Experience with hemoperfusion for organophosphate poisoning.

OBJECTIVE: To evaluate the usefulness of extracorporeal clearance techniques in the treatment of organophosphate poisoning, particularly hemoperfusion. DESIGN: Retrospective study. SETTING: An ICU of a general hospital. PATIENTS: Ten patients with organophosphate poisoning initially received classic treatment with gastric lavage and washing of the whole skin surface, as well as the administration of cathartics, activated charcoal, atropine, and obidoxime or pralidoxime. All patients underwent one to three hemoperfusions. MEASUREMENTS AND MAIN RESULTS: Plasma insecticide concentrations and cholinesterase activity were determined daily. Two to three biopsies of fat tissue were carried out at 1- to 2-wk intervals. The amount of the insecticide removed during hemoperfusions was also determined. Five patients presented with a prolonged nicotinic syndrome. Two of these patients showed sequelae of delayed neurotoxicity. Another two of the five patients died and the remaining patient recovered without sequelae. In none of the patients could > 0.1% of the total absorbed poison be removed by hemoperfusion. No changes in symptoms were observed after these procedures. Fat tissue concentrations of the insecticide were 20 to 50 times higher than the concentrations in plasma. Atropine decreased the intestinal transit time, and 10 days after poisoning, a powerful cathartic treatment indicated the persistence of gut content, which probably caused prolonged absorption of the toxin. CONCLUSIONS: Extracorporeal cleansing mechanisms did not remove any clinically important amount of insecticide from our patients due to the high lipid solubility of these agents and no changes in symptoms were observed after these methods. The use of atropine decreases bowel peristalsis. Early use of powerful cathartics could avoid protracted absorption of the poison stored in the gut, although the potential benefits of this therapy require confirmation by the performance of prospective, controlled investigations.     

Bilateral internuclear ophthalmoplegia in a patient with Wernicke's encephalopathy.

The most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis. Wernicke's encephalopathy has been reported as a cause of unilateral internuclear ophthalmoplegia but not of bilateral internuclear ophthalmoplegia. In this report, we present the case of a patient with a history of alcohol abuse and acute onset of bilateral internuclear ophthalmoplegia whose clinical course and diagnostic studies are most consistent with a diagnosis of Wernicke's encephalopathy.     

Treatment of perianal infection following bone marrow transplantation

PURPOSE: Bone marrow transplantation (BMT) is often associated with profound neutropenia. Allogeneic transplant recipients also have defects in both humoral and cellular immunity and thus are subject to increased risk of serious, often life-threatening, infection even beyond the period of granulocyte recovery. The current study was undertaken to evaluate patients who required operative intervention for perianal sepsis following BMT. METHODS: The bone marrow transplant database at a single institution was used to identify all patients diagnosed with perianal infections after autologous or allogeneic BMT. Charts were reviewed in a retrospective manner. RESULTS: Over a ten-year period ending in November 1993, 963 BMT were performed at the City of Hope National Medical Center. Twenty-four patients were diagnosed with perianal infections foEowing their transplants. Fifteen patients did not have purulent collections requiring drainage and were treated with antibiotics and supportive measures alone. Nine patients (37.5 percent) required surgical intervention between 10 and 380 days following transplantation. At the time of surgical intervention, seven patients had purulent collections and two patients had acute and chronic inflammation, tissue necrosis, and fibrosis. Of the two patients with an absolute neutrophil count less than 1,000, a purulent collection was found in one of the patients. Cultures taken from perianal abscesses were almost all polymicrobial, and the most common organisms were Escherichia coli, Bacteroides, Enterococcus,and Klebsiella.For those patients undergoing surgical intervention, mean time to complete wound closure by secondary intention was 37.6 days; five patients healed in less than 15 days, two patients healed at 93 and 114 days, and two patients had persistent, open wounds at time of death, which was unrelated to their perianal disease. Five patients were receiving systemic steroids at time of surgical intervention; this did not appear to affect time to wound healing. CONCLUSIONS: Perianal infections are a rare complication of BMT. Majority of these infections are polymicrobial, and organisms isolated are similar to those seen in the perianal infections of nonimmunosuppressed patients. Despite steroid use, granulocytopenia does not exclude the possible presence of purulent collections, and clinical examination should guide the decision for surgical drainage. In general, perianal wound healing is not prolonged in BMT patients.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

Preparatory activity in motor cortex reflects learning of local visuomotor skills

In humans, learning to produce correct visually guided movements to adapt to new sensorimotor conditions requires the formation of an internal model that represents the new transformation between visual input and the required motor command. When the new environment requires adaptation to directional errors, learning generalizes poorly to untrained locations and directions, indicating that such learning is local. Here we replicated these behavioral findings in rhesus monkeys using a visuomotor rotation task and simultaneously recorded neuronal activity. Specific changes in activity were observed only in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation. These changes adhered to the dynamics of behavior during learning and persisted between learning and relearning of the same rotation. These findings suggest a neural mechanism for the locality of newly acquired sensorimotor tasks and provide electrophysiological evidence for their retention in working memory.     

Patterns of protein kinase C isoenzyme expression in transitional cell carcinoma of bladder. Relation to degree of malignancy

We determined the pattern of protein kinase C (PKC) isoform expression in human cell lines by Western blotting and immunofluorescent staining techniques. In addition, we examined PKC isoform expression in tissue samples of transitional cell carcinoma (TCC) of the bladder. PKC delta, PKC beta II, and PKC eta were found primarily in the RT4 cell line (low-grade tumor), and PKC zeta was expressed most strongly in the SUP cell line (invasive tumor). In tissue samples of urinary bladder cancer, PKC isoenzymes were expressed differentially as a function of tumor stage and grade; expression of PKC beta II and PKC delta was high in normal tissue and in low-grade tumors and decreased with increasing stage and grade of TCC. The opposite pattern was seen with PKC zeta. The differences in expression of specific isoenzymes as related to levels of malignancy of the cell lines and tissue samples suggest that the PKC family has an important role in normal and neoplastic urothelium.     

Training in clinical genetics and genetic counseling in Asia

The status of training in clinical genetics and genetic counseling in Asia is at diverse stages of development and maturity. Most of the training programs are in academic training centers where exposure to patients in the clinics or in the hospital is a major component. This setting provides trainees with knowledge and skills to be competent geneticists and genetic counselors in a variety of patient care interactions. Majority of the training programs combine clinical and research training which provide trainees a broad and integrated approach in the diagnosis and management of patients while providing opportunities for research discoveries that can be translated to better patient care. The background on how the training programs in clinical genetics and genetic counseling in Asia evolved to their current status are described. Each of these countries can learn from each other through sharing of best practices and resources.     

Lipid and lipoprotein measurements in a normal, adult Cuban population

An attempt was made to determine the normal reference values of lipid- and lipoprotein levels (cholesterol), triglycerides, cholesterol in high- and low-density lipoproteins) in a selected, apparently healthy, Cuban population. Results were expressed as mean, and various percentiles of measured values; two ratios: Risk 1 (LDL-C/HDL-C) and Risk 2 (TC/HDL-C) were also calculated. Approximately 40% of the subjects aged 20 to 30 years had cholesterol values above 200 mg/dl. Females had significantly higher cholesterol HDL-C values than males, whereas the concentrations of LDL-C and LDL were higher in males. Risk 2 ratios were elevated in males. A correlation was shown between lipid levels and age. There was a strong negative correlation between HDL-C and relative body weight. It is suggested that obesity might be an individual risk factor in the population studied.     

Lipid and lipoprotein profiles in Cuban children of three age groups

We determined the lipid and lipoprotein levels in a selected group of apparently healthy adult Cuban subjects in a previous paper /27/. In this paper the basic lipid variables (TC, TG, HDL-C) in 271 healthy children are published. LDL-C levels were also calculated. A small, but continuous, rise was found in the TC level between 0 and 14 years in both sexes. The rise of TG was accompanied by HDL increase in girls but by LDL increase in boys. This phenomenon might explain the augmented susceptibility of men to ischaemic heart disease. Children at "high risk" should be identified (in case of positive family history of ischaemic heart disease) by cholesterol determinations, the borderline of the pathologic cholesterol levels seems to be very similar to that found in the USA, 170-190 mg/dl in the age group between 0 and 14 years.     

Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.