Biomedical subjects
Publications and source records attributed to M Misra.
Multiple cerebral infarcts, bilateral optic neuropathy with limb ischemia, following scorpion bite is documented. Vasospasm and autonomic storm due to envenomation is a plausible explanation for this symptom complex.
Spontaneous rupture of cerebral aneurysms typically results in subarachnoid hemorrhage. The primary goal of treatment of cerebral aneurysms is to prevent future rupture. Surgical clipping had been the mainstay of treatment of both ruptured and unruptured cerebral aneurysms. In 1991, Guglielmi detachable coil (GDC) embolization was introduced as an alternative method for treating selected patients with aneurysm. The goal of the treatment is prevent the flow of blood into the aneurysm sack by filling the aneurysm with coils and thrombus. Theoretically, there are several advantages of GDC over surgery. These procedures are performed under general anesthesia with the standard transfemoral approaches used in diagnostic angiography. Since its inception, GDC embolization has evolved as a result of both clinical experience and the introduction of technological improvements. We are now better at selecting aneurysms appropriate for coiling, which also have wide necks. Advances in GDC technology have also improved this method of treatment. Over the last several years, the number of coil sizes has been increased, multidimensional coils allowing safer initial coil placement have become available, and, more recently, softer coils have been introduced. Our current approach is to have both surgical and endovascular options for patients.
BACKGROUND: Cerebral vasospasm is a well-known and serious complication of aneurysmal subarachnoid hemorrhage. The means of monitoring and treatment of vasospasm have been widely studied. Each neurosurgical center develops a protocol based on their experience, availability of equipment and personnel, and cost, so as to keep morbidity and mortality rates as low as possible for their patients with vasospasm. METHODS: At the University of Illinois at Chicago, we have developed algorithms for the diagnosis and management of cerebral vasospasm based on the experience of the senior authors over the past 25 years. This paper describes in detail our approach to diagnosis and treatment of aneurysmal subarachnoid hemorrhage and vasospasm. Our discussion is highlighted with data from a retrospective analysis of 324 aneurysm patients. RESULTS: Over 3 years, 324 aneurysms were treated; 185 (57%) were clipped, 139 (43%) were coiled. The rate of vasospasm for the 324 patients was 27%. The rate of hydrocephalus was 32% for those patients who underwent clipping, and 29% for those coiled. The immediate outcomes for those who underwent clipping was excellent in 35%, good in 38%, poor in 15.5%, vegetative in 3%, and death in 8% of the patients. For those who underwent coiling the immediate outcome was excellent in 64%, good in 14.5%, vegetative in 2.5%, and death in 14.5% of the patients. These statistics include all Hunt and Hess grades. For those patients who underwent clipping, 51% were intact at 6 months follow-up, 15% had a permanent deficit, 10% had a focal cranial nerve deficit, and 2% had died from complications not directly related to the procedure. For those patients who had undergone coiling, 75% were intact at 6 months follow-up, 12.5% had a permanent deficit, and 12.5% had a cranial nerve deficit, with no deaths. CONCLUSIONS: The morbidity and mortality of cerebral vasospasm is significant. A good outcome after aneurysmal subarachnoid hemorrhage is dependent upon careful patient management in the preoperative, perioperative, and postoperative periods. The timely work-up and aggressive treatment of neurological deterioration, whether or not it is because of vasospasm, is paramount.
BACKGROUND: The decline of residual renal function (RRF) on dialysis has been reported to be slower in peritoneal dialysis (PD) then hemodialysis (HD). However, some clinicians have questioned whether this reported difference might not be caused by selection bias. In particular, if continuous ambulatory PD (CAPD) delivers only marginally adequate therapy as some clinicians speculate, then perhaps those patients on CAPD with low glomerular filtration rate (GFR) are purposefully switched to HD. If true, transferring CAPD patients with low GFR to HD could create a selection bias that very well may account for the differences in GFR between PD and HD. This is particularly problematic if one then censors patients at the time of transfer from PD to HD from analysis (that is, patients are no longer followed in the study once they have switched treatment modalities). When this occurs, the data are said to be informatively censored, a term used by statisticians to describe any kind of systematic bias associated with censored or incomplete data. In particular, informative censoring occurs when patients who die or transfer to another modality very early have an associated lower starting GFR or higher rate of decline of GFR than patients who either complete the study or who die or transfer much later. If patient dropout is indeed related to the rate of decline in GFR and if this relationship differs between PD and HD but is ignored in the analysis, then the results of such analysis may be biased. METHODS: This article analyzes the decline in GFR among 141 incident dialysis patients (39 HD and 102 PD) undergoing either HD or PD at the University of Missouri-Columbia. The decline in GFR was modeled as a nonlinear function of time, taking into account the possibility that missing values of GFR may be associated with patient dropout (death, transfer to another modality, or transplantation). To safeguard against this possibility, we utilized a conditional nonlinear mixed-effects model. The model was used to fit and compare each patient's GFR data to time adjusting for the patient's treatment modality (HD vs. PD), cause of dropout (death, transfer, transplant, lost to follow-up/study ended), and time to dropout. The model allowed a comparison of the starting GFR and the rate of decline in GFR between PD and HD adjusting for these three factors. RESULTS AND CONCLUSIONS: The results of our analysis suggest that such informative censoring is independent of treatment modality and that even after correcting for dropout caused by death or transfer to another modality, patients starting on PD have a lower rate of decline in GFR (that is, better preservation of GFR) than patients starting on HD.
It has become increasingly evident that the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage (SAH) which described the ischemic consequences of cerebral arterial constriction is complex and multifactorial. In an attempt to study cerebral vasospasm, numerous investigators have used experimental animal models that resemble cerebral vasospasm in humans. No ideal model for SAH has been found as yet, and hence the quest for such a model continues. We developed an endoscopic technique that permits a direct vision of internal carotid artery and puncturing the artery to provoke SAH. This model will closely reflect the clinical setting of an aneurysm rupture. The onset of SAH was characterized by a sudden decrease of cerebral blood flow (CBF) and cerebral blood volume (CBV) by at least 40% in the first 20 min. Following this initial drop, there was an increase in the CBF and the CBV, however, they remained significantly below the base line values, at the end of 1 h. This study describes a new model of SAH in rat that simulates the clinical phenomenon of ruptured intracranial aneurysm that also produces cerebral vasospasm.
The effects of the duration and time of food availability on stimulation of the photoperiodic responses (fattening and gain in body mass, and growth and development of testes) were investigated in the migratory blackheaded bunting (Emberiza melanocephala). Two experiments were performed. Experiment I examined the effects of a reduction in the duration of food supply in buntings that were subjected to long day lengths (16h:8h L:D) and received food ad libitum (group I) or for restricted durations, coinciding with the end of the lights-on period, of 8h (group II) and 4h (group III). Buntings of group I gained in body mass, whereas there was a mixed response in group II (half the birds gained and half lost body mass), and all birds of group III lost body mass. There was no effect on testis growth in groups I and II, but testes grew more slowly in group III. Experiment 2 investigated the effects of both the duration and the time of food availability. Of five groups of birds, group I was exposed to an 8h:16h L:D photoperiod, and groups II-V were exposed to 16h:8h L:D. Whereas birds of groups I and II received food ad libitum, those of groups III-V were fed only for 5 h, at zt 0-5 (group III), zt 5.5-10.5 (group IV) or zt 11-16 (group V), where zt = zeitgeber time and zt 0 refers to the beginning of the lights-on period. Apart from duration, the timing of food availability also had an effect on photoperiodic stimulation under the 16h:8h L:D photoperiod. Birds that were fed ad libitum fattened and gained in body mass, whereas among restricted feeding groups, only birds in the group fed during the first 5 h (zt 0-5, group III) showed a significant increase in body mass (albeit considerably lower than in the ad libitum group). Birds fed during the middle 5h (zt 5.5-10.5, group IV) showed an intermediate response, and those fed during the last 5h (zt 11-16, group V) lost body mass. Testicular growth was suppressed in birds that were fed for 5 h in the evening, but not in those fed for the same period in the morning or in the middle of the long day. Taken together, these results show that the duration of food supply and/or the time of day at which food is available affect photoperiodic stimulation of fattening and gain in body mass as well as the growth and development of gonads in the blackheaded bunting.
BACKGROUND: Paraclinoid aneurysms include those that are distal to the cavernous segment of the internal carotid artery and proximal to the posterior communicating artery. The purpose of this study was to review our experience with the endovascular treatment of this group of aneurysms, which are difficult to treat surgically. METHODS: Between June 1994 and April 1999, 66 patients (56 female, 10 male) with a mean age of 50.1 years (range 13-75, median 51) underwent endovascular treatment for 71 paraclinoid aneurysms. The mean size of the dome was 8.9 mm (range 3-25 mm, median 7) and the of neck was 3.8 mm (range 1.4-8 mm, median 4). Thirteen patients presented with acute subarachnoid hemorrhage, and 4 with previous subarachnoid hemorrhage. Six aneurysms produced mass effect with visual symptoms, 4 presented with transient ischemic attacks, and 44 were incidental. Nine patients had had previous unsuccessful surgery. All procedures were performed under general anesthesia and with systemic heparinization. RESULTS: Ninety endovascular procedures were performed on 71 aneurysms: GDC coiling in 78 (including 45 with the remodeling technique), permanent balloon occlusion in 9, and 3 had both GDC coiling and permanent balloon occlusion. In ten aneurysms it was not possible to place coils in the lumen of the aneurysm with the available technology and balloon occlusion was not indicated. Five of these were treated surgically and 5 remain untreated. All patients had immediate post procedure angiography. Of the 61 aneurysms that were treated, 46 (75%) have angiographic follow-up of 6 months or more. Morphological outcome following endovascular therapy for 61 aneurysms at last available follow-up showed > 95% occlusion in 52/61 (85.2%) and <95% in 9/61 (14.8%). Eight patients required surgery, 2 for partial coiling, 2 for refilling of a neck remnant, 2 for persistent mass effect and 2 for coil protrusion. In the 90 procedures performed, 2 (2.2%) patients had major permanent deficits (1 monocular blindness, 1 hemiparesis), 1 (1.1%) had a minor visual field cut, and 2 (2.2%) patients died from major embolic events. CONCLUSION: Properly selected paraclinoid aneurysms can be successfully treated by endovascular technology. The morbidity and mortality rate of the endovascular approach in our experience is equal to or better than the published surgical series of similar aneurysms. We recommend that the endovascular approach be given primary consideration in the treatment of paraclinoid aneurysms.
BACKGROUND: Surgery for intracranial aneurysms that have been treated by endovascular coiling is a new challenge for neurosurgeons and the need for it will undoubtedly continue to increase. The indications for, timing, and technique of surgery in our experience are described. METHODS: We have reviewed our experience with 11 patients who underwent surgery following endovascular coiling with Guglielmi detachable coils (GDCs) of an aneurysm. We analyzed the indications for surgery, surgical techniques used, and patient outcome. RESULTS: There were nine female and two male patients. The mean age was 49 years (range 13 to 67 years). The intervals between coiling and surgery were 1, 2, 3, 4, 7, 7, 10, and 14 days, 6 weeks, 2, 18, and 25 months. The indications for surgery were partial treatment (3), growth of residual neck (2), persistent mass effect of a giant aneurysm (1), mass effect from the coil ball (2), coil migration (2), and coil protrusion with embolic event (1). The coils were removed at the time of surgery from 9 of 11 aneurysms before clipping. In two cases it was possible to place a clip across the neck of the aneurysm without removing the coils, as the coils no longer occupied the neck. There were two permanent deficits directly related to the endovascular procedures. Two other patients who presented with subarachnoid hemorrhage had residual neurological deficits post surgery and one patient with a giant aneurysm had persistent visual loss. CONCLUSION: Surgery remains a viable option at any time for treating aneurysms that have been previously treated by GDC placement. The operative approach is determined by the need for coil removal and the duration since coiling.
PURPOSE: To describe the association between the presence of epithelial defects and the development of diffuse lamellar keratitis (DLK), "Sands of the Sahara" syndrome, following laser in situ keratomileusis (LASIK). SETTING: Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA. METHODS: In this retrospective study, the postoperative clinical course and surgical outcomes in 735 eyes of 358 consecutive patients who had myopic LASIK between December 1998 and August 1999 were reviewed. Of the 735 procedures, 680 were primary LASIK procedures and 55 were retreatments performed by lifting the existing flaps. The incidence and severity of DLK and the relationship of DLK to epithelial defects were tabulated. RESULTS: Diffuse lamellar keratitis developed in 9 of the 16 eyes that had postoperative epithelial defects. Seventeen eyes without epithelial defects also developed DLK. The presence of an epithelial defect increased an individual's risk of developing DLK 24 times (95% confidence interval, 13 to 45). In 8 eyes, the inflammation resolved following treatment with intense topical corticosteroids. One eye had irrigation under the flap because of dense central inflammation; the final outcome was mild inferior corneal steepening. All eyes recovered preoperative best spectacle-corrected visual acuities. CONCLUSION: Patients who have epithelial defects of any size following LASIK are at significantly increased risk of developing DLK.
BACKGROUND: Residual renal function (RRF) plays an important role in dialysis patients. Studies in patients on maintenance dialysis suggest that RRF is better preserved in patients receiving peritoneal dialysis (PD) vis-à-vis those receiving hemodialysis (HD). We speculated that regardless of the patient's type of therapy, the estimate obtained for the rate of decline in glomerular filtration rate (GFR) may be biased because of informative censoring associated with patient dropout. Informative censoring occurs when patients who die or transfer to another modality very early have associated with them a lower starting GFR or a higher rate of decline of GFR than patients who either complete the study or who die or transfer much later. If patient dropout is indeed related to the rate of decline in GFR and if this relationship is ignored in the analysis, then the estimate obtained of the rate of decline in GFR may be biased. METHODS: In an attempt to determine if there is a relationship between patient dropout and the decline in GFR, we reanalyzed the CANUSA data by modeling GFR as a nonlinear function of time with the rate of decline being exponential. RESULTS: This article highlights the significance of "informative censoring" when studying the decline of RRF on dialysis. The results show that for the CANUSA cohort, the mean initial GFR was significantly lower, and the rate of decline was significantly higher for patients who died or transferred to HD than for patients who were randomly censored or received a transplant. It is important to emphasize that the impact of informative censoring on previous analyses of the decline of RRF between PD versus HD is presently unclear. If bias caused by informative censoring is the same regardless of what therapy a patient is on, then conclusions from previous studies comparing the decline in GFR between PD and HD would still be valid. However, if the magnitude of the bias differs according to therapy, then additional adjustments would be needed to fairly compare the decline in GFR between PD and HD. Because this analysis is restricted to patients on PD, it would be scientifically incorrect to interpret previous studies solely on the basis of the results from this analysis. CONCLUSION: In any longitudinal study designed to estimate trends in an outcome measured over time, it is important that the analysis of the data takes into account any effect patient dropout may have on the estimated trend. This analysis demonstrates that among PD patients, both the starting GFR and the rate of decline in GFR are associated with patient dropout. Consequently, future studies aimed at estimating the rate of decline in GFR among PD patients should also account for any dependencies between dropout and GFR. Similarly, data analyzing for apparent differences in the rate of decline of GFR between PD and HD should also adjust for possible informative censoring.
OBJECT: Reports in the literature have offered discussions of the feasibility, efficacy, and safety of balloon-assisted Guglielmi detachable coil (GDC) placement in wide-necked intracranial aneurysms, which was first described by Jacques Moret as the "remodeling technique." In this article the authors summarize their results in a subset of aneurysms treated with GDCs using the remodeling technique. METHODS: This report contains a retrospective analysis of 72 patients with 75 aneurysms who underwent 79 endovascular procedures performed using the remodeling technique. Morphological outcome was determined at the end of each procedure and by reviewing available follow-up angiograms. Clinical assessments and outcomes are reported using a modified Glasgow Outcome Scale. Coils were placed in 66 (88%) of 75 aneurysms selected for treatment. In eight aneurysms (11%) treatment failures occurred due to the tortuosity of the vessel used to reach the aneurysms or because of balloon inadequacies. Incorporating all available follow-up data the authors found that 50 (78%) of 64 aneurysms were completely or subtotally (> 95%) occluded and eight (12%) of 64 were incompletely (< 95%) occluded. Since the time of coil placement, eight aneurysms have progressed to complete occlusion and another five have exhibited progressive thrombosis on follow-up angiograms. In three aneurysms there has been neck remnant growth. Surgical clipping was performed to treat six aneurysms after an initial coil placement procedure. Permanent incidences of morbidity were limited to four patients and there were three deaths directly related to the procedure. CONCLUSIONS: The remodeling technique shows promise in increasing the number of cerebral aneurysms amenable to treatment by endovascular coil placement, and offers an alternative approach to aneurysms that have met with failed surgical treatment or are surgically inaccessible. Long-term follow-up review is needed to determine the final outcome of aneurysms treated by this technique.
A vital conceptual difference between intermittent and continuous dialysis therapies is the difference in the relationship between Kt/V urea and dietary protein intake. For a given level of protein intake the intermittent therapies require a higher Kt/V urea due to the reasons mentioned above. The recently released adequacy guidelines by DOQI for intermittent and continuous therapies are based on these assumptions. The link between adequacy targets and patient survival is well documented for an intermittent therapy like HD. For a continuous therapy like CAPD however, the evidence linking improved peritoneal clearance to better survival is not as direct. However, present consensus allows one to extrapolate results based on HD. The concept of earlier and healthier initiation of dialysis is gaining hold and incremental dialysis forms an integral aspect of the whole concept. Tools like urea kinetic modeling give us valuable insight in making mathematical projections about the timing as well as dosing of dialysis. Daily home hemodialysis is still an underutilized modality despite offering best survival figures. Hopefully, with increasing availability of better and simpler machines its use will increase. Still several questions remain unanswered. Despite availability of data in hemodialysis patients suggesting that an increased dialysis prescription leads to a better survival, optimal dialysis dose is yet to be defined. Concerns regarding methodology of such studies and conclusions thereof has been raised. Other issues relating to design of the studies, variation in dialysis delivery, use of uncontrolled historical standards and lack of patient randomization etc also need to be considered when designing such trials. Hopefully an ongoing prospective randomized trial, namely the HEMO study, looking at two precisely defined and carefully maintained dialysis prescriptions will provide some insight into adequacy of dialysis dose and survival. In diabetic patients, the relationship between outcome and dialysis dose needs to be better defined. Data relating adequacy of dialysis to outcome in a pediatric population is not available. In dialysis therapy, the Risk/Dose (R/D) function does not bear a linear relationship. This together with a lack of proof equating peritoneal to renal clearance lends some uncertainty to the validity of the recommendation that there is a linear and constant decrease in RR for std (Kt/V) [equivalent standardized Kt/V calculated from average predialysis BUN for any frequency and/or combination of intermittent and continuous dialysis ref] up to 2.3 as reported in the CANUSA study. Due to the complex nature of this problem it may be prudent to undertake a multi-center trial with std (Kt/V) prospectively randomized to either 2.0 or 2.4. This would provide a reliable database to evaluate the R/D function over this critical range of normalized peritoneal urea clearance. Likewise in PD, the postulated linearity between dialysis dose and outcome needs to be studied in a prospective randomized manner. The amount of dialysis dose required for malnourished patients, diabetic and pediatric patients needs to be better defined. The role of aggressive dialysis in reversing malnutrition needs to be studied and studies need to be done to identify the most scientific use of V in malnourished patients. Justification of a healthy start/incremental dialysis based on outcome measures needs to be established and it's cost effectiveness validated by clinical trials. Again, a prospective randomized controlled trial comparing incremental dialysis with dietary protein restriction in patients with GFR < or = 10.5 ml/min/1.73 m2 with properly defined outcome measures like morbidity, mortality, decline of GFR and quality of life needs to be conducted. Comparisons of incremental hemodialysis and incremental peritoneal dialysis need to be made especially with regard to technique survival and preservation of residual renal function (RRF). (ABSTR
In this paper the rationale behind utilizing the brain tissue measurements of oxygen, carbon dioxide, pH and temperature is evaluated in the context of ischemia. These parameters were measured using an intraparenchymal multi-parametric brain tissue monitor (Paratrend 7). The need to establish the relevance of this type of monitoring becomes acute as further experience is gained using this kind of technology. Our experience with such a device is presented and is illustrated with two clinical cases. The potential caveats and areas of possible future work are also delineated.
Juxtaorbital spheroid wing or ridge meningiomas are the most common of the basal meningiomas. These are at times meningiomas en plaque, which in most patients do not have significant intracranial component. This article reviews the literature on en-plaque meningiomas and discusses the role of MR imaging and CT in the diagnosis of en-plaque meningiomas of the paraorbital region. The role of fat-suppression, gadolinium-enhanced, T1-weighted MR imaging is emphasized.
The evaluation of juxtaorbital anomalies with routine imaging, including CT and MR imaging, usually is insufficient for endovascular therapy planning. Cerebral angiography remains crucial to define detail necessary for endovascular therapy. This article provides an overview of the authors' approach and the endovascular therapies available to treat these lesions.
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Quantitative measurement of blood flow in cerebral vessels during aneurysm surgery can help prevent ischemic injury and improve patient outcome. The authors report a case of a superior cerebellar artery (SCA) aneurysm in which perivascular microflow probes were used to measure blood flow quantitatively in both the SCA and the posterior cerebral artery before and after aneurysm clipping. Following aneurysm clipping, blood flow in the SCA was reduced to less than 25% of its initial baseline value. Prompt detection of compromised blood flow gave the surgeon the opportunity to adjust the clip and restore SCA flow to its preclipping value within 5 minutes of initial clip placement. Quantitative vessel-flow measurements were integral to the safe progression of the operation and may have prevented an adverse neurological outcome in this patient. The recommended surgical technique and the principle of operation are described.
The HIV-1 Rev protein facilitates the export of incompletely spliced and unspliced viral mRNAs from the nucleus. Rev polymerizes into two types of filaments in vitro. In the presence of RNA, Rev forms poorly ordered structures, while in the absence of RNA it polymerizes into regular hollow filaments. We have determined the helical structure of the latter filaments by analysis of cryo-electron micrographs, taking into account STEM measurements of mass-per-unit-length. They are made up of Rev dimers, arranged in a six-start helix, with 31 dimers in 2 turns, a pitch angle of 45 degrees, and an interstrand spacing of 3.8 nm. Three-dimensional reconstruction at 2.1 nm resolution reveals a smooth outer surface and a featured inner surface, with outer and inner diameters of approximately 14.8 and approximately 10.4 nm, respectively. The Rev dimer has a "top-hat" shape with a cylinder approximately 3.2 nm in diameter and approximately 2.2 nm high, pointing inward: the thinner rim areas pack together to form the filament wall. Raman spectroscopy shows polymerized Rev to have approximately 54% alpha-helix and 20-24% beta-sheet content. Electron microdiffraction of aligned filaments reveals a broad meridional reflection at approximately (0.51 nm(-1, suggesting approximate alignment of the alpha-helices with the filament axis. Based on these data, a molecular model for the Rev filament is proposed.