Biomedical subjects

A K Gupta

Publications and source records attributed to A K Gupta.

At least 235 records · Page 13Linked to original sources

PubMed2000

Detection of xanthomegnin in epidermal materials infected with Trichophyton rubrum.

Xanthomegnin, a mutagenic mycotoxin best known as an agent of nephropathy and death in farm animals exposed to food-borne Penicillium and Aspergillus fungi, was first isolated about 35 y ago as a diffusing pigment from cultures of the dermatophyte, Trichophyton megninii. This study investigates the production of xanthomegnin by the most common dermatophytic species, Trichophyton rubrum, both in dermatologic nail specimens and in culture. In view of the labile nature of xanthomegnin, a chromatographic procedure was developed to allow high-performance liquid chromatography analysis within 1 h of sample extraction. In cultures, Tricho- phyton rubrum produced xanthomegnin as a major pigment that appears to give the culture its characteristic red colony reverse. Xanthomegnin was also repeatedly extracted from human nail and skin material infected by Trichophyton rubrum. The level of xanthomegnin present, however, varied among the clinical samples studied. Xanthomegnin was not detected in uninfected nails. These results show that patients with Trichophyton rubrum infections may be exposed to xanthomegnin, although the consequences of such an exposure are not currently known.

Chromatography, High Pressure Liquid↗

PubMed2000

alpha-MSH inhibits induction of C/EBPbeta-DNA binding activity and NOS2 gene transcription in macrophages.

BACKGROUND: alpha-Melanocyte-stimulating hormone (alpha-MSH) is an endogenous tridecapeptide that exerts anti-inflammatory actions and abrogates postischemic renal injury in rodents. alpha-MSH inhibits lipopolysaccharide (LPS)-induced gene expression of several cytokines, chemokines, and nitric oxide synthase-2 (NOS2), but the molecular mechanisms underlying these effects have not been clearly defined. To test the hypothesis that alpha-MSH inhibits the expression of inducible trans-activating factors involved in NOS2 regulation, we used RAW 264.7 macrophage cells to examine the effects of alpha-MSH on the activation of nuclear factor-kappaB (NF-kappaB) and CCAAT/enhancer binding protein-beta (C/EBPbeta), trans-acting factors known to be involved in LPS + interferon (IFN)-gamma induction of the NOS2 gene. METHODS: Gel shift assays were performed to identify NF-kappaB and C/EBP DNA binding activities in LPS + IFN-gamma-treated RAW 264.7 cells in the presence and absence of alpha-MSH. NOS2 promoter assays were conducted to identify the effects of alpha-MSH on LPS + IFN-gamma-mediated induction of NOS2 transcription. RESULTS: Gel shift assays demonstrated LPS + IFN-gamma induction of NF-kappaB and C/EBP family protein-DNA complexes in nuclei harvested from the cells. Supershift assays revealed that the C/EBP complexes were comprised of C/EBPbeta, but not C/EBPalpha, C/EBPdelta, or C/EBPepsilon. alpha-MSH (100 nmol/L) inhibited the LPS + IFN-gamma-mediated induction of nuclear DNA binding activity of C/EBPbeta, but not that of NF-kappaB (in contrast to reports in other cell types), as well as the activity of a murine NOS2 promoter-luciferase construct. In contrast, alpha-MSH (100 nmol/L) had no effect on the induction of NOS2 promoter-luciferase genes harboring deletion or mutation of the C/EBP box. CONCLUSIONS: These data indicate that alpha-MSH inhibits the induction of C/EBPbeta DNA binding activity and that this effect is a major mechanism by which alpha-MSH inhibits the transcription of the NOS2 gene. The inability of alpha-MSH to inhibit LPS + IFN-gamma induction of NF-kappaB in murine macrophage cells, which contrasts with inhibitory effects of the neuropeptide in other cell types, suggests that cell-type-specific mechanisms are involved.

Animals↗

PubMed2000

Multiparameter brain tissue monitoring--correlation between parameters and identification of CPP thresholds.

Continuous monitoring of brain interstitial gas concentrations allows direct regional evaluation of the pathophysiology of cerebral tissues. We have incorporated the Paratrend 7 (P7) multiparameter sensor into our established multimodal monitoring of head injured patients, to investigate the relationship between brain and arterial pO2, pCO2, and pH, as well as defining thresholds for cerebral perfusion pressure (CPP). A P7 sensor was inserted into the brain tissue of 40 adult head injured patients via a modified Camino bolt or triple lumen bolt. A second sensor was placed in the femoral artery for continuous monitoring of blood gases. Data signals from 19 monitored parameters were collected onto computer at the bedside for up to 14 days. No complications were seen. For individual patients the changes in brain tissue parameters showed large variations over 24 hours and the relationship between parameters varied considerably both between patients and during the period of monitoring any one individual. Changes related to periods of arterial desaturation, cerebral hypoperfusion and therapeutic manoeuvres could be seen. Good correlation was seen between brain pCO2 and arterial pCO2 (r = 0.58). Poor correlation was seen between CPP and brain pO2, and between brain pO2 and ICP. However, by grouping values for intracranial pressure (ICP) and CPP, thresholds for brain tissue pO2 were identified in 16 patients where CPP fell below 60 mmHg. No patients where CPP was always > 60 mmHg showed a significant threshold for a drop in brain pO2 (n = 16). In conclusion, the P7 shows potential as a monitor of regional brain oxygenation and for detection of potentially damaging secondary insults. The results must be interpreted whilst considering catheter position, autoregulation and systemic arterial changes for each individual.

Adolescent↗

PubMed2000

Head injury monitoring using cerebral microdialysis and Paratrend multiparameter sensors.

INTRODUCTION: Following head injury complex pathophysiological changes occur in brain metabolism. The objective of the study was to monitor brain metabolism using the Paratrend multiparameter sensor and microdialysis catheters. PATIENTS, MATERIAL AND METHODS: Following approval by the Local Ethics Committee and consent from the relatives, patients with severe head injury were studied using a triple bolt inserted into the frontal region, transmitting an intracranial pressure monitor, microdialysis (10 mm or 30 mm membrane; glucose, lactate, pyruvate, glutamate) catheter and Paratrend multiparameter (oxygen, carbon dioxide, pH and temperature) sensor. A Paratrend sensor was also inserted into the femoral artery for continuous blood gas analysis. RESULTS: 21 patients were studied with cerebral microdialysis for a total of 91 monitoring days (range 19 hours to 12 days). Of these, 14 patients were also studied with cerebral and arterial Paratrend sensors. The mean (+/- 95% confidence intervals) arterial and cerebral oxygen levels were 123 +/- 10.9 mmHg and 27.9 +/- 5.71 mmHg respectively. The arterial and cerebral carbon dioxide levels were 34.3 +/- 2.35 mmHg and 45.3 +/- 3.07 mmHg respectively. Episodes of systemic hypoxia and hypotension resulting in falls in cerebral oxygen and rises in cerebral carbon dioxide were rapidly detected by the arterial and cerebral Paratrend sensors. Systemic pyrexia was reflected in the brain with the cerebral Paratrend sensor reading 0.17 degree C (mean) higher than the arterial sensor. Elevations of cerebral glucose were detected, but the overall cerebral glucose was low (mean 1.57 +/- 0.53 mM 10 mm membrane; mean 1.95 +/- 0.68 mM 30 mm membrane) with periods of undetectable glucose in 6 patients. Lactate concentrations (mean 5.08 +/- 0.73 mM 10 mm membrane; mean 8.27 +/- 1.31 mM 30 mm membrane) were higher than glucose concentrations in all patients. The lactate/pyruvate ratio was 32.1 +/- 5.16 for the 10 mm membrane and 30.6 +/- 2.17 for the 30 mm membrane. Glutamate concentrations varied between patients (mean 15.0 +/- 10.5 microM 10 mm membrane; mean 28.8 +/- 17.8 microM 30 mm membrane). CONCLUSION: The combination of microdialysis catheters and Paratrend sensors enabling the monitoring of substrate delivery and brain metabolism, and the detection of secondary metabolic insults has the potential to assist in the management of head-injured patients.

Accidents, Traffic↗

PubMed2000

Prevalence and epidemiology of onychomycosis in patients visiting physicians' offices: a multicenter canadian survey of 15,000 patients.

A prospective, multicenter study to determine the epidemiology of onychomycosis was performed in the offices of 3 dermatologists and 1 family physician in Ontario, Canada. In the sample of 15,000 patients, abnormal-appearing nails were observed in 2505 persons (16. 7%). There were 1199 patients (8%) with toenail or fingernail onychomycosis confirmed on mycologic examination, with 1137 patients (7.6%) who had only pedal onychomycosis, 40 patients with toenail and fingernail onychomycosis (0.27%), and 22 patients (0.15%) with only fingernail onychomycosis. The condition was more common in male patients (P <.0001) and older persons (P <.0001). The ratio of onychomycosis in toenails/fingernails was 19:1. When onychomycosis was present in toenails, the ratio of distal/lateral subungual onychomycosis (DLSO) to white superficial onychomycosis to proximal subungual onychomycosis was 360:59:1. The extent of DLSO in toenails was mild (< or =25% nail involvement), moderate (26%-74% disease), and severe (> or =75% nail involvement) in 27.6%, 39.9%, and 32.5% of patients, respectively. After adjusting for the age and sex distribution of the general population, the projected rate of onychomycosis in Canada is 6.5% (95% confidence interval [CI], 6. 1%-6.9%). The organisms causing toenail onychomycosis were 90.5% dermatophyte, 7.8% nondermatophyte molds, and 1.7% Candida spp. The corresponding organisms causing fingernail onychomycosis were 70.8%, 0%, and 29.2%, respectively. In a large sample of 15,000 patients, abnormal-appearing nails were present in 17% of the sample with mycologic evidence of toenail or fingernail onychomycosis in 8%. The projected prevalence of onychomycosis in Canada is 6.5% (95% CI, 6. 1%-6.9%).

Adolescent↗

PubMed2000

A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns.

BACKGROUND: Onychomycosis, a fungal infection of the nail bed, is responsible for up to 50% of nail disorders. Although several surveys have been conducted in different parts of the world, there have been no multicenter epidemiologic surveys of onychomycosis in North America. OBJECTIVE: A 12-center study was undertaken to (1) determine the frequency of onychomycosis, (2) identify organisms recovered from the nails, and (3) determine the antifungal susceptibility of isolates. METHODS: A total of 1832 subjects participated in this study and completed a comprehensive questionnaire, and nail clippings were collected for potassium hydroxide examination and culturing. RESULTS: The frequency of onychomycosis, as defined by the presence of septate hyphae on direct microscopy and/or the recovery of a dermatophyte, was found to be 13.8%. In general, the dermatophyte isolates were susceptible to the antifungals tested. CONCLUSION: Because of the limited number of large-scale studies, the baseline incidence is not firmly established. However, the higher frequency of onychomycosis in this study may confirm the suspected increase in incidence of disease in North America.

Adolescent↗

PubMed2000

Ciclopirox nail lacquer solution 8% in the 21st century.

Ciclopirox nail lacquer solution 8% has been shown to be effective in the treatment of dermatophyte onychomycosis of mild to moderate severity Other studies report the effectiveness of ciclopirox nail lacquer in onychomycosis caused by Candida sp and nondermatophyte molds. Ciclopirox nail lacquer may also be valuable in the treatment of early cases of reinfection/relapse. Ciclopirox nail lacquer solution 8% may be an important adjunct to oral antifungal therapy in certain presentations that might be poorly responsive to oral antifungal therapy alone (eg, lateral onychomycosis, longitudinal spike, dermatophytoma, and extensive onycholysis). In some cases, surgical therapies may need to be considered in addition to, or in preference to, topical nail lacquer treatment. The use of ciclopirox nail lacquer solution 8% as an adjunct to oral antifungal therapy may widen the spectrum of activity of the combination because of the broad spectrum of coverage provided by the lacquer. The use of combination therapy may be synergistic in terms of efficacy, enabling a reduction in the duration and cumulative dosage of oral therapy. This could result in a decrease in the frequency and severity of systemic adverse effects associated with the oral antimycotics and the need to be vigilant about drug interactions. Studies need to be conducted to determine the place of combination oral and topical lacquer therapy in the management of onychomycosis.

Administration, Topical↗

PubMed2000

Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States.

BACKGROUND: Recently a novel topical nail lacquer, ciclopirox solution 8%, has been approved for the treatment of onychomycosis. OBJECTIVE: This was undertaken to determine the most cost-effective treatment for the treatment of dermatophyte onychomycosis of the toes in the United States in 2000. METHODS: The nature of the problem was defined. The drug comparators were ciclopirox nail lacquer, terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A decision analytic model that reflected the manner in which pedal tinea unguium is managed was produced. Studies that have evaluated the efficacy of the nail lacquer and the oral antifungal agents for this indication were identified. Appropriate studies were used in a meta-analysis to determine the mycologic and clinical response rates when the drug comparators are used for the treatment for toe dermatophyte onychomycosis. For each drug comparator a cost of regimen analysis was carried out. This is the sum of the drug acquisition cost, the cost of medical management, and the cost of managing adverse effects. Next, the expected cost of management was calculated, disease free days were determined, and a sensitivity analysis was conducted. RESULTS: For each comparator the meta-analytic average mycologic cure (MC) rate and clinical response (CR) rates were: ciclopirox nail lacquer (MC: 52.6 +/- 4.2%, CR: 52.4 +/- 9.0%), griseofulvin (MC: 41.1 +/- 20.4%, CR: 33.7 +/- 14.1%), itraconazole (continuous) (MC: 66.3 +/- 4.2%, CR: 70.3 +/- 4.2%), itraconazole (pulse) (MC: 70.8 +/- 5.7%, CR: 73.6 +/- 4.6%), terbinafine (MC: 77.2 +/- 4.0%, CR: 75.3 +/- 2.9%), and fluconazole (MC: 65.6 +/- 7.1%, CR: 66.5 +/- 11.7%). The cost of regimen for the drug comparators was: ciclopirox nail lacquer $325.2, griseofulvin $1413.1, itraconazole (continuous) $1410.2, itraconazole (pulse) $811.7, terbinafine $890.1, and fluconazole $966.8. The cost/mycologic cure rate and expected cost/expected symptom free day were, ciclopirox nail lacquer ($618.2, 1.69), griseofulvin $3438.2, 5.3), itraconazole (continuous) ($2126.9, 3.52), itraconazole (pulse) ($1146.4, 2.01), terbinafine ($1153.0, 2.14), and fluconazole ($1473.7, 2.10). The relative cost-effectiveness was ciclopirox nail lacquer 1.00, itraconazole (pulse) 1.19, fluconazole 1.24, terbinafine 1.27, itraconazole (continuous) 2.08, and griseofulvin 3.13. Sensitivity analysis indicated that ciclopirox nail lacquer was a cost effective alternative compared with the oral regimens of terbinafine, itraconazole (continuous), and griseofulvin when clinical response rate was used as the primary efficacy parameter. CONCLUSION: Ciclopirox nail lacquer solution 8% is a recent addition to the armamentarium of therapies available to the physician and patient for the treatment of onychomycosis. The nail lacquer is a cost effective agent compared with the oral antifungal therapies, terbinafine, itraconazole, fluconazole, and griseofulvin.

Administration, Oral↗

PubMed2000

Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis.

BACKGROUND: Onychomycosis is a relatively common condition affecting toenails more than fingernails. It is caused predominantly by dermatophytes. Onychomycosis can cause pain and discomfort and has the potential to be a source of morbidity. OBJECTIVE: We evaluated the efficacy and safety of ciclopirox nail lacquer solution 8% used to treat onychomycosis of the toe in the United States and in centers worldwide. METHODS: Two identically designed, double-blind, vehicle controlled, parallel group multicenter studies were performed in the United States to evaluate the use of ciclopirox nail lacquer to treat mild to moderate toe onychomycosis caused by dermatophytes. In the first study, 223 patients were randomized to treatment (ciclopirox group: 112, vehicle group: 111), and in the second study, 237 subjects were randomized (ciclopirox group: 119, vehicle group: 118). Before randomization, patients were to have clinical features of onychomycosis in at least one great toe with positive light microscopic examination and a positive dermatophyte culture. The test material was applied daily for a period of 48 weeks to all toenails and affected fingernails, covering the entire nail plate and approximately 5 mm of surrounding skin. At baseline, subjects had between 20% to 65% area of target nail involved. Physician's assessments were carried out every 4 weeks, and mycologic evaluation and photographic planimetry using standardized photographs were performed every 12 weeks during the 48 weeks of treatment. In studies conducted outside the United States, patients were also to have clinical, microscopic, and culture evidence of onychomycosis. However, these studies included some patients infected with nondermatophyte organisms (eg, Candida species), and the area of nail involvement was generally greater than observed in the US studies. Treatment regimens also varied in the non-US studies with lacquer applications that were sometimes less frequent than the once daily treatment used in the US studies (eg, alternate day or twice weekly). In addition, the typical duration of treatment was 6 months in the non-US studies as compared with 48 weeks in the United States. Outcome measures were similar to those used in the US trials, although a non-photographic planimetric method was used to quantify disease extent. RESULTS: Data from the pivotal US trials have demonstrated that ciclopirox nail lacquer 8% topical solution is significantly more effective than placebo in the treatment of onychomycosis caused by Trichophyton rubrum, and of mild to moderate toe onychomycosis without lunula involvement. At the end of the 48-week treatment period, the mycologic cure rate (negative culture and negative light microscopy) in study I was 29% vs 11% in the ciclopirox and vehicle groups, respectively. Similarly, the mycologic cure rate for study II was 36% vs 9%, respectively. In the non-US studies, the mycologic cure rates ranged from 46.7% to 85.7%. In addition, ciclopirox nail lacquer has demonstrated a broad spectrum of activity with efficacy against Candida species and some nondermatophytes in non-US studies. Ciclopirox nail lacquer is considered extremely safe regarding causally related treatment emergent adverse-effects (TEAEs), with most TFAEs transient and localized to the site of action (eg, erythema and application site reaction). In the US studies, TFAEs were generally mild and cleared while the patient continued to use the nail lacquer. CONCLUSIONS: Studies conducted worldwide demonstrate the efficacy of ciclopirox nail lacquer for the treatment of finger and toe onychomycosis. Both controlled and open-label studies confirm the excellent safety profile of this topical therapy. Thus, the nail lacquer provides a treatment choice with a favorable benefit-to-risk ratio. With its novel mechanism of action and its topical route of administration, ciclopirox nail lacquer offers an innovative approach to the treatment of this often difficult-to-manage disease

Administration, Topical↗

PubMed2000

Screening sandflies for natural infection with Leishmania donovani, using a non-radioactive probe based on the total DNA of the parasite.

Digoxigenin-labelled total, Leishmania donovani DNA was used as a probe to detect the parasite in Indian Phlebotomus argentipes. The probe was quite sensitive, detecting as little as 0.3 pg parasite DNA, equivalent to approximately 100 parasites. Positive signals could be detected in 12 (32%) of the 38 small (two- to 30-fly) pools of the wild-caught P. argentipes investigated and in a pool of 10 laboratory-bred P. argentipes fed on a patient with post-kala-azar dermal leishmaniasis. None of the wild-caught P. papatasi, P. sergenti or Sergentomyia sp. or of the newly emerged, laboratory-bred P. argentipes investigated were positive by this probe. The results indicate that such a probe may be very useful in screening sandflies for L. donovani, and so detecting the main vectors and transmission pathways of this parasite, in India and elsewhere.

Animals↗

PubMed2000

Tinea capitis.

Tinea capitis is a common dermatophyte infection of the scalp in children. Dermatophytes are classified into three genera; tinea capitis is caused predominantly by Trichophyton or Microsporum species. On the basis of host preference and natural habitat, dermatophytes are also classified as anthropophilic, geophilic and zoophilic. The etiological agents of tinea capitis usually fall in the first and last categories. In North America, tinea capitis is now predominantly due to Trichophyton tonsurans. During the past 100 years the most common North American organism for tinea capitis was initially Microsporum canis followed later by M. audouinii. In other parts of the world the epidemiology varies. Tinea capitis is generally observed in children over the age of 6 years and before puberty, with African Americans being the most affected group. Clinical presentations are seborrheic-like scale, 'black dot' pattern, inflammatory tinea capitis with kerion and tiny pustules in the scalp. The clinical diagnosis should be confirmed by mycological examination. Wood's light examination was of value in diagnosing tinea capitis due to M. canis and M. audouinii; however, it is not helpful in T. tonsurans tinea capitis. Asymptomatic carriers may be a significant reservoir of infection and spread of spores may also involve inanimate objects. Carriers may benefit from shampooing their hair. Treatment of tinea capitis requires an oral antifungal agent. The data from the use of terbinafine, itraconazole and fluconazole are promising and suggest that these agents have an efficacy similar to griseofulvin while shortening the duration of therapy. Both griseofulvin and the newer antimycotics have a favorable adverse-effect profile and are associated with high compliance.

Antifungal Agents↗

PubMed2000

Propofol anesthesia for craniotomy: a double-blind comparison of remifentanil, alfentanil, and fentanyl.

For patients undergoing craniotomy, it is desirable to have stable and easily controllable hemodynamics during intense surgical stimulation. However, rapid postoperative recovery is essential to assess neurologic function. Remifentanil, an ultra-short-acting mu-opioid receptor agonist, may be the ideal agent to confer the above characteristics. In this prospective randomized study, we compared the hemodynamic stability, recovery characteristics, and the dose of propofol required for maintaining anesthesia supplemented with an infusion of remifentanil, alfentanil, or fentanyl in 34 patients scheduled for supratentorial craniotomy. With routine monitors in place, anesthesia was induced with propofol (2-3 mg/kg), atracurium (0.5 mg/kg), and either remifentanil (1 microg/kg), alfentanil (10 microg/kg), or fentanyl (2 micro/kg). The lungs were ventilated with O2/air to mild hypocapnia. Anesthesia was maintained with infusions of propofol (50-100 microg/kg/min) and either remifentanil (0.2 microg/kg/min), alfentanil (20 microg/kg/h), or fentanyl (2 microg/kg/h). There were no significant differences among the groups in the dose of propofol maintenance required, heart rate, or mean arterial pressure. However, the time to eye opening (minutes) was significantly shorter in the remifentanil compared to the alfentanil group (6+/-3; 21+/-14; P = 0.0027) but not the fentanyl group (15+/-9). We conclude that remifentanil is an appropriate opioid to use in combination with propofol during anesthesia for supratentorial craniotomy.

Alfentanil↗

PubMed2000

Focal cortical-subcortical calcifications (FCSCs) and epilepsy in the Indian subcontinent.

PURPOSE: A focal cortical-subcortical calcification (FCSC) is a common finding on computed tomography (CT) in individuals with focal or generalized seizures in the Indian subcontinent. We sought to determine the relation of FCSCs to epilepsy by comparing the lobe of seizure origin by electroclinical and CT evaluations and to study the nature and severity of epilepsy associated with FCSCs. METHODS: The relation of these FCSCs to epilepsy/seizures was studied in 40 patients, seen for the first time to the neurology outpatient department of a tertiary care hospital. An attempt was made to classify seizures and determine their lobe of origin based on clinical-electroencephalographic (EEG) criteria of the International League Against Epilepsy (ILAE). The clinical lobe of origin was compared with the location of the FCSC on CT scan. In addition, records of the CT unit of the same hospital were reviewed retrospecitvely, to identify cases with an FCSC and their referral diagnoses. RESULTS: Thirty-one (77.5%) patients with FCSCs were considered to have localization-related epilepsy (frontal lobe epilepsy, 20; temporal lobe epilepsy, three; parietal lobe epilepsy, one; occipital lobe epilepsy, three; and definitely localization related but having ambiguous localization features, four) based on ictal semiology and EEG studies. Other ILAE categories in the cohort included epilepsy without unequivocal focal or generalized features (four patients; 10%), isolated seizures (one patient; 2.5%), juvenile absence epilepsy (one patient; 2.5%), and insufficient data to classify epilepsy (three patients; 7.5%). Radiologic sites for FCSCs included frontal (20; 50%), temporal (six; 15%), parietal (seven; 17.5%), and occipital (seven; 17.5%). Electroclinical and radiologic data were congruent in localizing and lateralizing seizures in 22 (55%) patients. The FCSC was truly incidental in one patient with juvenile absence epilepsy. Discordance between the clinical and radiologic localizations was noted in five (12.5%) instances. Magnetic resonance imaging (MRI) did not reveal additional lesions corresponding to lobes of origin as determined by electroclinical analysis. Discordance was surmised to be a result of seizure spread from a silent region to symptomatic cortex. In 12 (30%) patients, electroclinical and radiologic congruence could not be ascertained because ictal descriptions were either inadequate or ambiguous, and EEG findings were noncontributory. Review of 4,452 CT scans of brain performed in the CT unit revealed 29 (0.65%) cases with FCSCs in individuals with nonseizure disorders, that could be labeled as incidental. CONCLUSIONS: An FCSC is an important radiologic finding in localization-related epilepsy in the Indian subcontinent. The severity of epilepsy ranges from asymptomatic cases to daily seizures.

Adolescent↗

PubMed2000

Molecular differentiation of seven Malassezia species.

A system based on PCR and restriction endonuclease analysis was developed to distinguish the seven currently recognized Malassezia species. Seventy-eight strains, including authentic culture collection strains and routine clinical isolates, were investigated for variation in the ribosomal DNA repeat units. Two genomic regions, namely, the large subunit of the ribosomal gene and the internal transcribed spacer (ITS) region, were amplified by PCR, and products were digested with restriction endonucleases. The patterns generated were useful in identification of five out of seven Malassezia species. M. sympodialis was readily distinguishable in that its ITS region yielded a 700-bp amplified fragment, whereas the other six species yielded an 800-bp fragment. M. globosa and M. restricta were very similar in the regions studied and could be distinguished only by performing a hot start-touchdown PCR on primers for the beta-tubulin gene. Primers based on the conserved areas of the Candida cylindracea lipase gene, which were used in an attempt to amplify Malassezia lipases, yielded an amplification product after annealing at 55 degrees C only with M. pachydermatis. This specific amplification may facilitate the rapid identification of this organism.

Animals↗

PubMed2000

The phosphoprotein of rabies virus is phosphorylated by a unique cellular protein kinase and specific isomers of protein kinase C.

The phosphoprotein (P) gene of rabies virus (CVS strain) was cloned and expressed in bacteria. The purified protein was used as the substrate for phosphorylation by the protein kinase(s) present in cell extract prepared from rat brain. Two distinct types of protein kinases, staurosporin sensitive and heparin sensitive, were found to phosphorylate the P protein in vitro by the cell extract. Interestingly, the heparin-sensitive kinase was not the ubiquitous casein kinase II present in a variety of cell types. Further purification of the cell fractions revealed that the protein kinase C (PKC) isomers constitute the staurosporin-sensitive kinases alpha, beta, gamma, and zeta, with the PKCgamma isomer being the most effective in phosphorylating the P protein. A unique heparin-sensitive kinase was characterized as a 71-kDa protein with biochemical properties not demonstrated by any known protein kinases stored in the protein data bank. This protein kinase, designated RVPK (rabies virus protein kinase), phosphorylates P protein (36 kDa) and alters its mobility in gel to migrate at 40 kDa. In contrast, the PKC isoforms do not change the mobility of unphosphorylated P protein. RVPK appears to be packaged in the purified virions, to display biochemical characteristics similar to those of the cell-purified RVPK, and to similarly alter the mobility of endogenous P protein upon phosphorylation. By site-directed mutagenesis, the sites of phosphorylation of RVPK were mapped at S(63) and S(64), whereas PKC isomers phosphorylated at S(162), S(210), and S(271). Involvement of a unique protein kinase in phosphorylating rabies virus P protein indicates its important role in the structure and function of the protein and consequently in the life cycle of the virus.

Animals↗

PubMed2000

The human herpesvirus 8 homolog of Epstein-Barr virus SM protein (KS-SM) is a posttranscriptional activator of gene expression.

Homologs of the Epstein-Barr virus (EBV) SM protein exist in several human and nonhuman herpesviruses. Structure and function differ significantly among these proteins. We have cloned and characterized the human herpesvirus 8 (HHV8) gene, KS-SM, which is homologous to the EBV SM and herpes simplex virus ICP27 genes, from an HHV8-infected primary effusion lymphoma. KS-SM is shown to be a posttranscriptional activator of gene expression in cotransfection studies. KS-SM activated gene expression in a gene-specific, promoter-independent manner. In particular, KS-SM enhanced the expression of KDR/flk-1, a receptor for vascular endothelial growth factor (VEGF), in cotransfection studies. Since expression of KDR/flk-1 is increased in Kaposi's sarcoma and HHV8-infected cell cultures and VEGF enhances the proliferation of HHV8-infected cells, KS-SM may play a pathogenic role in Kaposi's sarcoma.

Amino Acid Sequence↗

PubMed2000

The implications and management of drug interactions with itraconazole, fluconazole and terbinafine.

The efficacy and safety of many pharmacological agents can be adversely affected by drug interactions. However, an appreciation of the mechanisms and incidence of these interactions, together with a knowledge of the patient's medical history, means that the majority are predictable and can be managed successfully. Drug interactions involving oral antifungal agents such as itraconazole, fluconazole and terbinafine have been studied extensively and are well understood. When problems are known to arise, they can often be overcome or minimised by varying the dosage regimens, or by drug monitoring. Where certain drugs are definitely contraindicated with antifungal agents, suitable alternatives can usually be found. Clinical trials and surveillance monitoring have demonstrated that when viewed in a wider context, drug interactions do not represent a particular safety problem for the newer oral antifungal agents. An improved understanding of the drug interaction processes and appropriate control measures mean that the high benefit-to-risk ratio of these medications can be maintained.

Administration, Oral↗

PubMed2000

Open-label study to evaluate the healing rate and safety of the Profore Extra Four-Layer Bandage System in patients with venous leg ulceration.

BACKGROUND: Venous ulcers are increasing in prevalence, especially since these are observed more frequently in the elderly, and the number of individuals in this age group is becoming a larger portion of the population. OBJECTIVE: To determine the healing rate and safety of the Profore Extra Four-Layer Bandage System in the management of venous leg ulcers. METHODS: In an open-label study, patients aged 18 years or older with venous leg ulcers were treated with a high compression four-layer bandage system in which a hydrocellular dressing was placed in contact with the wound. The combination is designated the "Profore Extra Four-Layer Bandage System." Follow-up visits took place weekly unless there was heavy exudation from the ulcer or if there was marked edema of the leg at the start of the study requiring reapplication of the bandage system. RESULTS: Fifteen patients were entered into the study (men 8, women 7, mean age 66 years, mean duration of ulcers 1.3 years). Thirteen of the 15 patients completed the study, with two withdrawals. In one patient who withdrew, the ulcer became infected and required treatment with antibiotics. The other termination from the study occurred for reasons unrelated to treatment. The ulcer in this patient healed in 7 weeks. Ten of the 13 patients (77%) who completed the study, and 10 (67%) of 15, who had enrolled experienced complete (100%) healing. Healing of > 80% of the ulcers occurred in 11 of 13 patients (85%) who completed the study and in 12 (80%) of 15 enrolled patients. No patient experienced a study-related adverse event. One patient developed contact dermatitis and was later found to have stasis dermatitis. It is unclear whether the initial event was contact or stasis dermatitis. CONCLUSION: In this open-label study, a high compression system, using the Profore Extra Four-Layer Bandage with a hydrocellular dressing in contact with the wound, was found to be effective and safe for the treatment of venous leg ulcers.

Aged↗