necessarily as a complex.     

Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Background/aimFamilial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia.Materials and methodsAll patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively.ResultsAmong 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively).ConclusionOur findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.     

Lactogenic Activity of Rats Stimulated by Gunnera Perpensa L. (Gunneraceae) from South Africa

Gunnera perpensa L. (Gunneraceae) is a medicinal plant used by Zulu traditional healers to stimulate milk production. The effect of an aqueous extract of the rhizome of the plant on milk production in rats was investigated. Female lactating rats that received oral doses of the extract of G.perpensa significantly (p<0.05) produced more milk than controls. The plant extract did not however, significantly influence the levels of prolactin, growth hormone, progesterone, cortisol, ALT, AST and albumin in the blood. The mammary glands of rats treated with the extract showed lobuloalveolar development. The extract (0.8 µg/ml) was also found to stimulate the contraction of the uterus and inhibit (23%) acetylcholinesterase activity. The cytotoxicity of the extract (LC₅₀) to two human cell lines (HEK293 and HepG2) was 279.43 µg/ml and 222.33µg/ml, respectively. It is inferred that the plant extract exerts its activity on milk production and secretion by stimulating lobuloalveolar cell development and the contraction of myoepithelial cells in the alveoli. It is concluded that Gunnera perpensa contains constituents with lactogenic activity that apparently contribute to its effectiveness in folk medicine.     

Effect of active Aβ immunotherapy on neurons in human Alzheimer's disease

Amyloid β peptide (Aβ) immunization of Alzheimer's disease (AD) patients has been reported to induce amyloid plaque removal, but with little impact on cognitive decline. We have explored the consequences of Aβ immunotherapy on neurons in post mortem brain tissue. Eleven immunized (AN1792, Elan Pharmaceuticals) AD patients were compared to 28 non‐immunized AD cases. Immunohistochemistry on sections of neocortex was performed for neuron‐specific nuclear antigen (NeuN), neurofilament protein (NFP) and phosphorylated‐(p)PKR (pro‐apoptotic kinase detected in degenerating neurons). Quantification was performed for pPKR and status spongiosis (neuropil degeneration), NeuN‐positive neurons/field, curvature of the neuronal processes and interneuronal distance. Data were corrected for age, gender, duration of dementia and APOE genotype and also assessed in relation to Aβ42 and tau pathology and key features of AD. In non‐immunized patients, the degree of neuritic curvature correlated with spongiosis and pPKR, and overall the neurodegenerative markers correlated better with tau pathology than Aβ42 load. Following immunization, spongiosis increased, interneuronal distance increased, while the number of NeuN‐positive neurons decreased, consistent with enhanced neuronal loss. However, neuritic curvature was reduced and pPKR was associated with Aβ removal in immunized patients. In AD, associations of spongiosis status, curvature ratio and pPKR load with microglial markers Iba1, CD68 and CD32 suggest a role for microglia in neurodegeneration. After immunization, correlations were detected between the number of NeuN‐positive neurons and pPKR with Iba1, CD68 and CD64, suggesting that microglia are involved in the neuronal loss. Our findings suggest that in established AD this form of active Aβ immunization may predominantly accelerate loss of damaged degenerating neurons. This interpretation is consistent with in vivo imaging indicating an increased rate of cerebral atrophy in immunized AD patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

A series of melanomas smaller than 4 mm and implications for the ABCDE rule

BACKGROUND: Although multiple studies have reported that a significant number of melanomas have diameters of less than or equal to 6 mm at the time of diagnosis, there has been only one series evaluating the proportion of melanomas less than 4 mm in diameter. OBJECTIVE: The objective of this study was to determine the proportion of melanomas, in a single-practitioner, general dermatology practice, with clinical diameters less than 4 mm. METHODS: Information regarding each new diagnosis of melanoma had been recorded during the study period of 2000-2004. Patient records and pathology reports were examined from these patients. RESULTS: Thirteen (13.7%) of the 95 melanomas had diameters less than 4 mm at the time of presentation, including five invasive and eight in situ melanomas. The defining clinical characteristic of these lesions was intensity of pigment. Three of these 13 melanomas, including one invasive and two in situ lesions, showed features of regression. CONCLUSIONS: The findings of this study support those authors who have suggested elimination of the 6-mm diameter criterion in the ABCDE rule. In addition, this study provides further evidence that dark colour as a diagnostic criterion for melanoma should be given more emphasis. The substitution of 'D' to represent dark instead of diameter is worthy of consideration to enhance the value of the ABCDE mnemonic.     

Planning for children whose parents are dying of HIV/AIDS. American Academy of Pediatrics. Committee on Pediatric AIDS, 1998-1999

Although the character of acquired immunodeficiency syndrome is changing into a chronic illness, it is estimated that by the end of this century, 80 000 children and adolescents in the United States will be orphaned by parental death caused by human immunodeficiency virus infection. Plans for these children need to be made to ensure not only a stable, consistent environment that provides love and nurturing, but also the medical and social interventions necessary to cope with the tragic loss. Pediatricians should become aware of local laws and community resources and initiate discussion early in the course of parental illness to facilitate planning for the future care and custody of the children. States need to adopt laws and regulations that provide flexible approaches to guardianship and placement of children orphaned by acquired immunodeficiency syndrome.     

Appendectomy history is associated with severe disease and colchicine resistance in adult familial Mediterranean fever patients

Background/aim Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it’s hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the course of FMF in the adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in the adulthood. Materials and methods All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files. Results Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs. 89.6%, p < 0.001) in appendectomized patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs. 2 attacks, p = 0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs. 5.9%, p = 0.038) due to involvement of more attack sites throughout the life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43 ± 0.6 mg vs. 1.27 ± 0.52 mg, p = 0.002) but colchicine resistance was also more common in these patients, 15% vs. 6.7% respectively, p < 0.001.ConclusionAppendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.