Extradural hematoma: analysis of factors influencing the courses of 161 patients

The clinical and computed tomographic (CT) findings in a series of 161 consecutive patients operated upon for postraumatic extradural hematoma are analyzed. Thirteen (8%) patients had delayed epidural hematoma formation. The overall mortality for the series was 12%, significantly lower than that observed during the prior "angiographic" period at the same unit (30%). Because all but 1 of the deaths occurred among the 66 patients unconscious at the time of operation (27% mortality in this subgroup), the authors sought differential factors between comatose and noncomatose patients at operation. There were no significant differences between these groups in age, sex, mechanism of injury, preoperative course of consciousness (lucid interval or not), or epidural hematoma location and shape. In contrast, significant differences were seen between the two subgroups in trauma-to-operation interval, hematoma volume, CT hematoma density (mixed low-high CT density vs. homogeneous hyperdensity), midline displacement, severity of associated intracranial lesions, and postoperative intracranial pressure (ICP). Patients comatose at operation usually evidenced a more rapid clinical deterioration (a shorter trauma-to-operation interval) and tended to have a large hematoma volume, a higher incidence of mixed CT density clot (hyperacute bleeding), more marked shift of midline structures, more severe associated lesions, and higher postoperative ICP levels.     

Admission stool guaiac test: use and impact on patient management.

PURPOSE: A stool guaiac test is often performed on newly hospitalized patients as part of the admission evaluation. However, little is known regarding the value of testing stool obtained by digital rectal examination. We sought to document the use of the admission stool guaiac test in a teaching hospital, to determine its diagnostic yield, and to assess its potential benefit to patients. MATERIALS AND METHODS: We performed a retrospective review of the medical records for 264 consecutive patients admitted to internal medicine services during a single month, of whom 202 received a stool guaiac test on admission. Information was collected on the frequency of guaiac testing, indications for testing, test results, and diagnoses established. RESULTS: Criteria were established to distinguish "clinically indicated" from "routine" use of the admission stool guaiac test. Indicated tests were positive more often than routinely performed tests (35% versus 11%, p less than 0.001). Most patients with positive tests received further testing for gastrointestinal disease, whether or not the test was indicated. Of 104 patients with indications, 25 were ultimately found to have gastrointestinal lesions, most of which were clinically important. Of 98 patients tested routinely, only four had diagnoses established, of whom three had benign conditions. Four of five patients with cancer had clinical indications for testing. The fifth was diagnosed only after he experienced gross rectal bleeding several days after admission. CONCLUSIONS: Like other commonly applied diagnostic tests, the stool guaiac test obtained during the admission physical examination is best reserved for patients whose clinical presentation provides a reason for testing. In patients without clinical indications, the test is of uncertain value and only infrequently leads to important diagnoses.     

Medial nucleus of the amygdala in the adult Syrian hamster: a quantitative Golgi analysis of gonadal hormonal regulation of neuronal morphology.

The medial nucleus of the amygdala (Me) processes both chemosensory and hormonal input. In the male Syrian hamster the integrity of this nucleus is essential for normal reproductive behavior. To determine if gonadal steroids modulate neuronal structure in this nucleus, the morphology of Golgi-stained neurons in the anterior and posterior regions of Me were compared in castrated and reproductively intact adult hamsters. In castrated males, neurons in the posterior, but not the anterior, region of Me undergo structural changes, as indicated by a decrease in the mean highest dendritic branch level and mean somal area compared to intact males. To further elucidate the importance of testosterone and its metabolites in maintenance of neuronal structure in the adult, seven groups of male Syrian hamsters were studied. Animals were castrated and received a blank silastic capsule or a capsule filled with either testosterone, dihydrotestosterone, or estradiol, or two capsules containing both metabolites, dihydrotestosterone and estradiol. Two groups of reproductively intact animals were included: brains from one group were processed simultaneously with the castrated and hormone-treated groups (control intact group), and the other group was processed at the beginning of the experiment. Animals were tested for mating behavior and flank glands were measured to test whether the capsules were effective in releasing the hormones into circulation. After a 12-week survival period, the brains were processed with Golgi stain and well-impregnated neurons from the posterior Me were quantitatively analyzed for somal area, highest dendritic branch, total dendritic length, and density of spines. All the measures analyzed revealed a consistent pattern of response to the different gonadal steroids. Castration resulted in a decrease in the mean somal area, the mean highest dendritic branch, and the percentage of neurons with tertiary branch segments. Dihydrotestosterone treatment also resulted in a significant decrease in somal area, mean highest dendritic branch, and percentage of neurons with tertiary dendritic branches. In addition, the total dendritic length and spine density on terminal dendrites were reduced in these brains. The remaining hormone treatment groups were not significantly different from the control group. These results suggest that in orchidectomized male Syrian hamsters, testosterone or its aromatized form, estradiol, but not dihydrotestosterone, is sufficient to maintain the normal morphology of the neurons in the posterior part of the medial nucleus of the amygdala.     

During active viscerocutaneous leishmaniasis the anti-P2 humoral response is specifically triggered by the parasite P proteins.

In this work we show that in the sera from dogs naturally infected with the protozoan parasite Leishmania infantum there are antibodies that react specifically against the parasite acidic ribosomal proteins LiP2a and LiP2b, and that each one of the Leishmania P proteins elicits a specific humoral immune response. Using synthetic peptides, the antigenic epitope of these proteins has been mapped in a single region located adjacent to the C-terminal domain highly conserved among the eukaryotic P proteins. The anti-P antibodies elicited during the Leishmania infection do not recognize the conserved C-terminal domain of the parasite P proteins, in contrast with the findings reported in Chagas' disease or systemic lupus erythematosus. The antigenic epitopes of the LiP2a and LiP2b are almost identical in amino acid sequence. No reactivity against Trypanosoma cruzi and human P proteins was found in sera from L. infantum-infected dogs.     

Cytokine gene expression in human peripheral blood mononuclear cells stimulated by mannoprotein constituents from Candida albicans.

The expression of cytokine genes in cultures of human peripheral blood mononuclear cells (PBMC) stimulated with mannoprotein constituents (MP) of Candida albicans has been studied by means of S1 nuclease mapping analysis, polymerase chain reaction, and enzyme-linked immunosorbent assay. MP induced early, consistent, and long-lasting production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, and IL-6 mRNAs. Similar results were obtained when the same PBMC cultures were stimulated with the purified protein derivative (PPD) from Mycobacterium tuberculosis or with IL-2, although lower levels of IL-6 mRNA were detected in IL-2-stimulated cells than in MP- or PPD-stimulated cells. MP, PPD, and IL-2 induced appreciable levels of granulocyte-macrophage colony-stimulating factor and gamma interferon, but only MP and PPD were able to induce IL-2 mRNA. MP were unable to stimulate a consistent expression of the genes encoding for IL-4, IL-5, and IL-10, while low, sometimes barely detectable levels of these cytokine mRNAs were observed in PPD- or IL-2-stimulated PBMC cultures. When protein synthesis of MP-stimulated PBMC was inhibited by cycloheximide, a superinduction of mRNAs for IL-4 and IL-10 and, more markedly, gamma interferon was observed. Overall, these results highlight the powerful, selective induction of cytokine gene expression by MP constituents of C. albicans in human PBMC cultures, thus providing some functional clues to explain the efficient state of the anticandidal response in normal human subjects.     

Differentiating molecular etiologies of Angelman syndrome through facial phenotyping using deep learning

Angelman syndrome (AS) is caused by several genetic mechanisms that impair the expression of maternally‐inherited UBE3A through deletions, paternal uniparental disomy (UPD), UBE3A pathogenic variants, or imprinting defects. Current methods of differentiating the etiology require molecular testing, which is sometimes difficult to obtain. Recently, computer‐based facial analysis systems have been used to assist in identifying genetic conditions based on facial phenotypes. We sought to understand if the facial‐recognition system DeepGestalt could find differences in phenotype between molecular subtypes of AS. Images and molecular data on 261 individuals with AS ranging from 10 months through 32 years were analyzed by DeepGestalt in a cross‐validation model with receiver operating characteristic (ROC) curves generated. The area under the curve (AUC) of the ROC for each molecular subtype was compared and ranked from least to greatest differentiable phenotype. We determined that DeepGestalt demonstrated a high degree of discrimination between the deletion subtype and UPD or imprinting defects, and a lower degree of discrimination with the UBE3A pathogenic variants subtype. Our findings suggest that DeepGestalt can recognize subclinical differences in phenotype based on etiology and may provide decision support for testing.     

Identification of secreted proteins of Mycobacterium tuberculosis by a bioinformatic approach

Proteins secreted by Mycobacterium tuberculosis are usually targets of immune responses in the infected host. Here we describe a search for secreted proteins that combined the use of bioinformatics and phoA' fusion technology. The 3,924 proteins deduced from the M. tuberculosis genome were analyzed with several computer programs. We identified 52 proteins carrying an NH(2)-terminal secretory signal peptide but lacking additional membrane-anchoring moieties. Of these 52 proteins-the TM1 subgroup-only 7 had been previously reported to be secreted proteins. Our predictions were confirmed in 9 of 10 TM1 genes that were fused to Escherichia coli phoA', a marker of subcellular localization. These findings demonstrate that the systematic computer search described in this work identified secreted proteins of M. tuberculosis with high efficiency and 90% accuracy.     

The GAA triplet-repeat sequence in Friedreich ataxia shows a high level of somatic instability in vivo,with a significant predilection for large contractions

Friedreich ataxia is commonly caused by large expansions of a GAA triplet-repeat (GAA-TR) sequence in the first intron of the FRDA gene. We used small-pool PCR to analyze somatic variability among 7190 individual FRDA molecules from peripheral blood DNA of subjects carrying 12 different expanded alleles, ranging in size from 241 to 1105 triplets. Expanded alleles showed a length-dependent increase in somatic variability, with mutation loads ranging from 47% to 78%. We noted a strong contraction bias among long alleles (>500 triplets), which showed a 4-fold higher frequency of large contractions versus expansions. Some contractions were very large; of all somatic mutations scored, approximately 5% involved contractions of >50% of the original allele length, and 0.29% involved complete reversion to the normal/premutation length (< or =60 triplets). These observations contrast sharply with the strong expansion bias seen in expanded CTG triplet repeats in myotonic dystrophy. No somatic variability was detected in >6000 individual FRDA molecules analyzed from 15 normal alleles (8-25 triplets). A premutation allele with 44 uninterrupted GAA repeats was found to be unstable, ranging in size from 6 to 113 triplets, thus establishing the threshold for somatic instability between 26 and 44 GAA triplets. Analysis of an additional 7850 FRDA molecules from serially passaged lymphoblastoid cell lines carrying nine expanded alleles (132-933 triplets) showed very low mutation loads, ranging from 0% to 6.2%. Our data indicate that expanded GAA-TR alleles in Friedreich ataxia are highly mutable and have a natural tendency to contract in vivo, and that these properties depend on multiple factors, including DNA sequence, triplet-repeat length and unknown cell-type-specific factors.