The advisory dean program: a personalized approach to academic and career advising for medical students.

Advising and mentoring programs for medical students vary in their official names, scope, and structures. Catalyzed by negative student feedback regarding career advising and a perceived disconnection between faculty and students, in academic year 2003-2004, Columbia University College of Physicians and Surgeons implemented its formal Advisory Dean (AD) Program and disbanded its former advising system that used faculty volunteers. The AD Program has become a key element for enhancing the students' professional development throughout their student training, focusing on topics including, but not limited to, career counseling, professionalism, humanism, and wellness resources. Advisory deans and the dean for student affairs, familiar with resources for academic development, student support, and extracurricular activities, operate at the nexus of the program, providing personalized mentoring and advising for each student. Fully supported by administration and faculty, the program has shown early success according to student feedback. Early feedback from the Class of 2006, who had been involved in our AD Program for three years, has been encouraging. Out of 152 students, 104 (68%) provided feedback, with 93 (89%) of the respondents reporting the AD Program as a valuable initiative. Expecting to further improve on this early positive response, the AD Program will continue to foster an environment conducive to a seamless transition from student to physician.     

The evolution and genesis of supraventricular waltz & duet

Objective. This study documents and traces the evolution of triple rhythm (Waltz) linking the great veins, corresponding systemic or pulmonary venous sinuses and pectinated right or left atrium in frog, turtle, snake and human hearts. Alternating rhythm (duet) between systemic and pulmonary veins has also been documented in these hearts. Material Studied. The hearts of six dead hammer-head sharks were examined with the naked eye. Air-breathing, fresh-water fish (three Channa striata and three Indian catfish) were anaesthetised with ketamine and their pharynx insufflated with oxygen. Six frogs, three turtles, and two snakes were anaesthetised, intubated and ventilated. Contractions of the exposed hearts of these animals were correlated with their electrocardiograms using superimposed videos. The human heart was observed carefully during surgery through median sternotomy or anterolateral thoracotomy by visual inspection especially during instillation of or recovery from cardioplegia. Digital videos were taken and studied in slow motion replay later. Observations. In the air-breathing fish, Channa striata and Indian catfish and presumably the shark, the cardinal veins and thin walled sinus venosus do not contract. In the frog, turtle, and snake there is sequential contraction of the systemic veins, systemic venous sinus and pectinated right atrium. Likewise, there is waltz on the arterial side. There is a duet between systemic and pulmonary veins, contractions of the former preceding the latter in the frog, turtle and snake. The observations are similar in the human heart except that the inferior vena cava does not contract. Conclusions. There is sequential contraction of the superior vena cava, the systemic venous sinus and the pectinated part of the right atrium in the human heart. Likewise, there is a waltz linking the terminal pulmonary veins, pulmonary venous sinus and pectinated part of the left atrium in the human heart. This waltz or triple rhythm, as well as a duet between the systemic and pulmonary veins are seen in frog, turtle and snake. The duet is also observable in the human heart, during recovery from cardioplegia. It is likely that the waltz and duet are conducted by a neurogenic mechanism. Clinical Implications. The understanding, preservation and restoration of the mechanism sustaining supraventricular waltz and duet is relevant to surgical and interventional procedures for control of atrial arrhythmia, Fontan circulation, technique for cardiac transplantation and planning atriotomies.     

Psychological aspects of 211 female patients attending a urodynamic unit

Psychological aspects of 211 female patients attending a Urodynamic Unit were assessed by means of standardized questionnaires. Patients with genuine stress incontinence (GSI) showed changes comparable to other patients with longstanding physical complaints. Patients with sensory urgency (SU) lacked self esteem and were more anxious than those with GSI. Patients with detrusor instability (DI) were as anxious and lacking in self esteem as patients with sensory urgency and additionally had morbid thoughts and worries and higher scores on the hysteria sub-scale of the Crown-Crisp Experiential Index. Roughly a quarter of all the patients reported that their urinary symptoms rendered life intolerable and they were as anxious, depressed and phobic as psychiatric inpatients.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

Gene therapy for diabetic peripheral neuropathy: A randomized,placebo‐controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth factor

AbstractVM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9 months (DPN 3‐1) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12 months (DPN 3‐1b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3‐1 was change from baseline in the mean 24‐h Numerical Rating Scale (NRS) pain score. In DPN 3‐1b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well‐tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3‐1. In DPN 3‐1b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3‐1b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3‐1b, symptomatic relief was maintained for 8 months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long‐lasting pain‐relieving effects of VM202 observed in DPN 3‐1b warrant another rigorous phase III study. Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Nonviral gene therapy can be used safely and practically to treat DPN.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.     

Novel human autoantibodies to phosphoepitopes on mitotic chromosomal autoantigens (MCAs).

BACKGROUND: Human autoantibodies to proteins of the mitotic apparatus have demonstrated clinical utility and usefulness as molecular probes for identification and characterization of novel autoantigens, as exemplified by autoantibodies to centromere proteins. In contrast, there have been very few reports of autoantibodies with reactivity to antigens located along mitotic chromosome arms, but not in interphase nuclei. The purpose of this study was to identify and characterize autoantibodies with reactivity to mitotic chromosomal antigens (MCAs) located exclusively on mitotic chromosome arms, and to determine if patients with these autoantibodies have common clinical features. METHODS: Routine immunofluorescence screening of serum samples referred for antinuclear antibody investigation over a 10-year period was used to identify autoantibodies to MCAs. MCAs were identified by exclusive immunofluorescence staining of mitotic chromosome arms with no staining of interphase nuclei. MCA-reactive sera were further characterized for patterns of staining on mitotic chromosome arms and sensitivities to chemical and enzymatic treatments, and for one of these sera, its ability to abrogate progression through mitosis when microinjected into cells. RESULTS: Of 60,000 sera screened for antinuclear antibodies by immunofluorescence, we identified three IgG autoantibodies reacting exclusively to MCAs. The anti-MCA autoantibodies did not react with condensed chromatin in spermatozoa or in apoptotic HeLa cells. Reactivity of all three sera was abrogated by treatment with protease, but not RNase, indicating that the MCAs are protein in nature and do not contain RNA epitopes. The three anti-MCA antibodies seem to react to three different antigens because they gave different patterns of staining of chromosome arms, reacted with chromosomes in different stages of mitosis, and displayed different sensitivities to treatment with DNase 1, salt, and phosphatases. Phosphatase treatment suggests that MCA1 and MCA2 contain serine/threonine phosphoepitope(s) and MCA3 tyrosine phosphoepitope(s). Loss of MCA2 reactivity to DNase 1 treatment and its retention after salt extraction suggests that it is a chromosomal scaffold protein. Sensitivity of all three MCAs to acid suggests that they are histone-like or histone-associated proteins. CONCLUSIONS: We report the identification of three novel MCA-reactive sera. Patient diagnoses included discoid lupus erythematosus, chronic lymphocytic leukemia, Sj?gren's syndrome, and polymyalgia rheumatica. The reactivity of anti-MCA antibodies with phosphoepitopes is likely to explain restriction of immunofluorescence staining to chromosome arms during mitosis. Microinjection of MCA1-reactive antibodies led to metaphase arrest, without any change in morphology of the mitotic spindle or metaphase chromosomes suggesting that MCA1 may have a role in sister chromatid separation.     

Predicting Short-Term Outcome of Primary Total Hip Arthroplasty : A Prospective Multivariate Regression Analysis of 12 Independent Factors

The purpose of this study was to investigate factors affecting the short-term outcome of primary total hip arthroplasty (THA) and develop a multivariate regression equation to predict the short-term outcome of primary THA. Prospectively collected data for 101 primary THAs performed at a single institution were used in this study. Twelve independent variables were analyzed via correlation and multivariate regression analyses. Correlation analyses showed that three variables significantly influenced Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function (PF) score at minimum follow-up of 1 year: preoperative WOMAC PF score (P < .0001), sex (GN, P = .0159), and the presence of preoperative comorbidities (CMB, P = .0246). Multivariate regression analysis yielded the following equation: Outcome = PF?0.45 − GN?9 + CMB?8 + 62, which can be used to predict the general short-term outcome of primary THA.     

Tip-apex distance of intramedullary devices as a predictor of cut-out failure in the treatment of peritrochanteric elderly hip fractures

A tip-apex distance (TAD) of greater than 25 mm has been shown to be an accurate predictor of lag screw cut-out when sliding hip screws (SHS) are used to treat peritrochanteric (PT) hip fractures. The purpose of this study was to determine which factors, including TAD, correlated with successful clinical outcomes of PT hip fractures surgically treated with intramedullary (IM) devices. A total of 192 patients were included in this retrospective study. The TAD values of this cohort were radiographically analysed at a mean follow-up of 13 months. This was correlated with limited functional status and the rate of revision for implant failure or inability to achieve fracture union. Only 82 patients had adequate follow-up to fracture union or definitive failure. There were 46 intertrochanteric (IT) hip fractures and 36 subtrochanteric (ST) fractures. Overall, seven patients (8.5%) went on to experience lag screw cut-out. The average TAD of the patients who did not cut-out was 18 mm, compared to 38 mm for those who did (p = 0.012). All patients who cut-out had IT fractures (p = 0.017). The percentage of cut-outs correlated directly to both the severity of IT fractures and the TAD. Using a cutoff of 25 mm there was a statistically significant difference in the incidence of lag screw cut-out (p < 0.001). As in sliding hip screws, surgeons should strive for a TAD less than 25 mm when using IM devices in the treatment of PT hip fractures to help avoid lag screw cut-out.