Computed tomographic investigation of serosal and intramural gastrointestinal pathology

Various cases are presented demonstrating the role of computed tomography (CT) in the assessment of serosal and bowel wall pathology. Reference is made to the morphology of the lesions. Illustrative examples of tumors, secondary malignant dissemination, irradiation injury to the gut, and intramural gas associated with ulcerative colitis, are all illustrated.     

PET network abnormalities and cognitive decline in patients with mild cognitive impairment.

Temporoparietal and posterior cingulate metabolism deficits characterize patients with Alzheimer's disease (AD). A H(2)(15)O resting PET scan covariance pattern, derived by using multivariate techniques, was previously shown to discriminate 17 mild AD patients from 16 healthy controls. This AD covariance pattern revealed hypoperfusion in bilateral inferior parietal lobule and cingulate; and left middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and cuneus; left fusiform and superior occipital gyri; and right parahippocampal gyrus and pulvinar. In an independent sample of 23 outpatients with mild cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score was evaluated as a predictor of cognitive decline. In this MCI sample, an H2(15)O resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8 (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In generalized estimating equations (GEE) analyses, controlling for age, sex, education, and baseline neuropsychological scores, increased AD pattern score was associated with greater decline in each neuropsychological test score over time (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming, WAIS-R digit symbol; Ps<0.01-0.001). In summary, a resting PET covariance pattern previously reported to discriminate AD patients from control subjects was applied prospectively to an independent sample of MCI patients and found to predict cognitive decline. Independent replication in larger samples is needed before clinical application can be considered.     

Efficient 12-mutation testing in the CFTR gene: a general model for complex mutation analysis

The identification of the cystic fibrosis transmembrane conductanceregulator (CFTR) gene has led to the identification of morethan 225 presumed disease-causing mutations at the locus. Thediagnosis of cystic fibrosis or the carrier state by directDNA analysis is hindered by this large number. A practical assaymust be able to detect enough mutations to achieve clinicallysignificant sensitivity. The use of allele-specifk oligonucleotideprobes is the most promising of the available methods. However,to date this has generally involved tedious probe-by-probe hybridizations,due to variations in the oligonucleotides' denaturation temperaturescaused by differences in their G-C base-pair content. We havedeveloped a rapid, cost-effective assay that simultaneouslydetects 12 CFTR mutations after multiplex polymerase-chain-reactionamplification of genomic DNA. The test may be readily extendedto detect additional mutations at minimal increase in the costper test or the turnaround time. We improve specificity andavoid the need for individual hybridizations by the use of tetramethylammoniumchloride to virtually eliminate the effects of G-C differences.Coupled with non-invasive sample-collection methods, this isan immediately practical assay for cystic fibrosis. More generally,it will serve as a model for the development of diagnostic testsin other genetic disorders involving complex mutation analysis.     

Increased prevalence of undernutrition in Parkinson's disease and its relationship to clinical disease parameters

Summary An anthropometric study was performed in 95 subjects (53 male, 42 female) with Parkinson's disease. Weight, height, triceps and biceps skin-fold thicknesses, and mid-arm circumference were recorded. A high incidence of undernutrition was found (23.6% of males and 22.5% of females, as defined by recent British guidelines). A subgroup of severely disabled patients with Parkinson's disease had a significantly lower mean body mass index than a similarly disabled control group with chronic pyramidal upper motor neuron lesions (males 20.6v 23.2 kg/m² p<0.05; females 20.6v 26.6 kg/m² p<0.01), suggesting that the undernutrition is not due to chronic illness or immobility alone. Correlation between anthropometric indices and clinical features of disease demonstrated that the presence of moderate or severe dyskinetic movements was the clinical parameter most strongly related to undernutrition. The reduction in anthropometric indices was most marked for skin fold thickness (related to percentage body fat) and least for arm muscle circumference (related to lean body mass); therefore the weight loss seen in Parkinson's disease is primarily due to fat loss rather than muscle loss.     

Effects of Ethanol in an Experimental Model of Combined Traumatic Brain Injury and Hemorrhagic Shock

Objectives: Given that clinical and laboratory studies suggest that ethanol and hemorrhagic shock (HS) potentiate traumatic brain injury (TBI), the authors studied the effects of ethanol in a model of combined TBI and HS.
Methods: A controlled porcine model of combined TBI and HS was evaluated for the effect of ethanol on survival time, hemodynamic function, and cerebral tissue perfusion. Anesthetized swine (17–24 kg) were instrumented, splenectomized, and subjected to fluid percussion TBI with concurrent 25-mL/kg graded hemorrhage over 30 minutes. Two groups were studied: control ( n = 11) and ethanol ( n = 11). Ethanol, 3.5 g/kg intragastric, was given 100 minutes prior to TBI/HS. Systemic and cerebral physiologic and metabolic parameters were monitored for 2 hours without resuscitation. Regional cerebral blood flow (rCBF) and renal blood flow were measured with dye-labeled microspheres. Data were analyzed with 2-sample t-test and repeated-measures ANOVA.
Results: Ethanol levels at the time of injury were 162 ± 68 mg/dL. Average TBI was 2.65 ± 0.35 atm. Survival time was significantly shorter in the ethanol group (60 ± 27 min vs 94 ± 28 min, p = 0.011). The ethanol group had significantly lower mean arterial pressure, cerebral perfusion pressure, and cerebral venous
O₂ saturation in the postinjury period. Cerebral O₂ extraction ratios and cerebral venous lactate levels were significantly higher in the ethanol group. A trend toward lower postinjury rCBF in all brain regions was observed in the ethanol group.
Conclusion: In this TBI/HS model, ethanol administration decreased survival time, impaired the hemodynamic response, and worsened measures of cerebral tissue perfusion.     

Dermatologic changes associated with interleukin 2 administration

We have prospectively evaluated the skin changes that occurred in ten patients who were undergoing immunotherapy with interleukin 2 (IL-2) and autologous lymphokine-activated killer cells to treat cancer. Serial skin biopsy specimens were obtained before therapy (baseline), during IL-2 administration, and during IL-2/lymphokine-activated killer cell infusion. All patients developed an eruption that was characterized by macular erythema, with burning and pruritus of the skin. It began after two or three days of IL-2 infusion and was usually localized to the head and neck; it occasionally became generalized (ie, erythroderma). The eruption resolved with desquamation within 48 to 72 hours after cessation of infusion of IL-2. Histologically, the changes were not specific. The only consistent immunohistological finding noted was the presence of DR+/Leu-4+ lymphoid cells surrounding blood vessels in the papillary dermis, with fewer of these cells in the epidermis. There was no difference between the clinical or histological features of the eruption that occurred with IL-2 alone and that which occurred with IL-2 and lymphokine-activated killer cell infusion, suggesting that the cutaneous effects were mediated by IL-2 alone.     

SI12Lymphocyte Subsets Following Autologous Transfer of CD25 Depleted Leukapheresis Products

The CXCL12/CXCR4 chemokine axis is a well characterized and important chemotactic stimulus/receptor unit that orchestrates the homing and migration of cells to the bone marrow and to ischemic tissues following tissue damage. Here, we demonstrate that the sialomucin, CD164, a regulator of haemopoietic precursor cell adhesion to stroma and entry of primitive CD34⁺CD38^lo/‐ precursor cells into cycle, modulates the migration of CD133⁺ cord blood cells to CXCL12 by associating with the CXCR4 receptor. This was demonstrated by a reduction in CD133⁺ cell migration on fibronectin to CXCL12 (i) by engaging the functional class II glycosylation‐dependent epitope on CD164 with the 103B2/9E10 class II but not the N6B6 class III antibody; and (ii) by RNAi knockdown of CD164 protein levels in CD133⁺ cells. The inhibition of migration was more pronounced in the more primitive CD34⁺CD38^lo/‐ cell subset. Similar studies using the Jurkat cell line confirmed these findings and led to further analyses using alternative chemokines. A direct association between CXCR4 and CD164 was demonstrated by the co‐localisation of CD164 with CXCR4 and VLA‐4 and VLA‐5 at the leading edge of CD133⁺ cells when CXCL12 was presented on fibronectin. This was further supported by immunoprecipitation studies that demonstrate in the absence of CXCL12, CXCR4 is associated only with VLA‐4 and VLA‐5 but on exposure to CXCL12, CD164 is rapidly recruited to the CXCR4 complex. Knock‐down of CD164 using siRNA revealed that signalling through CXCR4 via PKC‐ζ was significantly dampened. Our findings therefore support a novel association between three distinct families of cell surface receptors that regulate both cell migratory and proliferative responses and identify a CD164 as a key regulator of the CXCL12/CXCR4 axis.     

The value of bacterial culture during clean orthopedic surgery: a prospective study of 1,036 patients.

OBJECTIVE: To determine whether bacterial cultures of the wounds of patients undergoing clean orthopedic surgery would help predict infection. METHODS: During 1 year, 1,256 cultures were performed for 1,102 patients who underwent clean orthopedic surgery. Results were analyzed to evaluate their ability to predict postoperative infection. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of the cultures were 38%, 92%, 7%, and 99%, respectively. CONCLUSIONS: Cultures performed during clean orthopedic surgery were not useful for predicting postoperative infection.