Pernicious anemia in a young Bahraini female

Pernicious anemia (PA) is an autoimmune disorder associated with atrophic gastritis, presence of antibodies to gastric parietal cells and intrinsic factor (IF) and vitamin B2 malabsorption leading to megaloblastic anemia. It has a comparatively higher prevalence in people of North European origin, is uncommon in Arabs and usually affects the elderly. This report, the first from Bahrain, describes a rare case of PA in young female. The presenting symptoms, clinical and laboratory features were similar to those described in classical elderly Caucasian patients. No association with any other autoimmune disease was detected.     

Combined efficacies of lipoic acid and meso-2,3-dimercaptosuccinic acid on lead-induced erythrocyte membrane lipid peroxidation and antioxidant status in rats

One of the most intriguing phenomenon observed during lead toxicity has been attributed to lead-induced oxidative stress. The combined effect of DL-alpha-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced alterations in selected parameters, which are indicators of oxidative stress in erythrocytes, have been studied. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce toxicity. LA (25 mg/ kg body weight per day i.p.) and DMSA (20 mg/kg body weight per day i.p.) were administered individually and also in combination during week 6. Clinical evidence of toxic exposure was evident from the elevated blood lead levels (BPb) along with lowered levels of haemoglobin (Hb) and haematocrit (Ht). Lead-exposed animals showed enhanced membrane lipid peroxidation (LPO) in the erythrocytes. Damage to the erythrocyte membrane was evident from the decline in the activities of the transmembrane enzymes, viz., Na+, K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase. Lead-exposed rats also suffered an onslaught on the antioxidant defence system witnessed by lowered activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH). Serum glutamic-oxoloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were also elevated in lead-exposed rats. Treatment with either LA or DMSA reversed the lead-induced biochemical disturbances encountered by the erythrocytes, but combined treatment with LA and DMSA was very effective in mitigating all the parameters indicative of oxidative stress.     

Addition and omission analogs of the 13-residue antibacterial and hemolytic peptide PKLLKTFLSKWIG: structural preferences,model membrane binding and biological activities

The consequences of selective addition or deletion of polar amino acids in a 13-residue antibacterial peptide PKLLKTFLSKWIG on structure, membrane binding and biological activities have been investigated. The variants generated are (a) S and T residues replaced by K, (b) S and T residues deleted individually and together, (c) introduction of two additional K and (d) deletion of L and L with T. In the aqueous environment all the peptides were unordered. In trifluoroethanol, the spectra of peptides belonging to groups (a-c) suggest distorted helical conformation. Peptides in group (d) appear to adopt β-sheet conformation. The peptides bind to zwitterionic and negatively charged lipid vesicles, although to different extents. With the exception of peptides in group (d), all the other peptides exhibited comparable antibacterial activity against Escherichia coli and Staphylococcus aureus. However, the changes made in the peptides in groups (a-c) resulted in reduction of hemolytic activity compared to the parent peptide. Extent of binding to lipid vesicles composed of phosphatidylcholine and cholesterol appears to correlate with hemolytic activity. It appears that polar and charged residues play a major role in modulating the biological activities of the 13-residue peptide PKLLKTFLSKWIG. The 11-residue peptide-like PKLLKFLKWIG has selective antibacterial activity. Thus, by judicious engineering it should be possible to generate short peptides with selective antibacterial activity.     

Validation of the current eligibility criteria for focal therapy in men with localized prostate cancer and the role of MRI

Purpose

To validate current eligibility criteria for focal therapy (FT) in prostate cancer men undergoing radical prostatectomy (RP) and to assess the role of magnetic resonance imaging (MRI).

Methods

Retrospective analysis of 217 RP patients (2009–2016) with preoperative MRI (almost all in external institutions) and fulfillment of different FT eligibility criteria: unilateral tumor, clinical tumor stage ≤ cT2a, prostate volume ≤ 60 mL and either biopsy Gleason 3 + 3 or ≤ 3 + 4 and PSA ≤ 10 or ≤ 15 ng/mL. Multivariable logistic regression analyses (MVA) assessed the role of MRI to predict the presence of significant contralateral tumor or extracapsular extension (ECE), including seminal vesicle invasion. To quantify model accuracy, Receiver Operating Characteristics-derived area under the curve (AUC) was used.

Results

Of 217 patients fulfilling widest biopsy criteria and 113 fulfilling additional MRI criteria, 64 (29.7%) and 37 (32.7%) remained eligible for FT according to histopathological results. In MVA, fulfillment of MRI criteria reached independent predictor status for prediction of contralateral tumor but not for ECE. Addition of MRI resulted in AUC gain (57.5–64.6%). Sensitivity, specificity, PPV and NPV for MRI to predict contralateral tumor were: 41.8, 71.6, 70.9 and 42.6%, respectively. Virtually the same results were recorded for Gleason 3 + 3 and/or PSA ≤ 10 ng/mL.

Conclusions

Patient eligibility criteria for FT using biopsy criteria remained insufficient with respect to contralateral tumor disease. Although, MRI improves accuracy, it cannot safely exclude or minimize chance of significant cancer on contralateral prostate side. To date, stricter eligibility criteria are needed to provide more diagnostic reliability.

     

Biological approach to treatment of intra-articular proximal tibial fractures with double osteosynthesis

The treatment of intra-articular proximal tibial fractures is associated with complications, and much conflicting literature exists concerning the treatment of choice. In our study, an attempt has been made to develop an ideal and adequate treatment protocol for these intra-articular fractures. The principle of double osteosynthesis, i.e., lateral minimally invasive plate osteosynthesis (MIPO), was combined with a medial external fixator to treat 22 intra-articular proximal tibial fractures with soft tissue injury with a mean follow-up of 25 months. Superficial pin track infection was observed in one case, and no soft tissue breakdown was noted. Loss of articular reconstruction was reported in one case. Bridging callus was seen at 12 weeks (8 weeks-7 months). The principle of substitution or double osteosynthesis, i.e., lateral MIPO, was combined with a medial external fixator and proved to be a fairly good method of fixation in terms of results and complications.     

Asthma: new developments concerning immune mechanisms, diagnosis and treatment

PURPOSE OF REVIEW: This brief review discusses how recent research may modify our understanding of the immunology of asthma. Consideration is given to the possible impact that these observations may have upon diagnostic and therapeutic strategies. RECENT FINDINGS: New studies indicate that current conceptions regarding the balance between Th1 and Th2 systems may need modification. The relationship between infection and the development of asthma in children has proven to be much more complex than originally suggested by the 'hygiene hypothesis'. In addition, important genetic differences have been found in the response of asthmatic patients to therapeutic agents. SUMMARY: Greater insight into the mechanisms responsible for asthma and the introduction of new drugs will depend in part upon the development of reliable and simple methods for detecting airway inflammation. As the immunologic aspects of asthma are dissected, we can expect that many more potential targets for treatment will be discovered, but treatment may have to be individualized for genetic differences between different individuals.