Evaluation of the effect of neoadjuvant chemotherapy on tumor and axillary lymph nodes in locally advanced breast cancer： a study of 50 patients

Objective： The purpose of the study was to correlate between effect of pre-neoadjuvant chemotherapy （NACT） and post-NACT clinical, sonographic and pathologic features of the tumor and axillary lymph nodes （ALNs） and to raise the possibility of applying the concept of sentinel lymph node biopsy （SLNB） in patients with initially positive ALNs before NACT. Methods： A prospective study of 50 female patients with locally advanced breast cancer （LABC） with clinically palpable.and cytologically （under ultrasonographic guidance） positive ALNs. All patients received NACT and then referred for ultrasono- graphic assessment of the axilla regarding any detectable sonographic criteria of metastatic deposits in ALNs as well as the tumor size in relation to its prechemotherapy size, All patients were then subjected either to modified radical mastectomy or breast conserving surgery. The clinical, sonographic and pathological response of the tumor and the ALNs were documented, classified and correlated with each other. Results： Patients＇ mean age was 47.7±9.1 years. The mean clinical tumor size was 6.7 ± 1.4 cm; stage IliA that was presented in 32 patients （64%） and IIIB was presented in 18 patients （36%）. Chemotherapy was given for a median of 4 cycles, there was reduction of the mean clinical tumor size from 6.7 ± 1.4 cm to 4.3 ± 2.7 cm （P 〈 0.001）. Clinical response was complete in 5 （10%） tumors, complete pathological tumor response （post-neoadjuvant） was detected in 6 （16%） of patients. Complete clinical nodal response （post-neoadjuvant） in 23 （46%） axillae, on sonographic assessment of the axilla, response was complete in 17 （34%） axillae. Complete pathological nodal response occurred in 16 （32%） axillae. Out of 17 axillae that showed complete sonographic response 11 axillae showed complete pathological nodal response （P 〈 0.001）. Conclusion： Formal axillary lymph node dissection can be avoided and replaced by SLNB post NACT in patients with L     

An experimental study on ulcerative colitis as a potential target for probiotic therapy by Lactobacillus acidophilus with or without “olsalazine”

Traditional medical treatments for ulcerative colitis (UC) are still compromised by its adverse effects and not potent enough to keep in remission for long-term periods. So, new therapies that are targeted at specific disease mechanisms have the potential to provide more effective and safe treatments for ulcerative colitis. Probiotics is recently introduced as a therapy for ulcerative colitis. In the present study, Lactobacillus acidophilus was selected as a probiotic therapy to investigate its effects in oxazolone-induced colitis model in rats that mimics the picture in human. The rats were grouped (8 rats each) as normal control group (Group I), Group II served as untreated oxazolone-induced colitis, Group III oxazolone-induced colitis treated with probiotic L. acidophilus (1 × 10⁷ colony-forming units (CFU)/mL/day oral for 14 days), Group IV oxazolone-induced colitis treated with olsalazine (60 mg/kg/day oral for 14 days), Group V oxazolone-induced colitis treated with probiotic L. acidophilus and olsalazine in the same doses and duration. Disease activity index (DAI) was recorded, serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and intrleukin-6 (IL-6) was assessed as inflammatory markers and the histopathological picture of the colon of each rat was studied. Disease activity index (DAI) showed significant positive correlation with the elevated serum levels of CRP (r = 0.741, p < 0.05), TNF-α (r = 0.802, p < 0.05) and IL-6 (r = 0.801, p < 0.05). Treatment with either L. acidophilus (group III) or olsalazine (group IV) resulted in significant reduction in serum levels of CRP, TNF-α and IL-6, as well as disease activity index (DAI). Treatment with combination of L. acidophilus and olsalazine (group V) offered more significant reduction in serum levels of CRP, TNF-α, IL-6 and disease activity index (DAI) when compared to either group II (untreated group), group III (treated with L. acidophilus) or group IV (treated with olsalazine). So, it was concluded that L. acidophilus probiotic could be recommended as adjuvant therapy in combination with olsalazine to achieve more effective treatment for ulcerative colitis. For application in human, this needs to be verified in further clinical studies.     

Physiological impairment in mild COPD

Chronic obstructive pulmonary disease (COPD) is a common and often progressive inflammatory disease of the airways, alveoli and microvasculature that is both preventable and treatable. It is well established that smokers with mild airway obstruction, as spirometrically defined, represent the vast majority of patients with COPD, yet this population has not been extensively studied. An insidious preclinical course means that mild COPD is both underdiagnosed and undertreated. In this context, recent studies have confirmed that even patients with mild COPD can have extensive physiological impairment, which contributes to poor perceived health status compared with non‐smoking healthy controls. This review describes the heterogeneous pathophysiology that can exist in COPD patients with only mild airway obstruction on spirometry. It exposes the compensatory adaptations that develop in such patients to ensure that the respiratory system fulfils its primary task of maintaining adequate pulmonary gas exchange for the prevailing metabolic demand. It demonstrates that adaptations such as increased inspiratory neural drive to the diaphragm due to combined effects of increased mechanical loading and chemostimulation underscore the increased dyspnoea and exercise intolerance in this population. Finally, based on available evidence, we present what we believe is a sound physiological rationale for earlier diagnosis in this population.     

Serum cystatin C as an early predictor of acute kidney injury in preterm neonates with respiratory distress syndrome

Abstract

Preterm neonates with respiratory distress syndrome (RDS) are at increased risk of acute kidney injury (AKI). Our study aimed at determining whether serum cystatin C (sCysC) on day 3 of life (D3) can early predict AKI in preterm neonates with RDS. This prospective study was conducted on 75 preterm neonates; 50 with RDS and 25 without RDS. On D3, sCysC, serum creatinine (sCr) and blood urea nitrogen (BUN) were measured and estimated glomerular filtration rate (eGFR) was calculated. sCr and BUN levels were measured again on days 5 and 7. Neonates were evaluated for development of AKI during first week of life according to the modified pediatric RIFLE (pRIFLE) criteria. Thirteen neonates with RDS developed AKI (26%).There was no significant difference between RDS and control groups with respect to sCysC. RDS neonates with AKI had significantly higher sCysC than those without AKI (1.62?±?0.12 versus 1.16?±?0.09?mg/l; p?<?.001). RDS grade III–IV neonates had significantly higher sCysC than RDS grade I–II. There was a significant positive correlation between D3 sCysC and (D5 and D7 sCr and BUN). Receiver operating characteristic (ROC) curve showed that D3 sCysC can predict AKI in preterm neonates with RDS at a cutoff point of >1.3?mg/l with sensitivity of 92.30% and specificity of 96%. We conclude that neonates with RDS are at increased risk of AKI. sCysC on day 3 of life can predict AKI earlier than Cr and eGFR.     

Musculoskeletal manifestations in patients with malignant disease

To detect and describe the incidence of musculoskeletal manifestations in different malignant diseases as well as their relation to the treatment received whether by chemotherapy or radiation therapy. Sixty patients with different malignant diseases were included in this study, 45 with solid tumors and 15 patients with hematological malignancy. The mean age was 46.55 ± 11.04 years and the mean disease duration was 2 ± 0.75 years. The patients were fully examined for any rheumatologic involvement, laboratory investigations were performed as well as dual energy X-ray absorptiometry study for bone densitometry. Treatment strategies were assessed including the chemotherapeutics, radiation therapy, and/or surgery. Myalgias and arthralgias were the most frequent followed by flexor tenosynovitis, frozen shoulder, and fibromyalgia syndrome. Hypertrophic osteoarthropathy was seen in five patients, cutaneous vasculitis in two patients as well as arthritis. Osteonecrosis was present in one of the lunate carpal bones of a patient with non-Hodgkin’s lymphoma (1.67%) and receiving high dose steroids. Rheumatoid factor was positive in four patients, three of which had hepatitis C virus positivity and cryoglobulins. Anti-neutrophil cytoplasmic antibody was negative in all the studied patients. The bone mineral density was significantly reduced in the patients with malignancy compared to the control. Mild to moderate osteoporosis was present, being more evident in the spine and forearm. The bone loss was higher in those with solid tumors and even more obvious in those receiving aromatase inhibitors. Musculoskeletal manifestations occurring during malignancies and following the treatment represent a significant percentage of symptoms and signs which may raise a clue to differential diagnosis.     

E-SHAP: An effective treatment in selected patients with relapsed non-Hodgkin's lymphoma

BACKGROUND:: The optimal treatment of relapsed or refractory non-Hodgkin'slymphoma is unknown. The reported encouraging results of a salvageregimen, E-SHAP (etoposide 40 mg/m²/day x 4, methyl prednisolone500 mg daily x 4, cytosine arabinoside 2 gm/m² one dose andcisplatinum 25 mg/m²/day x 4), at the MD. Anderson Hospitalin Texas, which resulted in a 65% response rate, could not bereproduced in the United Kingdom (0% response). PATIENTS AND METHODS:: Twenty-six patients with relapsed (n = 16) or refractory (n= 10) non-Hodgkin's lymphoma were treated at our Centre by amodified E-SHAP regimen (cytosine arabinoside 1 gm/m² one dose).The treatment was intended as remission induction before BMT(n = 16), as salvage by itself (n = 5) and for palliation ofsymptoms (n = 5). RESULTS:: The overall response rate was 72% (CR = 7 and PR = 11). A comparisonof Kaplan-Meier curves showed a statistically significant improvementin median relapse-free survival in patients who had previouslyachieved CR (p = 0.0012), no bulky disease (P = 0.0006) andno B-symptoms (P = 0.0004). The toxicity was acceptable: 8 instancesof febrile neutropenia, 2 of reversible renal impairment and2 symptomatic electrolyte abnormalities. No fatal toxicitieswere encountered. The median time to treatment failure was 191days and median overall survival was 190 days. CONCLUSIONS:: E-SHAP is an active combination chemotherapy when used as asalvage regimen or for remission induction before bone marrowtransplantation in selected patients with relapsed non-Hodgkin'slymphoma. Patients who previously achieved CR, with low tumourburden and no B-symptoms are the best candidates for this treatment.It has a limited palliative effect. non-Hodgkin's lymphoma, salvage chemotherapy, etoposide, cisplatinum     

Factors influencing the participation of gastroenterologists and hepatologists in clinical research

Background  

Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.     

Hyperglycemia and reactive oxygen species mediate apoptosis in aortic endothelial cells through Janus kinase 2

The generation of reactive oxygen species (ROS) has been implicated in the perturbation of endothelial function and cell death. However, the specific signaling pathways which mediate and modifying this response have not been fully elucidated. Therefore, in this study we tested the hypothesis that activation of JAK2 is involved in the aortic endothelial cell (EC) response to ROS. When ECs were exposed to HG (25 mM) for 6 h or ROS (i.e., H(2)O(2) (100 microM)) for 1 h and returned to normal medium we found a decrease in cell density and morphologic signs of apoptosis. Furthermore, incubation of ECs with HG and H(2)O(2) also resulted in the tyrosine phosphorylation of JAK2. In addition, pretreatment of ECs with AG-490, an inhibitor of JAK2, prevented nuclear fragmentation, whereas inhibitors of Jun kinase (SP 600125), MAP kinase (PD 98059), Src kinase (PP2) or PI-3 kinase (wortmannin) were without effect. Finally, immunoblot analysis of caspase-3 and PARP cleavage confirmed a role for activation of JAK2 in both HG- or ROS-induced apoptosis, based on inhibition by either AG-490 or adenoviral transfection with a dominant-negative JAK2 mutant. In conclusion the activation of JAK2 plays a pivotal role in oxidant stress-induced commitment of ECs to apoptosis, based on studies with HG and H(2)O(2).     

Low diversity of Alkhurma hemorrhagic fever virus, Saudi Arabia, 1994-1999

Alkhurma hemorrhagic fever virus (genus Flavivirus, AHFV) was recently identified as the agent of a viral hemorrhagic fever in Saudi Arabia and characterized serologically and genetically as a variant genotype of Kyasanur Forest disease virus (KFDV). Since viral diagnosis and vaccine development may be hindered by genetic diversity, this study was intended to address AHFV genetic heterogeneity. Eleven strains isolated from hospitalized patients from 1994 to 1999 in Saudi Arabia were sequenced in the envelope, NS3, and NS5 genes. Homologous sequences were compared and used to look for patterns reflecting specific evolution associated with spatiality, temporality, infection pathway, and disease prognosis. Genetic analyses showed low diversity, which suggests a slow microevolution. Evaluation of divergence times showed that AHFV and KFDV ancestral lineage diverged 66-177 years ago, and the diversity observed within the studied AHFV strains reflected a 4- to 72-year period of evolution.