Cerebral Blood Flow and Marrow Diffusion Alterations in Children with Sickle Cell Anemia after Bone Marrow Transplantation and Transfusion.

BACKGROUND AND PURPOSE: Hematopoietic marrow hyperplasia and hyperperfusion are compensatory mechanisms in sickle cell anemia. We have observed marrow diffusion and arterial spin-labeling perfusion changes in sickle cell anemia following bone marrow transplantation. We aimed to compare arterial spin-labeling perfusion and marrow diffusion/ADC values in patients with sickle cell anemia before and after bone marrow transplantation or transfusion. MATERIALS AND METHODS: We reviewed brain MRIs from patients with sickle cell anemia obtained during 6 consecutive years at a children's hospital. Quantitative marrow diffusion values were procured from the occipital and sphenoid bones. Pseudocontinuous arterial spin-labeling perfusion values (milliliters/100 g of tissue/min) of MCA, anterior cerebral artery, and posterior cerebral artery territories were determined. Territorial CBF, whole-brain average CBF, and marrow ADC values were compared for changes before and after either bone marrow transplantation or transfusion. Bone marrow transplantation and transfusion groups were compared. Two-tailed paired and unpaired Student t tests were used; P < .05 was considered significant. RESULTS: Fifty-three examinations from 17 patients with bone marrow transplantation and 29 examinations from 9 patients with transfusion were included. ADC values significantly increased in the sphenoid and occipital marrow following bone marrow transplantation in contrast to patients with transfusion (P > .83). Whole-brain mean CBF significantly decreased following bone marrow transplantation (77.39 ± 13.78 to 60.39 ± 13.62 ml/100 g tissue/min; P < .001), without significant change thereafter. CBF did not significantly change following the first (81.11 ± 12.23 to 80.25 ± 8.27 ml/100 g tissue/min; P = .47) or subsequent transfusions. There was no significant difference in mean CBF between groups before intervention (P = .22). CONCLUSIONS: Improved CBF and marrow diffusion eventuate following bone marrow transplantation in children with sickle cell anemia in contrast to transfusion therapy.

Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

OBJECTIVE: To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). METHODS: This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. RESULTS: We studied 219 patients (53% males) with a median (25th-75th percentiles [p25-p75]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p25-p75) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. CONCLUSION: Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment.

Idiopathic hyperostosis of the calvaria in five young bullmastiffs.

A new calvarial hyperostotic syndrome (CHS) in young bullmastiffs is described. Calvarial hyperostotic syndrome clinically resembles canine craniomandibular osteopathy (CMO) and human infantile cortical hyperostosis (ICH), but it is unique in that there is progressive and often asymmetric skull bone involvement, and the population affected appears to be only young, male bullmastiff dogs. Characteristic radiographic findings consist of cortical thickening of the calvaria with irregular, bony proliferation over the frontal, temporal, and occipital bones. Histopathological examination shows that the trabeculae of the calvarial diploë are thickened and contiguous with a sunburst-like pattern of subperiosteal trabeculae composed of woven and lamellar bone tissue, accompanied by loose fibrovascular tissue and a variable inflammatory response comprised predominantly of neutrophils. In 80% of the cases presented, the lesion was self-limiting. The etiology remains unknown; however, traumatic, neoplastic, and degenerative conditions do not appear to be primary factors in the etiopathogenesis of the syndrome. It may be that this syndrome has a familial component, similar to that described for CMO and ICH.

Reliability model from the in vitro durability tests of a left ventricular assist system.

A reliability test of the Novacor N100PC left ventricular assist system (LVAS) with valved conduits, including a pump/drive unit with compact controller and LVAS monitor was performed. The initial test objective was to demonstrate sufficient reliability for clinical use as a long-term circulatory support system. The subsequent objective, a test to failure, was intended to provide an assessment of the durability of the design and to determine the LVAS wearout modes. Testing began in April 1993 and was performed with 12 systems on gravity-feed mock circulatory loops. The pump/ drive units were submersed in body temperature saline for the duration of the test. Each of the LVAS units was operated at nominal afterloads of 75, 90, and 105 mm Hg, with test conditions varied to yield nominal pump outputs of 5.6, 7.1, and 8.3 L/min. Failure was defined as the inability of the LVAS to maintain an average pump output of 4 L/min or an average output pressure of 60 mm Hg. After 3 years, all systems remained on test, with durations of 2.3 to 3.0 years. Analysis of the testing to that date, using a constant hazard rate model, indicated a minimum demonstrated reliability of 94% at a 60% confidence level, or 86% at a 90% confidence level, for a 2 year mission time. This greatly surpasses the reliability level included in the STS-ASAIO Long-Term Mechanical Circulatory Support System Reliability Recommendation (80% reliability, 60% confidence level for a 1 year mission time). In the subsequent test-to-failure protocol, all systems ran failure-free for at least 3 years. System failures occurring at longer durations were caused by a single common cause: wear of the energy converter's armature support bearings and shafts. The wearout mode was gradual and could be diagnosed noninvasively before failure. An analysis using a Weibull model was performed, using the test durations of those devices that failed, those that were electively removed from test for analysis of the wear mode, and those that continued on test. As of April 1998, the test results showed a reliability, at a 60% confidence level, of >99.9% for a 1 year mission time, 99.5% for a 2 year mission, and 92.0% for a 3 year mission (>99.9%, 98.3%, and 85.9% for equivalent mission times, at a 90% confidence level). Systems continue on test after as long as 4.9 years.

Surgical treatment of idiopathic pericardial effusion in the dog: 25 cases (1978-1993).

Twenty-five cases of canine idiopathic pericardial effusion are described. All were treated surgically and underwent thoracotomy and pericardectomy, with histopathological evaluation of the resected pericardial sac. No tumor, infection, granulation tissue, or foreign body was found. Thirteen of the 25 dogs were golden retrievers, and all were large or giant breeds. Three (12%) died in the immediate postoperative period, and four (16%) died within one year of signs possibly related to the original condition. Eighteen (72%) survived at least 18 months; seven died or were euthanized for reasons unrelated to pericardial effusion (median, 44 months); and 11 were still alive at last contact (median, 61 months).

Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature.

An extensive, although largely forgotten, literature addresses the utility of adjunctive corticosteroid therapy in the management of tuberculosis. Corticosteroid therapy probably improves neurological outcomes of, and decreases mortality due to, tuberculous meningitis of moderate severity. Although therapy for tuberculous pericarditis is simplified (with less need for operative intervention) by adjunctive corticosteroid administration and there are fewer deaths, the incidence of subsequent constriction is not changed. The signs and symptoms of typical reactivation tuberculous pneumonia, tuberculous pleurisy, and probably primary tuberculous disease (with lymphadenopathy) seem to decrease rapidly with corticosteroid therapy, although no differences in final outcomes have been observed. Corticosteroid regimens used in most studies varied greatly in duration and dosage and generally caused significant side effects. Corticosteroids do not appear to diminish the efficacy of adequate antimycobacterial therapy. Adjunctive corticosteroid therapy appears to offer significant short-term but (other than for tuberculous meningitis and effusive pericarditis) minimal long-term benefit for patients with tuberculosis.

Does this patient have appendicitis?

Appendicitis is a common cause of abdominal pain for which prompt diagnosis is rewarded by a marked decrease in morbidity and mortality. The history and physical examination are at least as accurate as any laboratory modality in diagnosing or excluding appendicitis. Those signs and symptoms most helpful in diagnosing or excluding appendicitis are reviewed. The presence of a positive psoas sign, fever, or migratory pain to the right lower quadrant suggests an increased likelihood of appendicitis. Conversely, the presence of vomiting before pain makes appendicitis unlikely. The lack of the classic migration of pain, right lower quadrant pain, guarding, or fever makes appendicitis less likely. This article reviews the literature evaluating the operating characteristics of the most useful elements of the history and physical examination for the diagnosis of appendicitis.

Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen.

PURPOSE: A line of transgenic mice containing the simian virus (SV) 40 T-antigen (T-ag) gene driven by the beta-luteinizing hormone (BLH) promoter developed bilateral retinoblastoma and primitive neuroectodermal tumors (PNET) of the midbrain. Midbrain tumors arose from the subependymal layer of the cerebral aqueduct. Bilateral ocular and brain tumors ("trilateral") were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin). To gain insight into the regulatory mechanisms involved in central nervous system tumorigenesis, the authors examined brain tumors from four lines of SV40 T-ag mice with different promoters. METHODS: Formalin-fixed brain tumors were examined from four lines of transgenic mice containing different promoters linked to the protein coding region of the enhancerless SV40 T-ag oncogene. Transgenes contained the following promoters: BLH, mouse 1.8-kb IRBP, human 1.3-kb IRBP, and alpha A-crystallin. RESULTS: Mice with a 1.8-kb IRBP promoter develop retinal photoreceptor and pineal tumors. Intracranial tumors arising from the subependymal layer of the third ventricle also were observed. Mice with a 1.3-kb IRBP promoter exhibit bilateral retinal PNET and PNET originating from the subependymal layer of the third ventricle. Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the midbrain. CONCLUSIONS: Ocular tumors in these mice may be ascribed to the promoter-driven, tissue-specific expression of SV40 T-ag. The common finding of PNET arising from the subependymal layer of the diencephalon is unlikely to be promoter related. These findings indicate that a regulatory region specific to the subependymal layer of the cerebral aqueduct and third ventricle resides in the structural region of the SV40 T-ag gene.

Angioleiomyoma of the nasopharynx in a dog.

A polypoid angioleiomyoma was surgically removed from the nasopharynx of a 1-year-old, male golden retriever. The polypoid mass recurred 4 months later and was again excised. There was no sign of regrowth 13 months postoperatively. This is, apparently, the first reported angioleiomyoma occurring in the dog.

Cost analysis of objective structured clinical examinations.

BACKGROUND: The costs of objective structured clinical examinations (OSCEs) and other patient-centered examinations have not been well established. The published literature contains cost estimates ranging from $21 to over $1,000 per examinee. This wide range in cost estimates is due in part to both a lack of a consistent definition as to what should be included as an expense and a lack of understanding of how these expenses can be minimized. METHOD: In 1993-94 the authors conducted a literature review and defined and subcategorized costs related to the production and implementation of an OSCE into costs for personnel, standardized patients (SPs), and administration. An analysis was undertaken of how each of the subcategory costs can be minimized. RESULTS: Costs for physicians, patient trainers, support personnel, and data analysis are negligible if the personnel who perform these duties do so as part of their overall academic responsibilities. Costs for SPs can be minimized by developing a cadre of experienced patients as well as professional personnel who participate in a comprehensive program in which SPs are used in both teaching and evaluative modes. This contributes to the development of a psychometrically valid OSCE with a minimum number of stations and decreased costs. Administrative costs are fixed and not amenable to significant cost saving. A detailed cost analysis of a comprehensive OSCE given at the end of an Introduction to Clinical Medicine course at one institution is presented, illustrating the practical aspects of these cost-containment methods. CONCLUSION: Based on these considerations it appears financially feasible for an individual academic institution to develop and implement an OSCE.

Severe pruritus associated with lymphoma in a dog.

A dog with chronic pruritus that was refractory to antibiotic, corticosteroid, and antihistamine treatment was found to have lymphoma involving the spleen and associated lymph nodes. Pruritus rapidly resolved on removal of the tumor and recurred on reappearance. The association of generalized pruritus with an occult malignant process may be difficult to assess, but after excluding the more common causes of pruritus, a visceral malignancy should be considered.

Thymoma in two ferrets.

A cranial mediastinal mass was observed radiographically in two 5-year-old adult male ferrets (Mustela putorius furo), both with histories of chronic episodic vomiting, dyspnea, and lethargy. Malignant lymphoma, a common neoplasm observed in ferrets, was considered the most likely diagnosis. Cardiomegaly and splenomegaly were also present. Histologically both mediastinal masses were composed of thymic epithelial cells and small lymphocytes, establishing a diagnosis of thymoma. Thymoma should now be included in the differential diagnosis of a cranial mediastinal mass in ferrets.

Chylous ascites in cats: nine cases (1978-1993).

Medical records of 9 cats with chylous ascites that underwent exploratory celiotomy were reviewed. In 7 cats, chylous ascites was associated with intra-abdominal neoplasia: 4 cats had an unresectable tumor (hemangiosarcoma, 3 cats; paraganglioma, 1 cat) within the mesenteric root; 2 had malignant lymphoma of the small intestine and mesenteric lymph nodes; and 1 had lymphangiosarcoma of the abdominal wall. In 2 cats, chylous ascites was associated with nonneoplastic diseases: 1 cat had severe biliary cirrhosis and an extrahepatic portosystemic shunt; the other had steatitis caused by vitamin E deficiency. Three cats were euthanatized or died at the time of surgery, and 5 cats were euthanatized within 3 months of surgery. One cat with malignant lymphoma responded well to chemotherapy and lived for 14 months after surgery.

Hepatic plasmacytoma and biclonal gammopathy in a cat.

A 13-year-old castrated male domestic shorthair cat was evaluated because of weight loss, despite a good appetite. The most remarkable abnormality was a total serum protein concentration of 12.4 g/dl, with a globulin concentration of 9.4 g/dl. Serum protein electrophoresis revealed a biclonal spike in the gamma region. At necropsy, 2 discrete plasmacytomas were found in the liver, without bone marrow involvement or amyloidosis.

Surgical treatment of thymoma in cats: 12 cases (1987-1992).

Twelve cats with thymoma were treated by surgical excision of the tumor alone. None of the cats received radiotherapy or chemotherapy. Two cats died or were euthanatized during the immediate postoperative period: 1 because of postsurgical hemorrhage, and the other because of an associated fungal pleuritis. None of the remaining 10 cats developed evidence of local tumor recurrence or metastases. Six of the cats were alive after follow-up periods ranging from 6 to 36 months (mean, 21 months; median, 21 months). Three cats were euthanatized 18 months, 32 months, and 45 months following surgery for unrelated problems, and 1 cat died as a result of trauma sustained 62 months postoperatively. Myasthenia gravis developed postoperatively in 2 of the cats.

Analyzing and adjusting for variables in a large-scale standardized-patient examination.

BACKGROUND: Structuring a clinical performance examination that uses standardized patients (SPs) for large groups of examinees often involves the use of two or more parallel forms of the examination with different SPs portraying the same case on the different forms. In addition, each form may be administered more than once on different days and/or in different locations. METHOD: To determine the effects of critical variables, such as day of examination, time of day (AM/PM), which of two simultaneous forms were taken, and sequencing effects, a univariate nested factorial analysis of variance was conducted for each of four annual SP examinations (1990-1993) at the University of Texas Southwestern Medical School. The examinations were given to approximately 200 second-year students per year at the end of their Introduction to Clinical Medicine course, and were graded on a pass/fail basis. RESULTS: Statistically significant differences were found for the following variables: (1) time of day (AM or PM) and day were significant but were inconsistent and of small magnitude; (2) sequencing for the first two stations was significant in each form of the examination and in all four years; and (3) form-within-case differences (i.e., differences between SPs) were significant between the two forms of the examination in each year of administration. To minimize the impacts of these variables, two mean equating formulas were applied to the scores. Few examinees' pass/fail status would have been affected by either adjustment. CONCLUSION: The parallel-forms examination format is minimally affected by the variables evaluated and is a fair pass/fail assessment of a student's performance. Mean equating is a valuable tool in minimizing the possibly unfair impact of variables on pass/fail decisions for homogeneous student populations.

Esophageal plasmacytoma in a dog.

A 14-year-old spayed female dog of mixed breeding had a 3-week history of regurgitation of food occasionally mixed with blood. An esophagram revealed a mass in the caudal portion of the esophagus. The mass was partially removed through esophagoscopy. Evaluation of light microscopy, immunoperoxidase technique, and electron microscopy was consistent with an esophageal plasmacytoma. Surgical excision of the esophageal plasmacytoma was performed. Dogs with esophageal plasmacytoma appear to have a good prognosis.

Brain stem abscesses: cure with medical therapy, case report, and review.

A patient with a brain stem abscess that was cured with medical therapy alone is described. The English-language literature on brain stem abscesses is reviewed. Computed tomography (CT) and magnetic resonance imaging (MRI) have revolutionized the rapidity with which the diagnosis can be made and have markedly changed the prognosis for patients with brain stem abscesses. To my knowledge, all patients whose brain stem abscesses have been diagnosed by MRI or CT have survived although some have had neurological residuals. Patients are usually treated with surgical excision or aspiration along with antibiotics. Our patient was treated with medical therapy alone, and this case represents the fourth reported cure with this treatment modality. Medical therapy may be anticipated to cure patients with brain stem abscesses whose conditions are diagnosed expeditiously with CT or MRI techniques.

Neonatal toxoplasmosis in littermate cats.

Toxoplasmosis was diagnosed histologically in 9 kittens and 1 queen from 5 liters. In litter 1, four 3-month-old Siamese kittens and the queen were affected. The queen died of generalized toxoplasmosis, and her kittens died or were euthanatized 20, 22, or 28 days later. In litter 2, two of 3 Abyssinian 4- and 4.5-month-old kittens died of toxoplasmosis. In litter 3, an Abyssinian, delivered by cesarean section, became ill 17 days after delivery, and died 2 days later because of toxoplasmic hepatitis and pneumonia. In litter 4, three kittens, approximately 1 month old, were shedding Toxoplasma gondii-like oocysts, and the organism was identified histologically in tissues of 1 of them. In litter 5, one 3-week-old kitten out of 4 became ill. Toxoplasma gondii-like oocysts were found in feces and T gondii organisms were found in histologic sections of tissues.