Biomedical subjects
Publications and source records attributed to T J O'Brien.
Terra firma-forme dermatosis (TFFD) is a relatively common but usually unrecognized clinical problem. The cause is unknown. The changes usually occur on the neck in childhood as dirty brown patches that cannot be removed with soap but are easily removed with alcohol. Terra firma-forme dermatosis may be mistaken for acanthosis nigricans.
PURPOSE: The pathophysiologic basis for the [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) temporal lobe hypometabolism in patients with hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is largely responsible for the regional hypometabolism in HS. METHODS: Regions of interest (ROIs) on FDG-PET scanning were determined in the medial, lateral, and posterior temporal lobe, thalamus, and basal ganglia. A right/left asymmetry index for each ROI was calculated. These results were correlated with hippocampal magnetic resonance imaging (MRI) volume ratios. RESULTS: There was no correlation between the magnitudes of the FDG-PET asymmetry index and the MRI volume ratio for the mesial or lateral temporal regions (r = -0.09, r = -0.04). When the right/left asymmetry index was compared with the right/left hippocampal volume ratio, correlations for the mesial temporal ROI (r = 0.79, p < 0.0001) and lateral temporal ROI (r = 0.57, p < 0.0005) were found. These, however, simply indicated that both tests accurately reflect the side of the epileptogenic region. The concordance of the side of relative hypometabolism of the FDG-PET with the side of the hippocampal atrophy was higher for the mesial temporal region (100%) than for the lateral (77.5%). CONCLUSIONS: The lack of correlation between the magnitudes of the ratios argues against hippocampal atrophy and cell loss having a central role in the FDG-PET temporal hypometabolism.
PURPOSE: Because focal encephalomalacia is an important cause of medically intractable partial epilepsy and few studies have evaluated the efficacy and the safety of resecting focal-encephalomalacias to improve seizure control, we studied a cohort of 17 consecutive patients who underwent resection of encephalomalacias in the frontal lobes as a treatment of their intractable epilepsy. METHODS: We evaluated several factors for their value in predicting postsurgical seizure control. Pre- and postsurgical magnetic resonance imaging (MRI) scans were reviewed independently by 2 blinded investigators. RESULTS: At a median of 3 years of follow-up (range 0.6-7.5 years), 12 patients (70%) were seizure-free or had only rare seizures. The presence of a focal fast frequency discharge (focal ictal beta pattern) at the beginning of seizures on scalp EEG was predictive of seizure-free outcome (p = 0.017), even among patients who had complete resection of their encephalomalacias (p = 0.016). There was no significant differences in outcome with regard to age at the time of the injury that caused encephalomalacia, interval between injury and onset of seizures, duration of presurgical seizure history, presurgical seizure frequency, age at surgery, or the completeness of encephalomalacia resection. The analysis regarding completeness of encephalomalacia resection almost reached significance, suggesting that it may also be an important predictive factor (p = 0.051). CONCLUSIONS: We conclude that surgery is a very effective treatment for intractable frontal lobe epilepsy (FLE) secondary to encephalomalacias. Patients are more likely to become seizure-free if they have a focal ictal beta discharge on their scalp EEG. Complete resection of the encephalomalacia should be attempted, since our results suggest that this may be a favorable predictive factor. Moreover, the operative strategy for our patients entailed, whenever possible, complete resection of the encephalomalacias and of the adjacent electrophysiologically abnormal tissues.
Evidence is presented suggesting that CA125 is a serine and/or threonine phosphoprotein and that its secretion from the human amnion WISH cell line is closely linked to its phosphorylation. It is also indicated that regulation of CA125 secretion requires protein(s) tyrosine phosphorylation. WISH cells treated with a tyrosine phosphatase inhibitor, vanadate/ H2O2, resulted in increased levels of CA125 secretion. Exposure of vanadate-treated cells to epidermal growth factor further enhanced this secretory activity. Immunohistochemistry of vanadate-treated cells resulted in a substantial increase in not only cytoplasmic tyrosine phosphoproteins but also in membrane-associated CA125 when stained with the PY20 anti-phosphotyrosine and M11 anti-CA125 monoclonal antibodies, respectively. M11 immunoprecipitation of CA125 from cells labelled with [32P]-orthophosphate was analyzed by SDS-PAGE and autoradiography. Immunoprecipitates from cell lysates demonstrated that a phosphoprotein of > 200 kD was isolated and immunoreacted with both the OC125 and M11 anti-CA125 monoclonal antibodies by Western blotting. CA125 immunoprecipitated from vanadate-treated cells showed a marked increase in cell-associated CA125 phosphorylation. Although CA125 could be immunoprecipitated from WISH cell media incubated with [32P]-orthophosphate in the presence or absence of vanadate as detected by Western blotting, autoradiographic analysis of the Western blots revealed no [32P]-labelled CA125 co-migrating with the 200-kD plus molecule detected by M11. When the PY20 anti-phosphotyrosine monoclonal antibody was used as the probe, no tyrosine-phosphorylated CA125 was detected in cell lysates.
A prospective, randomized, double-blind study of 437 patients undergoing arthroscopic diagnostic and operative procedures found that no deep infections occurred in any patient and only one superficial infection occurred in a patient who did not receive prophylactic antibiotics. One patient had a mild allergic reaction to the antibiotic that resolved after treatment with Benadryl. These results suggest that the routine use of prophylactic antibiotics is not indicated for patients undergoing arthroscopic surgery and that the slight risk of infection is outweighed by the cost of the antibiotics and the slight risk of allergic reaction.
Five patients with breakage of instrumentation when using the cannulated 3.5 mm screw system for fracture fixation are reported. Four 1.25 mm guide wires were sheared off by the cannulated drill and one 3.5 mm cannulated tap sleeve fractured. This article presents potential dangers when using the cannulated 3.5 mm screw system for general fracture care.
OBJECTIVE: Reduced trophoblastic migration into the decidua during the first half of pregnancy is a fundamental abnormality in preeclampsia. CA 125 and insulin-like growth factor binding protein-1 are major endometrial proteins whose primary sources are decidual epithelial and stromal cells, respectively. We hypothesized that reduced trophoblastic invasion in pregnancies destined for preeclampsia would affect the maternal vascular deportation of these decidual proteins. STUDY DESIGN: CA 125 and insulin-like growth factor binding protein-1 concentrations were analyzed by radioimmunoassays of plasma from preeclamptic and matched control patients in a longitudinal, nested case-control study. RESULTS: CA 125 concentrations did not differ with respect to pregnancy outcome or trimester. Midtrimester plasma insulin-like growth factor binding protein-1 concentrations were significantly lower in women who later had preeclampsia compared with normal pregnant controls. CONCLUSION: These findings provide biochemical evidence that abnormalities of trophoblastic invasion affect the maternal vascular deportation of a decidual stromal protein. Lower circulating concentrations of insulin-like growth factor binding protein-1 in women destined to have preeclampsia were observed 12 to 26 weeks before the onset of clinical signs of this syndrome.
This study aims to determine whether there are important clinico-electrical differences between patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS) and those with TLE secondary to a discrete temporal neocortical lesion (NL). The case histories, interictal EEG, seizure semiology, ictal EEG and postoperative outcome of 46 pathologically proven patients (31 MTS and 15 NL) were compared. A history of febrile convulsions (FC) was more common in MTS patients (58% versus 26%, P < 0.05), as was a history of a significant cerebral event at < 4 years of age (22% versus 0%, P < 0.05). There were no statistically significant differences in the incidence or nature of auras. No statistically significant differences between the groups were found in the interictal-EEG. With ictal semiology dystonic posturing occurred more frequently in MTS patients (mean 52% versus 26%, P < 0.05). Facial grimacing/ twitching occurred earlier in the seizures of NL patients (median 19 s versus 35 s, P < 0.05). There was an increased frequency of fast rhythmic sharp waves (> 4 Hz) in the ictal-EEG of MTS patients (mean 81% versus 60%, P = 0.05). The patients with NL developed bilateral ictal EEG changes more often (mean 55% versus 26%, P < 0.05) and more rapidly (mean 23 s versus 74 s, P < 0.005). The onset of ictal EEG seizure activity was bilateral more often in patients with NL (20% versus 4%, P < 0.005). There were no significant differences between the two groups for any of the video-EEG features, in terms of whether or not the feature occurred at least once in an individual patients. There was a tendency for MTS patients to have a higher seizure-free postsurgical outcome (87% versus 60%, P = 0.057). However, all the NL patients who were not free of seizures had had an incomplete lesion resection. We conclude that there are a number of clinico-electrical differences between patients with mesial TLE (MTLE) and patients with neocortical TLE (NCTLE), but that none of these are sufficient to allow a distinction to be made in an individual patient.
BACKGROUND: The speed, quality, and cost of mask induction of anesthesia and laryngeal mask airway insertion or tracheal intubation were studied in young non-premedicated volunteers given high inspired concentrations of sevoflurane (6 to 7%). METHODS: Twenty healthy persons who were 19 to 32 years old participated three times, received 6 l/min fresh gas flow, and were randomized to receive 6 to 7% sevoflurane in 66% nitrous oxide/28% oxygen by face mask until tracheal intubation (treatment 1) or until laryngeal mask airway insertion (treatment 3), or 6 to 7% sevoflurane without nitrous oxide to tracheal intubation (treatment 2). Participants exhaled to residual volume and took three vital capacity breaths of the gas mixture; thereafter ventilation was manually assisted. The time of exposure to the inhaled gas was varied for consecutive participants. It was either increased or decreased by 30-sec increments based on the failure or success of the preceding volunteer's response to laryngoscopy and intubation after a preselected exposure time. Failure was defined as poor jaw relaxation, coughing or bucking, or inadequate vocal cord relaxation. RESULTS: Loss of the lid-lash reflex in unpremedicated young volunteers was achieved in 1 min and did not differ among groups. Average time (and 95% confidence interval) for acceptable conditions for LMA insertion was achieved in 1.7 (0.7 to 2.7) min, and all participants had an immediate return of spontaneous ventilation. The time for acceptable tracheal intubating conditions after manual hyperventilation by mask was 4.7 (3.7 to 5.7) min and 6.4 (5.1 to 7.7) min in treatments 1 and 2, respectively. There were no cases of increased secretions or laryngospasm. The incidence of breath holding and expiratory stridor ("crowing") was 7.5% and 25%, respectively, during treatment 1 and 15% and 40%, respectively, during treatment 2. CONCLUSIONS: The induction of anesthesia to loss of lid reflex in young non-premedicated adults approaches the speed of intravenous induction techniques. No untoward airway responses were noted during mask induction of anesthesia with a three-breath technique. In response to intubation, no adverse airway responses, including jaw tightness, laryngospasm, and excessive coughing or bucking, occurred in participants whose duration of mask administration of sevoflurane met the appropriate times (as determined in this study).
Desmosomal junctions contain two classes of desmosomal cadherin, the desmocollins and the desmogleins, each of which occurs as three distinct isoforms. To investigate the role of the "skin-type" desmosomal cadherins (desmocollin 1 and desmoglein 1) in the formation of keratinized epithelial structures, we have now cloned full-length mouse desmocollin 1 complementary deoxyribonucleic acid and examined the expression of desmocollin 1 and desmoglein 1 and messages during murine embryonic development by in situ hybridization. In the general body epidermis, desmocollin 1 and desmoglein 1 transcripts both showed considerable upregulation at 15.5 d, which is after the onset of stratification and before the start of keratinization. Before this the epidermis expressed low levels of desmocollin 1 message, although the desmoglein 1 signal was always stronger and more extensive. In the tongue, expression of desmocollin 1 message occurred several days after desmoglein 1 and coincided with the formation of the keratinizing filiform papillae. Desmoglein 1 message was also detected in epithelial tissues in which desmocollin 1 was absent, suggesting that expression of the two "skin-type" desmosomal cadherins was not tightly coupled during embryonic development. Human desmocollin 1 monoclonal antibodies that cross-reacted with mouse skin and tongue indicated that desmocollin 1 protein was first expressed in those outermost epithelial cells destined to form the keratinized layers of the stratum corneum or the papillae. The results suggest that expression of desmocollin 1 is closely associated with the keratinization of epithelial tissues during mouse development.
Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We report a patient with an unusual form of reflex epilepsy in whom seizures are induced by tooth brushing. Magnetic resonance imaging (MRI) demonstrated a right posterior frontal low-grade tumor predominantly involving the precentral gyrus. Video-telemetry demonstrated right-sided epileptiform activity during a typical induced complex partial seizure. An ictal single photon emission computed tomography (SPECT) scan showed an area of hyperfusion that corresponded to the MRI lesion on coregistration with a surface-matching technique. A subsequent coregistered interictal SPECT scan demonstrated hypoperfusion in the same region. Ours is the first report to demonstrate a structural focus in this unusual form of reflex epilepsy. Possible mechanisms to explain the induction of the seizures are discussed.
We evaluated the immunohistological (IH) characteristics of 22 different antibodies that were submitted for study in the frame of the TD-1 ISOBM Workshop on monoclonal antibodies against CA125. Information on relative affinities and epitope similarities was obtained from a parallel immunochemical study. Antibodies were tested at concentrations of 10 and 1 micrograms/ml on frozen and paraffin sections. Paraffin sections were stained according to the streptavidin-biotin complex protocol, and frozen sections according to a two-step immunoperoxidase technique. Aminoethylcarbazole served as the chromogen. The tissues were from normal proliferative endometrium (formalin-fixed paraffin-embedded) material and clear-cell adenocarcinoma of the ovary (formalin-fixed paraffin-embedded and frozen material). Sections were scored for staining in epithelial cells, basal, apical and diffuse cytoplasmic and in stromal components. Intensity was graded as 1, 2 or 3 for epithelial cells and as -1, -2 or -3 for stroma. The cumulative scores for each antibody expressed the discriminative properties of specific epithelial staining against background. M11 and M11-like antibodies, as well as OC125 and OC125-like antibodies, in general showed good staining results. Although there was a trend for high-affinity antibodies to show higher scores, there was no clear relationship between affinity and staining result. For nine antibodies (ZR45, MA602-1, K102, K94, K90, OV185, K97, K96, OV198), the reactions in paraffin and frozen sections were of similar intensity. Most of these were of low affinity with one exception: antibody ZR45, a rat monoclonal antibody (MAb) which had a high relative affinity. For eight antibodies (M11, K101, MA602-6, ZS33, B27.1, B43.13, K93, OC125), a loss of specific staining was observed in frozen sections. All but two of these antibodies (MA602-6 and OC125) were of high relative affinity. With four antibodies (K91, ZR38, K95, K100), the reverse situation was observed. One (K100) was of low affinity, two (K95 and K91) of high affinity and the fourth (ZR38) was a rat MAb of high affinity. Mainly due to the increased cytoplasmic staining in carcinoma, the reactivity in paraffin sections was less extensive in normal endometrium compared to ovarian carcinoma for the majority of antibodies, irrespective of their affinity or epitope group. The IH characterization of these antibodies may be of help in selecting antibodies with specific properties for further comparative studies. The reactivity of normal endometrium with all useful antibodies makes it a good candidate for standard external IH tissue control.
OBJECTIVE: To monitor the occurrence of the hook effect in measurements of peritoneal fluid CA 125 levels using two different immunoenzymatic second generation assays (ETI-II and EIA-II), and to compare these results with those obtained using the respective immunoradiometric versions of the assays (IRMA-II and ELSA-II). STUDY DESIGN: CA 125 levels were determined in peritoneal fluid and serum samples obtained from 45 women with gynecological diseases. The assays were carried out using IRMA-II and ETI-II (Sorin Biomedica) and ELSA-II and EIA-II (CIS Bio International) assays. Occurrence of the hook effect and linearity of the assays were evaluated. Statistical analyses were performed by Wilcoxon's test and linear regression analysis. RESULTS: Undiluted peritoneal fluids, assayed for their CA 125 content, showed falsely underestimated values of the antigen when IRMA-II and ELSA-II assays were performed. The phenomenon disappeared only at high dilutions of the sample (> 50). Conversely, immunoenzymatic ETI-II and EIA-II assays performed on undiluted peritoneal fluids did not show underestimated CA 125 values. CA 125 values obtained by immunoenzymatic assay were lower than those obtained using their respective immunoradiometric versions at a dilution of 1:100 (P < 0.001). A good correlation was observed between ELSA-II and EIA-II (r = 0.929) CA 125 values. CONCLUSION: The EIA-II immunoenzymatic assay appears to be more suitable for CA 125 measurement in peritoneal fluid in that it is not subject to the hook effect and its results correlated well with those obtained via its immunoradiometric version.
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The brown forehead ring (linea fusca), a distinctive but infrequently recognized pattern of facial pigmentation, is described. The history of this sign is recounted. In modern times it seems to be associated with other well recognized patterns of facial pigmentation, chemical photosensitizers and excessive sun exposure. Three cases in adult males are described and the different aetiologies illustrated.
A 67 year old woman with an extensive oropharyngeal carcinoma developed acrokeratosis paraneoplastica. She suffered severe pain in the fingers and toes and experienced some symptomatic relief with psoralen ultraviolet A therapy.
A case of invasive streptococcal disease is presented. Bacteraemic spread from a peritonsillar abscess produced acral purpuric plaques that blistered and ulcerated. Histology showed a vasculitic picture. Group A beta-haemolytic Streptococcus was cultured from the skin biopsy and seen on Gram stain.