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Biomedical subjects

E Jacob

Publications and source records attributed to E Jacob.

At least 19 recordsLinked to original sources
PubMed2006

Delayed reepithelialization and scarring deregulation following drug-induced toxic epidermal necrolysis.

A 51-year-old Caucasian woman developed severe drug-induced toxic epidermal necrolysis (TEN) due to allopurinol. The withdrawal of the culprit drug was unfortunately delayed, and dramatic retardation of reepithelialization was observed. At that stage of disease evolution, an inflammatory cell infiltrate was present in the dermis. Coverage of eroded lesions by frozen cultured keratinocyte allografts failed to hasten reepithelialization compared to ungrafted sites. This unusual protracted TEN evolution was followed by the development of extensive hypertrophic and keloid scars. Several biopsies were taken over 6 months. The histologic presentation of the grafted and ungrafted eroded scar tissues looked similar. Both the number and size of the Factor XIIIa-positive dermal dendrocytes, as well as the number of alpha-actin-positive myofibroblasts showed a marked increase between weeks 2 and 12 after grafting. They were reduced after 6 months when the scarring process was stabilized. alpha1 [IV] collagen was never expressed over the eroded scars. Similar to burn patients, delayed reepithelialization might be a risk factor for abnormal scarring in TEN. Cultured keratinocyte allograft apparently offered no improvement in reepithelialization and did not prevent abnormal scarring in this TEN patient.

Allopurinol↗
PubMed2006

Skin immunoglobulin deposition following intravenous immunoglobulin therapy in toxic epidermal necrolysis.

Human intravenous immunoglobulins (IVIg) which contain anti-CD95 antibodies have been proposed to treat toxic epidermal necrolysis (TEN). Presently, there is no evidence that IVIg reach the keratinocytes in TEN patients. The aim of this study was to assess the Ig distribution in the serum, blister fluid and skin of six consecutive TEN patients treated with IVIg (1 g/kg/day) for 3 days. They were compared with five TEN patients who only received supportive therapy. In all patients, IgA, IgM and IgG concentrations were measured in the serum and blister fluid using an immuno-nephelometric method. Immunohistochemistry was performed on skin biopsies taken from both TEN clinically involved and uninvolved skin to search for IgG deposits. On admission, the IgG concentrations were significantly higher in both TEN serum and TEN blister fluid compared with their respective IgA and IgM contents. The IgG, IgA and IgM concentrations in blister fluid were significantly lower than their respective serum concentrations. The serum and blister fluid IgG concentrations, but not that of IgA and IgM, were markedly increased at the completion of the IVIg treatment. By contrast, they remained unchanged in the TEN patients that were untreated with IVIg. In the IVIg-treated patients, the IgG intraepidermal deposits raised markedly in both TEN-involved and uninvolved skin. This was not the case in patients who did not receive IVIg. These results suggest that IVIg perfusions brought a prominent increase in IgG concentration in the serum, blister fluid and epidermis of both TEN-involved and clinically uninvolved skin. The presence of potentially protective IgG in TEN epidermis following IVIg treatment could help limiting the disease progression.

Adolescent↗
PubMed2005

Cystic lesion of the parotid following drug-induced toxic epidermal necrolysis (Lyell's syndrome).

A 32-year-old woman developed a unilateral cyst of the duct of parotid gland 4 months after severe oral involvement of drug-induced toxic epidermal necrolysis (TEN). The pathomechanism leading to the TEN epidermal destruction had presumably involved the salivary epithelium as well, leading to the development of the cystic lesion. The patient had low serum lipase levels, but high serum amylase levels at the time of TEN. These serological markers could represent a clue for the risk of developing cystic lesions of the large salivary glands following TEN.

Adult↗
PubMed2004

A fuzzy guided genetic algorithm for operon prediction.

MOTIVATION: The operon structure of the prokaryotic genome is a critical input for the reconstruction of regulatory networks at the whole genome level. As experimental methods for the detection of operons are difficult and time-consuming, efforts are being put into developing computational methods that can use available biological information to predict operons. METHOD: A genetic algorithm is developed to evolve a starting population of putative operon maps of the genome into progressively better predictions. Fuzzy scoring functions based on multiple criteria are used for assessing the 'fitness' of the newly evolved operon maps and guiding their evolution. RESULTS: The algorithm organizes the whole genome into operons. The fuzzy guided genetic algorithm-based approach makes it possible to use diverse biological information like genome sequence data, functional annotations and conservation across multiple genomes, to guide the organization process. This approach does not require any prior training with experimental operons. The predictions from this algorithm for Escherchia coli K12 and Bacillus subtilis are evaluated against experimentally discovered operons for these organisms. The accuracy of the method is evaluated using an ROC (receiver operating characteristic) analysis. The area under the ROC curve is around 0.9, which indicates excellent accuracy. CONTACT: roschen_csir@rediffmail.com.

Algorithms↗
PubMed2004

[Severe paroxysmal drug eruptions].

Some drug reactions showing cutaneous expression exhibit a paroxysmal course. These diseases encompass the toxic epidermal necrolysis, the drug hypersensitivity syndrome, and the acute generalized exanthematic pustulosis. These syndromes are associated with dismal outcome. They represent medical emergencies needing hospitalization in specialized care units.

Acute Disease↗
PubMed2002

Influence of hypoxia and of hypoxemia on the development of cardiac activity in zebrafish larvae.

Cardiac activity and anaerobic metabolism were analyzed in zebrafish larvae raised under normoxia (PO(2) = 20 kPa) and under chronic hypoxia (PO(2) = 10 kPa) at three different temperatures (25, 28, and 31 degrees C). Heart rate increased with development and with temperature. Under normoxia, cardiac output increased significantly at high temperature (31 degrees C), but not at 28 or at 25 degrees C. Under chronic hypoxia, however, heart rate as well as cardiac output increased at all temperatures in larvae at about hatching time or shortly thereafter. Cardiac activity of larvae raised for 2 wk after fertilization with a reduced hemoglobin oxygen-carrying capacity in their blood (hypoxemia; due to the presence of CO or of phenylhydrazine in the incubation water) was not different from control animals. Whole body lactate content of these animals did not increase. Thus there was no indication of a stimulated anaerobic energy metabolism. The increase in cardiac activity observed during hypoxia suggests that at about hatching time receptors are present that sense hypoxic conditions, and this information can be used to induce a stimulation of convective oxygen transport to compensate for a reduction in bulk oxygen diffusion in the face of a reduced oxygen gradient between environmental water and tissues. Under normoxia, however, the PO(2) gradient between environmental water and tissues and diffusional oxygen transport assure sufficient oxygen supply even if hemoglobin oxygen transport in the blood is severely impaired. Thus, under normoxic conditions and with a normal metabolic rate of the tissues, convective oxygen transport is not required until approximately 2 wk after fertilization.

Anaerobiosis↗
PubMed2002

[Deep vein thrombosis in a burn patient].

Association between deep venous thrombosis (DVT) and pulmonary embolism is probably an underestimated problem in the thermally injured patients. However, those patients display important risk factors according to Virchow's triad. This article reports on three unrecognised DVT's accompanying burns which were characterized by absence of healing or edema. The pathophysiology of this issue is then discussed with respect to the specific area of the thermally injured patient. It is our belief that local inflammatory phenomenon play a major part in the genesis of DVT associated with chronic non-healing burns.

Adult↗
PubMed2001

Treatment of drug-induced toxic epidermal necrolysis (Lyell's syndrome) with intravenous human immunoglobulins.

Toxic epidermal necrolysis (TEN) is a rare drug-induced life-threatening disease. Currently, the disease is only treated by supportive and antiseptic measures. Quite recently intravenous immunoglobulins (IG) were shown to be a promising TEN treatment. The rationale for their use is based on the fact that keratinocyte apoptosis in TEN involves the CD95 (APO-1/Fas) cell surface receptor-ligand system. We successfully treated a TEN patient with high dose of intravenous IG. The clinical recovery appeared exceptionally rapid. Immunohistochemistry showed that the IG action probably developed on the CD95 receptor-ligand system at the keratinocytes surface.

Aged↗
PubMed2001

Prevalence of gestational thyrotoxicosis in Asian women evaluated in the 8th to 14th weeks of pregnancy: correlations with total and free beta human chorionic gonadotrophin.

OBJECTIVES: The prevalence of gestational transient thyrotoxicosis (GTT) in Europeans evaluated during the 8th to 14th weeks of pregnancy is 2-3%. However, there is evidence that GTT may be more common in some Asian populations. The aims of this study were to evaluate the prevalence of thyroid hormone abnormalities in Asian women in their 8th to 14th weeks of pregnancy using highly sensitive free T4 and TSH assays and to correlate these with total and free beta-hCG levels. DESIGN AND PATIENTS: One hundred and eighty-four consecutive unselected Asian (Singaporean) pregnant women seen at ante-natal clinics for the first time and who were in their 8th to 14th weeks of pregnancy were tested. MEASUREMENTS: Serum free T4, free T3, TSH, total beta-hCG and free beta-HCG levels were measured on the Vitros ECi system (Johnson & Johnson Ortho-Clinical Diagnostics, Amersham, UK) which employs chemiluminescent immunochemical technology. This free T4 assay is free of biases related to serum binding capacity. The TSH assay used was a third generation assay. Thyrotrophin-receptor antibody (TRAb) levels were measured using LUMItest TRAK (BRAHMS Diagnostica, Berlin, Germany). RESULTS: Two subjects (1.1%) were found to have Graves' disease. Elevated free T4, free T3, total T3 and suppressed TSH were seen in 14.8%, 3.3%, 26.4% and 33.0% of the remaining 182 pregnant women, respectively. Total and free beta-hCG correlated negatively with TSH (r = -0.30, P < 0.0001 and r = -0.29, P < 0.0001, respectively), positively with fT4 (r = 0.283, P < 0.001 and r = 0.253, P < 0.001) and fT3 (r = 0.273, P < 0.001 and r = 0.204, P < 0.01). 11.0% of cases had gestational thyrotoxicosis (GT) defined as elevated free T4 (> 19.1 pmol/l), suppressed TSH (< 0.36 mIU/l) and TRAb levels within the reference interval (0-0.9 U/l). The prevalence of GT was significantly higher in patients tested at 8-11 weeks compared to those evaluated at 12-14 weeks (14.4% vs. 4.7%, P < 0.05). Total beta-hCG (P = 0.0002), free beta-hCG (P < 0.0001) and free T4 (P = 0.02) levels were higher and TSH levels (P = 0.01) lower in patients tested at 8-11 weeks. Significant positive correlations between both total and free beta-hCG with free T4 were seen at 8-11 weeks but not in patients tested at 12 weeks or later. TT3 levels were similar in the two groups. CONCLUSIONS: Using sensitive assays, the prevalence of gestational thyrotoxicosis in Asian women was found to be 11.0% and was significantly higher in subjects at 8-11 weeks of gestation than at 12-14 weeks. The positive correlation between hCG and free T4 seen in patients tested at 8-11 weeks was absent in patients tested at later stages of the first trimester. Future studies investigating the entity of gestational thyrotoxicosis, at least in Asian patients, should focus on patients at earlier stages of gestation than currently practised.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed2001

The pain experience of patients with sickle cell anemia.

Sickle cell anemia is a genetic disorder that affects 1 in 600 black infants in the United States. The painful crisis is one of its most characteristic manifestations and consists of pain in the extremities, back, abdomen, or chest. It may occur in 4 phases and may be precipitated by a variety of factors. The frequency, location, duration, severity, and character of pain differ both within and among patients. The pain may be localized, involve several areas, be diffuse, or be migratory. The intensity of pain varies from mild to excruciating and is perceived to be more intense by those who have experienced other forms of pain such as postoperative pain. Patients with sickle cell anemia who experience frequent painful crises exhibit problems with self-concept and low self-esteem, anxiety, depression, dissatisfaction with body image, poor school performance, social isolation, decreased participation in normal activities of daily living, and poor peer and family relationships. The periodic and unpredictable episodes can be incapacitating and may affect the way children see and feel about themselves, the way they relate to other people, the goals they set for themselves, and the way they approach a range of activities and situations. Research is very limited, and most of the available literature is based on personal observations, opinions, and anecdotal reports. The purpose of this report is to describe the phases of a painful episode as well as to examine the predisposing factors to, defining characteristics of, and patient outcomes associated with a painful crisis from sickle cell anemia.

Activities of Daily Living↗
PubMed2001

Pain management in sickle cell disease.

The unpredictable, recurrent, intense, and frequently persistent nature of pain associated with sickle cell disease poses a difficult challenge in terms of management. A wide variability exists in the way painful episodes are managed. Variations in practice reflect different views about the suitability of opioids, the efficacy of parenteral administration, and the risk of dependence on opioids. Consequently, the acute and chronic pain associated with sickle cell disease often is undertreated or inappropriately managed. Although medical staff fear that patients might abuse pain medication and become psychologically dependent, patients are more concerned about the side effects associated with analgesics. Some patients may persuade staff to give them more analgesics, engage in clock-watching, and request specific medications or dosages; these patients often are perceived as manipulative or demanding. However, these patients are knowledgeable about their medications and doses that have worked in the past. Requests for specific medications and dosages should not be interpreted as indications of drug-seeking behavior, but clinicians should communicate with these patients, make accurate assessments, and provide adequate doses of opioid analgesics. The American Pain Society recognized that the undertreatment of pain and inappropriate management of pain in sickle cell disease seem to be common. A Clinical Practice Guideline was developed to provide evidence-based recommendations that could potentially improve pain management. The purpose of this report is to describe the pharmacologic strategies used to manage pain associated with sickle cell disease, examine issues and challenges related to pain management as well as concerns and fears related to addiction, and explain the administration of opioids as recommended by the American Pain Society.

Analgesics, Non-Narcotic↗
PubMed2000

Variability of analgesic practices for hospitalized children on different pediatric specialty units.

This study examined the differences in the prescription and administration of analgesics in eight pediatric specialty units. Medical records of patients (n = 153) who were reported by nurses to be having pain were reviewed. Results showed that there were variations in the type of analgesics prescribed and administered in the different units. Mean doses of opioids were slightly subtherapeutic. The mean doses of the nonsteroidal anti-inflammatory drugs and adjuvants were all within the therapeutic range. There were large intervals between doses of medications. Because few patients had pain scores recorded before and after analgesic administration, evidence of relief was inconclusive, and the actual effectiveness of analgesics could not be consistently evaluated. Undertreatment of pain may result from administration of subtherapeutic analgesic doses, long intervals between administrations of doses, lack of proper documentation to guide practice, or a combination of these reasons.

Analgesics↗
PubMed2000

Crohn disease arthropathy: antigens in synovial fluid share epitopes with strains of two species of viridans streptococci.

BACKGROUND: There is evidence to suggest that Crohn disease is caused by an immunologic response to an unknown intestinal luminal antigen, probably of bacterial origin. The reported demonstration of yersinia antigen in the synovial fluid of patients with yersinosis therefore prompted a search for bacterial antigens in the synovial fluid of patients with Crohn arthropathy. METHODS: Antisera were raised in rabbits to synovial fluids obtained from seven patients with Crohn arthropathy and from seven 'control' subjects with other forms of arthropathy. These antisera were used to probe sonicates of the bacteria cultured from the gastric juice of patients with gastric Crohn disease. RESULTS: The antisera made from the Crohn synovial fluids, but none of those made from the controls, reacted uniquely with antigens in sonicates of strains of two species of viridans streptococci (Streptococcus parasanguis and an atypical S. oralis) isolated from four of the five patients with gastric Crohn disease. CONCLUSIONS: These findings suggest that the arthropathy of Crohn disease and, possibly, the intestinal disease itself may involve an immunologically mediated inflammatory response to these antigens.

Animals↗
PubMed1999

cDNA cloning, bacterial expression, in vitro renaturation and affinity purification of the zinc endopeptidase astacin.

Astacin (EC 3.4.24.21) from the freshwater crayfish (Astacus astacus) is a prototype for the metzincin superfamily and for the astacin family of zinc peptidases, enzymes which are involved in hatching processes, embryonic patterning and tissue remodelling. Here we report on the cloning and overexpression in Escherichia coli of an astacin cDNA which was reverse-transcribed from crayfish midgut-gland mRNA. A cDNA construct based on this clone was generated which comprised the nucleotide sequence encoding mature astacin devoid of the signal and propeptide. This construct was cloned into the pET3a vector and used to transform E. coli BL21(DE3) cells. Recombinant astacin was purified from inclusion bodies and dissolved under reducing conditions. For folding, the protein was diluted into neutral buffer containing l-arginine, GSH and EDTA. Eventually, Zn(2+) was added by dialysis and the fraction of active enzyme was affinity-purified on immobilized Pro-Leu-Gly hydroxamate. As shown by superimposition of the corresponding three-dimensional structures, this inhibitor binds to a region of the active-site cleft that is conserved in most metzincins. Therefore this principle behind this affinity technique, originally introduced for fibroblast collagenase by Moore and Spilburg [Biochemistry (1986) 25, 5189-5195], is applicable throughout the metzincin superfamily of metalloproteases, despite their otherwise differing cleavage specificities. Recombinant astacin is active on gelatine zymograms and in a quenched fluorescence assay, yielding kinetic parameters comparable with those of wild-type astacin purified from crayfish stomach.

Amino Acid Sequence↗
PubMed1999

Use of cefazolin microspheres to treat localized methicillin-resistant Staphylococcus aureus infections in rats.

BACKGROUND: In a previous study, the topical administration of biodegradable, controlled-release poly-(dl-lactide-co-glycolide) cefazolin microspheres could effectively prevent surgical wound infections with a sensitive strain of Staphylococcus aureus in an experimental animal model. The objective of the current study was to evaluate and compare the efficacy of topical antibiotic therapy with cefazolin microspheres to systemic cefazolin therapy for the treatment of experimental rat surgical wounds contaminated with a methicillin-resistant strain of S. aureus (MRSA). METHODS: A local infection model in rats was used. MRSA was used to infect pockets surgically produced in the paraspinous muscles. Groups of rats received either topical cefazolin microspheres, topical cefazolin powder, parenteral cefazolin, or no treatment. Feces were cultured to evaluate the effect of antibiotic therapy on gut flora. RESULTS: The rate of clinical wound infection following topical application of cefazolin microspheres (13%) was significantly lower than the 53% infection rate observed in rats who had received a 2-week course of systemic cefazolin therapy (P = 0.046). Moreover, single-dose topical antibiotic therapy with cefazolin microspheres completely eradicated MRSA from the wounds of 7 of 15 (47%) animals. There was no statistically significant difference, however, in the rate of clinical wound infection between rats whose wounds were treated topically with free cefazolin powder and those treated with systemic cefazolin (P = 0.12). Importantly, selection of antibiotic-resistant bacteria was associated with systemic but not local cefazolin therapy. CONCLUSION: The results of this study suggest that topical antibiotic therapy with controlled-release cefazolin microspheres may be effective for the prevention of wound infection with both methicillin-sensitive and methicillin-resistant strains of S. aureus in selected surgical procedures that are at high risk of developing postoperative wound infection.

Administration, Topical↗
PubMed1999

Pain in hospitalized children: pediatric nurses' beliefs and practices.

A descriptive design was used to gather information regarding nurses' beliefs and documentation practices related to pain assessment and management in children. Pediatric nurses (n = 260) from eight hospital units completed a child and pain survey. Nurses' pain-related documentations on children (n = 153) were also examined. Results showed inconsistency between what nurses believe about pain assessment and management and their documentation of practice. Nurses believed that assessment is the first step toward alleviating pain in children. However, it was not evident in their documentations that nurses used developmentally appropriate tools for assessment or for evaluation of children's responses to pain management strategies.

Adult↗