Clevidipine rapidly and safely reduces blood pressure in acute intracerebral hemorrhage: the ACCELERATE trial.

BACKGROUND: Intracerebral hemorrhage (ICH) causes 10-15% of primary strokes, with mortality related to hematoma volume. Blood pressure (BP) reduction may attenuate hematoma expansion. ACCELERATE (the Evaluation of Patients with Acute Hypertension and Intracerebral Hemorrhage with Intravenous Clevidipine Treatment) is a pilot study representing the first evaluation of safety and efficacy of intravenous clevidipine for the rapid treatment of hypertension in ICH patients. METHODS: ICH patients with a systolic BP (SBP) >160 mm Hg who present within 6 h (n = 27) or 12 h (n = 10) of symptoms were prospectively enrolled, treated with open-label clevidipine until SBP ≤160 mm Hg was achieved and then titrated to keep target SBP between 140-160 mm Hg. RESULTS: A total of 35 patients with baseline median Glasgow Coma Scale score of 12, median NIH Stroke Scale score of 14, mean SBP of 186 mm Hg and a mean time from onset of symptoms of 5.5 h received clevidipine. Median time to achieve SBP target range was 5.5 min. All patients achieved target SBP within 30 min; 96.9% achieved target SBP with clevidipine monotherapy. CT scans showed minimal hematoma volume change for the overall population (median change 0.01 ml, -2.9%). Mild/moderate hypotension was reported in 3 patients and resolved with dose reduction or drug discontinuation. CONCLUSION: Clevidipine monotherapy was effective and safe for rapid BP reduction in this cohort of critically ill ICH patients. Overall, patients showed minimal hematoma expansion with BP reduction, suggesting that rapid BP control with clevidipine may have a beneficial impact on hematoma expansion and warrants further investigation.

Anterior uveal spindle cell tumor in a cat.

PURPOSE: To describe a case of anterior uveal spindle cell tumor in a cat with features similar to spindle cell tumor of blue eyed dogs. METHODS: A 10-year-old female spayed domestic short-haired cat was referred for an iris mass OS. The mass was solitary, nodular, nonpigmented, located medially, and causing dyscoria. A diagnosis of a benign epithelial tumor was suggested by a FNA of the mass. The cat was lost to follow-up for 2 years, after which time she re-presented with glaucoma, blindness and grossly evident iridal mass enlargement OS. Transconjunctival enucleation was performed and the globe submitted for histopathology. RESULTS: Histopathology of the enucleated globe revealed the superior iris to be infiltrated and effaced by a large population of neoplastic spindle cells. The cells were arranged in streams and bundles and exhibited Antoni-A and Antoni-B tissue patterns, which are characteristic of Schwann cell tumors. Mitotic figures were rare and cellular pleomorphism moderate. Immunohistochemical staining was positive for S-100 protein and glial fibrillary acidic protein (GFAP), and negative for Melan-A. Interestingly, there was no histological evidence of glaucoma. CONCLUSIONS: Based on its histopathologic characteristics, this iris tumor was diagnosed as a Schwann cell variant of a peripheral nerve sheath tumor (PNST) closely resembling the spindle cell tumor of blue-eyed dogs. Anterior uveal PNST has not been previously reported in cats to the authors' knowledge. The presence of Antoni type A and type B tissue patterns along with immunohistochemical staining may facilitate a diagnosis of PNST and rule out malignant melanoma.

Advancing the study of stroke in women: summary and recommendations for future research from an NINDS-Sponsored Multidisciplinary Working Group.

BACKGROUND AND PURPOSE: Women have poorer outcomes from stroke than men. Women also have risk factors that are unique, including pregnancy and hormone therapy. Hormone therapy for postmenopausal replacement increased the risk of ischemic stroke according to results of the Women's Health Initiative clinical trials. Based on the current understanding of the mechanisms of action of estrogen, the reasons for this increased risk are uncertain. One method to better understand the reasons for this increased risk is to re-evaluate estrogen's role in the neurovascular unit, simplistically comprised of the neurons, glia, and endothelial cells, as well as the processes of inflammation, and hemostasis/thrombosis. Besides the role of estrogen there are many gaps of knowledge about issues specific to women and stroke. SUMMARY OF REVIEW: A multidisciplinary workshop was held in August 2005 to summarize the current evidence for estrogen and, more generally, stroke in women, and to provide recommendations for future basic, preclinical, and clinical research studies. CONCLUSIONS: These studies may ultimately change the approach to stroke prevention and treatment in women.

Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy.

BACKGROUND AND PURPOSE: Although long-term outcome determinants in acute ischemic stroke (AIS) patients have been defined, less is known about those predicting hyperacute worsening after thrombolytic therapy (TT). We investigated predictors of short-term clinical worsening (National Institutes of Health Stroke Scale [NIHSS] change > or =4 within 24 hours of admission). METHODS: We studied 201 AIS patients who received TT within 6 hours of symptom onset. We determined baseline demographics, comorbidities, NIHSS at baseline and at 24 hours after TT, head computed tomography scan before and within 24 hours after TT, and angiographic recanalization in patients treated with intra-arterial (IA) thrombolysis. Significance of relationships was evaluated by t test or Wilcoxon signed rank sum test. Logistic regression model (LRM) was fitted to determine independence of significant variables. RESULTS: Of 201 patients, 13% worsened, 39% improved, and 48% remained unchanged 24 hours after TT. Most patients (72%) received IA thrombolysis. Patients who deteriorated, compared with those who improved, were more likely to have complicating intracranial hemorrhage (ICH; P<0.001), absent recanalization (P=0.026), and higher blood glucose (BG; P=0.049). Hyperglycemia (>150 mg/dL) was greater in patients who worsened even in presence of recanalization (P=0.004, odds ratio [OR] 6.47). LRM showed that adjusted OR for increased risk of bad outcome and mortality for an increase of BG by 50 mg/dL is 1.56 and 1.38, respectively. CONCLUSIONS: Hyperglycemia and ICH are independent predictors of hyperacute worsening in AIS patients receiving TT. Although recanalization is the purpose of IA thrombolysis, its impact on clinical improvement may not be apparent without strict BG control.

Effect of human albumin administration on clinical outcome and hospital cost in patients with subarachnoid hemorrhage.

OBJECT: Human albumin is used to induce hypervolemia (central venous pressure [CVP] > 8 mm Hg) after subarachnoid hemorrhage (SAH). Unfortunately, human albumin may increase the mortality rate in critically ill patients; because of this, its use became restricted in the authors' hospital in May 1999. The goal of this study was to determine the effect of human albumin on outcome and cost in patients with SAH before and after this restriction was put into place. METHODS: All patients with aneurysmal SAH who were admitted to the authors' institution between May 1998 and May 2000 were studied. Basic demographic information, dosage of human albumin given, length of stay, and the incidence of in-hospital deaths and complications were collected. The authors obtained Glasgow Outcome Scale (GOS) scores at 3 months after SAH (good outcome, GOS > or = 4). Data were analyzed using t-test and chi-square analysis. Logistic regression was used to identify independent associations between use of human albumin and outcome. The authors studied 140 patients: 63 who were admitted between May 1998 and May 1999 (Group 1) and 77 treated between June 1999 and May 2000 (Group 2). Two subgroups of patients were further analyzed. Group 1 patients who received human albumin (albumin subgroup, 37 patients) and Group 2 patients who would have received albumin under the old protocol (that is, those who failed to achieve CVP > 8 mm Hg after normal saline administration; nonalbumin subgroup, 47 patients). Patients in the nonalbumin subgroup were more likely to be male (38% compared with 16%), to experience hypertension (55% compared with 30%), to suffer from hypomagnesemia (49% compared with 5.4%), and to have hydrocephalus (47% compared with 27%). There was a trend for these patients to have more vasospasm (28% compared with 19%, p = 0.2). Patients in the albumin subgroup were more likely to have a good outcome at 3 months. CONCLUSIONS: Administration of human albumin after SAH may improve clinical outcome and reduce hospital cost.

Effects of oral administration of diphenhydramine on pupil diameter, intraocular pressure, tear production, tear film quality, conjunctival goblet cell density, and corneal sensitivity of clinically normal adult dogs.

OBJECTIVE: To evaluate the effects of oral administration of diphenhydramine on pupil diameter, intraocular pressure (IOP), tear production, tear film quality, corneal sensitivity, and conjunctival goblet cell density (GCD) in clinically normal adult dogs. ANIMALS: 12 healthy adult dogs. PROCEDURES: All dogs received diphenhydramine (2.2 mg/kg, PO, q 12 h) for 21 days. Conjunctival biopsy samples were obtained immediately before (day 1) and after (day 21) treatment with diphenhydramine and conjunctival GCDs were determined. Gross ophthalmic examinations and fluorescein staining of corneas were performed, and pupil diameter, corneal sensitivity, IOP, tear production, and tear film breakup time were determined prior to administration of diphenhydramine on days 1 through 5 and on day 21; pupil diameter and IOP measurements were repeated on each of those days at 20 and 40 minutes and 1, 3, 6, and 8 hours after administration of diphenhydramine. Data were analyzed to detect differences among values for dogs. RESULTS: Clinically important increases in pupil diameter were not detected after administration of diphenhydramine to dogs. Day 1 corneal sensitivity and tear film breakup time for dogs were significantly higher than day 21 values for those variables. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that oral administration of diphenhydramine to healthy adult dogs was not likely to acutely induce glaucoma or keratoconjunctivitis sicca. However, effects of diphenhydramine in dogs with keratoconjunctivitis sicca or primary glaucoma or dogs genetically predisposed to development of those conditions were not determined. Administration of diphenhydramine to dogs decreased corneal sensitivity and tear film breakup time, although these effects were not clinically important.

Ophthalmic examination findings in a group of retired racing Greyhounds.

OBJECTIVE: To characterize the frequency and types of ophthalmic findings in a group of retired racing Greyhounds. MATERIALS AND METHODS: Complete ophthalmic examinations of both eyes of 100 retired racing Greyhounds were performed. Anterior segment examinations were performed by slit-lamp biomicroscopy. Tear production was measured by Schirmer tear test. Intraocular pressures were obtained by applanation tonometry. The posterior segments were examined by binocular indirect ophthalmoscopy following pharmacologic dilation. A photographic record of abnormalities was obtained whenever possible. RESULTS: Mean tear production by Schirmer tear test was 21 mm/min (range 11-30 mm/min). Mean intraocular pressure by applanation tonometry was 16 mmHg (range 9-28 mmHg). The most prevalent anterior segment findings were cataracts (17% dogs, 11% eyes), corneal degeneration/scarring (6% dogs, 4% eyes), and suspected typical and atypical 'pannus' (total 4% dogs, 4% eyes). The most prevalent posterior segment abnormalities were vitreal degeneration (31% dogs, 38% eyes) and chorioretinal degeneration/scarring (7% dogs, 4% eyes). Other findings included anterior chamber vitreal strands, stretched lens zonules, periocular alopecia, a case of mild unilateral chemosis, and a distichium. CONCLUSIONS: Ophthalmic abnormalities are not uncommon in retired racing Greyhounds.

Central corneal thickness in koi fish: effects of age, sex, body length, and corneal diameter.

OBJECTIVE: To establish the central corneal thickness (CCT) of normal koi fish by ultrasonic pachymetry, and its relationship to age, sex, body length and corneal diameter. METHODS: Age, sex and body length of 33 koi fish (17 male and 16 female fish) were recorded. Horizontal and vertical corneal diameters of each eye were obtained using Jameson calipers. Central corneal thickness of all eyes was measured by ultrasonic pachymetry. Intraocular pressure (IOP) by rebound tonometry was obtained for a subgroup of nine koi (18 eyes). RESULTS: Mean central corneal thickness was 325.9 microm. Central corneal thickness of female koi was greater than CCT of male fish (P < 0.01). Central corneal thickness increased with increasing age overall and within both sexes (P < 0.01). Central corneal thickness increased with increasing body length (P < 0.001). For male and female fish, CCT increased with increasing horizontal and vertical corneal diameters (P < 0.01). Mean horizontal corneal diameter (HCD) was 8.05 mm, mean vertical corneal diameter (VCD) was 7.38 mm, and HCD was consistently greater than VCD. Mean IOP of a subgroup of these koi was 4.9 mmHg by rebound tonometry. CONCLUSIONS: Koi CCT increases with increasing age, body length and corneal diameter.

Penetrating keratoplasty in a California Brown Pelican.

Fresh homologous penetrating keratoplasty (PK) was performed on the left cornea of a young adult female California Brown Pelican (Pelecanus occidentalis) for the treatment of vision-threatening corneal scarring and granulation tissue. The procedure appeared to be highly successful based on short-term clinical follow-up and histopathology results. However, the patient died from unrelated causes before long-term follow-up could be obtained.

The effect of elective phacofragmentation on central corneal thickness in the dog.

OBJECTIVE: To characterize the short- and intermediate-term effects of elective phacofragmentation on central corneal thickness (CCT) in the dog. METHODS: Forty-three dogs (66 eyes) undergoing elective phacofragmentation cataract surgery over an 8-month period at a single private ophthalmology referral clinic were enrolled in the study. Central corneal thickness was measured by ultrasonic pachymetry just prior to surgery, 1 day following surgery, 1 week postoperatively, 1 month postoperatively, and more than 2 months postoperatively. Statistical comparisons were made using descriptive and inferential statistical methods with a level of significance set at P < 0.05. RESULTS: The initial mean CCT of 611 microm increased dramatically to 741 microm 1 day postphacofragmentation. Mean CCT remained slightly elevated (666 microm) at 1 week postoperatively, but became indistinguishable from preoperative measurements by 1 month postsurgery (626 microm) and remained so at the > 2-month time period (618 microm). The change over time and trends remained statistically significant and remarkably similar, even when adjusted separately for age, gender, surgeon status, diabetic status, cataract type, and total surgery time (all P < 0.0001). Corneas of diabetic dogs were thicker than those of nondiabetic dogs at all time periods, and the overall effect of diabetic status was significant (P = 0.016). There was a sharper increase from the preoperative to 1-day postoperative CCT in the diabetic group compared to the nondiabetic group. The mean CCT of the pseudophakic group took longer to return to baseline than the aphakic group. The mean CCT of the foldable intraocular lens (IOL) group took longer to return to baseline than both the rigid IOL and aphakic groups. Dogs with documented in-hospital postoperative intraocular pressure spikes (> 25 mmHg) developed a greater 1-day postsurgical increase in CCT. It appears that there was a sharper decrease in mean CCT from 1 month to more than 2 months postoperatively in the postoperative hypertension group. CONCLUSIONS: Elective phacofragmentation cataract surgery results in an increase in CCT in dogs, but this increase is transient. Particular care may be indicated to protect the endothelium of diabetic patients undergoing phacofragmentation. These data do not clearly support an advantage of the small-incision cataract surgery made possible by the use of foldable IOLs.

Length of stay and mortality in neurocritically ill patients: impact of a specialized neurocritical care team.

OBJECTIVE: To determine predictors of in-hospital and long-term mortality and length of stay in patients admitted to the neurosciences critical care unit. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: Neurosciences critical care unit of a large academic tertiary care hospital. PATIENTS: Adult patients (n = 2381) admitted to our neurosciences critical care unit from January 1997 to April 2000. INTERVENTIONS: Introduction of a specialized neurocritical care team. MEASUREMENTS AND MAIN RESULTS: Data obtained from the database included demographics, admission source, length of stay, neurosciences critical care unit and hospital disposition, admission Acute Physiology and Chronic Health Evaluation (APACHE) III score, and principal and secondary diagnoses. The introduction of a neurocritical care team in September 1998 was also collected, as was death at 1 yr after admission. Univariate analysis was carried out using Student's t-test, Mann-Whitney U test, or chi-square test (significance, p < .05). A logistic regression model was used to create a prediction model for in-hospital and long-term mortality. A general linear model was used to determine predictors of length of stay (after log transformation). Independent predictors of in-hospital mortality included APACHE III (odds ratio, 1.07 [1.06-1.08]) and admission from another intensive care unit (odds ratio, 2.9 [1.4-6.2]). The presence of a neurocritical care team was an independent predictor of decreased mortality (odds ratio, 0.7 [0.5-1.0], p = .044). Admission after the neurocritical care team was implemented was associated with reduced length of stay in both the neurosciences critical care unit (4.2 +/- 4.0 vs. 3.7 +/- 3.4, p < .001) and the hospital (9.9 +/- 8.0 vs. 8.4 +/- 6.9, p < .0001). There was no difference in readmission rates to the intensive care unit or discharge disposition to home before and after the neurocritical care team was established. The availability of the neurocritical care team was not associated with significant changes in long-term mortality. Factors independently associated with long-term mortality included female gender, admission from another intensive care unit, APACHE III score, and being moderately disabled before admission. CONCLUSION: Introduction of a neurocritical care team, including a full-time neurointensivist who coordinated care, was associated with significantly reduced in-hospital mortality and length of stay without changes in readmission rates or long-term mortality.