Lethal Tuberculosis in a Previously Healthy Adult with IL-12 Receptor Deficiency

A 33-year-old man was admitted in hospital due to fever, generalized lymphadenopathy, and hepatosplenomegaly. He had a history of anti-tuberculosis treatment in the previous 3 years. Despite normal chest radiograph, a sputum sample was smear-positive for acid-fast bacilli, and polymerase chain reaction was positive for Mycobacterium tuberculosis complex. Drug susceptibility test revealed resistance to isoniazid and rifampin. Evaluation of the patient’s immune system revealed IL-12Rβ1 deficiency. The patient died of disseminated tuberculosis (TB), despite appropriate antibiotic treatment. This is the first IL-12 receptor-deficient patient presenting with disseminated TB in adulthood, without any previous relevant medical history. This diagnosis should be considered in selected adult patients with unexplained, overwhelming TB. IL-12Rβ1 deficiency is a genetic etiology of severe TB in adults and should be considered in adult patients with disseminated TB.     

Synthesis and Biological Evaluation of Coumarin Derivatives as Inhibitors of Mycobacterium bovis (BCG)

The coumarin compounds are an important class of biologically active molecules, which have attractive caught the attention of many organic and medicinal chemists, due to potential pharmaceutical implications and industrial applications. We herein report the one‐pot procedure for the efficient synthesis of coumarin derivatives using commercially available substrates via isocyanide‐based multicomponent condensation reactions. These compounds were evaluated for anti‐mycobacterium activity against Mycobacterium bovis (Bacillus Calmette–Guerin). The preliminary results indicated that all of the tested compounds showed relatively good activity against the test organism. The compounds 7e , 7l , and 7m showed high anti‐tuberculosis activity.     

Interventions promoting adherence to cardiovascular medicines

Background Cardiovascular diseases (CVDs) are a large burden on the healthcare system. Medicines are the primary treatment for these diseases; however, adherence to therapy is low. To optimise treatment and health outcomes for patients, it is important that adherence to cardiovascular medicines is maintained at an optimal level. Therefore, identifying effective interventions to improve adherence and persistence to cardiovascular therapy is of great significance. Aim of the Review This paper presents a review of the literature on interventions used in the community setting which aim to improve adherence to cardiovascular medicines in patients with hypertension, dyslipidaemia, congestive heart failure or ischaemic heart disease. Methods Several databases (Medline, EMBASE, PsychINFO, IPA, CINAHL, Pubmed, Cochrane) were searched for studies which were published from 1979?C2009, evaluated interventions intended to improve adherence to cardiovascular medicines in the community setting, had at least one measure of adherence, and consisted of an intervention and comparison/control group. Results Among 36 eligible studies (consisting of 7 informational, 15 behavioural, 1 social, and 13 combined strategy interventions), 17 (1 informational, 10 behavioural, and 6 combined) reported a significant improvement in adherence and/or persistence. Behavioural interventions were the most successful. Twenty-one studies (4 informational, 9 behavioural, and 8 combined) also demonstrated improvements in clinical outcomes, though, effects were frequently variable, contradictory and not related to changes in adherence. Conclusion Several types of interventions are effective in improving adherence and/or persistence within the CVD area and in the community setting. Behavioural interventions have shown the greatest success (compared to other types of interventions); and adding informational strategies has not resulted in further improvements in adherence. Improving adherence and persistence to cardiovascular medicines is a dynamic process that is influenced by many factors, and one which requires long term multiple interventions to promote medicine taking in patients     

Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.     

TCRzetadim lymphocytes define populations of circulating effector cells that migrate to inflamed tissues

The T-cell receptor zeta (TCRzeta) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRzeta expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRzeta expression and effector function in T cells. We report here that TCRzeta(dim) lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRzeta(bright) counterparts, TCRzeta(dim) cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRzeta(dim) T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRzeta(dim) T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRzeta(dim) T cells make them promising cellular targets for the treatment of chronic inflammatory disease.     

Evaluation serum levels of Insulin Growth Factor-1 (IGF-1) and its association with clinical parameters in severe COVID-19

Inflammopharmacology - Severe coronavirus disease-2019 (COVID-19) is associated with dysregulated immune response and extreme inflammatory injury. Considering the role of insulin growth factor-1...     

Infantile bladder rupture during voiding cystourethrography

Bladder rupture is rare during infancy and most of reported cases had urethral obstruction or neurogenic bladder. We report two cases of infantile bladder rupture during voiding cystourethrography (VCUG). This report reinforces the criteria for proper VCUG imaging procedure. Consideration of expected bladder volume for body weight, and close monitoring of bladder pressure and injection speed could prevent such complications.