Necrotizing enterocolitis associated with in utero and breast milk exposure to the selective serotonin reuptake inhibitor, escitalopram.

A term neonate presenting with necrotizing enterocolitis following in utero and breast milk exposure to the newest serotonin selective reuptake inhibitor, escitalopram, is described.

Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles.

Evidence supporting a broad role for the inactivation of the p53 gene in human tumorigenesis has been provided by studies showing that the p53 gene is mutated in many human cancers. In this study, we report on the mutational status of the p53 gene in prostate cancer cells and provide functional evidence that the wild-type p53 gene may have a role in suppressing prostatic tumorigenesis. Sequence analysis of exons 5-8 of the p53 gene reveals that three of five prostate cancer cell lines (TSUPr-1, PC3, DU145) contain mutations which alter the amino acid sequence of this most highly conserved portion of the gene. One of two primary prostatic cancer specimens examined also contained a mutation in this region. Transfection of the wild-type p53 gene versus a mutated p53 gene into two cell lines with p53 mutations results in reduced colony formation. Wild-type p53 gene expression is apparently incompatible with continued growth of these tumor cells inasmuch as none of the colonies which formed after wild-type transfections retain the transfected p53 sequences. Immunocytochemical data indicate that prostate carcinoma cells expressing the transfected wild-type p53 gene are growth arrested because they exhibit a reduced level of thymidine incorporation into DNA. This study is the first report of p53 gene mutations in prostate cancer cells and suggests a functional role for the p53 gene in suppressing prostatic tumorigenesis.

ras gene mutations in human prostate cancer.

Point mutations at codons 12, 13, or 61 of the Ha-, Ki-, and N-ras genes are able to convert these normal cellular genes into activated oncogenes. Previous studies have shown that ras gene mutations occur in a variety of human solid tumors and may be important in the pathogenesis of some of these tumors. In order to test the hypothesis that ras gene mutations may be associated with prostate cancer, we have used an oligodeoxynucleotide hybridization assay to detect wild-type and mutant alleles in genomic DNA from prostate tumors and prostate tumor cell lines amplified using the polymerase chain reaction. Twenty-four primary prostate tumors (23 acinar tumors and one ductal tumor) and five prostate tumor cell lines were examined for mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes. Two mutations were detected: an A----G transition causing a glutamine to arginine amino acid substitution at codon 61 of the Ha-ras gene in a primary prostatic duct adenocarcinoma and a G----T transversion causing a glycine to valine amino acid substitution at codon 12 of the Ha-ras gene in a prostate tumor cell line (TSU-PR1) derived from a lymph node metastasis. While the overall frequency of ras gene mutations in prostate tumors is low, when these mutations do occur they may have a role in the progression of disease or the development of the unusual ductal variant of prostatic adenocarcinoma.

Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer.

Allelic loss studies have been instrumental in identifying tumor suppressor gene loci in a variety of cancers. In this study we analyzed prostate cancer specimens from 52 patients for allelic loss using 8 polymorphic probes for the short arm of chromosome 8. Overall, 32 of 51 (63%) informative tumors showed loss of at least one locus on chromosome 8p. The most frequently deleted region is observed at chromosome 8p22-8p21.2. Loss of one allele is identified in 14 of 23 (61%) tumors at D8S163, in 15 of 32 (47%) tumors at lipoprotein lipase, and in 20 of 29 (69%) tumors at MSR, all on 8p22. Loss of one allele is identified in 16 of 27 (59%) tumors at D8S220 at 8p21.3-8p21.2. In addition to frequent loss of one allele at the MSR locus, one metastatic prostate cancer sample demonstrated homozygous deletion of MSR sequences. Loci telomeric and centromeric to this region are largely retained. A chromosome 8p deletion map is constructed and defines the smallest region of overlap to a 14-cM interval at 8p22 between D8S163 and lipoprotein lipase, flanking the MSR locus. Evidence of chromosome 8q multiplication at locus D8S39 was detected in 5 of 32 (16%) tumors, all of which demonstrated loss with at least one probe on chromosome 8p. This study extends the previous finding of frequent loss of chromosome 8p in prostate cancer by defining a common region of loss of heterozygosity at 8p22 and a homozygous deletion of the MSR locus contained within this region. This is the first homozygous deletion identified in the genome of a human prostate cancer and the highest rate of loss yet reported on chromosome 8p in cancer. These results strongly suggest the presence of a tumor suppressor gene in this region which is frequently inactivated in prostate cancer.

Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer.

E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.

An uncertain role for p53 gene alterations in human prostate cancers.

Inactivation of the p53 gene has been implicated in prostate cancer progression. To determine the role of p53 inactivation in the progression of clinical prostatic carcinomas, we assessed 67 tumors derived from patients with clinically localized disease for chromosome 17p and p53 gene allelic loss, p53 gene mutations using single-strand conformational polymorphism and direct sequencing, and p53 protein expression using immunohistochemical staining. Of 55 informative tumors, 10 demonstrated loss of 17p or the p53 gene; however, only a single tumor had a mutation in its remaining p53 allele. Significant p53 overexpression was observed in 2 of 38 tumors, and 9 others had faint staining of a few nuclei ( < 1%). p53 overexpression occurred in no informative tumor with allelic loss or mutation. In a 1-7-year follow-up, positive immunohistochemical staining did not confer an increased risk of recurrence (risk of recurrence, 0.86, P = 0.78), whereas allelic loss of chromosome 17p appeared to be highly correlated with recurrence (risk of recurrence, 3.7, P = 0.003). In an unrelated group of 42 patients with metastatic prostate cancer, p53 overexpression was found in 26 tumors (62%), and 15(36%) had high grade staining. Neither the presence nor the degree of expression correlated with time to progression or time to death. This series suggests that p53 gene inactivation is rare in primary prostatic tumors, not essential to the development of prostate cancer metastases, and of limited use as a prognostic marker in patients with primary or metastatic disease. Another gene or genes on chromosome 17p may be involved in prostate cancer progression.

Extracellular Vesicles in Molecular Diagnostics: An Overview with a Focus on CNS Diseases.

All known cells continuously release nanoscale lipid membrane-enclosed packets. These packets, termed extracellular vesicles (EVs), bear the signature of their cells of origin. These vesicles can be detected in just about every type of biofluid tested, including blood, urine, and cerebrospinal fluid. The majority comes from normal cells, but disease cells also release them. There is a great interest in collecting and analyzing EVs in biofluids as diagnostics for a wide spectrum of central nervous system diseases. Here, we will review the state of central nervous system EV research in terms of molecular diagnostics and biomarkers.

Diagnostic Accuracy of PET, SPECT, and Arterial Spin-Labeling in Differentiating Tumor Recurrence from Necrosis in Cerebral Metastasis after Stereotactic Radiosurgery.

BACKGROUND AND PURPOSE: Radiographic assessment of cerebral metastasis after stereotactic radiosurgery remains a major challenge in neuro-oncology. It is often difficult to distinguish tumor progression from radiation necrosis in this setting using conventional MR imaging. The objective of this study was to compare the diagnostic sensitivity and specificity of different functional imaging modalities for detecting tumor recurrence after stereotactic radiosurgery. MATERIALS AND METHODS: We retrospectively reviewed patients treated between 2007 and 2010 and identified 14 patients with cerebral metastasis who had clinical or radiographic progression following stereotactic radiosurgery and were imaged with arterial spin-labeling, FDG-PET, and thallium SPECT before stereotactic biopsy. Diagnostic accuracy, specificity, sensitivity, positive predictive value, and negative predictive value were calculated for each imaging technique by using the pathologic diagnosis as the criterion standard. RESULTS: Six patients (42%) had tumor progression, while 8 (58%) developed radiation necrosis. FDG-PET and arterial spin-labeling were equally sensitive in detecting tumor progression (83%). However, the specificity of arterial spin-labeling was superior to that of the other modalities (100%, 75%, and 50%, respectively). A combination of modalities did not augment the sensitivity, specificity, positive predictive value, or negative predictive value of arterial spin-labeling. CONCLUSIONS: In our series, arterial spin-labeling positivity was closely associated with the pathologic diagnosis of tumor progression after stereotactic radiosurgery. Validation of this finding in a large series is warranted.

Iterative probabilistic voxel labeling: automated segmentation for analysis of The Cancer Imaging Archive glioblastoma images.

BACKGROUND AND PURPOSE: Robust, automated segmentation algorithms are required for quantitative analysis of large imaging datasets. We developed an automated method that identifies and labels brain tumor-associated pathology by using an iterative probabilistic voxel labeling using k-nearest neighbor and Gaussian mixture model classification. Our purpose was to develop a segmentation method which could be applied to a variety of imaging from The Cancer Imaging Archive. MATERIALS AND METHODS: Images from 2 sets of 15 randomly selected subjects with glioblastoma from The Cancer Imaging Archive were processed by using the automated algorithm. The algorithm-defined tumor volumes were compared with those segmented by trained operators by using the Dice similarity coefficient. RESULTS: Compared with operator volumes, algorithm-generated segmentations yielded mean Dice similarities of 0.92 ± 0.03 for contrast-enhancing volumes and 0.84 ± 0.09 for FLAIR hyperintensity volumes. These values compared favorably with the means of Dice similarity coefficients between the operator-defined segmentations: 0.92 ± 0.03 for contrast-enhancing volumes and 0.92 ± 0.05 for FLAIR hyperintensity volumes. Robust segmentations can be achieved when only postcontrast T1WI and FLAIR images are available. CONCLUSIONS: Iterative probabilistic voxel labeling defined tumor volumes that were highly consistent with operator-defined volumes. Application of this algorithm could facilitate quantitative assessment of neuroimaging from patients with glioblastoma for both research and clinical indications.

A proposed comprehensive grading system to predict outcome for surgical management of intracranial aneurysms.

OBJECTIVE: By conducting a review of clinical outcomes for patients with aneurysms treated using current microneurosurgical techniques and intensive care unit management, we determined that grading systems based only on the clinical condition of the patient failed to produce a significant stratification of outcome between individual grades of patients. We hypothesized that outcome prediction for patients surgically treated for intracranial aneurysms could be improved by including factors other than clinical condition that were also strongly associated with outcome. METHODS: To identify potential factors for inclusion in a risk prediction tool, we conducted a multivariate logistic regression analysis of patient- and lesion-specific factors suspected to be associated with outcome in a series of 434 aneurysm operations. Factors that were strongly associated with outcome were used to develop a comprehensive grading system. In the system, 1 point is assigned for Hunt and Hess Grade IV or V, Fisher Scale score of 3 or 4, aneurysm size greater than 10 mm, patient age older than 50 years, and if the lesion is a giant (> or =25 mm) posterior circulation lesion. By adding the total points, a 5-point grading system (Grades 0-5) is obtained. RESULTS: Age of patient, size of aneurysm, severity of subarachnoid hemorrhage (Fisher Scale evaluation of density of blood present as revealed by computed tomography), and clinical condition (Hunt and Hess grade) were each independently and strongly (relative risk, >4) associated with long-term outcome. In addition, there was a trend for increased risk with larger (>25 mm) posterior circulation lesions. When applied to the study population, individual grades on the new grading scale correlated well with actual outcome. In a prospective assessment of the system as applied to an additional 72 operations with at least 1 year of follow-up, the correlation of individual grades and outcome was strong and validated the retrospective findings. CONCLUSION: This new grading system is easy to apply, separates patients into groups with markedly different outcomes, and is comprehensive, allowing for more accurate prediction of surgical outcome for both unruptured and ruptured cerebral aneurysms.

One-year outcome after decompressive surgery for massive nondominant hemispheric infarction.

OBJECTIVE: Massive cerebral infarction is often accompanied by early death secondary to transtentorial herniation. We have tested the hypothesis that decompressive hemicraniectomy for massive nondominant cerebral infarction is lifesaving in a series of 14 patients presenting with right hemispheric infarction and clinical signs of uncal herniation and impending death. We have further analyzed, in prospective follow-up examinations, the levels of physical, psychiatric, and social disabilities in these patients. METHODS: The methods used included retrospective analysis to determine rates of immediate mortality and morbidity after surgical intervention. Prospective follow-up data were obtained to determine the level of recovery in surviving patients after 1 year. Standardized measures of outcome to assess physical, psychiatric, and social recovery included the Barthel Index, Zung Depression Scale, and Reintegration to Normal Living Index. RESULTS: With decompressive hemicraniectomy, we were able to prevent death secondary to transtentorial herniation in all cases; 11 patients experienced long-term survival after the procedure, and three deaths were related to non-neurological causes. We observed that 8 of the 11 surviving patients were at home, were functioning with minimal to moderate assistance, and had Barthel scores greater than 60. The remaining three patients were severely disabled. Seven of the 11 survivors were able to walk at 1 year after undergoing the procedure. Depression and failure to reintegrate socially were experienced by most patients. CONCLUSION: This series confirms the lifesaving nature of hemicraniectomy in patients deteriorating because of cerebral edema after infarction. In patients younger than 50 years, recovery to a state of near-independence is possible.

Factors associated with reintegration to normal living after subarachnoid hemorrhage.

OBJECTIVE: Recent reports have suggested improvement in the last decade in global outcome measures after subarachnoid hemorrhage (SAH), particularly in patients presenting in good initial neurological status. We used a standardized self-report instrument, the Reintegration to Normal Living (RNL) Index, to assess a patient-based quality of life measure and a self-report of work status. We tested the hypothesis that several patient-based factors were related to these outcomes, including depressive symptoms, physical disability, age, and initial Hunt and Hess grade. Using these data, we report the total management morbidity and mortality at 1 to 5 years after SAH for patients initially presenting in good neurological condition. METHODS: The study population consisted of 246 consecutive patients admitted to our tertiary care center with aneurysmal SAH in good neurological condition (Hunt and Hess Grades I-III). Patients underwent either surgical (92%), endovascular (7%), or medical (1 %) management of aneurysmal SAH. Eighty-three percent of surviving patients completed a written or telephone questionnaire incorporating the Barthel Index, the Zung Self-rating Depression Scale, the RNL Index, and a work status assessment. RESULTS: An aneurysm-related mortality rate of 6% was observed in the patient population. Fifty-five percent of patients reported a complete reintegration into their normal living situation, as measured by the RNL Index. Sixty-seven percent of previously full-time workers returned to a full-time status. Thirty-six percent of patients reported depressive symptoms, and 23% of patients reported physical disability. In a multivariate model, the two factors that contributed most to an impairment of reintegration were depression and physical disability, whereas a failure to return to work was related to older age and a higher-grade initial neurological status. CONCLUSION: In this series of patients undergoing multimodality management of lower-grade SAH, more than one-half of patients subsequently reported a normal reintegration into their social situation, as assessed by the RNL Index. Standardized assessments of cofactors associated with impaired reintegration revealed that depressive symptoms and physical disability played a strong role in overall reintegration. Standardized assessments, such as the RNL Index, offer the potential for improved comparison of different treatment regimens and specific therapeutic targeting of factors, such as depression, which contribute to decreased quality of life.

Management outcomes for ruptured and unruptured aneurysms in the elderly.

OBJECTIVE: In a patient older than 70 years, the decision to treat an intracranial aneurysm remains difficult whether it is ruptured or unruptured. We sought to review our institutional risks of treatment of such lesions in the context of the risks of rupture and its associated morbidity and mortality in this age group. METHODS: One hundred twenty-nine consecutive patients aged 70 years or older, who were treated at a single institution for an intracranial aneurysm, were retrospectively reviewed. Forty patients were treated for unruptured aneurysms, and 89 patients presented after subarachnoid hemorrhage. Seven additional patients in this age group who had solely intracavernous lesions, as well as one patient with a dolichoectatic fusiform basilar lesion, were excluded. Management outcomes were assessed using a modification of the Glasgow Outcome Scale, and additional physical and functional disability was assessed using the Barthel index and the Reintegration to Normal Living index. RESULTS: Six-month outcomes for the unruptured group were: excellent, 70%; good, 15%; fair, 5%; poor, 7.5%; and death (2.5%). Outcomes for all patients with ruptured lesions (including those not offered aggressive therapy) were: excellent, 34%; good, 9%; fair, 5.6%; poor, 3.4%; and death, 45%. Long-term follow-up was performed by questionnaire to assess physical and functional disability. Although physical disability (Barthel index) was similar among survivors, the Reintegration to Normal Living index, a global assessment of function, was significantly higher in patients with unruptured aneurysms (84.8 versus 70.1; P = 0.05), which highlights the disabling effects of hemorrhage. CONCLUSION: On the basis of an individual treatment center's management risks, annual aneurysmal rupture rates can be estimated that justify treatment in this difficult patient population. Despite recent controversy regarding aneurysmal hemorrhage rates, we think that symptomatic unruptured aneurysms should be treated and good results can be achieved, even in older patients.

Results after surgical and endovascular treatment of paraclinoid aneurysms by a combined neurovascular team.

OBJECTIVE: Advances in surgical and endovascular techniques have improved treatment for paraclinoid aneurysms. A combined surgical and endovascular team can formulate individualized treatment strategies for patients with paraclinoid aneurysms. Patients who are considered to be at high surgical risk can be treated endovascularly to minimize morbidity. We reviewed the clinical and radiographic outcomes of 238 paraclinoid aneurysms treated by our combined surgical and endovascular unit. METHODS: From 1991 to 1999, the neurovascular team treated 238 paraclinoid aneurysms in 216 patients at the Massachusetts General Hospital. The modality of treatment for each aneurysm was chosen based on anatomic and clinical risk factors, with endovascular treatment offered to patients considered to have higher surgical risks. One hundred eighty aneurysms were treated by direct surgery, 57 were treated by endovascular occlusion, and one was treated by surgical extracranial-intracranial bypass and endovascular internal carotid artery balloon occlusion. Locations were transitional, 12 (5%); carotid cave, 11 (5%); ophthalmic, 131 (55%); posterior carotid wall, 38 (16%); and superior hypophyseal 46 (19%). Lesions contained completely within the cavernous sinus were excluded from this analysis. RESULTS: Using the Glasgow Outcome Scale (GOS), overall clinical outcomes were excellent or good (GOS 5 or 4), 86%; fair (GOS 3), 7%; poor (GOS 2), 4%; and death (GOS 1), 3%. Among the surgically treated patients, 90% experienced excellent or good outcomes (GOS 5 or 4), 6% had fair outcomes (GOS 3), 2% had poor outcomes (GOS 2), and 3% died (GOS 1). Among the endovascularly treated patients, 74% had excellent or good outcomes (GOS 5 or 4), 12% had fair outcomes (GOS 3), 10% had poor outcomes (GOS 2), and 4% died (GOS 1). The overall major and minor complication rate from surgery was 29%, with a 6% surgery-related permanent morbidity rate and a mortality rate of 0%. The overall major and minor complication rate from endovascular treatment was 21%, with a 3% endovascular-related permanent morbidity rate and a 2% mortality rate. Visual outcomes for patients who presented with visual symptoms were as follows: improved, 69%; no change, 25%; worsened, 6%; and new visual deficits, 3%. In general, angiographic efficacy was lower in the endovascular treatment group. CONCLUSION: A combined team approach of direct surgery and endovascular coiling can lead to good outcomes in the treatment for paraclinoid aneurysms, including high-risk lesions that might not have been treated in previous surgical series.

A longitudinal ethics curriculum for medical students and generalist residents at the Medical College of Georgia.

Medical ethics is an important instructional area for both the undergraduate student pursuing a generalist education and generalist residents. With the support of a Generalist Physician Initiative (GPI) award from The Robert Wood Johnson Foundation, the Medical College of Georgia has implemented a longitudinal experience in clinical ethics spanning the four undergraduate years to make this area more meaningful and clinically relevant. This report outlines the structure and content of this four-year curriculum, which has been developed and implemented in a stepwise fashion since 1996. Course themes and students' activities during the four years are described. Since 1997, a shared curriculum in ethics--developed for residents in internal medicine, family medicine, and pediatric generalist programs--has been provided in combined interdepartmental conferences as part of a broader interdepartmental generalist curriculum. Early evaluation findings and plans for future evaluation programs are also described.

Temporary vessel occlusion for aneurysm surgery: risk factors for stroke in patients protected by induced hypothermia and hypertension and intravenous mannitol administration.

Temporary vessel occlusion is an effective technique used by microvascular surgeons to facilitate dissection and permanent clipping of cerebral aneurysms; however, several questions remain regarding the overall safety of this technique. To identify technical and patient-specific risk factors for perioperative stroke, the authors examined a series of patients in whom induced hypertension and mild hypothermia and intravenous mannitol administration were used as protection during temporary vessel occlusion for aneurysm clipping. The study comprises a nonconcurrent prospective analysis of 132 consecutive aneurysm clippings performed with the aid of temporary vascular occlusion and a specific antiischemic anesthetic protocol at the Massachusetts General Hospital from 1991 to 1993. Factors studied included duration of the temporary clip application, number of occlusive episodes, patient age and neurological status, presence of preoperative subarachnoid hemorrhage (SAH), and intraoperative aneurysm rupture ("forced" temporary clipping), as well as whether proximal vessel occlusion or complete aneurysm trapping was used. In a univariate analysis, patient age, intraoperative aneurysm rupture, temporary clipping lasting more than 20 minutes, clipping between the 4th and 10th day after SAH, and multiple clipping episodes were all significantly associated with stroke outcome. Multivariate logistic regression revealed that intraoperative aneurysm rupture (relative risk 5.6, p = 0.02) and a duration of temporary clip application that lasted more than 20 minutes (relative risk 9.4, p = 0.04) were independently associated with stroke outcome. Overall, 5.2% of the patients had postoperative clinical strokes. Based on their findings the authors conclude that temporary clipping is a safe adjunct to aneurysm surgery, particularly when the duration of clipping is short.

Combined surgical and endovascular techniques of flow alteration to treat fusiform and complex wide-necked intracranial aneurysms that are unsuitable for clipping or coil embolization.

OBJECT: Certain intracranial aneurysms, because of their fusiform or complex wide-necked structure, giant size, or involvement with critical perforating or branch vessels. are unamenable to direct surgical clipping or endovascular coil treatment. Management of such lesions requires alternative or novel treatment strategies. Proximal and distal occlusion (trapping) is the most effective strategy. In lesions that cannot be trapped, alteration in blood flow to the "inflow zone," the site most vulnerable to aneurysm growth and rupture, is used. METHODS: From 1991 to 1999 the combined neurosurgical-neuroendovascular team at the Massachusetts General Hospital (MGH) managed 48 intracranial aneurysms that could not be clipped or occluded. Intracavernous internal carotid artery aneurysms were excluded from this analysis. By applying a previously described aneurysm rupture risk classification system (MGH Grades 0-5) based on the age of the patient, aneurysm size, Hunt and Hess grade, Fisher grade, and whether the aneurysm was a giant lesion located in the posterior circulation, the authors found that a significant number of patients were at moderate risk (MGH Grade 2; 31.3% of patients) and at high risk (MGH Grades 3 or 4; 22.9%) for treatment-related morbidity. The lesions were treated using a variety of strategies--surgical, endovascular, or a combination of modalities. Aneurysms that could not be trapped or occluded were treated using a paradigm of flow alteration, with flow redirected from either native collateral networks or from a surgically performed vascular bypass. Overall clinical outcomes were determined using the Glasgow Outcome Scale (GOS). A GOS score of 5 or 4 was achieved in 77.1%, a GOS score of 3 or 2 in 8.3%, and death (GOS 1) occurred in 14.6% of the patients. Procedure-related complications occurred in 27.1% of cases; the major morbidity rate was 6.3% and the mortality rate was 10.4%. Three patients experienced aneurysmal hemorrhage posttreatment; in two patients this event proved to be fatal. Aneurysms with MGH Grades 0, 1, 2, 3, and 4 were associated with favorable outcomes (GOS scores of 5 or 4) in 100%, 92.8%, 71.4%, 50%, and 0% of instances, respectively. CONCLUSIONS: Despite a high incidence of transient complications, intracranial aneurysms that cannot be clipped or occluded require alternative surgical and endovascular treatment strategies. In those aneurysms that cannot safely be trapped or occluded, one approach is the treatment strategy of flow alteration.

The neonatologist as primary care physician.

Although trained first as pediatricians, neonatologists are not typically viewed as primary care physicians. However, given their particular training and expertise, patient population, and interaction with families as the newborn's first physician in many settings, neonatologists may rightly be viewed as the most appropriate primary care physician for newborns with medical or surgical problems. We review the fundamental underpinnings of primary care medicine with particular attention to how the neonatologist functions in such capacities. Neonatologist can contribute greatly to ensuring continuity of care for the sick newborn, the comprehensive nature of that care, and the coordination of care. Neonatologists' interactions with elements of the community to which the newborn will be discharged are an asset, as is their ability to work as part of a team. Given recent changes in practice management, the availability of neonatologists in the United States, and the desire for full-service mother and infant care capabilities in community hospitals, the primary care role of neonatologists bears recognition and support in today's changing healthcare marketplace.

Diagnosis of suspected intracranial metastases. Role of direct tissue examination.

Accurate histologic diagnosis is often critical to the appropriate choice of treatment of patients suspected of harboring brain metastases. In most cases, frame based stereotactic biopsy can provide an accurate histologic diagnosis with minimal risk of morbidity. In addition, newer modalities allow for efficient coupling of stereotactic biopsy with treatment in a single session. These include frameless stereotactic systems that facilitate the combination of open biopsy and resection as well as biopsy procedures that are combined with focal interstitial or external beam irradiation. These techniques provide increasingly convenient and effective means of achieving both diagnosis and treatment of cerebral metastases.

Neonatologists and bioethics after Baby Doe.

The use of hospital ethics committees or infant care review committees has been recommended for difficult decision making. In a survey of military and civilian neonatologists, ethics committees had been established in 27 of their 28 hospitals and fewer than 50% had infant care review committees. Despite the frequently of potential cases for committee review, they were seldom consulted. Inquiry into the educational background of respondents revealed that at least 62% of neonatologists had received ethics education during their professional careers. Most made difficult decisions in conjunction with parents or used a multidisciplinary patient care conference. The use of these conferences antedated any federal regulations. Sixty-seven percent indicated that the Baby Doe regulations had affected neither their thinking about ethical issues nor their practice. In 13 different hypothetical cases in delivery room, intensive care nursery, and long-term care settings, the provision of comfort care, limited care, or withdrawal of support was noted by a sizable percentage of neonatologists; exceptions included meningomyelocele and trisomy 21. The need for ethics committee input in decision making for neonates is questionable.