A practical approach to vascular pathology in pulmonary hypertension

Pulmonary hypertension (PH) is the common physiological denominator in an otherwise heterogeneous disease. While pulmonary hypertension itself is not a pathologists' diagnosis, various patterns of pulmonary vasculopathy may be recognized in pulmonary hypertension. These patterns of vasculopathy are at the basis of classification, as they point towards (groups of) risk factors and aetiology. However, as surgical lung biopsy is a high risk procedure in PH, the role for histopathological evaluation is now mainly in retrospective evaluation on explanted lung or tissue obtained at autopsy, taking clinical work-up, including haemodynamic parameters and HRCT imaging, into account. Such multidisciplinary evaluation and classification may help assess the prognosis, including risk of recurrence in a transplant, and possible risk of PH in family members. More generally, systematic evaluation may identify clues as to pathogenesis and may help to fill the knowledge gap between histopathology and non-invasive diagnostic procedures such as imaging. This will hopefully eventually lead to a patho-physiologic rationale for classification, and to improved treatment strategies. This review aims to offer some practical guidelines for pathologists, pointing out pitfalls along the way.     

Hypertension and the development of New onset chronic kidney disease over a 10 year period: a retrospective cohort study in a primary care setting in Malaysia

Background

Little is known about the rate of progression to chronic kidney disease (CKD) among hypertensive patients, particularly at the primary care level. This study aims to examine risk factors associated with new onset CKD among hypertensive patients attending a primary care clinic.

Methods

This is a 10-year retrospective cohort study of 460 patients with hypertension who were on treatment. Patient information was collected from patient records. CKD was defined as a glomerular filtration rate <60?ml/min per 1.73?m² (Cockcroft-Gault equation). Multiple logistic regression statistics was used to test the association in newly diagnosed CKD.

Results

The incidence of new CKD was 30.9% (n?=?142) with an annual rate of 3%. In multivariate logistic regression analysis, factors associated with development of new onset of CKD among hypertensive patients were older age (odds ratio [OR] 1.123, 95% confidence interval [CI] 1.078-1.169), presence of diabetes (OR 2.621, 95% CI 1.490-4.608), lower baseline eGFR (OR 1.041, 95% CI 0.943-0.979) and baseline hyperuricaemia (OR 1.004, 95% CI 1.001-1.007).

Conclusions

The progression to new onset CKD is high among urban multiethnic hypertensive patients in a primary care population. Hence every effort is needed to detect the presence of new onset CKD earlier. Hypertensive patients who are older, with underlying diabetes, hyperuricaemia and lower baseline eGFR are associated with the development of CKD in this population.

     

Appropriateness of vancomycin therapeutic drug monitoring and its outcomes among non-dialysis patients in a tertiary hospital in Singapore

Background Vancomycin therapeutic drug monitoring (TDM) is commonly performed to ensure safe and effective use of the antibiotic. Aim of Study To evaluate appropriateness of vancomycin TDM and its outcomes in Singapore General Hospital. Method A retrospective, cross-sectional study was conducted between 1 January 2014 and 28 February 2014 involving patients who received?≥?1 dose of intravenous vancomycin with TDM. Patient demographics and relevant vancomycin TDM data were collected from medical records. Results Of 746 vancomycin troughs measured among 234 patients, 459 troughs (61.5%) were taken inappropriately, with a median time of 2.6 h (interquartile range 1.1–4.3) before the next scheduled dose. Inappropriate interpretation of vancomycin troughs resulted in 41 unnecessary dose suspensions, 24 dose changes, and 102 unchanged vancomycin doses. The cost incurred due to inappropriate interpretation and measurement after discontinuation of treatment was US$7286. No differences in rates of vancomycin related nephrotoxicity, ototoxicity, recurrent infection, development of infection secondary to vancomycin resistant microorganism and mortality were observed (p?>?0.05). Conclusion This study highlighted a high incidence of inappropriate vancomycin TDM which has led to increased healthcare cost.     

Reemergence of pertussis in the highly vaccinated population of the Netherlands: observations on surveillance data

We analyzed pertussis reporting, death, hospitalization, and serodiagnostic data from 1976 to 1998 to help explain the cause of the 1996 pertussis outbreak in the Netherlands. The unexpected outbreak was detected by an increase in pertussis reporting and by other surveillance methods. In 1996, according to reporting and serologic data, the increase in pertussis incidence among (mostly unvaccinated) children less than 1 year of age was similar to the increase in hospital admissions. Among older (mostly vaccinated) persons, the increase in hospital admissions was relatively small. The increase in pertussis incidence was higher among vaccinated than among unvaccinated persons of all ages. This resulted in lower estimates of vaccine effectiveness. The proportion of pertussis infections resulting in recognizable symptoms may have increased among vaccinated persons because of a mismatch of the vaccine strain and circulating Bordetella pertussis strains. The small immunogenicity profile of the Dutch vaccine may have resulted in greater vulnerability to antigenic changes in B. pertussis.     

Comparative analysis of p53 gene mutations and protein accumulation in human non-small-cell lung cancer

A series of 54 resected primary non-small-cell lung carcinomas was analyzed for p53 gene mutations and for p53 protein accumulation and the findings were correlated with clinical parameters. Mutations in exons 5 through 8 of the p53 gene were identified by a denaturing gradient gel electrophoresis (DGGE) assay and cycle sequencing, whereas p53 protein accumulation was detected in paraffin-embedded tissue by immunostaining using 2 different murine monoclonal antibodies (MAbs) (BP53-12 and DO7). A p53 gene mutation and/or p53 protein accumulation was found in 37 of 54 tumors. Mis-sense mutations were closely associated with positive immunostaining, which was intense in 15 out of 17 cases with a mutation. In 10 tumors, obvious p53 accumulation was detected in the absence of mutations in exons 5 through 8. Conversely, only one of 8 p53 non-sense mutations led to detectable p53 accumulation. The most frequent single base changes were G → T transversions and C → T transitions. The presence of a p53 alteration was not related to age, tumor size, stage or histology. However, we found a significant inverse correlation between p53 alterations and the presence of a K-ras mutation. This was reflected in the overall postoperative survival data: patients with p53 alterations in their tumors tended to have a better prognosis than those without a p53 alteration; however, this difference was lost when cases with a K-ras mutation were omitted from the analysis. © 1995 Wiley-Liss, Inc.     

Protection and humoral immune responses against Bordetella pertussis infection in mice immunized with acellular or cellular pertussis immunogens

In the present study, protection against Bordetella pertussis infection and humoral immunological responses in mice has been assessed upon immunization with custom-made acellular pertussis vaccines (ACVs) and whole-cell pertussis vaccine (WCV). Mice were immunized, next intranasally infected with B. pertussis and during 14 days the number of bacteria in the trachea and lungs and the level of serum antibodies were determined. ACV contained five immunogens, filamentous hemagglutinin, pertactin, fimbriae serotypes 2 and 3, and chemically detoxified pertussis toxin (PMC-5), or three immunogens, filamentous hemagglutinin, pertactin, and genetically detoxified (BC-3) or chemically detoxified pertussis toxin (SKB-3). Immunization with a high or low dose of ACV or WCV resulted in significant protection against B. pertussis, with differences in the degree of protection between the vaccines. The lowest protection was found with a low dose of SKB-3 and WCV. The pattern of cytokine production by spleen cells of immunized, non-infected, mice indicated that T-helper 1 cells are activated by vaccination with WCV, and T-helper 1 and T-helper 2 cells are involved in the immune response upon vaccination with ACVs. Each vaccine stimulated the production of IgG, but not IgA, antibodies. In mice immunized with ACV, elimination of B. pertussis from trachea and lungs correlated significantly with the titre of IgG1, but not IgG2a, antibodies.     

Targeting to Fcgamma receptors, but not CR3 (CD11b/CD18), increases clearance of Bordetella pertussis

In the absence of opsonizing antibodies, Bordetella pertussis, the causative agent of pertussis, readily binds to phagocytes via complement receptor 3 (CR3). After opsonization with antibodies, binding is mediated by IgG receptors (FcgammaR). The effect of targeting B. pertussis to either FcgammaR or CR3 was studied. The fate of unopsonized B. pertussis, IgG-opsonized B. pertussis, and B. pertussis opsonized with bispecific antibodies (BsAbs) directed to CR3 or FcgammaRII/-III was compared. IgG antibodies mediated binding and phagocytosis of B. pertussis via FcgammaR by polymorphonuclear leukocytes (PMNL) in vitro. Opsonization of B. pertussis with BsAbs directed against either CR3 or FcgammaRII/-III facilitated PMNL phagocytosis; however, in vivo studies with BsAb revealed that FcgammaR-mediated uptake facilitates B. pertussis clearance, in contrast to uptake via CR3. Targeting of B. pertussis to FcgammaRII/-III in mice deficient in FcgammaRII or FcgammaRIII indicated that the protective effect is attributable to FcgammaRIII. Competition between uptake via CR3 or FcgammaR may determine the outcome of natural infection.     

Parents' perceptions towards their child's use of inhaled medications for asthma therapy

Objective : Understanding patients' and their parents' perceptions towards asthma medication is important in developing strategies to ensure patient compliance. In this study, parents' perceptions towards their children's use of inhaled medication for asthma treatment were evaluated.
Methodology : A questionnaire was administered by interviewing parents of 210 asthmatic children attending the Department of Paediatrics, National University Hospital.
Results : Our results showed that 76/210 (36%) of parents either felt opposed to inhaler therapy and/or preferred oral medications. The main reasons for their reluctance to use inhalers were related to fear of dependence, side effects and overdosage, and the child's dislike for inhalers. A third of these parents felt that inhalers were only indicated for very severe asthma.
Conclusions : We conclude that a significant proportion of parents have reservations regarding the use of inhalers for the treatment of asthma. These factors should be taken into consideration when planning an effective asthma education programme.