Familial hemiplegic migraine: a clinical comparison of families linked and unlinked to chromosome 19

We compared the clinical characteristics of 50 patients from three unrelated families with familial hemiplegic migraine (FHM) linked to chromosome 19, with those of 20 patients from two families with FHM not linked to chromosome 19. We found no significant differences for age at onset, frequency and duration of attacks, duration of the paresis, and occurrence of basilar migraine symptoms. In the linked families, significantly more patients reported unconsciousness during attacks (39%, vs 15%; p<0.05) and provocation of attacks by mild head trauma (70% vs 40%; p< 0.05). In one linked family patients also displayed chronic progressive cerebellar ataxia, whereas in one unlinked family benign infantile convulsions occurred in addition to FHM. Interestingly, so far an association with cerebellar ataxia was only described in chromosome 19-linked families. FHM linked to chromosome 19 and FHM unlinked to chromosome 19 do not differ with respect to clinical features.     

Red cell loss following orthopedic surgery: the case against postoperative blood salvage

BACKGROUND: Expensive devices have been developed for the collection and transfusion of blood salvaged after hip or knee arthroplasty. STUDY DESIGN AND METHODS: The volume of salvaged red cells was measured for the first 6 hours after operation. This volume was compared to total red cell loss during hospitalization and to the volume of allogeneic red cells transfused. RESULTS: Mean postoperative red cell loss in 31 patients following hip replacement was 55 +/− 29 mL and that in 20 patients following knee replacement was 121 +/− 50 mL. The 6-hour wound drainage represented 8.7 and 16.8 percent of overall red cell loss during hospitalization for hip and knee replacement, respectively. The transfusion of postoperatively salvaged red cells would have supplanted transfusion of less than one-third of a unit of allogenic blood after hip replacement and two-thirds of a unit after knee replacement. Only three patients (5.9%) lost red cell volume in the drainage equivalent to or in excess of 1 unit of red cells (180 mL). The volume of red cells salvaged postoperatively bore no relationship to perioperative red cell losses as a whole. CONCLUSION: The relatively small red cell loss in the postoperative period in most arthroplasty patients does not appear to justify the routine use of this technique for the recovery of autologous blood.     

Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor

The extracellular matrix (ECM) of cultured bovine aortic endothelial cells (BAEs) was analyzed by immunoblotting and reverse fibrin autography and shown to contain type 1 plasminogen activator inhibitor (PAI-1). Most PAI-1 in the ECM formed complexes with exogenously added tissue-type plasminogen activator (tPA), demonstrating that this PAI-1 was functionally active. The resulting tPA/PAI-1 complexes were recovered in the reaction solution, indicating that the PAI-1 in such complexes no longer bound to ECM. The PAI-1 could not be removed by incubating ECM in high salt (2 mol/L NaCl), sugars (1 mol/L galactose, 1 mol/L mannose), glycosaminoglycans (10 mmol/L heparin, 10 mmol/L dermatan sulfate), or epsilon-aminocaproic acid (0.1 mol/L). However, PAI-1 could be extracted from ECM by treatment with either arginine (0.5 mol/L) or potassium thiocyanate (2 mol/L), or by incubation under acidic conditions (pH 2.5). ECM depleted of PAI-1 by acid extraction was able to bind both the active and latent forms of PAI-1. In this instance, most of the bound PAI-1 did not form complexes with tPA, indicating that the latent form was not activated as a consequence of binding to ECM. Although the PAI-1 activity in conditioned medium decayed with a half-life (t 1/2) of less than 3 hours, the t 1/2 of ECM- associated PAI-1 was greater than 24 hours. These data suggest that PAI- 1 is produced by cultured BAEs in an active form and is then either released into the medium where it is rapidly inactivated or into the subendothelium where it binds to ECM. The specific binding of PAI-1 to ECM protects it from this inactivation.     

Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized,phase III,Myeloma XI trial

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n=2,042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib, and dexamethasone (CVD) was administered before autologous stem-cell transplantation to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation, eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI]: 0.75-0.96; P=0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI: 0.63-0.93; P=0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI: 0.58-0.93; HR for OS, 0.78; 95% CI: 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI: 0.43-0.84; HR for OS, 0.70; 95% CI: 0.42-1.15) and ultra-high-risk cytogenetics (HR for PFS, 0.67; 95% CI: 0.41-1.11; HR for OS, 0.65; 95% CI: 0.34-1.25). Among patients randomized to lenalidomide maintenance (n=451) or observation (n=377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI: 0.37-0.60; P<0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance. The trial was registered with the EU Clinical Trials Register (EudraCT 2009-010956-93) and ISRCTN49407852.     

Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.     

Short-term outcomes of a program developed to inculcate research essentials in undergraduate medical students

Background:

Participation in research during undergraduate studies may increase students’ interest in research and inculcate research essentials in them.

Aims:

The purpose of this study was to evaluate the effectiveness of the mentored student project (MSP) program.

Settings and Design:

In the MSP program, students in groups (n = 3 to 5) undertook a research project, wrote a scholarly report, and presented the work as a poster presentation with the help of a faculty mentor. To begin with, the logic model of the program was developed to identify short-term outcomes of the program on students, mentors, and the institution. A quasi-experimental design was used to measure the outcomes.

Materials and Methods:

A mixed method evaluation was done using a newly-developed questionnaire to assess the impact of the MSP on students’ attitude, a multiple-choice question (MCQs) test to find out the impact on students’ knowledge and grading of students’ project reports and posters along with a survey to check the impact on skills. Students’ satisfaction regarding the program and mentors’ perceptions were collected using questionnaires. Evidence for validity was collected for all the instruments used for the evaluation.

Statistical Analysis:

Non-parametric tests were used to analyze data. Based on the scores, project reports and posters were graded into A (>70% marks), B (60-69% marks), and C (<59% marks) categories. The number of MSPs that resulted in publications, conference presentation and departmental collaborations were taken as impact on the institution.

Results:

Students’ response rate was 91.5%. The students’ attitudes regarding research changed positively (P = 0.036) and score in the MCQ test improved (P < 0.001) after undertaking MSP. Majority of project reports and posters were of grade A category. The majority of the items related to skills gained and satisfaction had a median score of 4. The MSPs resulted in inter-departmental and inter-institutional collaborations, 14 publications and 15 conference presentations. An area for improvement noted was to have the MSP implemented in the curriculum without increasing students’ overall workload and stress.

Conclusion:

The study identified strengths and weaknesses of the MSP program. Our model of undergraduate research project may be incorporated in undergraduate medical programs to foster positive attitude and knowledge base about scientific research and to instil research skills among students.KEY WORDS: Attitude, knowledge, mentored, outcome, research, skills, student     

Successful treatment of Fusarium keratitis with cornea transplantation and topical and systemic voriconazole

A case of invasive Fusarium keratitis in a previously healthy male patient was treated successfully with cornea transplantation and systemic and topical voriconazole after treatment failure with topical amphotericin B and systemic itraconazole. Topical voriconazole was well tolerated, and, in conjunction with the oral administration, it resulted in a high level of the drug in the anterior chamber of the eye (which was 160% of the plasma drug level).     

Acute pyelonephritis with renal abscesses and acute renal failure after salmonella infection

Urinary tract infections, renal abscess formation and acute renal failure (ARF) after salmonella infection are rarely reported in children. We present a previously healthy teenager who developed ARF with renal abscess formation after salmonella infection, in whom we believe that acute salmonella pyelonephritis was the main causative factor for ARF and not dehydration, shock or rhabdomyolysis, which have already been described in the literature. With prolonged antibiotic treatment and adequate hydration, the boy’s condition improved, but chronic kidney disease was unfortunately inevitable. Conclusion: Salmonella pyelonephritis has, according to our knowledge, not yet been described to be the main causative factor of ARF in previously healthy children, as was the case in our patient. Long‐term antibiotic treatment of at least 6 weeks is probably a must in such patients, even though chronic kidney disease could not have been prevented.