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Samson Yaregal,1 Nebiyu Bekele,1 Yonathan Gebrewold,2 Abilo Tadesse1 1Department of Internal Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 2Department of Radiology, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaCorrespondence: Abilo TadesseDepartment of Internal Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaEmail abilo.tadesse@yahoo.cmBackground: Neuromyelitis optica spectrum disorder is an autoimmune, astrocytopathic CNS disease, mainly involving the optic nerves, spinal cord, and brain stem regions. The “International Panel for NMOSD Diagnosis (IPND) Diagnostic Criteria” was implemented to define the disorder.Case Presentation: A 38-year-old patient presented with visual loss of eight months’ duration and weakness of the lower extremities of one week’s duration. The patient had bilateral optic atrophy on fundoscopic examination, and flaccid paraplegia with sensory loss below T4 level. Serological tests for syphilis, HIV infection, and SLE were negative. Aquaporin-4 antibody test was not done due to limited clinical setup. T2-spine MRI revealed long central thoracic segment (T3 to T6) hyperintense lesion with mild cord expansion. Long segment central canal dilation (syrinx) was noted in the cord proximal to the lesion. Diagnosis of opticospinal variant, NMOSD was made using IPND diagnostic criteria. The patient was started on dexamethasone 50 mg, IV, four times daily (QID) for one week, and changed to prednisolone 1 mg/kg (40 mg) PO daily for one month, to be tapered over three-to-six months. The patient was scheduled to initiate azathioprine 50 mg PO twice daily.Conclusion: The case emphasizes the existence of neuromyelitis optica spectrum disorder in clinical settings of the developing world. High index of suspicion of this rare disease is required to avoid delayed diagnosis and treatment.Keywords: neuromyelitis optica spectrum disorder, Northwest Ethiopia

Nebiyu Bekele,1 Nebiyu Mesfin,1 Tigest Hailu,2 Abilo Tadesse1 1Department of Internal Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 2Department of Radiology, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaCorrespondence: Abilo TadesseDepartment of Internal Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaEmail abilo.tadesse@yahoo.comBackground: Paroxysmal sympathetic hyperactivity (PSH) is a neurologic syndrome characterized by paroxysmal and simultaneous occurrence of hypertension, hyperpyrexia, tachycardia, tachypnea, diaphoresis and dystonic posturing due to surge in sympathetic outflow after acquired brain injuries. Diagnosis of PSH is made using the paroxysmal sympathetic hyperactivity-assessment measure (PSH-AM) score, which comprises “clinical features severity” (CFS) score and “diagnosis likelihood tool” (DLT) score.Case presentation: A 35-year-old woman diagnosed to have echo-proven chronic rheumatic heart disease for 25 years. Percutaneous balloon mitral valvotomy was done 6 weeks previously for severe mitral stenosis. Left atrial thrombus was detected after the procedure and anticoagulant (warfarin) was initiated. She presented with severe headache and repeated vomiting of 1 day duration on arrival to the hospital. She had frequent seizure attacks with subsequent loss of consciousness on third day of admission. Diagnosis of status epilepticus secondary to intracranial hemorrhage due to warfarin toxicity was made after CT-scan revealed acute subdural hematoma and ventricular bleeding. Then she was transferred to medical intensive care unit (ICU), intubated and put on mechanical ventilator. Anti-epileptic drugs, antibiotics, vitamin K and fresh frozen plasma were given. She developed paroxysms of hypertension, tachycardia, tachypnea, hyperpyrexia, diaphoresis and decerebrate posturing after 7 days of neurological insult. She had normal inter-ictal EEG tracing during cyclic autonomic surge. CFS score was 11 and DLT score was 10. In sum, PSH-AM score was 21, suggested “probable” diagnosis of PSH. Morphine, diazepam, propranolol and gabapentin were given in combination to treat PSH. Severity of autonomic storm started to improve on second week of ICU admission. On the third week of admission, her clinical condition deteriorated suddenly, she developed asystole and died of cardiac arrest despite cardiopulmonary resuscitation (CPR).Conclusion: ’Clinical scoring’ was used used to diagnose PSH, since there was no any confirmatory test. Cocktail of drugs were required to treat catecholamine surge in PSH.Keywords: paroxysmal sympathetic hyperactivity; PSH, intracranial hemorrhage, warfarin toxicity

Avocado (Persea Americana) is a major crop in Kenya but its potential to generate income is limited by challenges associated with production and marketing. The objective of this study was to assess the impact of participation in collective marketing on the incomes of smallholder avocado farmers in Kigumo Sub-County, Murang'a County, Kenya. Data was collected from 300 randomly selected households comprising of 150 participants and 150 non-participants of collective marketing. Data collected included demographic characteristics, socio-economic and institutional factors, farmers' income, and market information. Propensity Score Matching (PSM) models were employed to estimate the impact of participation in collective marketing on incomes. Results showed that farmers who participated in collective marketing benefitted from increased production and better sales. Participation in avocado collective marketing increased farmers' incomes by an average of 32.95% during the three consecutive years considered (2018, 2019, and 2020). Participants produced significantly higher avocado fruits (1251.3 kg) compared to non-participants (889.7 kg) in 2020. Participants also fetched better prices of 7.5Ksh per fruit compared to non-participants who sold their fruits at 5Ksh. Based on our findings, we recommend that farmers should participate more in collective marketing so as to improve the incomes from their avocado production. Policymakers should also promote a collective marketing strategy through interventions such as improving access to avocado collection centers and provision of market infrastructures.

Nigatu Addisu Bekele,1 Jarsso Tadesse Hirbu2 1Department of Pharmacy, College of Medical and Health Sciences, Dilla University, Dilla, Ethiopia; 2Department of Internal Medicine, College of Medical and Health Sciences, Dilla University, Dilla, EthiopiaCorrespondence: Nigatu Addisu Bekele Tel +251-934 08 8585Email nigatua@du.edu.etPurpose: To assess antimicrobial use-related problems and associated factors among patients admitted to medical wards of Dilla University Referral Hospital.Patients and Methods: A hospital-based prospective observational study design was employed to assess the antimicrobial use-related problems among adult patients admitted to Dilla University Referral Hospital from 5 March to 4 September 2018. The antimicrobial therapy was reviewed to assure compliance with the recommendations of the national guidelines or evidence-based international clinical guidelines and drug therapy problem was identified. The logistic regression model was fit to determine the association between the different factors and the occurrence of drug therapy problems. Odds ratio was used to show a comparison of factors contributing to drug therapy problems. Statistical significance was considered at p-value < 0.05.Results: In this follow-up to 229 participants, the prevalence of antimicrobial therapy-related problem was 70.74%. “Noncompliance to therapy” was the most frequent DTP experienced by 68 (29.69%) of the patients followed by “needs additional drug therapy” seen among 31 (13.54%) patients. “Adverse drug reaction” was the least and experienced by 7 (3.06%) patients. Others include: dosage too low among 22 (9.61%), dose too high among 17 (8.30%), unnecessarily prescribed antimicrobials among 17 (7.42%) and ineffective antimicrobials among 8 (3.49%) patients. Compared with those who used less than four drugs, the use of four to six (AOR: 4.024) and seven and above (AOR: 13.516) drugs were determinants for antimicrobial use problems. Additionally, infectious cases not addressed by the national guideline (AOR: 3.328) and the unavailability of appropriate lab values results within 48 hours of hospital admission (AOR: 1.285) were determinants for antimicrobial use problems.Conclusion: Antimicrobial use problem was prevalent with 0.94-problems-per-patient. Polypharmacy, coverage of national guidelines and availing laboratory values within 48 hours of hospital admission were independent determinants of antimicrobial use problems.Keywords: antimicrobials, drug therapy problems, Dilla University Referral Hospital

Diabetic peripheral neuropathy is the most prominent microvascular complication of diabetes mellitus and the leading cause of ulceration, amputation, and extended hospitalization. Evidence regarding the magnitude and factors associated with diabetic peripheral neuropathy is not well documented in Ethiopia, particularly in the study area. A facility-based cross-sectional study was conducted among 293 adult type 2 diabetic patients who were on treatment and follow-up from May to June 31, 2023. To select participants in the study, a systematic random sampling method was utilized. Data were collected using semi-structured questionnaires and medical record reviews. The Michigan Neuropathy Screening Instrument (MNSI) was employed to assess diabetic peripheral neuropathy. To model the association between diabetic peripheral neuropathy and independent variables, binary logistic regression model was used. An adjusted odds ratio with a 95% confidence interval was used to estimate the association and statistical significance was proclaimed at a p-value < 0.05. The magnitude of diabetic peripheral neuropathy was 14.3% (95% CI 10.4-18.0). It was 13.4% (95% CI 8.4-19.1) among males and 15.4% (95% CI 10.1-22.2) among females. Age above 60 years (AOR = 5.06, 95% CI 1.60-15.96), being rural resident (AOR = 2.41; 95% CI 1.15-5.06), duration of diabetes above 5 years (AOR = 2.48, 95% CI 1.16-5.27) and having comorbid hypertension (AOR = 2.56, 95% CI 1.24-5.28) were independently associated with diabetic peripheral neuropathy. One in seven adult type 2 diabetes patients in the study area had diabetic peripheral neuropathy. Factors such as age, place of residence, duration of diabetes, and comorbid hypertension showed positive associations with diabetic peripheral neuropathy. Thus, it is imperative to give special consideration to diabetic patients who are elderly, living in rural areas, experiencing a prolonged duration of diabetes, or dealing with comorbid hypertension., (© 2024. The Author(s).)

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results in progressive weakness of skeletal muscles including respiratory muscles. Epidemiological and clinical aspects of ALS are derived from a few world regions with very little representation of low- and middle-income countries. We therefore set out to determine the epidemiological and clinical phenotype of individuals with ALS in Ethiopia. Methods: Multicenter retrospective analysis was conducted using clinical records from ALS patients seen in Ethiopia at Tikur Anbessa Specialized Hospital and Yehuleshet specialty clinic between January 2016 and August 2021. The data collected included clinical characteristics, disease-related symptoms, a revised ALS functional rating scale, and medications. Results: Patients in Ethiopia had a younger age of onset with a mean age of disease onset of 51.9 years. 2.9% of patients had juvenile ALS, and the male-to-female ratio was almost 2:1. 4.9% had a positive family history of the disease. 68% of patients had spinal region involvement at onset, while 32% had bulbar region involvement at onset. Riluzole was used by 31% of ALS patients. 20.6% of patients had some respiratory symptoms, but none received a standard respiratory function assessment. 33.3% of patients were wheelchair-bound. Conclusion: In this retrospective study spanning 5 years, we examined the clinical phenotype of ALS in Ethiopian patients. Our findings suggest that most patients had clinically definite ALS with spinal region involvement. Further research, including genetic and epigenetic information, is necessary to understand the early onset of the disease in Ethiopia.

Background: Stroke is one of the most common causes of disability among adults. Post-stroke depression (PSD) is a frequent neuropsychiatric complication in stroke patients. Despite the increasing prevalence of stroke, there is a paucity of data on PSD and its determinants among stroke survivors in developing countries like Ethiopia. We aim to assess the factors associated with PSD in survivors of stroke., Method: A hospital-based unmatched case-control study was conducted during the period of February to July 2020 at University of Gondar Hospital among stroke survivors. Study subjects were recruited consecutively. Socio-demographic and clinical data were obtained from patients' interviews and medical record reviews. A diagnosis of PSD was made using the Patient Health Questionnaire (PHQ-9). EpiData version 3.1 was used to enter data, and SPSS version 26 was used to analyze it. Bivariate and multivariate logistic regressions were fitted to identify associated variables. The adjusted odds ratio (AOR) with 95% confidence interval (CI) and p-value 0.05 were used to determine the significance of the association., Result: A total of 240 stroke survivors were included in the study (80 cases and 160 controls). The mean age was 60.8 years (SD ± 14.3) with an equal sex distribution. Variables statistically associated with PSD were male gender (AOR = 3.5, 95% CI: 1.64-7.46 C, P-value = 0.001), subcortical location of the largest lesion (AOR = 2.42, 95% CI: 1.06-5.56, p-value = 0.036), severity of the stroke (AOR = 52.34, 95% CI:10.64-256.87, p-value = 0.000), physical disability (AOR = 5.85. 95% CI:1.94-17.65, p-value = 0.002), previous history of stroke or transient ischemic attack (AOR = 5.90, 95% CI:2.04-17.10, p-value = 0.001) and ischemic heart disease (AOR = 9.97, 95% CI:3.4-29.22, p-value = 0.000)., Conclusion: Important factors in the occurrence of PSD in this study include prior history of stroke, physical disability, severity of the stroke, subcortical location of the lesion, male gender, and ischemic heart disease. Stroke patients with such factors need routine screening for PSD, particularly in LMICs where there is uncoordinated post-stroke care, a shortage of neurologists and mental health practitioners., (© 2022. The Author(s).)

Background: Epilepsy is characterized by two or more unprovoked recurrent seizures, which often respond to available antiseizure medications. However, seizure control among epileptic patients in the developing world is low. Factors determining seizure control among epileptic patients were not evidently explored in the study setting., Objectives: This study aimed to determine the magnitude of uncontrolled seizures and associated factors among epileptic patients at the University of Gondar hospital., Methods: This cross-sectional study was conducted at the University of Gondar hospital, Northwest Ethiopia. A convenience sampling method was used to recruit study subjects. Controlled seizure was defined as seizure freedom for the past 1 year. Logistic regression analysis was used to identify factors associated with seizure control. A p -value < 0.05 was used to declare a significant association., Results: A total of 320 study subjects were included in the study. The mean (±SD) age of patients was 27.5 ± 7.6 years. More than half (182/320, 57%) of epileptic patients had uncontrolled seizures. Five or more pretreatment seizure episodes (adjusted odds ratio = 3.98, 95% confidence interval: 1.81-8.75, p  = 0.001), less than 2 years on anti-seizure medications (adjusted odds ratio = 8.64, 95% confidence interval: 3.27-22.85, p  < 0.001), taking 2 or more ASMs (adjusted odds ratio = 2.48, 95% confidence interval: 1.23-5.02, p  = 0.011), poor adherence to ASMs (adjusted odds ratio = 9.37, 95% confidence interval: 4.04-21.75, p  < 0.001), and living at a single trip distance from hospital equaled 1 h or more (adjusted odds ratio = 4.20, 95% confidence interval: 2.11-8.41, p  < 0.001) were significantly associated with uncontrolled seizures., Conclusion: The dose of a preferred anti-seizure medication should be optimized before combinations of anti-seizure medications are used. Adherence to anti-seizure medications should be reinforced for better seizure control. Epilepsy care should be integrated into primary health care services in the catchment region., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Introduction: Warfarin is a widely used oral anticoagulant in clinical practice. It has variable intraindividual and interindividual dose response and a narrow therapeutic index. Therefore, it requires frequent and regular international normalized ratio (INR) determination to maintain the INR within the therapeutic range. The study evaluated parameters of anticoagulation control among patients on warfarin., Methods: A cross-sectional study was conducted at University of Gondar hospital. A consecutive sampling method was used to recruit study subjects. The anticoagulation control was evaluated by determining the proportion of desired INRs and the proportion of time spent in the therapeutic range (TTR). Logistic regression analysis was used to identify associated factors with adequate TTR. A P value <0.05 was used to declare significant association., Result: A total of 338 study subjects were included in the study. The mean age of patients was 48.8 (SD = 16.4) years. Atrial fibrillation was the commonest indication for warfarin therapy. One-third (33%) of study subjects achieved the desired INRs of 2.0-3.0, while about one-tenth (13%) of patients attained good INR control (TTR ≥ 65%). Multivariate logistic regression analysis revealed no significant association of sociodemographic and clinical characteristics with good TTR outcome., Conclusion: The level of anticoagulation control with warfarin among study subjects was very low. The authors recommend to implement a validated warfarin-dose titration protocol and to establish anticoagulation clinics to mitigate the low anticoagulation level., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Zelalem Liyew et al.)

We describe a case of a 59-year-old man with severe heterozygous familial hypercholesterolemia (FH) and elevated lipoprotein(a) presenting with severe aortic stenosis, treated with transcatheter aortic valve replacement (TAVR). His history also includes premature coronary artery disease requiring coronary artery bypass surgery at age 48 and a stroke at age 55. His pre-treatment lipid values include an LDL-Cholesterol (LDL-C) of 458 mg/dL, total cholesterol of 588 mg/dL, and lipoprotein (a) level of 351 nmol/L. Since his FH diagnosis, he has received several lipid-lowering agents including statins, bile acid sequestrants, nicotinic acid derivatives, and PCSK9 inhibitors. This case reflects the association of FH and elevated lipoprotein(a) with aortic stenosis and TAVR as a viable and effective treatment., (Copyright © 2021. Published by Elsevier Inc.)

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; P =0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m 2 versus 29±6 kg/m 2 ; P <0.001), hypertension (82% versus 50%; P <0.001), diabetes (39% versus 15%; P <0.001), and current smoking (16% versus 8%; P =0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; P =0.004) and other lipid-lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60-1.49; P =0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid-lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.

Visual loss is a rare but potentially devastating postoperative complication of prone spinal surgery with a reported incidence of 0.017 to 0.1 percent. We present a case of post-operative bilateral visual loss in a patient who had a laminectomy in prone position under general anesthesia. A 17-year-old male patient with large syringomyelia extending from C2 - T2 level had a surgical procedure done under general anesthesia (GA) in prone position that lasted four hours. After the surgical procedure, the patient presented to the Ophthalmology Clinic of Princess Marina Hospital, with a complaint of visual loss of the right eye followed by left, of one week duration. The patient never had a visual impairment in the past. Physical examination, fundal examination and CT scan revealed no primary cause for the visual loss. In this patient the absence of any finding in the optic disc and the retina and the normal CT scan, suggests that the most likely diagnosis is posterior ischemic optic neuropathy. The patient was treated with prednisolone tablet daily and showed mild improvement in vision.

Background: Sofosbuvir is a chain-terminating nucleotide analogue inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase that is efficacious in subjects with HCV genotype 1-6 infection. Sofosbuvir resistance is primarily conferred by the S282T substitution in NS5B., Methods: NS5B sequencing and susceptibility testing of HCV from subjects infected with genotypes 1-6 who participated in phase 2 and 3 sofosbuvir clinical trials was performed., Results: No NS5B variants present at baseline among 1645 sofosbuvir-treated subjects were associated with treatment failure; sofosbuvir susceptibility was within 2-fold of reference. Among 282 subjects who did not achieve sustained virologic response, no novel sofosbuvir resistance-associated variants were identified, and the NS5B changes observed did not confer significant reductions in sofosbuvir susceptibility. In 1 subject with S282T observed at relapse 4 weeks after sofosbuvir monotherapy, the resistant variant (13.5-fold reduced sofosbuvir susceptibility, replication capacity <2% of control) became undetectable by deep sequencing 12 weeks after treatment. L159F and V321A were identified as treatment-emergent variants but did not confer resistance to sofosbuvir in the replicon system., Conclusions: These data demonstrate a uniform susceptibility of subject-derived HCV to sofosbuvir, and also show that selection of sofosbuvir-resistant HCV is exceedingly rare and is associated with a significant reduction in viral fitness., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The combination of cytarabine and fludarabine was associated with superior clinical outcomes compared with those of high-dose cytarabine in relapse acute myeloid leukemia (AML). We conducted a phase I study combining oxaliplatin with cytarabine and fludarabine therapy for patients with relapsed or refractory AML., Patients and Methods: Between January 2008 and November 2009, 27 patients were registered in the study. Patients had histologically confirmed disease, performance status 0 to 2, and adequate organ function. The treatment regimen consisted of increasing doses of oxaliplatin (25, 30, or 35 mg/m(2)/d) on days 1 to 4 (escalation phase), and fludarabine (30 mg/m²) and cytarabine (500 mg/m²) on days 2 to 6, every 28 days for ≤ 6 cycles. The dose-limiting toxicity was defined as any symptomatic grade ≥ 3 nonhematologic toxicity lasting ≥ 3 days and involving a major organ system., Results: Of 27 patients, 12 were treated in the dose-escalation phase and 15 at the maximum tolerated dose for oxaliplatin (30 mg/m²; expansion phase). All patients were evaluable for toxicity and response. Only 1 patient received the second cycle; the remaining patients received no further study treatment, owing to slow recovery from toxicities or physician decision. Grade 3-4 drug-related toxicities included diarrhea (grade 4) and elevated levels of bilirubin (grade 3) and aspartate transaminase (grade 3). In all, 3 patients had a complete remission and 2 patients complete response without platelet recovery., Conclusion: Oxaliplatin, cytarabine, and fludarabine therapy had antileukemic activity in patients with poor-risk AML, but it was associated with toxicity. Different schedules and doses may be better tolerated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: Numerous chemotherapeutics are used in the treatment of high-grade glioma (HGG). The purpose of this study was to evaluate the therapeutic value of vincristine (VCR) in the treatment of HGGs., Materials and Methods: A meta-analysis of HGG studies was performed to evaluate and compare the efficacy of chemotherapy drugs using observed and predicted median overall survival and survival gain as previously described., Results: Patient cohorts treated with VCR-containing-regimens had a significant survival gain advantage over cohorts treated with other chemotherapy drugs (p<0.0001). VCR was most effective in treating newly diagnosed adult (p<0.0001) and elderly (p=0.0001) patients. When VCR was combined with nimustine, carmustine, cytarabine or etoposide, the effect was antagonistic, but when VCR was combined with lomustine, procarbazine, cyclophosphamide, dacarbazine, hydroxyurea, or cisplatin it was synergistic., Conclusion: Results from this study suggest that VCR should be included in chemotherapy regimens for patients being treated for newly diagnosed or recurrent HGG.

Epidermal growth factor receptor (EGFR) has been extensively targeted in the treatment of non-small cell lung cancer, producing responses in a small number of patients. To study the role of ligand expression in mediating response to EGFR antagonism, we injected NCI-H441 [EGFR and EGF/transforming growth factor-alpha (TGF-alpha) positive] or PC14-PE6 (EGFR positive and EGF/TGF-alpha negative) human lung adenocarcinoma cells into the lungs of nude mice. We randomized the mice to receive treatment with the EGFR tyrosine kinase inhibitors gefitinib or AEE788 or vehicle. Treatment of mice bearing NCI-H441 but not PC14-PE6 lung tumors resulted in a significant reduction in primary tumor growth, pleural effusion, and lymph node metastasis. Immunohistochemical analyses revealed that NCI-H441 and PC14-PE6 cells expressed EGFR but that the expression of EGF/TGF-alpha was high in NCI-H441 cells and very low in PC14-PE6 cells. Consequently, EGFR was activated in both tumor and tumor-associated endothelial cells in the NCI-H441 tumors but not in the PC14-PE6 tumors. Antagonism of EGFR signaling by treatment of mice with AEE788 decreased proliferation and increased apoptosis of both tumor cells and tumor-associated endothelial cells in NCI-H441 tumors but not in PC14-PE6 tumors. However, after transfection of PC14-PE6 cells with TGF-alpha, lung tumors derived from the transfected cells expressed and activated EGFR in both tumor and tumor-associated endothelial cells and tumors responded to treatment with AEE788. Collectively, these results strongly suggest that the response of human lung cancers growing orthotopically in mice to the inhibition of EGFR signaling is determined by ligand (EGF/TGF-alpha) expression by tumor cells. Our findings provide an additional explanation for the susceptibility of lung cancers to treatment with EGFR tyrosine kinase inhibitors.

Background: The current American Joint Committee on Cancer (AJCC) esophageal cancer staging for nodal status is difficult to interpret and is based solely on lymph node location relative to the primary tumor's esophageal location. Recent reports suggest that the number of lymph nodes involved is also an important factor. We reviewed our esophageal experience to propose an improved nodal staging system., Methods: In all, 1,027 patients with resected esophageal cancer from 1970 to 2005 were reviewed. Lymph nodes stations were assigned according to AJCC criteria. Overall survival was assessed by Kaplan-Meier analysis. The impact of location, number of involved lymph nodes, and use of preoperative chemotherapy or radiation therapy, or both, was assessed., Results: Nonregional nodal involvement (n = 17) was associated with decreased survival compared with regional (n = 441) or celiac nodal (n = 73) involvement (3-year: 0% versus 24% and 23%; p < 0.001). The number of involved lymph nodes was strongly associated with survival (3-year: 0 nodes = 63%, 1 to 3 nodes = 31%, more than 3 nodes = 13%; p < 0.001), and multivariable Cox proportional-hazards analysis suggested that the location and number of involved lymph nodes were independent predictors of survival (p < 0.001). We propose a modified nodal staging system that designates celiac nodes as regional and includes number of involved nodes: pN0, no nodes (3 years = 63%, n = 496); pN1-regional, 1 to 3 nodes (3 years = 32%, n = 292); pN2-regional, more than 3 nodes (3 years = 14%, n = 222); pN3-nonregional node (3 years = 0%, n = 17 [p < 0.0001]). This modified nodal staging system better predicts survival than the current AJCC nodal staging system in which survival for pN1 (3 years = 24%) and pM1a (3 years = 23%) do not differ (p = 0.67). The use of induction before surgical resection did not alter the predictive effect of the new nodal staging system., Conclusions: Modification of the AJCC nodal classification system to incorporate the number of involved lymph nodes with regional and nonregional node location simplifies and better predicts long-term survival than does the current AJCC nodal system.

Background: Gender-based violence exists in all societies and individual woman experience it in every social and economic group. Different studies in Africa have showed that there are significant percentages of females that have suffered from the violence. Most societies encourage manifestation of manliness through violence in workplace, among friends and in the community as a whole., Objective: The study tried to see the prevalence of Gender-based Violence and the various patterns and correlates of Gender-Based Violence among female high-school students, Northwest Ethiopia., Methodology: This study is a cross--sectional study done on 367 female high--school students who were given self-administered questionnaires to assess the prevalence of gender-based violence against these students in Dabat High school., Result: This study showed 11.4% of the students have started sexual intercourse and of these, 33.3% were raped cases. Twenty percent (20.4%) from the total of 367 students have survived attempted rape. In addition 44% of the students were sexually harassed. Among the study participants considerable proportion are mainly responsible for the housework. Around 8% of the students have undergone Female Genital Mutilation., Conclusion: Generally, the prevalence of gender-based violence is high in Dabat High-School, Northwest Ethiopia and attention should be given by policy-makers and law enforcing bodies to adequately address the problem.

New biomarkers for head and neck squamous cell carcinoma (HNSCC) patients are being sought to help predict disease outcome, guide treatment, and develop new treatments. In the present study, the association between a novel functional C/T polymorphism in the core promoter of cytosine DNA methyltransferase (DNMT) 3B6 and overall survival of HNSCC patients was investigated. Genomic DNA was extracted from tumor tissue and leukocytes from each HNSCC patient. We used the PCR-restriction fragment length polymorphism (PCR-RFLP) assay to determine the DNMT3B genotype. Kaplan-Meier product-limit method and univariate/multivariate Cox proportional hazard models were used to correlate DNMT3B genotype with overall survival of HNSCC patients who underwent surgical resection. There was a marked association between DNMT3B C/T polymorphism and overall survival of HNSCC patients (P=0.004). The homozygotes (CC-genotype and TT-genotype) survived significantly longer than the heterozygotes (CT-type). The multivariate Cox proportional hazard modeling showed that HNSCC patients with CT-genotype had a hazard ratio of 4.829 over patients with CC-genotype or TT-genotype. A DNMT3B C/T polymorphism has been correlated with survival differences in HNSCC patients. If validated in larger studies, this polymorphism might be used to identify deleterious patterns of gene silencing by methylation in HNSCC.

Background: The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population., Methods: Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability., Results: The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups., Conclusions: ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy., (Copyright 2003 American Cancer Society.)

AKT, a downstream mediator of phosphatidylinositol 3'-kinase, is activated in non-small cell lung cancer (NSCLC), but we have not yet defined the stage of malignant transformation at which AKT is activated in the bronchial epithelium. We performed immunohistochemical analysis of activated AKT [phosphorylated (p)-AKT Ser(473)] in tissue specimens of normal bronchial epithelium, bronchial hyperplasia and squamous metaplasia ("reactive" epithelium), bronchial dysplasia, and NSCLC. Among NSCLC specimens, immunohistochemical findings were correlated with patient demographics, tumor stage, histology, and survival. We observed p-AKT expression in 12 of 44 (27.3%) normal bronchial biopsy specimens, 4 of 9 (44.4%) reactive epithelium specimens, 22 of 25 (88%) dysplastic specimens, and 25 of 76 (33%) NSCLC specimens. Among patients with resected early-stage or locally advanced NSCLC, p-AKT expression had no effect on tumor stage, histology, or survival. Of the histological groups examined, bronchial dysplasia specimens expressed p-AKT most frequently, supporting AKT activation as an early event in lung cancer progression. Given its role as a mediator of malignant transformation, p-AKT should be investigated as a potential target in future lung cancer prevention studies.