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Biomedical subjects

A K Gupta

Publications and source records attributed to A K Gupta.

At least 289 records · Page 16Linked to original sources
PubMed1999

Erythroderma: a comparison between HIV positive and negative patients.

UNLABELLED: Background Erythroderma has protean underlying causes. There have been isolated case reports suggesting an association between erythroderma and the human immunodeficiency virus (HIV). OBJECTIVE: To describe and characterize further the prevalence, etiology, and metabolic sequelae of erythroderma in HIV positive and negative patients. In a subset of patients, clinicopathologic correlation was performed. METHOD: One hundred and thirty-eight consecutive patients were prospectively recruited over a one and a half year period at the skin clinic of King Edward VIII Hospital. Demographic, clinical, biochemical, and histologic data were recorded. RESULTS: Seventy-five per cent of the patients were black, 22.5% Indian, and 2.5% white. The men to women ratio was 1.9 : 1. The mean age was 34. 7 years (range, 1 month to 85 years). Forty-three per cent of patients were HIV positive, of whom 90% were black. The commonest causes of erythroderma in the total sample were atopic dermatitis (23.9%), psoriasis (23.9%), and drug reactions (22.5%). The commonest cause in the HIV positive group was drug reactions (40.6%), the commonest being ethambutol (30.8%). HIV positive patients had a significantly lower (P < 0.05) white cell count (7.6 vs. 10.5 x 109 /L), hemoglobin (11.1 vs. 12.6 g/dL), platelets (278.3 vs. 378.0 x 109 /L), and albumin (25.4 vs. 28.7 g/L) and significantly higher serum urates (0.6 vs. 0.4 mM/L) than HIV negative patients. HIV positive patients did not have a significant increase in the number of episodes of erythroderma. Clinicopathologic correlation was greatest with psoriasis in the HIV negative group and with psoriasis and drug reactions in the HIV positive group. CONCLUSIONS: A large proportion of erythrodermic patients in this study were HIV positive. Inflammatory dermatoses were the commonest cause of erythroderma in all the patients studied. Drug reactions were the commonest cause in HIV positive patients. In the young black patient, erythroderma may be a marker for HIV infection.

Adolescent↗
PubMed1999

Non-randomized comparison of surgical modalities for paranasal sinus mycoses with intracranial extension.

Mycotic infections of paranasal sinuses are frequently reported in southern Asia. Aspergillus and Mucor species are the predominant ones. Intracranial extension of paranasal sinus mycoses is a difficult problem to manage. We report 18 cases of paranasal sinus mycoses with intracranial extensions. The commonest manifestations were nasal discharge (67%), nasal obstruction (50%), ocular symptoms such as proptosis (44%), telecanthus (39%) and ophthalmoplegia. Computerized tomography scans were found to be quite informative regarding the nature and extent of the disease (100% sensitivity and 78% specificity). A combined intracranial-extracranial approach (six cases) gave a distinct advantage over only adopting an extracranial approach (12 cases). A 17% incidence of CSF leak was noted by adopting only an extracranial approach as well as a recurrence in four cases out of the 12 that were treated using this method (P < 0.05). A slight increase in morbidity was associated with the combined intracranial-extracranial treatment, but no recurrence or significant complications were noted in this approach.

Adolescent↗
PubMed1999

Pre-operative management of congenital choledochal cyst with ultrasound-guided percutaneous choledochalcystostomy.

Choledochal cyst is a rare congenital anomaly of the biliary system, presenting in infancy. Two cases of choledochal cyst (one infected) with grossly deranged liver function tests and associated biliary atresia, which were successfully managed pre-operatively by sonoguided percutaneous choledochalcystostomy, are reported here. The use of this technique in the treatment of patients such as these is proposed.

Choledochal Cyst↗
PubMed1999

Monitoring of brain metabolism during aneurysm surgery using microdialysis and brain multiparameter sensors.

The aim of the study was to monitor brain metabolism during aneurysm clipping using microdialysis and multiparameter sensors, particularly to investigate the effects of temporary clipping of vessels. Microdialysis catheters (n = 10) and Paratrend brain multiparameter (O2, CO2, pH and temperature) sensors (n = 15) were inserted into the cerebral cortex via a specially designed triple bolt prior to craniotomy. Baseline brain O2 levels ranging from 15-45 mmHg (2.0-6.0 kPa) and glucose levels from 0.5-3 mmol l-1 were stable during uneventful periods. The mean lactate/pyruvate (L/P) ratio ranged from 32 to 65 (normal < 30), indicating a tendency towards anerobic metabolism in all patients. Overall, short periods of temporary clipping (< 3 min; n = 6) were well tolerated producing no significant reduction in brain O2 (pre-clip mean 23 mmHg (3.0 kPa) vs. post-clip mean 20 mmHg (2.6 kPa)) or elevation of the L/P ratio (pre-clip mean 42 vs. post-clip mean 43). Two patients with prolonged temporary clipping showed derangements in the Paratrend parameters associated with increases in the L/P ratio. The results demonstrated that the monitored variables remained stable during uneventful procedures, including transient temporary clipping, but adverse events such as prolonged temporary clipping resulted in pronounced changes in brain metabolism. Monitoring of metabolism during aneurysm surgery may be of benefit in selected patients.

Adult↗
PubMed1999

Enhanced thermogenesis in rats by a composite Indian herbal preparation-I and its mechanism of action.

OBJECTIVE: A composite Indian herbal preparation-I (CIHP-I) containing ingredients derived from 7 different plants and asphalt was tested for its adaptogenic activity and its mechanism of action was investigated. DESIGN: CIHP-I was tested using the cold-hypoxia-restraint (C-H-R) animal model in which the restrained rats were exposed to 5 degrees C at 428 mm Hg atmospheric pressure. Rectal temperature (Trec) of the rats was continuously monitored during the exposure and the recovery periods. The time for fall of Trec to 23 degrees C and its recovery to 37 degrees C were used as indices of endurance and the adaptogenic activity. Carbohydrate and lipid parameters were investigated to find out the nature of fuel being used during thermogenesis. RESULTS: After 12 weeks of administration of an oral dose of 7.5 mg/kg(-1)/day(-1), CIHP-I was found to possess significant adaptogenic activity. CIHP-I helped improve resistance to C-H-R induced hypothermia (Trec 23 degrees C) in animals by increased mobilization of free fatty acids (FFA) from adipose tissue. Blood glucose and muscle glycogen levels were maintained. CIHP-I treatment restricted the release of creatine phosphokinase (CPK) into the circulation during C-H-R exposure. CONCLUSIONS: The results suggested that CIHP-I is a strong adaptogen. It improved cold resistance during C-H-R exposure and enhanced recovery from hypothermia. The energy-dependent cell membrane permeability was maintained. Stored lipids were mobilised and possibly used for thermogenesis in preference to carbohydrates.

Adipose Tissue↗
PubMed1999

Dynamic cerebral autoregulation during sevoflurane anesthesia: a comparison with isoflurane.

UNLABELLED: We investigated dynamic cerebral pressure autoregulation awake and during 1.5 minimum alveolar anesthetic concentration (MAC) sevoflurane or isoflurane anesthesia in 16 patients undergoing nonintracranial neurosurgical procedures. All patients received a standardized anesthetic, and their lungs were ventilated with 1.5 MAC volatile anesthetic in 100% oxygen to normocapnia. Routine monitors included electrocardiogram, pulse oximetry, end-tidal capnography, and continuous noninvasive blood pressure. In addition, middle cerebral artery blood velocity (Vmca) was measured continuously using transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was tested by inducing a rapid transient decrease in mean arterial pressure by deflation of large thigh cuffs, which were placed around both thighs and inflated to 100 mm Hg above systolic pressure. The Vmca response to the decrease in blood pressure was fitted to a series of curves to determine the rate of dynamic cerebral autoregulation (dRoR). Awake dRoR values were similar in the isoflurane and sevoflurane groups, 32 +/- 2%/s and 29 +/- 2%/s, respectively. dRoR decreased to 5 +/- 1%/s during isoflurane anesthesia but to only 24 +/- 2%/s during sevoflurane anesthesia. We conclude that dynamic cerebral autoregulation is better preserved during sevoflurane than isoflurane anesthesia in humans. IMPLICATIONS: We investigated the effect of sevoflurane and isoflurane on dynamic cerebral pressure autoregulation using transcranial Doppler ultrasonography. At 1.5 minimum alveolar anesthetic concentration, dynamic autoregulation was better preserved during sevoflurane than isoflurane anesthesia.

Adult↗
PubMed1999

Measuring brain tissue oxygenation compared with jugular venous oxygen saturation for monitoring cerebral oxygenation after traumatic brain injury.

UNLABELLED: Jugular bulb oximetry is the most widely used method of monitoring cerebral oxygenation. More recently, measurement of brain tissue oxygenation has been reported in head-injured patients. We compared the changes in brain tissue oxygen partial pressure (PbO2) with changes in jugular venous oxygen saturation (SjVO2) in response to hyperventilation in areas of brain with and without focal pathology. Thirteen patients with severe head injuries were studied. A multiparameter sensor was inserted into areas of brain with focal pathology in five patients and outside areas of focal pathology in eight patients. A fiberoptic catheter was inserted into the right jugular bulb. Patients were hyperventilated in a stepwise manner from a PaCO2 of approximately 35 mm Hg to a PaCO2 of 22 mm Hg. There was no significant change in cerebral perfusion pressure or arterial partial pressure of oxygen with hyperventilation. In areas without focal pathology, there was a good correlation between changes in SjVO2 and PbO2 (deltaSjVO2 and deltaPbO2; r2 = 0.69, P < 0.0001). In areas with focal pathology, there was no correlation between deltaSjVO, and APbO2 (r2 =0.07, P = 0.23). In this study, we demonstrated that measurement of local tissue oxygenation can highlight focal differences in regional cerebral oxygenation that are disguised when measuring SjVO2. Thus, monitoring of PbO2 is a useful addition to multimodal monitoring of patients with traumatic head injury. IMPLICATIONS: Brain oxygenation is currently monitored by using jugular bulb oximetry, which attracts a number of potential artifacts and may not reflect regional changes in oxygenation. We compared this method with measurement of brain tissue oxygenation using a multiparameter sensor inserted into brain tissue. The brain tissue monitor seemed to reflect regional brain oxygenation better than jugular bulb oximetry.

Adult↗
PubMed1999

rRNA gene internal transcribed spacer 1 and 2 sequences of asexual, anthropophilic dermatophytes related to Trichophyton rubrum.

The ribosomal region spanning the two internal transcribed spacer (ITS) regions and the 5.8S ribosomal DNA region was sequenced for asexual, anthropophilic dermatophyte species with morphological similarity to Trichophyton rubrum, as well as for members of the three previously delineated, related major clades in the T. mentagrophytes complex. Representative isolates of T. raubitschekii, T. fischeri, and T. kanei were found to have ITS sequences identical to that of T. rubrum. The ITS sequences of T. soudanense and T. megninii differed from that of T. rubrum by only a small number of base pairs. Their continued status as species, however, appears to meet criteria outlined in the population genetics-based cohesion species concept of A. R. Templeton. The ITS sequence of T. tonsurans differed from that of the biologically distinct T. equinum by only 1 bp, while the ITS sequence of the recently described species T. krajdenii had a sequence identical to that of T. mentagrophytes isolates related to the teleomorph Arthroderma vanbreuseghemii.

Arthrodermataceae↗
PubMed1999

Association with the cellular export receptor CRM 1 mediates function and intracellular localization of Epstein-Barr virus SM protein, a regulator of gene expression.

Splicing and posttranscriptional processing of eukaryotic gene transcripts are linked to their nuclear export and cytoplasmic expression. Unspliced pre-mRNAs and intronless transcripts are thus inherently poorly expressed. Nevertheless, human and animal viruses encode essential genes as single open reading frames or in the intervening sequences of other genes. Many retroviruses have evolved mechanisms to facilitate nuclear export of their unspliced mRNAs. For example, the human immunodeficiency virus RNA-binding protein Rev associates with the soluble cellular export receptor CRM 1 (exportin 1), which mediates nucleocytoplasmic translocation of Rev-HIV RNA complexes through the nuclear pore. The transforming human herpesvirus Epstein-Barr virus (EBV) expresses a nuclear protein, SM, early in its lytic cycle; SM binds RNA and posttranscriptionally activates expression of certain intronless lytic EBV genes. Here we show that both the trans-activation function and cytoplasmic translocation of SM are dependent on association with CRM 1 in vivo. SM is also shown to be associated in vivo with other components of the CRM 1 export pathway, including the small GTPase Ran and the nucleoporin CAN/Nup214. SM is shown to be present in the cytoplasm, nucleoplasm, and nuclear envelope of transfected cells. Mutation of a leucine-rich region (LRR) of SM inhibited CRM 1-mediated cytoplasmic translocation and SM activity, as did leptomycin B, an inhibitor of CRM 1 complex formation. Surprisingly, however, leptomycin B treatment and mutation of the LRR both led to SM becoming more tightly attached to intranuclear structures. These findings suggest a model in which SM is not merely a soluble carrier protein for RNA but rather is bound directly to intranuclear proteins, possibly including the nuclear pore complex.

Animals↗
PubMed1999

CCAAT/enhancer binding protein-beta trans-activates murine nitric oxide synthase 2 gene in an MTAL cell line.

Nitric oxide production by nitric oxide synthase 2 (NOS2) has been implicated in epithelial cell injury from oxidative and immunologic stress. The NOS2 gene is transcriptionally activated by lipopolysaccharide (LPS) and cytokines in medullary thick ascending limb of Henle's loop (MTAL) cells and other cell types. The 5'-flanking region of the NOS2 gene contains a consensus element for CCAAT/enhancer binding proteins (C/EBP) at -150 to -142 that we hypothesized contributes to NOS2 trans-activation in the mouse MTAL cell line ST-1. Gel shift assays demonstrated LPS + interferon-gamma (IFN-gamma) induction of C/EBP family protein-DNA complexes in nuclei harvested from the cells. Supershift assays revealed that the complexes were comprised of C/EBPbeta, but not C/EBPalpha, C/EBPdelta, or C/EBPepsilon. NOS2 promoter-luciferase genes harboring deletion or mutation of the C/EBP box exhibited lower activities in response to LPS + IFN-gamma compared with wild-type NOS2 promoter constructs. Overexpression of a C/EBP-specific dominant-negative mutant limited LPS + IFN-gamma activation of the NOS2 promoter. In trans-activation assays, overexpression of C/EBPbeta stimulated basal NOS2 promoter activity. Thus C/EBPbeta appears to be an important trans-activator of the NOS2 gene in the MTAL.

Animals↗
PubMed1999

Safety of itraconazole in diabetic patients.

BACKGROUND: Onychomycosis and dermatomycoses can result in serious complications in patients with underlying chronic diseases such as diabetes. To avoid these complications, these dermatological disorders need to be treated efficiently, for example with the triazole antifungal itraconazole. Itraconazole can inhibit the metabolism of drugs by CYP 3A4 and therefore might affect the efficacy of antidiabetic agents. OBJECTIVE: To investigate this, we assessed the safety of itraconazole in diabetic patients with onychomycosis or dermatomycoses. METHODS: We reviewed pharmacokinetic and safety data from clinical trials and postmarketing surveillance over the past 10 years. RESULTS: Postmarketing surveillance (a review of all adverse-event reports in patients receiving itraconazole concomitantly with insulin or an oral antidiabetic agent) revealed 15 reports suggestive of hyperglycemia and 9 reports suggestive of hypoglycemia; in most patients, no change in antidiabetic effect was reported. From clinical trials including a total of 189 diabetic patients treated with itraconazole for various infections (mainly systemic infections and vaginal candidiasis), only one itraconazole-related adverse event was recorded; this was a case of aggravated diabetes in a renal transplant recipient who was also receiving cyclosporine. Adverse effects due to drug-drug interactions are not expected in diabetic patients receiving oral antidiabetic agents that are not metabolized through the CYP 3A4 system (e.g. tolbutamide, gliclazide, glibenclamide, glipizide and metformin). CONCLUSION: Itraconazole can be used safely and efficiently for the treatment of dermatological disorders in diabetic patients.

Antifungal Agents↗
PubMed1999

The use of itraconazole to treat cutaneous fungal infections in children.

BACKGROUND: Cutaneous mycoses such as tinea capitis, onychomycosis and some cases of tinea corporis/cruris, and tinea pedis/manus require oral antifungal therapy. There is relatively limited data regarding the use of the newer oral antifungal agents, e.g. itraconazole, in the treatment of these mycoses in children. OBJECTIVE: We wished to determine the efficacy and safety of itraconazole continuous therapy in the management of cutaneous fungal infections in children. METHODS: Children with cutaneous mycoses were treated with itraconazole in an open-label manner in 4 studies. For tinea capitis, the treatment regimens using itraconazole continuous therapy were: study 1, 3 mg/kg/day for 4 or 8 weeks; study 2, 5 mg/kg/day for 6 weeks, and study 3, 5 mg/kg/ day for 4 weeks. In a different trial, study 4, itraconazole continuous therapy 5 mg/kg/day was used to treat toenail onychomycosis (duration: 12 weeks), tinea corporis/ cruris (duration: 1 week) and tinea pedis/manus (duration: 2 weeks). RESULTS: The efficacy rates at follow-up 12 weeks from the start of therapy in children with tinea capitis treated using the itraconazole continuous regimen were: clinical cure (CC) and mycological cure (MC) in study 1 (n = 10, Trichophyton violaceum all patients), CC 50%, MC 86%; in study 2 (n = 35, Microsporum canis 22 patients, Trichophyton sp. 12 patients), CC 82.8%, MC 80%, and in study 3 (n = 16, M. canis 11 patients, Trichophyton sp. 5 patients), (CC 66.7%, MC 78.5%. Itraconazole was also effective in the treatment of dermatomycoses in 24 children (study 4). The CC and MC rates at the follow-up 8 weeks from the start of therapy in children with dermatomycoses and 12 months in children treated for onychomycosis were: onychomycosis (n = 1, T. rubrum), CC 100%, MC 100%; tinea corporis (n = 12, M. canis 10 patients), CC 100%, MC 90%; tinea cruris (n = 3, Trichophyton sp. 2 patients), CC 100%, MC 100%; tinea manus (n = 1, T. rubrum), CC 100%, MC 100%, and tinea pedis (n = 7, T. rubrum), CC 100%, MC 100%). Adverse effects consisted of a cutaneous eruption in 1 (1.2%) of the 85 children, with mild, transient, asymptomatic elevation of liver function tests (less than twice the upper limit of normal) in 2 (3.4%) of 58 children in whom monitoring was performed. CONCLUSIONS: Itraconazole is effective and safe in the treatment of tinea capitis and other cutaneous fungal infections in children.

Antifungal Agents↗
PubMed1999

Itraconazole and terbinafine in perspective. From petri dish to patient.

This paper compares the antifungal activity and efficacy of itraconazole and terbinafine in vitro with their experimental activity and efficacy in vivo in patients with superficial fungal infections (tinea pedis and onychomycosis). Onychomycosis and tinea pedis are often treated with oral antifungals. With the introduction of newer agents, such as terbinafine and itraconazole, efficacy and safety have been improved. In vitro evaluation showed somewhat better results for terbinafine over itraconazole against dermatophytes, but in vivo results were at least equivalent. Moreover, according to ex vivo studies, itraconazole is a broad-spectrum agent with higher cure rates than terbinafine for fungal infections other than dermatophytosis (e.g., Candida infections). A meta-analysis of data from all published clinical trials comparing the efficacy and safety of terbinafine and itraconazole revealed similar high cure rates (> 70%) for both antifungal agents and similar adverse-event profiles. Both treatments were safe and well tolerated. Antifungal research has responded to the challenges of treating superficial infections by developing effective, well-tolerated, fast-acting antifungal therapies. The reduction in treatment duration also has led to improved patient compliance. The most notable difference between itraconazole and terbinafine is the 1-week pulse regimen available with itraconazole as opposed to the continuous treatment course available for terbinafine.

Administration, Oral↗
PubMed1999

Safety of itraconazole pulse therapy for onychomycosis. An update.

After experience with more than 34 million patients over 10 years, the safety of itraconazole and its potential drug-drug interactions are well known. In clinical trials, the average incidence of adverse events with a 1-week pulse regimen was 18% in pooled safety data (n = 2,867); only 2.2% of patients dropped out. In direct comparative trials, the incidence of mild and reversible adverse effects was comparable for itraconazole and terbinafine (31% and 28%, respectively) during treatment. The rate of permanent withdrawal because of adverse events was 3.6% for itraconazole and 7.5% for terbinafine (P < .05). Itraconazole was significantly better tolerated as evaluated by the investigator and patients. The analysis of the elderly subpopulation showed that patients 65 and older tolerated itraconazole pulse well, with only 20% experiencing mild and reversible side effects (total group). In direct comparative trials, itraconazole also produced fewer adverse effects than terbinafine (13% vs 32%, respectively). As newer oral antifungal agents gain widespread use, clinicians need to be aware of their potential drug-drug interactions and their possibly serious adverse events. However, pooled data from the 1-week itraconazole pulse regimen indicated a favorable safety profile, and a dose increase to 400 mg had no impact on safety.

Aged↗
PubMed1999

Onychomycosis in diabetes. Management considerations.

With exciting recent developments in the field of medical mycology and a new generation of oral antifungal agents, there has been renewed interest in the management of onychomycosis. Epidemiologic surveys report an overall disease prevalence of 2% to 13% and evidence of steadily rising incidence worldwide. Onychomycosis, beyond being a mere cosmetic nuisance, as it has been labeled historically, can be a serious infection that may have a deleterious impact on patients' overall quality of life and well-being. Across medical disciplines, onychomycosis is well recognized as being arduous both to diagnose and to manage. In addition to the importance of treating onychomycosis in the general population, there is strong clinical impetus to treat patients with concomitant conditions in order to prevent primary disease-related complications that, ultimately, can be life-threatening.

Antifungal Agents↗
PubMed1999

Management of onychomycosis in children.

Onychomycosis is less common in children than in adults. When onychomycosis is suspected, appropriate mycologic tests should be carried out for confirmation. Tinea pedis may be associated with onychomycosis. Family members also may have onychomycosis or tinea pedis. Oral antifungal therapy is required, particularly when the extent of onychomycosis is moderate or severe. The longest clinical experience with antifungal therapy is with griseofulvin, a drug that has to be administered for several months. The newer oral antifungal agents for the treatment of onychomycosis in children include itraconazole, terbinafine, and fluconazole. Pulse therapy with itraconazole given either in oral solution or capsule form, is the preferred regimen. Terbinafine (continuous) or fluconazole (intermittent) regimens are other treatment options. It is important to take steps to reduce the risk of reinfection and to treat tinea pedis at an early stage.

Adolescent↗
PubMed1999

Management of tinea capitis. A status report.

Tinea capitis is the most common pediatric fungal infection, usually affecting school-age children. It is caused by a dermatophyte from the genus Trichophyton or Microsporum. The predominant pathogens vary according to geographic location. Infection rates are higher in urban regions, especially those with overcrowded living conditions. In the United States, the incidence is highest among African-American children and appears to be significantly lower among Asian Americans. Tinea capitis may persist into adulthood, especially in females with Trichophyton tonsurans infection. Tinea capitis also has been reported in neonates, infants, and elderly patients.

Administration, Oral↗