Pineal germinoma: MR imaging

Magnetic resonance (MR) imaging characteristics of pineal germinomas are described in seven patients imaged with MR and computed tomography (CT). In patients with symptoms of an enlarging process in the quadrigeminal plate cistern, MR imaging was as sensitive as CT scanning in detecting the mass. MR imaging did not detect a normal-sized, calcified neoplastic gland. Germinoma, germinoma with embryonal cell carcinoma elements, and pineoblastoma demonstrated different MR signal characteristics. Although direct coronal and sagittal MR images were useful in defining the relationship of the tumor to the posterior third ventricle, Sylvian aqueduct, and vein of Galen, the ease, rapidity, and sensitivity of CT scanning suggest that CT should remain the modality of choice for initial evaluation and screening of the pineal region, especially in the younger pediatric population, in whom detection of calcification may provide the only clue of an abnormality.     

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.     

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.     

Quality of life following primary vs. redo transthoracic paraesophageal hernia repairs

The purpose of this study was to compare the quality of life (QOL) and functional results of 42 patients undergoing primary (60%) and 23 patients undergoing redo (40%) transthoracic paraesophageal hernia repairs. All patients had a floppy Nissen or Belsey anti-reflux repair with or without a Collis gastroplasty. Morbidity occurred in 12% of patients and was similar between groups (P=1.0). Overall QOL scores were not different between groups. Patients undergoing initial repair were found to have significantly higher QOL scores related to their GERD symptoms (P=0.02). Postoperative GERD symptom scores were not significantly different between groups for heartburn, regurgitation, epigastric/chest pain, or cough. Redo patients had more bloating (P=0.02) and dysphagia (P=0.04). Overall, total GERD scores were higher in the redo group compared to the initial group indicating worse GERD-related dysfunction in the redo group (15.8+/-3.8 vs. 6.3+/-1.6, P=0.03). Functional and QOL analysis of transthoracic paraesophageal hernia repairs indicates that redo procedures are associated with a higher incidence of specific gastrointestinal symptoms and worse GERD-related QOL when compared to initial procedures. These differences, while statistically significant, have limited clinical relevance as the overall QOL was not different between groups and low GERD symptom scores were found in both groups.     

Type II cell proliferation related to migration of inflammatory cells into the lung

Enhanced proliferation of epithelial cells in the lung is usually associated with some form of cellular injury. However, increased epithelial cell proliferation has also been observed in the absence of morphological signs of cellular injury. The nature of the stimuli to cell proliferation in the absence of cell injury is not clear. We hypothesized that one stimulus to epithelial cell proliferation in the absence of morphological injury to lung cells was the migration of inflammatory cells through the epithelium from the vasculature. This hypothesis was tested by comparing proliferation in the lungs of normal mice with that of white blood cell (WBC)-depleted mice when migration of WBC was stimulated by carbon instillation. White blood cell depletion in mice was accomplished with injections of 89SrCl2 (irradiated group). Sixteen days later, when WBC levels were reduced by about 64%, 4 mg colloidal carbon was instilled intratracheally into both normal and irradiated mice. At intervals of 1 through 4, 7, and 14 days after carbon instillation, four mice in each group were given ip tritiated thymidine and killed 1 hr later, and the lungs lavaged and prepared for electron microscopy and light microscope autoradiography. Analysis of lavage fluid revealed about 69% fewer cells in the irradiated mice compared to the normal mice at 1 day. There was no electron microscopic evidence of injury to the alveolar epithelium in either the normal or irradiated mice but there was increased proliferation of Type II cells. The proliferative response of Type II cells was 100 and 300% greater in the normal lung compared to irradiated mice at 3 and 4 days after carbon instillation, respectively. These data support the hypothesis that epithelial cell proliferation in the lung, in the absence of cellular injury, is related to the migration of WBC into the lung.     

A 17-year-old with rash, fever, myalgias, and nephritis

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.