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D F Brown

Publications and source records attributed to D F Brown.

At least 55 records · Page 3Linked to original sources

Neuropathologic evidence that the Lewy body variant of Alzheimer disease represents coexistence of Alzheimer disease and idiopathic Parkinson disease.

We undertook this study to investigate the neuropathologic relationships among Alzheimer disease (AD), idiopathic Parkinson disease (PD), and the Lewy body variant of AD (AD/LBV). We retrieved 30 autopsy cases in which Lewy bodies (LB) had been identified in the substantia nigra (SN) in routine hematoxylin-eosin-stained sections. Twenty-two of the cases had a primary clinical diagnosis of dementia and neuropathologic changes of AD; 12 of these demented patients also had clinical parkinsonism. Eight cases had clinical and neuropathologic evidence of PD with minimal or no AD neuropathology, though 6 had clinical dementia. Controls consisted of 6 cases of AD without SN LB by hematoxylin-eosin, and 5 neurologically normal aged controls. Paraffin sections of SN, superior temporal gyrus, and cingulate gyrus from each case were immunostained with rabbit anti-ubiquitin antiserum, randomized, and analyzed individually by light microscopy, and the density of LB-like profiles in each section were graded. None of 5 nondemented aged controls showed any neocortical LB, even though 2 had significant numbers of incidental SN LB by ubiquitin immunostaining. Of 6 AD cases without SN LB by hematoxylin-eosin, 3 had rare SN LB on ubiquitin stain, 1 of which showed rare neocortical Lewy-like profiles. Seven of 8 PD cases showed neocortical LB, including the 6 with dementia. Twenty-one of 22 AD cases with SN LB showed ubiquitin-immunoreactive Lewy-like bodies in the neocortex that were statistically significantly greater in number than in either pure PD or pure AD cases. The frequent occurrence of LB in the neocortex in PD alone suggests that AD/LBV likely represents mixed AD/PD. However, AD neuropathology may favor or promote the formation of neocortical LB in patients who go on to develop mixed AD/PD pathology.

Aged↗

Neocortical synapse density and Braak stage in the Lewy body variant of Alzheimer disease: a comparison with classic Alzheimer disease and normal aging.

Substantial numbers of cortical and subcortical Lewy bodies are seen in approximately one quarter of patients whose brains show sufficient histopathologic changes for a neuropathologic diagnosis of definite Alzheimer disease (AD). This subset of cases has been named the Lewy body variant of AD (LBV). Despite comparable dementia and the presence of neocortical senile plaques in LBV patients, the overall burden of neuropathologic changes, in particular neurofibrillary tangles (NFT), is less than in classic AD. While NFT frequency correlates with dementia severity in classic AD, the cognitive impairment in patients with LBV cannot be completely explained by such changes. Since several studies have suggested a role for synapse loss in relation to dementia severity in classic AD, we decided to investigate the role of synapse loss as a candidate for the cognitive impairment of LBV. The Braak staging method is based upon the distribution and severity of neurofibrillary changes, and one therefore would expect LBV cases to be assigned to lower Braak stages. In the present study we assigned a Braak stage to 14 LBV cases, 31 classic AD cases, and a group of 10 non-demented aged controls. We compared the severity of synapse loss as determined by ELISA immunoassay for synaptophysin and Braak stage among the three diagnostic groups. When compared to normal controls, synaptophysin concentrations were statistically significantly lower in both demented groups. There was comparable synapse loss in LBV and AD despite significantly lower Braak stages in the LBV cases. These results suggest a major role for loss of synapses as the substrate of cognitive impairment in LBV.

Aged↗

Hormone receptor immunoreactivity in hemangioblastomas and clear cell renal cell carcinomas.

Several primary central nervous system (CNS) neoplasms, including meningiomas, spinal cord ependymomas, and acoustic nerve schwannomas, express hormone receptors. In the present study, we investigated hormone receptor immunoreactivity in hemangioblastomas on the basis of recent reports of these tumors complicating pregnancy. We also evaluated cases of renal cell carcinoma (RCC) metastatic to the CNS, hypothesizing that estrogen receptor (ER), progesterone receptor (PR), or androgen receptor (AR) immunoreactivity might help to distinguish between these histologically similar neoplasms. Immunohistochemical analysis for ERs, PRs, and ARs was performed on paraffin-embedded sections of 27 hemangioblastomas, 12 primary clear cell RCCs, and 5 clear cell RCCs metastatic to the CNS. All of the hemangioblastomas demonstrated PR immunoreactivity, whereas 10 of 12 primary RCCs were negative. In addition, four of the five metastatic RCC were PR positive. All but one primary RCC were ER negative. AR immunoreactivity was seen in three hemangioblastomas, five primary RCCs, and one metastatic RCC. Although hormone receptor immunoreactivity was unable to distinguish between hemangioblastoma and clear cell RCC metastatic to the CNS, the identification of PR immunoreactivity in hemangioblastomas is a new finding that might have adjuvant therapy treatment implications.

Adolescent↗

Supratentorial giant cell ependymoma: a case report.

Ependymomas are neoplasms of the central nervous system that are capable of demonstrating remarkably heterogeneous histologic features. These tumors originate from ependymal cells lining the ventricles, the choroid plexus, the central canal of the spinal cord, and the filum terminale, so they are therefore seen throughout the neuraxis. We describe the case of a 26-year-old man who experienced a 3-week history of right-sided numbness and a 1-week history of worsening bifrontal headache. Computed tomographic scanning and magnetic resonance imaging of his head demonstrated an irregularly enhancing mass involving the left medial frontal lobe, with extension across the corpus callosum and expansion into the body and atrium of the left lateral ventricle. Histologic, immunohistochemical, and electron microscopic findings were consistent with an anaplastic ependymoma. Unique to this neoplasm was the presence of multiple tumor giant cells. The presence of pleomorphic tumor giant cells is a characteristic feature of the subependymal giant cell astrocytoma, and it is also commonly seen in pleomorphic xanthoastrocytoma and glioblastoma multiforme. Bizarre giant cells were recently described in two filum terminale ependymomas. This report presents the first case of a supratentorial giant cell ependymoma with anaplastic features.

Adult↗

Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype.

In this study, we report our results on the proliferative activity of ependymomas as determined by MIB-1 (also known as Ki-67) immunohistochemical analysis, and we compare our results with those obtained by immunolabeling with monoclonal antibodies to p53 and bcl-2 proteins to assess whether expression correlated with ependymoma subtype or tumor grade. The study included 4 myxopapillary ependymomas (Grade I of the World Health Organization [WHO] scale), 10 subependymomas (WHO Grade I), 17 ependymomas (WHO Grade II), 2 papillary ependymomas (WHO grade II), and 4 anaplastic ependymomas (WHO Grade III). The MIB-1 proliferation index was significantly higher in tumors diagnosed as anaplastic ependymoma (P < .001), with a moderate level of correlation (Kendall's tau-b = 0.557, asymptotic standard error = 108). In addition, one ependymoma (WHO Grade II) not considered overtly anaplastic by routine histologic criteria showed a high MIB-1 labeling index, suggesting that the MIB-1 proliferation index might be a more objective indicator of tumor grade. The remaining WHO Grade I and Grade II ependymomas showed low proliferative activity. bcl-2 oncoprotein expression was identified in all of the four myxopapillary and in both papillary ependymomas. An additional observation was the correlation of p53 expression with increasing WHO grade. These data suggest that high MIB-1 and p53 immunolabeling might be objective indicators of high grade in ependymomas that do not otherwise meet routine histologic criteria for high-grade ependymoma. Subsequent clinicopathologic analyses will be important in assessing whether these markers are useful as independent predictors of survival.

Adolescent↗

Systemic calciphylaxis associated with massive gastrointestinal hemorrhage.

A 38-year-old woman with insulin-dependent diabetes mellitus, hypertension, and end-stage renal disease developed digital ischemia, widespread cutaneous necrosis and eschar formation of both lower extremities, and extensive ulceration of the large intestine and cecum resulting in gastrointestinal hemorrhage. A mesenteric arteriogram revealed multiple stenotic areas and filling defects of the superior mesenteric artery and its tributaries, suggestive of vasculitis. A diagnosis of calciphylaxis was suspected, on antemortem skin biopsy, and was later confirmed by postmortem examination. This case further documents the relationship between calciphylaxis and significant visceral injury, and it represents, to our knowledge, the first case of calciphylaxis associated with massive gastrointestinal hemorrhage.

Adult↗

Mode of chemotherapy does not affect complications with an implantable venous access device.

BACKGROUND: Few reports have been made regarding the long term safety of implantable venous access devices used for the delivery of chemotherapeutic agents. The authors' goals were to determine the frequency of complications in patients receiving chemotherapy with these devices; to determine whether complications were associated with the mode of chemotherapy delivery (push/bolus or infusional regimens); and to evaluate the influence of other risk factors, including home-based versus hospital-based administration. METHODS: A total of 152 oncology patients at the John L. McClellan Memorial Veterans Administration Medical Center in Little Rock, Arkansas (ages 26-81 years; mean age, 62 years), who underwent surgical placement of an Infus-a-Port (Strato, Inc., Beverly, MA) between May 1, 1992 and May 31, 1994, were evaluated retrospectively for postplacement device complications, such as infection, thrombosis, and mechanical failure. RESULTS: Twenty-seven patients experienced 1 complication each: 17 episodes of device-related sepsis, cellulitis, or fever of unknown origin; 8 episodes of thrombosis or catheter occlusion; 1 episode of drug extravasation; and 1 mechanical failure. Patient age, frequency of port accession, mode of chemotherapy delivery, tumor type, and neutropenia were evaluated as risk factors, but none was statistically significant. Complications were more frequent during the first 90 days after implantation, but they continued to occur throughout the observation period. CONCLUSIONS: Complications attributable to an implantable venous access device were infrequent in this patient population. No differences in complications for patients receiving home-based versus hospital-based chemotherapy administration were noted, opening the possibility of significant time and cost savings with home treatment.

Adult↗

Renal ultrasonography.

Renal US is one of several imaging modalities available to the emergency physician in the evaluation of patients with acute urologic disorders. It offers excellent anatomic detail without exposure to radiation or contrast agents but does not assess renal function. It is particularly useful in the evaluation of renal colic, although its role here may decrease with increasing availability of helical CT. It also has an important role in excluding bilateral renal obstruction as the cause of acute renal failure. Doppler renal US is likely to take on a more prominent role in the evaluation of renal trauma and is the diagnostic study of choice to rule out renal vein thrombosis. Bedside emergency renal US performed and interpreted by emergency physicians with limited training and experience is gaining in use and acceptance. Its role at present is primarily to identify unilateral hydronephrosis in patients with suspected renal colic. This role is likely to expand in the future as emergency US use grows and technology advances. Bedside emergency renal US may eventually be used in the evaluation of patients with acute renal failure, suspected renal vein thrombosis, and renal trauma.

Acute Disease↗

Quality assessment of glycopeptide susceptibility tests: a European collaborative study. European Glycopeptide Resistance Group.

The ability of seventy clinical laboratories in nine European countries to detect glycopeptide resistance in Gram-positive bacteria was investigated. Results of routine tests were compared with those on the same strains by a reference method in national co-ordinating laboratories. In addition, control strains were tested by some of the participants. Errors in reporting susceptibility of Staphylococcus aureus to teicoplanin and vancomycin and coagulase-negative staphylococci to vancomycin were < 1%. With coagulase-negative staphylococci however, 44 (3.4%) teicoplanin susceptible isolates were reported intermediate and six (0.4%) resistant; 18 (58.1%) of 31 teicoplanin intermediate isolates were reported susceptible and five (16.1%) resistant; and six of nine teicoplanin resistant isolates were reported susceptible and two intermediate. All seven isolates of enterococci intermediate to vancomycin were reported susceptible. Distribution of a known vancomycin intermediate strain of E. gallinarum indicated problems with vancomycin susceptibility testing (44.4% reported susceptible, 32.7% intermediate, 32.1% resistant) and identification (only 34.1% correct) of this organism. Two of 28 teicoplanin resistant enterococci and three of 30 vancomycin resistant isolates were reported susceptible. Among other organisms, one resistant Lactobacillus sp. was reported susceptible to teicoplanin and vancomycin. In reporting teicoplanin susceptible organisms, there were fewer errors with comparative/Stokes methods than with most other methods and more errors with the ATB and Sceptor methods than most other methods. None of the methods used were reliable for testing teicoplanin intermediate and resistant coagulase-negative staphylococci or low-level vancomycin resistant enterococci. Alternative methods, such as breakpoint screening, should be considered for detecting glycopeptide resistance.

Anti-Bacterial Agents↗

A pseudo-outbreak of respiratory infection with Acinetobacter species.

We describe an apparent outbreak of respiratory infection with Acinetobacter species involving 14 patients over 8 days. Epidemiological investigation revealed two consecutive pseudo-outbreaks of infection caused by two consecutive, unrelated laboratory errors in the processing of sputum, nasopharyngeal, and endotracheal aspirates.

Acinetobacter↗

Expression of telomerase RNA component correlates with the MIB-1 proliferation index in ependymomas.

Although there is general agreement that certain morphologic subtypes of ependymoma are benign, the biologic behavior of other ependymal neoplasms is poorly understood and not clearly related to conventional histopathologic criteria. The absence of universally accepted standards has prompted the search for more objective biologic markers. Telomerase is an RNA-containing enzyme associated with immortality in proliferating stem cells and many tumors. We investigated the proliferative activity of 26 ependymomas as determined by MIB-1 immunolabeling and compared the results with the in situ expression of human telomerase RNA (hTR) and WHO tumor grade. The study included 9 WHO grade I ependymomas (6 subependymomas and 3 myxopapillary ependymomas), 13 WHO grade II ependymomas, and 4 anaplastic (WHO grade III) ependymomas. The proliferation index (PI) and telomerase RNA expression were significantly increased in grade III ependymomas (p < 0.0001 for PI and p = 0.0015 for hTR). In these tumors, the PI and hTR expression were highly correlated (p = 0.0001). Of note, a single case designated grade II showed both increased proliferative activity and the highest hTR expression detected in this series of ependymal neoplasms. Our results suggest that the PI and hTR expression may be important biologic markers, independent of other histopathologic criteria of tumor grade. Future studies examining the correlation of MIB-1 cell kinetics and hTR expression with clinical parameters in selected ependymoma subtypes are needed to determine the prognostic relevance of these markers.

Adolescent↗

Human telomerase RNA expression and MIB-1 (Ki-67) proliferation index distinguish hemangioblastomas from metastatic renal cell carcinomas.

Hemangioblastomas are low-grade, capillary rich neoplasms of the cerebellum and spinal cord that can occur sporadically or in the setting of Von Hippel-Lindau syndrome. The present study analyzed the utility of proliferation potential in differentiating hemangioblastoma from RCC metastatic to the central nervous system using a MIB-1 (Ki-67) labeling index and assessment of expression of the RNA component of telomerase. Immunohistochemical analysis for epithelial membrane antigen (EMA) and MIB-1 was performed on paraffin-embedded sections of 27 hemangioblastomas and 5 RCC metastatic to the central nervous system. All but one hemangioblastoma demonstrated low or negative MIB-1 immunoreactivity, while 4 of 5 RCC metastases had moderate or high labeling indices. Telomerase RNA expression was assessed in 10 hemangioblastomas and in all 5 metastatic RCC by in Situ hybridization. All 10 hemangioblastomas demonstrated a lack of expression of telomerase RNA, while all 5 metastatic RCCs showed moderate to strong expression. Our results suggest that the MIB-1 labeling index is useful in differentiating hemangioblastoma from metastatic RCC and assessment of telomerase expression can also provide novel information on the difference in growth potential of these tumors.

Adolescent↗

Rosenthal fibers and eosinophilic granular bodies in a classic acoustic schwannoma.

We describe unique features seen in a case of classic acoustic schwannoma. In the central portion of the tumor, abundant Rosenthal fibers and occasional eosinophilic granular bodies were present. Rosenthal fibers are homogeneous eosinophilic structures commonly seen in central nervous system lesions, such as pilocytic astrocytoma, or in the gliotic tissues adjacent to slowly growing neoplasms and some congenital malformations. Eosinophilic granular bodies are also structural markers of slow-growing, well-differentiated neuroglial neoplasms, such as pleomorphic xanthoastrocytoma, ganglion cell tumors, and pilocytic astrocytoma. To the best of our knowledge, however, these two structures have never before been described in schwannomas.

Adult↗

Growth after discontinuation of recombinant human growth hormone therapy in children with chronic renal insufficiency. The Genentech Cooperative Study Group.

OBJECTIVES: The impact of a pause in treatment with recombinant human growth hormone (rhGH) during the course of chronic renal insufficiency (CRI) once target height (50th percentile for mid-parental height) is reached and the impact of cessation of rhGH treatment after successful renal transplantation were evaluated. Prepubertal patients with CRI included in a multicenter, randomized, double-blind, placebo-controlled trial who either reached target height or received a renal transplant, or both, were included in this report. Patients in the placebo group may have initiated pubertal development at the time rhGH treatment was begun. STUDY DESIGN: Growth velocity (measured in centimeters per year) and standardized height score (SDS) in 22 patients who had a pause in rhGH therapy after attainment of target height were evaluated serially before and after the pause, and 30 patients, 4 of whom were also included in the pause group, who discontinued rhGH therapy at the time of transplantation were followed as long as 68 months after transplantation. RESULTS: Six of twenty-two patients (two of whom subsequently underwent transplantation) continued with the pause in treatment for a mean (+/-SD) duration of 25.5 +/- 26.9 months (group 1), and 16 of 22 resumed rhGH therapy after pausing for a mean (+/-SD) of 9.0 +/- 4.6 months (group 2). The mean (+/-SD) growth velocity during the pause in group 1 was 5.1 +/- 1.8 cm/yr and in group 22.7 +/- 1.7 cm/yr. After reinstitution of rhGH in group 2, the mean (+/-SD) growth velocity increased to 7.2 +/- 1.7 cm/yr. The mean (+/-SD) height SDS in the 30 patients who discontinued rhGH therapy at the time of transplantation was -2.8 +/- 0.9 at baseline (initiation of rhGH therapy), -1.6 +/- 1.3 at the time of transplantation, and -1.7 +/- 1.2 at last follow-up. The mean (+/-SD) growth velocity was 5.1 +/- 4.7 cm/yr after transplantation, and the mean (+/-SD) delta (delta) height SDS was -0.07 +/- 0.5 at last follow-up. CONCLUSIONS: A pause in rhGH treatment in children with CRI after attainment of target height leads to maintenance of height SDS in 27% and a marked reduction in growth velocity, requiring reinstitution of rhGH therapy, in 73%; discontinuing rhGH treatment at the time of transplantation does not result in substantive posttransplantation "catch down" growth.

Body Height↗

Accuracy of serology for the diagnosis of Helicobacter pylori infection--a comparison of eight kits.

AIMS: To determine the accuracy of eight commercially available kits for the serological diagnosis of Helicobacter pylori infection, and hence whether a serology service could be introduced to reduce endoscopy workload. METHODS: Eighty four patients newly presenting to their general practitioners with dyspepsia were recruited. Gold standard diagnosis of H pylori infection was obtained both by a histological examination of gastroduodenal biopsy specimens and by the 14C-urea breath test (UBT). The performance of six quantitative and two qualitative enzyme linked immunosorbent assays for H pylori IgG, used according to the manufacturers' instructions, with serum samples obtained during the endoscopy visit, were compared. RESULTS: The study population had a median age of 45 years, and the prevalence of H pylori infection was 35%. With one exception, where the patient had received a course of anti-H pylori treatment between endoscopy and UBT, there was 100% concordance in the results of the two gold standard techniques. Discordant serology results were more common in patients aged > 50 years (42% of the total) than in younger patients (21%), and this was most noticeable in uninfected patients. The sensitivity of the kits was good (90-100%), but specificity was more variable (76-96%), and the rate of equivocal results was unacceptably high in some cases (0-12%). The overall accuracy of the kits ranged from 83 to 98%. Two kits in particular performed well (Pylori-Elisa II, Bio-Whitaker and Premier, Launch; qualitative) with 98% and 100% accuracy, respectively. CONCLUSIONS: In a symptomatic population with a prevalence of H pylori infection of 35%, particularly in patients aged < 50 years, some but not all serology kits may be used as a highly accurate and inexpensive alternative to the gold standard techniques.

Adult↗

Trichinella spiralis infection in pigs in eastern Bolivia.

Trichinellosis in pigs in Bolivia was first documented in 1993 following a small abattoir survey in a rural community in the Bolivian Altiplano. The present study investigated the presence of antibodies to Trichinella spiralis in pigs in the 2 largest departments in terms of pig production in Bolivia. Three geographically separate abattoir surveys were conducted to cover the major production areas in the Departments of Santa Cruz and Chuquisaca. Sera were tested using an enzyme-linked immunosorbent assay. Of the 1,327 sera analysed from the 3 areas, 13.4% overall tested positive. Results from the 3 individual surveys varied from 10.2% seropositivity to 17.1 per cent. However, within each of the 3 sample areas, highly significant variation in seropositivity was encountered, with those areas with the most extensive production systems having the highest percentage of positive sera. Such variation is probably due to differences in nutrition with foraging and household waste being important components of pig diets in extensive production systems. The results of this study were similar to those obtained from the previous survey in the Altiplano and indicate that trichinellosis is present throughout Bolivia and is a potentially important public health problem.

Abattoirs↗

Recombinant human growth hormone in infants and young children with chronic renal insufficiency. Genentech Collaborative Study Group.

Children with chronic renal insufficiency (CRI) secondary to congenital structural abnormalities frequently have significant growth retardation by 2 years of age. In a multicenter placebo-controlled study of the use of recombinant human growth hormone (rhGH), 30 of 125 (24%) participants were < 2.5 years of age at enrollment. Since the treatment arms of the study were balanced for age at randomization, data for these patients were examined for efficacy and safety. During the first 2 years of the study, approximately two-thirds of the patients (n = 19) received rhGH 0.05 mg/kg per day subcutaneously and one-third (n = 11) received placebo injections. At entry into the study, the mean (+/- SD) calculated creatinine clearance was 29.2 +/- 14.3 (range 12.0-63.7) ml/min per 1.73 m2 in the rhGH-treated group and 23.3 +/- 15.1 (range 8.0-59.4) ml/min per 1.73 m2 in the placebo-treated group. The 1st year growth rate was 14.1 +/- 2.6 cm/year for the rhGH-treated group and 9.3 +/- 1.5 cm/year in the placebo-treated group (P < 0.00005). During the 2nd year of the study, the growth rate was 8.6 +/- 1.2 cm/year in the rhGH-treated group compared with 6.9 +/- 1.0 in the placebo group (P = 0.025). The delta height standard deviation score was +2.0 +/- 0.7 for the rhGH-treated group compared with -0.2 +/- 1.1 in the placebo-treated group (P < 0.00005) during the 2 years of the study. Minor adverse events occurred with similar frequency in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

'Fifteen percent of microbiology reports are wrong!': further experience with an internal quality assessment and audit scheme.

Infection control teams critically depend on the quality of the diagnostic microbiology laboratories with which they are associated. Internal quality assessment (IQA) by specimen resubmission measures the consistency of laboratory performance and can be adapted for medical audit, but few laboratories appear to include these techniques as part of their quality control procedures. We established an IQA scheme in our bacteriology laboratory in May 1989, and the mean discrepancy rate for the first two years was nearly 15%. During the next two years covered by this report, the scheme was extended to include audit of the consistency of medical microbiologists' comments on reports, and a standardized scoring scheme was introduced. Results from the scheme are collated and analysed thrice yearly, and laboratory techniques altered and extra staff training planned to reduce discrepancies. Four thousand four hundred and fourteen specimens (1.4% workload) were resubmitted, and 325 (7.4%) gave discrepant results. During the two years, the overall discrepancy rate fell consistently from 9.4 to 3.2%. Fifty-three discrepancies (1.2%) were in microscopy, and 243 (5.5%) were between culture results. Substantial decreases in technical discrepancies followed training initiatives in sputum bacteriology, and training in anaerobic recognition and improved illumination in the anaerobic cabinet. Problems of consistent recognition of staphylococci and of urine isolates in mixed culture, and of faecal microscopy have proved difficult to eradicate. There was a 20.3% discrepancy rate between medical comments, but only 0.4% would have been likely to result in different patient outcomes. The cost of running the scheme was 4474 pounds per annum, equating to a surcharge of 0.058 pounds to each of our routine diagnostic specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic Errors↗