Third, fourth, and sixth cranial nerve palsies following closed head injury.

BACKGROUND: The relationship between the circumstances and severity of closed head injury (CHI) and the clinical and imaging features of cranial nerve 3, 4, and 6 palsies has not been rigorously addressed in a large study. METHODS: Retrospective chart review of 210 consecutive patients with CHI examined at a single tertiary care center from 1987 to 2002. Patients were located by searching the ophthalmology inpatient consultation and neuro-ophthalmology outpatient databases and hospital emergency room billing codes for a diagnosis of traumatic 3, 4, or 6 cranial nerve palsy (Cranial Nerve Injury Group) and a diagnosis of CHI without traumatic 3, 4, or 6 nerve palsy (Control Group). The Cranial Nerve Injury Group was then subdivided into two groups: those with injuries to an individual cranial nerve and those with multiple (including bilateral) cranial nerve injuries. Comparisons between groups were based on age, gender, type of accident, Glasgow Coma Scale (GCS), documented loss of consciousness (LOC), type of ocular injury, presence of systemic injury, need for rehabilitation, physical therapy and cognitive scores, and imaging features. RESULTS: The Cranial Nerve Injury Group had a significantly higher severity of head injury, more CT abnormalities, and worse short-term neurologic outcomes as compared with the Control Group. These trends were also found when each cranial nerve injury subgroup was compared with the Control Group. Those with cranial nerve 3 palsy had the most severe head injury; those with cranial nerve 4 palsy had an intermediate level of head injury; and those with cranial nerve 6 palsy had the lowest level of head injury. There were no consistent associations between the location of the imaging abnormalities and which cranial nerve was damaged. CONCLUSIONS: CHI with palsy of an ocular motor nerve was more severe than CHI without ocular motor nerve palsy, as measured by the GCS, intracranial and skull imaging abnormalities, and a greater frequency of inpatient rehabilitation. Palsy of cranial nerve 3 was associated with relatively more severe CHI than was palsy of cranial nerves 4 or 6. The location of the imaging abnormalities did not correlate with a particular cranial nerve injury.     

Cytokine-activated natural killer cells exert direct killing of hepatoma cells harboring hepatitis C virus replicons.

Hepatitis C virus (HCV)-specific impairments in host immunity have been described at multiple levels of the innate and adaptive response, which may lead to viral persistence in the majority of infections. Understanding of HCV-associated immune defects could lead to novel therapeutic advances. Natural killer (NK) cells, the major effector cells of the innate immune system, are functionally impaired in chronic HCV infection. It has been suggested that this phenotype is a result of virus-specific defects in antigen-presenting cells (APCs) that regulate NK cell activity, as normal NK function is restored when they are stimulated ex vivo. In this study, we used human NK cell cytotoxicity assays to evaluate the activation-induced effects of NK cells on the HCV replicon-containing hepatic cells. We found that cytokine-activated NK cells were capable of inducing an HCV-associated, perforin/granzyme-dependent lysis of human hepatoma cells and that this required direct cellular contact and was independent of MHC class I expression levels. In contrast, on removal of cytokine stimulation, NK cells failed to exert any direct cytolytic effect on replicon targets. These findings suggest an important underlying mechanism by which NK cells control HCV infection and, with appropriate understanding of HCV-associated immune defects, could lead to novel therapeutic advances.     

Evolution of the sperm aster after microinjection of isolated human sperm centrosomes into meiotically mature human oocytes

This study examined the feasibility of isolating and transferringthe centrosome-containing region of spermatozoa to mature humanoocytes. The findings demonstrate that individual sperm centrosomescan be transferred and are capable of nucleating maternal tubulinto form a well-developed sperm aster in the recipient oocyte.The results are discussed with respect to centrosome functionin early human development and applications in clinical in-vitrofertilization in the treatment of certain forms of male factorinfertility.     

Cortical circumferential profile of SPECT cerebral perfusion in Alzheimer''s disease

We developed a semiautomatic method termed “cortical circumferential profiling” for objective analysis of cerebral cortex function in emission tomographic neuroimaging studies. This method treats cortex as a continuous ring near the outer brain edge. A computer algorithm samples the cortex at 60 contiguous, equiangular locations, using 1-cm² samples. These values are plotted as a function of cortical angle to produce the cortical circumferential profile. This method was used in a study of regional cerebral perfusion in 15 patients with Alzheimer's disease and 8 elderly control subjects using N-isopropyl [I-123]-iodoamphetamine. Cortical circumferential profiling decreases variability, examines the entire cortex within slices at preselected levels above the orbital-meatal line, and facilitates intrasubject and intersubject comparisons.     

Clerkship directors' perceptions of the impact of HCFA documentation guidelines.

PURPOSE: Chart notes are used to support billing codes under the evaluation and management guidelines of the Health Care Financing Administration (HCFA), in addition to serving as a record of the visit. To better understand the effect of the HCFA documentation guidelines, the authors collected data on how the guidelines affect participation by university- and community-based faculty in clinical education programs. METHOD: In 2000, the authors sent six copies of their questionnaire to the associate deans of the 125 U.S. medical schools and requested they distribute them to all core clerkship directors. The questionnaire consisted of multiple-choice and short-answer questions regarding documentation of medical visits, participation of community-based faculty, understanding of HCFA documentation guidelines, and effects on education programs. RESULTS: The response rate was about 50%. Most of the 379 clerkship directors who responded (77%) stated they were aware the HCFA documentation guidelines include specifications regarding the role medical students can play and documentation of medical visits, and 64% indicated they were concerned the guidelines would affect their educational programs. Concerns included the loss of student independence and active participation in the patient care environment (37), time constraints and the changing balance between education and service (16), loss of faculty and decreased morale (11), and decreased quality of care for patients (7). CONCLUSION: Leaders of medical education must work to modify these guidelines to protect the quality of patients' care, while maximizing students' educational opportunity and participation.     

Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial.

PURPOSE: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma. PATIENTS AND METHODS: A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate. RESULTS: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v N0, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P =.009) and shorter time to recurrence (P <.0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment. CONCLUSION: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.     

Laboratory routines cause animal stress.

Eighty published studies were appraised to document the potential stress associated with three routine laboratory procedures commonly performed on animals: handling, blood collection, and orogastric gavage. We defined handling as any non-invasive manipulation occurring as part of routine husbandry, including lifting an animal and cleaning or moving an animal's cage. Significant changes in physiologic parameters correlated with stress (e.g., serum or plasma concentrations of corticosterone, glucose, growth hormone or prolactin, heart rate, blood pressure, and behavior) were associated with all three procedures in multiple species in the studies we examined. The results of these studies demonstrated that animals responded with rapid, pronounced, and statistically significant elevations in stress-related responses for each of the procedures, although handling elicited variable alterations in immune system responses. Changes from baseline or control measures typically ranged from 20% to 100% or more and lasted at least 30 min or longer. We interpret these findings to indicate that laboratory routines are associated with stress, and that animals do not readily habituate to them. The data suggest that significant fear, stress, and possibly distress are predictable consequences of routine laboratory procedures, and that these phenomena have substantial scientific and humane implications for the use of animals in laboratory research.