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Biomedical subjects

M Levin

Publications and source records attributed to M Levin.

At least 19 recordsLinked to original sources

Reduction of the anticoagulant activity of glycosaminoglycans on the surface of the vascular endothelium by endotoxin and neutrophils: evaluation by an amidolytic assay.

The processes that underlie the coagulopathy observed in severe infection are not fully understood, but seem to be due to an imbalance in the antithrombotic, and prothrombotic properties of the vascular endothelium. Sulphated glycosaminoglycans (GAGs) present on the vessel wall represent an important component of the non-thrombogenic nature of the endothelium. We have modified an amidolytic assay to study the functional ability of GAGs on human umbilical vein endothelial cells (HUVECS), and investigate the effect of E. coli endotoxin and neutrophils on HUVEC surface anticoagulant activity (SAA). Neither endotoxin alone, nor separated neutrophils at lower concentrations (less than 10(6) neutrophils per ml), had major effects on endothelial SAA. When activated neutrophils were incubated with HUVECS pre-stimulated with endotoxin, a significant decrease in SAA was seen using either plasma (mean percentage of control 67.8% +/- sem 7.8; p < 0.02) or purified ATIII (mean percentage of control 69% +/- sem 4.6; p < 0.001). We suggest that alterations in endothelial surface GAGs may occur during sepsis and inflammation, and that this may have important consequences for vascular function. This system will allow the further study of the role of GAGs in the intravascular thrombosis of severe sepsis, and other inflammatory diseases.

Anticoagulants

Complete recovery from hemorrhagic shock and encephalopathy.

We describe three infants (aged 9 weeks to 4 months) with the classic features of hemorrhagic shock and encephalopathy syndrome, including sudden onset of shock, neurologic disturbance, bleeding, disseminated intravascular coagulation, and impaired hepatic and renal function. Unlike the cases previously described, all three children recovered rapidly without evidence of long-term neurologic damage. These findings may modify the perception that this disorder has a uniformly bad outcome.

Brain Diseases

Varicella-zoster virus (VZV)-specific cytotoxicity after immunization of nonimmune adults with Oka strain attenuated VZV vaccine.

Cytotoxic, proliferative, and serum IgG antibody responses to varicella-zoster virus (VZV) were measured monthly in 29 young adults for 3 months following primary immunization with the Oka strain attenuated VZV vaccine. No subjects had lymphocytes stimulated to VZV-specific cytotoxicity at study entry although lymphocytes from 2 subjects proliferated when stimulated by VZV antigen. The percentages of subjects with positive major histocompatibility complex class II-restricted cytotoxic responses at 1, 2, and 3 months after immunization were 54%, 69%, and 66%, respectively. Correlations between cytotoxic, proliferative, and antibody responses were highest in the first month after immunization; lower but still statistically significant after the second month; and not apparent by the third month. The data suggest that antibody and cell-mediated immune responses to VZV immunization develop in parallel after immunization, but these effector mechanisms are independently regulated by 3 months after immunization.

Adult

Guidelines for the use of fresh frozen plasma. British Committee for Standards in Haematology, Working Party of the Blood Transfusion Task Force.

Fresh frozen plasma should only be used to treat bleeding episodes or prepare patients for surgery in certain defined situations. Definite indications for the use of FFP: 1. Replacement of single coagulation factor deficiencies, where a specific or combined factor concentrate is unavailable. 2. Immediate reversal or warfarin effect. 3. Acute disseminated intravascular coagulation (DIC). 4. Thrombotic thrombocytopenic purpura (TTP). Conditional uses: FFP only indicated in the presence of bleeding and disturbed coagulation: 1. Massive transfusion. 2. Liver disease. 3. cardiopulmonary bypass surgery. 4. Special paediatric indications. No justification for the use of FFP: 1. Hypovolaemia. 2. Plasma exchange procedures. 3. 'Formula' replacement. 4. Nutritional support. 5. Treatment of immunodeficiency states.

Adult

Does computed tomography have a role in the evaluation of complicated acute bacterial meningitis in childhood?

The authors examined the records of 30 children with bacterial meningitis to review the role of computed tomography (CT) of the brain in acute management of the disease. CT was normal for 10 patients, six of whom had clinical evidence of raised ICP. CT identified an underlying surgical abnormality in two patients with progressive focal neurological signs. One patient had unsuspected gross hydrocephalus diagnosed by CT, which required neurosurgery. This study shows that the management of bacterial meningitis is influenced by CT in only a minority of cases; for patients with clinical signs of raised ICP, it was found to be insensitive in confirming the clinical diagnosis and establishing an underlying cause. However, CT remains valuable in the management of children with progressive neurological signs for whom neurosurgical intervention may be necessary.

Acute Disease

Streptococcus associated toxic shock.

In the past few years, there appears to have been a change in the spectrum of disease caused by group A beta-haemolytic streptococcus (GABHS), and a toxic shock-like syndrome caused by this organism has recently been described in adults. We report four children with an acute illness characterised by rapid progression of shock, erythematous rash, multisystem organ involvement, electrolyte derangements, and desquamation who fulfil the previously established diagnostic criteria for toxic shock syndrome. Three of the children had extensive cutaneous and soft tissue infection and the fourth had peritonitis. All four developed bacteraemia. Treatment included aggressive cardiovascular resuscitation and antibiotic therapy. Although no patient died, they suffered multiple and severe complications requiring prolonged treatment and hospitalisation. Streptococcal toxic shock syndrome is a separate and clearly defined entity occurring in previously healthy children.

Cardiopulmonary Resuscitation

Alteration in glycosaminoglycan metabolism and surface charge on human umbilical vein endothelial cells induced by cytokines, endotoxin and neutrophils.

There is increasing evidence that the glycosaminoglycan (GAG) component of the vascular endothelium is important in regulating vascular permeability, thromboresistance and cellular interactions. We have investigated the GAG metabolism of cultured human umbilical vein endothelial cells (HUVEC) in response to a range of inflammatory stimuli. Using both chemical measurement of cellular and supernatant GAGS and 35S labelling to identify newly synthesised GAGS, interleukin 1 (IL1), tumour necrosis factor (TNF) and interferon gamma (IFN gamma) were shown to influence sulphated GAG metabolism significantly. IL1 and TNF caused a marked increase in culture supernatant GAGS and a concomitant reduction in cell-associated GAGS. This was shown histochemically to be associated with a marked reduction and redistribution of endothelial surface anionic sites. The addition of neutrophils to HUVEC pretreated with Escherichia coli endotoxin, IL1 or TNF resulted in a further reduction in both cellular GAGS and surface anionic sites. These results suggest that changes in endothelial cell GAG metabolism during inflammation may contribute to the disturbance of vascular endothelial homeostasis associated with infectious and inflammatory states.

Adult

Real-time sonography in ocular trauma.

Real-time sonography was evaluated retrospectively in 71 consecutive patients with ocular trauma. A total of 51 vitreous hemorrhages, 20 hemorrhages in the anterior chamber, 22 retinal detachments, seven choroidal detachments, five foreign bodies, and 12 dislocated lenses were identified sonographically. In 10 instances (three choroidal detachments, six retinal detachments, and one lens dislocation), these sonographic findings were not apparent on clinical examination. One hemorrhage of the anterior chamber was missed on sonography. Both sonography and clinical examination failed to visualize one retinal detachment. The results of this study show that real-time sonography is valuable in the assessment of ocular trauma and supplements clinical examination with valuable information.

Adult

Trypanosoma cruzi: aberrant expression of class II major histocompatibility complex molecules in skeletal and heart muscle cells of chronically infected mice.

In isolated skeletal, heart, and smooth muscle cells from BALB/c and C3H/HeJ mice infected with different strains of Trypanosoma cruzi the presence of class II MHC molecules was investigated by immunocytochemical techniques. We employed single muscle fibers instead of conventional cryostat sections to obtain a more accurate antigen localization. Approximately half of the skeletal muscle cells isolated from the rectus femoris expressed Ia antigens on their surface, irrespective of the mouse or parasite strain combination. Ia expression was apparent only at 30 days postinfection and thereafter. The heart muscle cells expressed class II molecules only at 1 and 3 months postinfection. In no case did the smooth muscle cells from infected mice express Ia antigens. Studies of the same molecules in the noninfected animals gave constantly negative results. We conclude that in the course of the chronic infection of mice with T. cruzi, ectopic expression of class II MHC molecules occurs at the surface of skeletal and heart muscle cells, providing a possible mechanism for explaining the anti-striped muscle autoreactivity present in Chagas' disease.

Animals

Trypanosoma cruzi: cellular and antibody response against the parasite in mice immunized with a 19-amino acid synthetic peptide.

Several monoclonal antibodies were prepared against the flagellar fraction of Trypanosoma cruzi epimastigotes (Tulahuén strain, stock Tul 2). One of them, FCH-F8-4, has previously shown biologic activity against the parasite (complement-mediated lysis and neutralization of the trypomastigote infectivity). Immunopurified antigens using this monoclonal antibody elicited a protective immune response in mice. Two recombinant cDNA clones were detected with this anti-flagellar fraction monoclonal antibody on a lambda gt11 expression library prepared from T. cruzi epimastigote mRNA. The insert of one of these cDNA clones, lambda(FCH-F8-4)1 (150 bp) coded for a 19-amino acid peptide (PAFLGCSSRFSGSFSGVEP). This insert hybridized with a 5.0-kb mRNA from epimastigotes. The beta-galactosidase fusion protein was produced in lysogenic bacteria. The monoclonal antibody recognized the epitope present in the fusion protein after western blotting of the crude lysate. A synthetic peptide (SP4) containing the complete sequence of lambda(FCH-F8-4)1 was constructed on solid phase. This peptide was able to inhibit the ELISA reactivity (in a range from 13 to 52%) of flagellar fraction immunized mouse sera and when administered (coupled to KLH or alone) to BALB/c mice with Bordetella pertussis as adjuvant, it induced a humoral and cellular immune response which was detected by ELISA, immunofluorescence, blotting, and DTH reactions against T. cruzi antigens. The immune response obtained indicates that this synthetic peptide resembles the parasite antigen conformation and could be useful for diagnosis purposes or be able to elicit immunoprotection against T. cruzi infection.

Amino Acid Sequence

EEG features and their evolution in the acute phase of haemorrhagic shock and encephalopathy syndrome.

Serial EEGs have been carried out during the acute phase of haemorrhagic shock and encephalopathy syndrome (HS&E) in 22 infants and children aged 3 months to 14 years. Most patients presented with fits and coma and all had shock with bleeding and disseminated intravascular coagulation (DIC). The initial EEG showed prolonged runs of often rhythmic discharges which fluctuated in amount and amplitude with varying distribution and morphology ("electrical storms"). Over a period of days the "electrical storms" gradually decreased leaving only low amplitude EEG activities or evolving to electrocerebral silence (7 cases). Fifteen patients died and all five children with multifocal "electrical storms" who survived showed gross neurological handicap. The rather distinctive EEG pattern is unusual in the context of an acute encephalopathy outside the neonatal period although similar "electrical storms" may be seen in a less extreme form in infants and children with other conditions associated with DIC. This EEG pattern presumably reflects changes in the cerebral microcirculation which in HS&E are usually relentlessly progressive and associated with devastating cortical damage.

Adolescent

Varicella-zoster virus-specific immunity after herpes zoster.

The frequency of varicella-zoster virus (VZV)-specific T lymphocytes was higher in elderly subjects who had herpes zoster infections than in age-matched controls. This increase in T cell response persisted for at least 2 years while antibody levels to VZV returned to control values at this time. There were no differences in T cell or antibody responses to VZV between individuals with and without postherpetic neuralgia. Elderly subjects who had not had herpes zoster had a comparable increase in VZV-specific T responder cell frequency after immunization with Oka strain VZV. The data suggest that the potential for a boost in T cell response to VZV persists in the elderly, and that immunization can elicit a T cell response in this age group.

Adult

Erythroderma, palmoplantar keratoderma and profound failure to thrive in an infant.

The case is reported of a female infant, who at the age of 3 months developed severe erythroderma, marked hyperkeratosis of the palms and soles and subsequently extreme growth failure and intermittent diarrhoea. Her course was complicated by life-threatening infections but detailed investigation revealed no recognized underlying metabolic or immune abnormality.

Dermatitis, Exfoliative

Herpes simplex encephalitis with relapse.

Three children are described in whom herpes simplex encephalitis (HSE) followed a clearly biphasic course. The secondary deterioration may be due to a resurgence of the viral infection and calls into question the adequacy of current treatment regimens for HSE. Alternatively, a postinfectious neuroallergic process may be active in which case immunomodulatory treatment might be more appropriate than further antiviral treatment.

Acyclovir