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Biomedical subjects

D C Miller

Publications and source records attributed to D C Miller.

At least 163 records · Page 9Linked to original sources

Pathology of craniopharyngiomas: clinical import of pathological findings.

Craniopharyngiomas are benign neoplasms, thought to be of maldevelopmental origin, which occur in both children and adults in the sella and suprasellar regions. There are two distinctive histologic patterns, 'adamantinomatous' and 'squamous papillary', but transitional or mixed examples occur. Prior suggestions that squamous papillary tumors are found 'only' in adults, 'never' calcify, do not invade brain, and are associated with a better outcome ('no' recurrences, better clinical status) are partially correct, but rare pediatric examples occur, rare examples have calcification, and in our study of 56 patients with craniopharyngiomas treated at New York University there was no statistically significant difference in brain invasion or recurrence rates for squamous papillary as compared to adamantinomatous types. Brain invasion, commonly seen in craniopharyngioma specimens, is not a predictor of recurrence.

Adult↗

Alterations in left ventricular twist mechanics with inotropic stimulation and volume loading in human subjects.

BACKGROUND: Left ventricular (LV) twist, the longitudinal gradient of circumferential rotation about the LV long axis, may play an important role in the storage of potential energy at end systole and its subsequent release as elastic recoil during early diastole; however, the effects of load and inotropic state on LV systolic twist and diastolic untwist in human subjects have not previously been characterized. METHODS AND RESULTS: Six cardiac transplant recipients with 12 implanted radiopaque midwall LV myocardial markers were studied 1 year after transplantation. Biplane cinefluoroscopic marker images and LV pressure were recorded during control conditions and after afterload augmentation (methoxamine, 5 to 10 micrograms.kg-1 x min-1), inotropic stimulation (dobutamine, 5 micrograms.kg-1 x min-1), and preload augmentation (volume loading with normal saline). Systolic twist dynamics were assessed by maximum twist (Tmax[rad/cm]), peak negative twist rate (-dT/dtmin[rad.cm-1 x s-1]), and the slope of the twist normalized-ejection fraction relation (T-nEFR, Msys[rad/cm]) during systole. Diastolic untwist was assessed by the peak positive untwist rate (+dT/dtmax [rad.cm-1 x s-1]) and the slopes (rad/cm) of the T-nEFR during early diastole (Mear-dia) and mid diastole (Mmid-dia). Compared with control values, LV pressure and volume loading had no significant effect on Tmax, -dT/dtmin, or Msys; however, inotropic stimulation significantly increased all parameters describing systolic twist (Tmax: -0.10 +/- 0.03 versus -0.06 +/- 0.02 rad/cm, P < .001; -dT/dtmin: -0.72 +/- 0.19 versus -0.44 +/- 0.22 rad.cm-1 x s-1, P < .001; Msys: -0.10 +/- 0.03 versus -0.06 +/- 0.01 rad/cm, P < .001). Pressure loading had no effect on early diastolic untwisting; however, dobutamine significantly increased M(ear)-dia (-0.24 +/- 0.06 versus -0.13 +/- 0.04 rad/cm, P < .0001) and +dT/dtmax (0.78 +/- 0.24 versus 0.45 +/- 0.16 rad.cm-1 x s-1, P < .001). Conversely, volume loading significantly decreased M(ear)-dia (-0.08 +/- 0.04 versus -0.13 +/- 0.04 rad/cm, P < .05). M(ear)-dia correlated directly with LV contractile state (as assessed as maximum dP/dt, r = .60, P < .0001) and inversely with end-systolic volume (r = -.87, P < .0001) but was unrelated to stroke volume (r = .08, P = .30) or LV afterload (estimated as effective arterial elastance, r = .08, P = .29). Mmid-dia did not change during any intervention. CONCLUSIONS: In conscious human transplant patients, (1) pressure and volume loading do not affect systolic LV twist; (2) dobutamine augments systolic twist and early diastolic untwisting, suggesting more end-systolic potential energy storage and early diastolic elastic recoil with enhanced inotropic state; (3) volume loading decreases early diastolic untwisting, possibly reflecting diminished recoil forces after preload augmentation associated with larger end-systolic volumes (ESV); and (4) M(ear)-dia correlates strongly with ESV (in an inverse fashion), and less strongly, but directly, with LV dP/dtmax.

Adult↗

Dynamics of normal and ischemic canine papillary muscles.

This investigation was designed to elucidate the dynamics of the left ventricular (LV) papillary muscles. Miniature tantalum myocardial markers were placed on the tip and base of each papillary muscle in six dogs. Markers were also implanted into the LV myocardium to define two orthogonal equatorial diameters and the long-axis dimension. Two weeks later, after recovery from thoracotomy, markers were visualized by biplane fluoroscopy, and video images were recorded during control conditions, after autonomic blockade, after inotropic stimulation with calcium, after methoxamine infusion (to increase afterload), and after blood volume augmentation (to increase preload). Two days later, radiographic recordings were made before and after occlusion of the left circumflex coronary artery. Computer-aided analysis of the video recordings was used to determine three-dimensional coordinates of the markers. It was found that before circumflex coronary occlusion, the dynamics of both papillary muscles closely mimicked the dynamics of the LV as a whole. The papillary muscles shortened during ejection and lengthened during diastole. Their lengths changed minimally during the isovolumic periods, and this behavior was not altered by any of the interventions except coronary occlusion. During circumflex coronary artery occlusion, the ischemic posterior papillary muscle lengthened during isovolumic contraction and most of ejection and shortened only when LV pressure began to fall. Hence, we believe that previous studies demonstrating papillary muscle lengthening during isovolumic contraction and shortening during isovolumic relaxation may have been confounded by coexistent myocardial ischemia or stunning.

Animals↗

Cervicomedullary tumors in children: a distinct subset of brainstem gliomas.

We reviewed the clinical course of 17 children who underwent surgical resection of an intra-axial cervicomedullary tumor between 1980 and 1992. The clinical symptoms, which reflected medullary dysfunction in nine children and cervical cord deficits in eight, were present for a mean of 2.1 years before diagnosis (range, 2 months to 7.5 years), and for at least 1 year in 80% of the patients. Neurodiagnostic imaging (MRI in 14, CT in 3) showed the tumor epicenter in the medulla in 11 and in the upper cervical cord in six. Surgery was performed for newly diagnosed tumor in 11 children, and for progressive disease in six who had received prior radiotherapy. The surgical resection was gross total in two and partial (60 to 95%) in fifteen. Fifteen patients had low-grade glial tumors (10 astrocytomas, four gangliogliomas, and one mixed glioma), and two had anaplastic gangliogliomas. Four-year progression-free and total survival rates after surgery for patients who had surgery as initial therapy were 70 and 100%; for those who had surgery at the time of progression, these were 41 and 62%. Postsurgical neurologic complications occurred in five children. Four of these children had received prior radiotherapy. Two of them already had severe preoperative deficits and three had moderate deficits that worsened after surgery. Twelve patients with mild deficits were unchanged or improved postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome.

Pathological and clinical data from 56 patients operated on for craniopharyngioma since 1981 were analyzed to determine the utility of dividing patients with this tumor into distinct clinical groups based on recognized pathological type and to determine the prognostic import of brain invasion. Of the tumors in the 30 adult patients, 66% were adamantinomatous, 28% were squamous papillary, and the remainder were mixed. However, of the tumors in the 26 children, 96% were adamantinomatous and none were pure squamous papillary (P < 0.01). Forty-six percent of the children compared with 17% of the adults had brain invasion (P < 0.01). Brain invasion was present in 37% of the adamantinomatous but in only 13% of the squamous papillary tumors. Seventy-seven percent of the children underwent gross total resection (GTR) compared with 27% of the adults (P < 0.01). Sixty-three percent of the squamous papillary tumors underwent GTR compared with 54% of the adamantinomatous and mixed tumors. Follow-up ranged from 7 to 187 months (mean, 49 mo). After subtotal resection, with or without radiation therapy, 58% of the tumors recurred compared with 17% recurrence after GTR (P < 0.01), with a mean time to recurrence of 34 months. In both tumor histological types, subtotal resection was associated with a higher rate of tumor recurrence compared with gross total resection. Among the subtotally resected craniopharyngiomas, 2 of the 3 (67%) squamous papillary and 11 of the 21 (52%) adamantinomatous and mixed tumors recurred. In contrast, among the totally resected tumors, none of the 5 squamous papillary and only 5 of the 25 (20%) adamantinomatous and mixed tumors recurred. There were no significant differences in Karnofsky performance status score, mortality rate, or visual and endocrine outcomes when comparing patients based on histological tumor type. When controlling for age and extent of resection, we found that brain invasion had no significant effect on recurrence rate in totally resected tumors. Based on the limited number of patients in this series, we conclude as follows. 1) Contrary to previous reports, squamous papillary craniopharyngiomas, like adamantinomatous tumors, may recur when subtotally resected. 2) For both tumor variants, the most significant factor associated with craniopharyngioma recurrence is the extent of surgical resection rather than histopathological subtype. 3) Contrary to prior hypotheses, brain invasion in totally resected tumors does not predict higher recurrence. 4) GTR is associated with a significantly lower recurrence rate and can be achieved without sacrificing functional outcome.

Adolescent↗

Comparison of live and carcass equations predicting percentage of cutability, retail product weight, and trimmable fat in beef cattle.

Forty-four Hereford-sired steers were measured ultrasonically for backfat and longissimus muscle area between the 12th and 13th ribs before slaughter and visually appraised for fatness, overall muscling, and frame. Carcass measurements associated with USDA yield and quality grades were measured and recorded. Carcasses were fabricated into closely trimmed, boneless subprimals at 1.27- and .32-cm fat trim levels. Cutability percentage (percentage of retail cuts from the cold carcass weight) and kilograms of retail product were defined three ways. The first definition included only retail cuts from the round, loin, rib, and chuck. The second included the above plus adjusted lean trim from the round, loin, rib, and chuck, and, finally, total retail product from the entire carcass. Kilograms (TOTFAT) and percentage (PERFAT) of trimmable fat were also calculated. Stepwise regression procedures were used for live and carcass trait model development predicting cutability percentages, kilograms of retail product, and trimmable fat. Fat measurements accounted for the largest portion of variation in cutability percentage and PERFAT. Weight measurements accounted for the major sources of variation in predicting kilograms of retail product and TOTFAT. Final models using live animal traits ranked the steers equally as well for cutability percentages as the original USDA cutability equation and stepwise, developed carcass equations (P > .10). Final models using live animal or carcass equations ranked the animals equally for kilograms of retail product yield (P > .10).

Adipose Tissue↗

Evaluation of machine, technician, and interpreter effects on ultrasonic measures of backfat and longissimus muscle area in beef cattle.

Before slaughter, 44 Hereford-sired steers were measured ultrasonically for backfat (UFAT) and longissimus muscle area (ULMA) between the 12th and 13th ribs by three technicians (TECH) using two different machines (MACH) on two consecutive days (DAY). Each TECH interpreted (INT) his own images in addition to other TECH images. The absolute values of the difference between the 2 DAY's ultrasound measurements for ULMA (magnitude of LMAR) and UFAT (magnitude of FATR) were analyzed with a model including fixed effects of MACH and TECH with a random effect of steer and all interactions. For both magnitude of LMAR and magnitude of FATR, MACH x TECH was significant (P < .10). Correlations between the 2 DAY's measurements ranged from .36 to .90 and .69 to .90 for ULMA and UFAT, respectively. Simple statistics to quickly evaluate TECH and MACH were developed. Root mean squared errors (RMSE) and error standard deviations (ESD) between repeated measurements ranged from 3.89 to 11.32 and 3.93 to 11.34 cm2 for ULMA and .12 to .20 cm and .12 to .20 cm for UFAT, respectively. For accuracy, the absolute values of the difference between the ultrasound and carcass measurement for fat (magnitude of FATD) and longissimus muscle area (magnitude of LMAD) were analyzed with a model accounting for fixed effects of DAY, TECH, and MACH and a random effect of steer with all higher-order interactions. For magnitude of LMAD, TECH x MACH was a significant source of variation (P < .001). Also, a similar model was fit that included the fixed effects of TECH, MACH, and INT and a random effect of steer with all interactions. The MACH x INT interaction was found to be significant for magnitude of LMAD (P < .05). From this research, TECH and MACH differences do exist. Ultrasound is a valid means of measuring carcass traits in live steers if appropriate personnel and equipment are selected.

Adipose Tissue↗

Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors.

To characterize some of the genetic events underlying the development of glioblastoma multiforme, the authors analyzed 65 astrocytic tumors (seven pilocytic astrocytomas, eight astrocytomas, 16 anaplastic astrocytomas, and 34 glioblastomas multiforme) for loss of heterozygosity for chromosome 17p, loss of heterozygosity for chromosomes 10p and 10q, amplification of the epidermal growth factor receptor (EGFR) gene, and amplification of the oncogenes N-myc, c-myc, and N-ras using Southern blot analysis. Alterations of the p53 gene (positive immunostaining for p53 protein in tumors with or without p53 gene mutations) in these 65 tumors were analyzed previously. None of the 65 tumors showed amplification or rearrangement of N-myc, c-myc, or N-ras oncogenes. The molecular analysis presented here demonstrates distinct variants of astrocytic tumors, with at least three genetic pathways leading to glioblastoma multiforme. One pathway was characterized by 43 astrocytomas with alterations in p53. Glioblastomas with p53 alterations may represent tumors that progress from lower-grade astrocytomas. This variant was more likely to show loss of chromosome 17p than tumors without p53 alterations (p < 0.04). Seventy-five percent of tumors with loss of one 17p allele demonstrated mutations in the p53 gene. Loss of chromosome 10 was associated with progression from anaplastic astrocytoma (13%) to glioblastoma (38%) (p < 0.04). Amplification of the EGFR gene was a rare (7%) but late event in tumor progression (p < 0.03). A second pathway was characterized by six astrocytomas without p53 alterations and may represent clinically de novo high-grade tumors. These tumors were more likely to show amplification of the EGFR gene (83%) than tumors with p53 alterations. Sixty percent of tumors with EGFR amplification also showed loss of chromosome 10; loss of chromosome 17p was infrequent in this variant. One or more alternative pathways were characterized by 16 astrocytomas without p53 alterations and with none of the genetic changes analyzed in this study. Glioblastomas are a heterogeneous group of tumors that may arise via multiple genetic pathways.

Adolescent↗

Actuarial versus actual risk of porcine structural valve deterioration.

Actuarial analysis, using nonparametric (e.g., life table or Kaplan-Meier) or parametric (statistical modeling) methods, is used to describe and compare survival probabilities by allowing for partial survival times (censoring). Although devised to describe freedom from death, this method has been extended to nonfatal complications, such as freedom from tissue valve failure. However, the risk described for nonfatal events is that which a patient would experience provided he were immortal. And patients with valve disease have a relatively high risk of dying, generating the question: "What is the chance the valve will fail before the patient dies?" To answer this more practical (for individual patient management and population resource allocation) question requires an estimate of what we call actual failure, that is, the percentage of patients whose valve will actually fail before they die. This risk is less than the risk which the usual actuarial curve describes. This difference increases with patient age, because older patients have a lower risk of tissue failure and a higher risk of death than younger patients.

Actuarial Analysis↗

Coronary bypass grafting with biological grafts in a canine model.

BACKGROUND: Poor patency rates have limited the success of biological vascular grafts in the coronary artery position. Recently, two bovine internal mammary arterial grafts have been developed for possible use as coronary artery bypass graft (CABG) conduits: (1) Denaflex grafts (Baxter Health-care Co, 3-mm ID) treated with polyepoxy compounds and with heparin ionically bound to the luminal surface and (2) Bioflow grafts (Bio-Vascular, Inc, 3-mm ID) treated with dialdehyde starch. METHODS AND RESULTS: Thirty dogs underwent CABG with either a Denaflex (n = 20) or Bioflow (n = 10) graft to the left circumflex coronary artery (LCx). The left main coronary artery (n = 12) or proximal LCx (n = 18) was then ligated. Six-month patency (Kaplan-Meier) for Denaflex grafts was 44 +/- 13% (+/- SEM), compared with 12 +/- 11% for Bioflow grafts, but this difference did not reach statistical significance (P = .56). Among grafts open at 14 days, however, there were no occlusions among six Denaflex grafts versus five occlusions among seven Bioflow grafts. At 6 months, all six surviving Denaflex grafts appeared normal, while the only remaining patent Bioflow graft was angiographically dilated and had diffuse luminal irregularities. At 1 year, three Denaflex grafts angiographically had no dilation, stenosis, or luminal irregularities. Macroscopically, all explanted long-term (6 to 12 months) Denaflex grafts had a smooth, clean luminal surface, whereas the only patent Bioflow graft had multifocal thrombi. Microscopically, all Denaflex grafts had minimal degenerative changes, but the Bioflow graft had transmural linear cracks and medial deterioration. CONCLUSIONS: These data suggest that long-term (> 6-month) patency is possible with small-caliber, low-flow biological grafts in the canine coronary position, although both types of grafts are prone to early occlusion. If these early failures are excluded, the Denaflex graft appears to be associated with better long-term patency and an absence of degenerative changes.

Animals↗

Surgical management of aortic dissection in patients with the Marfan syndrome.

BACKGROUND: Aortic dissection is one of the most lethal potential complications in patients with the Marfan syndrome. METHODS AND RESULTS: Among 360 patients undergoing operative treatment of aortic dissection between 1963 and 1992, 40 had the Marfan syndrome. There were 24 men and 16 women with a mean age of 35 +/- 9 years (+/- 1 SD; range, 15 to 54 years). These patients included 16 with acute type A, 2 with acute type B, 18 with chronic type A, and 4 with chronic type B aortic dissections. The aortic arch was involved in 29 cases. Preoperative complications included acute aortic valvular insufficiency in 13 patients, rupture into the pericardial space in 3, and loss of peripheral pulses in 9. The site of primary intimal tear was the ascending aorta in 25 patients, the aortic arch in 2, the descending aorta in 7, and not identified in 6. Operations included ascending aortic and aortic valvular replacement (with or without coronary artery reimplantation) in 22 patients, ascending aortic replacement alone in 5, and descending thoracic aortic replacement in 9. Four operative deaths (10 +/- 5% [+/- 70% confidence limits]) occurred in 3 acute patient-years and 1 chronic type A patient-years. Long-term follow-up (216 patient-years; range, 1 month to 22 years; mean, 5.4 years) revealed 15 late deaths, 7 from late aortic sequelae. The overall actuarial survival estimates were 71 +/- 8%, 54 +/- 10%, and 22 +/- 11% at 5, 10, and 15 years, respectively. Twenty late aortic operations were required in 14 patients. CONCLUSIONS: Despite satisfactory early results, the long-term survival of patients with the Marfan syndrome was suboptimal (albeit similar to those without the Marfan syndrome). Future progress will pivot on reducing the incidence of aortic dissection in these patients with medical therapy and/or earlier surgical intervention and enhanced postoperative serial imaging surveillance of the entire aorta.

Actuarial Analysis↗

Left ventricular torsional dynamics immediately after mitral valve replacement.

BACKGROUND: Cardiac operations and cardiopulmonary bypass are associated with a host of unphysiological consequences that have widespread systemic effects. Since previous investigations in human cardiac transplant recipients had demonstrated that left ventricular (LV) torsional deformation was a sensitive method to detect subclinical LV dysfunction during acute rejection, we studied LV systolic torsion and diastolic recoil preoperatively and postoperatively in a canine model using myocardial marker techniques. METHODS AND RESULTS: Seven dogs underwent placement of LV subepicardial myocardial markers and creation of mitral regurgitation. Three months later, the animals underwent high-speed, biplane videofluoroscopic analysis for determination of LV systolic function and regional LV systolic torsional deformation and diastolic recoil. The animals then underwent chordal-sparing mitral valve replacement and were restudied 1 to 2 hours postoperatively. One to 2 hours after the cardiac operation, regional maximal systolic torsional deformation decreased significantly in all three LV regions on the lateral LV wall, as well as in the apical and apical-equatorial regions on the anterior wall. During early systole, minimal regional systolic torsion increased significantly in all regions on the lateral wall, as well as in the apical level of the posterior wall. Heterogeneous decreases in torsional deformation were also seen during the early diastolic filling period. CONCLUSIONS: Regional systolic torsional deformation and diastolic recoil are markedly perturbed early after a cardiac operation and its associated manipulations. Such changes, however, may potentially serve as sensitive tools to assess the impact of different techniques of intraoperative management, including newer methods of myocardial protection.

Animals↗

Effects of left ventricular support on right ventricular mechanics during experimental right ventricular ischemia.

BACKGROUND: Left ventricular (LV) assist device (LVAD) support has been associated with right ventricular (RV) failure in humans, but the etiology remains unknown. Mechanical LV support apparently does not induce RV pump failure in normal hearts, but controlled studies of LV assistance in hearts with preexistent RV dysfunction have been limited. Therefore, this study was performed to determine if LVAD support impairs RV systolic mechanics during acute RV ischemia. METHODS AND RESULTS: Five closed-chest, autonomically blocked, sedated dogs were studied after placement of an LVAD (LV-femoral artery bypass), right coronary artery (RCA) occluder, and 27 miniature radiopaque tantalum markers into the LV and RV walls for independent computation of RV and LV volumes. Biplane videofluoroscopic marker images and hemodynamic data were recorded before RCA occlusion with the LVAD off (maximum LV pressure [LVPmax] = 119 +/- 25 mm Hg), after 3 minutes of RCA occlusion with the LVAD off (LVPmax = 84 +/- 18 mm Hg), and then with the LVAD on (LVPmax = 26 +/- 32 mm Hg). Global RV contractility (end-systolic elastance [RV Ees] and preload recruitable stroke work [RV PRSW]), RV power output, and the mechanical (pump) efficiency of converting potential energy to external work (ratio of RV stroke work/total pressure-volume area) were calculated. As expected, with RCA occlusion there were major decreases in RV Ees (from 2.5 +/- 1.2 to 1.4 +/- 0.5 mm Hg/mL, P < .005) and RV PRSW (15 +/- 4 versus 9 +/- 4 mm Hg, P < .001). RV power output (overall pump performance) declined by 39 +/- 20% (P < .025), and mechanical efficiency fell by 38 +/- 13% (P < .001). After initiation of mechanical LV support, however, there was no further impairment of RV contractility or power output (P > .80). Pulmonary artery input impedance (RV afterload) decreased from 848 +/- 628 to 673 +/- 577 dyne.sec-1.cm-5 (P < .01), which led to a 26 +/- 29% improvement in RV pump efficiency (P < .001). CONCLUSIONS: While right coronary artery occlusion significantly reduced RV systolic performance, LVAD support during acute RV ischemia did not further impair RV contractility or power output. Furthermore, since RV afterload fell with LV unloading, the mechanical pump efficiency of the right ventricle actually improved. These observations demonstrate that LVAD support does not directly induce RV failure in canine hearts with acute isolated RV ischemia.

Animals↗

Predicting recurrence of intracranial meningiomas. A multivariate clinicopathologic model--interim report of the New York University Medical Center Meningioma Project.

A series of 105 primary intracranial meningiomas, a subset of a larger project on over 800 such tumors, was assessed for clinical and histopathologic factors that might be predictive of recurrence. Predicting recurrence of meningiomas after a surgical resection and the criteria for and clinical importance of a diagnosis of "malignant" meningiomas are controversial issues. Using a multivariate logistic regression analysis, the data from these 105 patients suggest that the single most powerful predictor of recurrence within 5 years after tumor resection is the mitotic index of the tumor. The other powerful factor for predicting recurrence was the extent of resection. Other factors traditionally associated with recurrence or a diagnosis of malignancy were not significant factors for predicting recurrence according to this study.

Brain↗

High frequency of p53 protein accumulation without p53 gene mutation in human juvenile pilocytic, low grade and anaplastic astrocytomas.

We analysed 31 non-glioblastoma astrocytomas for alterations in p53 protein expression and for mutations in the p53 gene. Immunohistochemistry detected p53 protein accumulation in 71% (five of seven) of juvenile pilocytic astrocytomas (WHO grade I), 63% (five of eight) of astrocytomas (WHO grade II), and 63% (10 of 16) of anaplastic astrocytomas (WHO grade III). The single strand conformation polymorphism (SSCP) assay of exons 2-11 of the p53 gene and direct DNA sequencing identified p53 mutations in 14% (one of seven) of grade I, 25% (two of eight) of grade II, and 19% (three of 16) of grade III astrocytomas. This is the first report of a p53 mutation in grade I juvenile pilocytic astrocytomas. Immunohistochemistry and SSCP analyses gave concordant results in 55% (17 of the 31) of the tumors. A total of 14 tumors, 60-80% within each grade, showed p53 protein accumulation in the absence of detectable mutations of the p53 gene. No mdm-2 gene amplification was found in these tumors. The similar frequency of p53 alterations in tumors of grades I-III suggests that the p53 gene plays a significant role early in the formation of astrocytomas rather than late in tumor progression to higher grade. The data suggest that mechanisms other than p53 gene inactivation by mutation or mdm-2 complex formation result in the accumulation of P53 protein in > 70% of non-glioblastoma astrocytomas.

Adolescent↗

Neuropathology of AIDS in surgical biopsy specimens.

In this brief review of the surgical neuropathology of AIDS we have emphasized that, although there are obvious and meaningful similarities between the autopsy descriptions of AIDS-related CNS disease and those we have seen in surgical specimens, there are also some clear differences in terms of which types of lesions are likely to undergo biopsy. It is also clear that the smaller samples allowed by neurosurgical procedures, particularly in stereotaxic biopsies, can limit the expression of the full pathologic pattern of these entities as expected from autopsy evaluations. Nevertheless, useful diagnostic information is readily and routinely obtained when the surgical sampling is carefully planned and when the tissues obtained are properly handled. There is a role, however, a limited one, for frozen sections in intraoperative consultations. The best diagnostic study is a careful perusal of a good hematoxylin and eosin stain, but judicious use of histochemical and immunohistochemical methods can be essential to a proper diagnosis in selected cases.

AIDS Dementia Complex↗