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Biomedical subjects

A K Gupta

Publications and source records attributed to A K Gupta.

At least 145 records · Page 8Linked to original sources
PubMed2002

Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent.

AIMS: Promising pre-clinical results from laboratory studies of neuro-protective drugs for the treatment of patients with stroke and head injury have not been translated into benefit during clinical trials. The objective of the study was to assess the feasibility of administrating a potential neuro-protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury in order to determine the effect of the agent on surrogate endpoints and penetration into the brain. METHODS: Multimodality monitoring including cerebral and peripheral microdialysis was applied to five head-injured patients on the neuro-intensive care unit. Chlormethiazole (0.8%) was administered as a rapid (10 ml min(-1)) intravenous loading infusion for 5 min followed by a slow (1 ml min(-1)) continuous infusion for 60 min. The following parameters were monitored: heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, continuous arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial temperature, cerebral tissue oxygen pressure, cerebral tissue carbon dioxide pressure, cerebral pH, cerebral temperature, electroencephalograph (EEG), bi-spectral index, plasma glucose, plasma chlormethiazole, and cerebral and peripheral microdialysis assay for chlormethiazole, glucose, lactate, pyruvate and amino acids. RESULTS: Despite achieving adequate plasma concentrations, chlormethiazole was not detected in the peripheral or cerebral microdialysis samples. The drug was well tolerated and did not induce hypotension, hyperglycaemia or withdrawal seizures. The drug did not change the values of the physiological or chemical parameters including levels of GABA, lactate/pyruvate ratio and glutamate. The drug did, however, induce EEG changes, including burst suppression in two patients. CONCLUSIONS: Chlormethiazole can be safely given to ventilated patients with severe head injury. There was no evidence of hypotension or withdrawal seizures. Combining a pilot clinical study of a neuro-protective agent with multimodality monitoring is feasible and, despite the lack of effect on physiological and chemical parameters in this study, may be a useful adjunct to the development of neuro-protective drugs in the future. Further investigation of the capability of microdialysis in this setting is required. By investigating the effect of a drug on surrogate end-points, it may be possible to identify promising agents from small pilot clinical studies before embarking on large phase III clinical trials.

Adult↗
PubMed2002

Measurement of liver tissue oxygenation after orthotopic liver transplantation using a multiparameter sensor. A pilot study.

The currently used methods of monitoring liver perfusion and oxygenation after liver transplantation have major limitations in clinical use. We describe the use of a multiparameter sensor to enable continuous monitoring of liver tissue oxygen tension, carbon dioxide tension and hydrogen ion concentration in the early postoperative period in 12 patients after liver transplantation. The sensor was inserted under direct vision via the falciform ligament into the liver before skin closure. Tissue oxygen tension values decreased in the first 24 h and subsequently increased to a mean (SD) = 7.3 (2.8) kPa at 48 h after surgery. This was associated with a decrease in the degree of acidosis. There were no complications attributable to the sensor. This study demonstrates that continuous measurement of liver oxygen tension, carbon dioxide tension and pH is possible. This technique may be useful as a continuous monitor to help identify grafts at risk of ischaemia.

Adult↗
PubMed2002

Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients.

BACKGROUND: One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. OBJECTIVE: To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. METHODS: Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved 'treatment success' (Global Assessment Score </= 2, erythema, pruritus, and papulation/induration/oedema scores </= 1) entered the double-blind Maintenance Phase. They continued with regular emollients and were randomized at a 2 : 1 ratio to either intermittent FP or vehicle, once daily 4 days per week for 4 weeks followed by once daily 2 days per week for 16 weeks. Subjects who relapsed on intermittent FP were discontinued from the study. Those who did not relapse continued for an additional 24 weeks on intermittent dosing for safety monitoring. RESULTS: A total of 372 (247 paediatric, 125 adult) subjects were enrolled into the Stabilization Phase. Of these, 348 (231 children, 117 adults) were randomized into the Maintenance Phase. Analysis of the primary efficacy parameter showed that subjects receiving intermittent FP cream (twice per week), in addition to regular daily emollients in the Maintenance Phase, were 7.7 times less likely to have an AD relapse than subjects receiving intermittent vehicle cream/emollients [Mantel-Haenszel (MH) estimate of the odds ratio, 95% confidence interval (CI) 4.6, 12.8; P < 0.001]. Paediatric subjects were 8.1 times less likely to have an AD relapse (95% CI 4.3, 15.2; P < 0.001) and adult subjects were 7.0 times less likely to have an AD relapse (95% CI 3.0, 16.7; P < 0.001). For subjects receiving intermittent FP cream/emollient, the median time to relapse could not be estimated as the majority remained controlled at 20 weeks. For those receiving intermittent vehicle/emollient, the median time to relapse was 4.7 weeks. For paediatric and adult groups, this was 5.1 and 4.1 weeks, respectively. Median exposure to FP for all subjects was 337 days. There was only one study drug-related adverse event (acne) and there were no reports of skin thinning or atrophy associated with the use of FP cream in paediatric or adult subjects. CONCLUSIONS: In paediatric and adult subjects, once stabilized with regular FP treatment, the risk of relapse of AD can be significantly reduced by extended intermittent dosing with FP cream in addition to regular emollient therapy.

Administration, Topical↗
PubMed2002

Pityriasis versicolor.

UNLABELLED: Pityriasis versicolor is a common superficial fungal infection of the skin. It is caused by Malassezia spp., which are normal human saprophytes. Under certain conditions, both exogenous and endogenous, the fungus can convert from a yeast to a pathogenic mycelial form. This alteration results in mild inflammation of the skin, and in characteristic clinical and histological changes. The taxonomy of Malassezia spp. has recently been modified to include six obligatorily lipophilic species, all of which can be found on human skin, plus one non-obligatorily lipophilic species, which only rarely colonizes human hosts. LEARNING OBJECTIVES: At the conclusion of this learning activity, participants should be aware of the role of Malassezia in the development of pityriasis versicolor, the clinical and histological changes arising from this dermatosis, and the diagnosis and treatment of this disorder.

Administration, Cutaneous↗
PubMed2002

Tacrolimus: a review of its use for the management of dermatoses.

The newly developed immunomodulator tacrolimus (FK506) is the first of a new class of agents that have enormous potential to change the way that dermatoses are treated and managed. Tacrolimus has been found to be active in a topical formulation with the latter exerting its effects by acting on the signal transduction pathways inside T cells and inhibiting gene transcription. The result is decreased responsiveness of T cells to antigens. Percutaneous absorption of tacrolimus is higher in diseased skin as opposed to healthy skin and, therefore, the drug will be taken in at progressively lower quantities as lesions heal. There is limited systemic absorption of tacrolimus over the course of therapy. The most extensive experience with tacrolimus has been in treating atopic dermatitis. In numerous trials, tacrolimus ointment 0.03-0.3% has shown to be effective in reducing the symptoms and severity of atopic dermatitis in adults and the paediatric population. Furthermore, there have been no significant toxic effects associated with topical therapy with tacrolimus. The most common complaint is that of local irritation after applying the ointment. This is generally transient and the patient is able to continue with therapy. The other dermatoses where tacrolimus has been used include contact dermatitis, psoriasis and pyoderma gangrenosum.

Administration, Oral↗
PubMed2002

Onychomycosis: strategies to improve efficacy and reduce recurrence.

Fungal infections may be difficult to treat for several reasons. It is important to obtain the correct diagnosis, and select the appropriate antifungal agent and route. General considerations that may be associated with recurrent infections are, a genetic predisposition and suboptimal bioavailability of drug, resulting in insufficient concentration at the target site. The aetiologic organism, the severity of disease, other coexisting diseases, concomitant drug intake, and the presence of fungal infection at other sites are some factors that determine the choice of antifungal therapy and its route of administration, oral vs. topical lacquer. Local factors such as the thickness of the nail, presence of lateral onychomycosis, longitudinal spike, dermatophytoma and severe onycholysis are some factors that may determine the choice of secondary measures such as mechanical or topical treatment. Booster or supplemental therapy may be of benefit when the response to initial treatment is poorer than expected and unlikely to result in complete response. Steps should be taken to reduce the possibility of recurrence once cure has been achieved.

Administration, Oral↗
PubMed2002

Fungicidal activities of commonly used disinfectants and antifungal pharmaceutical spray preparations against clinical strains of Aspergillus and Candida species.

The antifungal efficacy of commercial chemical disinfectants and pharmaceutical antifungal agents against medically important moulds and yeast species was investigated. Chlorine, phenol, sodium dodecyl sulfate and quaternary ammonium salts were the chemical disinfectants, and bifonazole and terbinafine were the antifungal pharmaceutical products tested against clinical isolates of Aspergillus and Candida species. Fungal inocula were obtained from conidial preparations of two A. ochraceus strains and yeast cells of C. albicans, C. krusei and C. parapsilosis. The antifungal activities were evaluated either by determining the kill rate in a cell suspension media at different contact periods, or by examining the viability and growth on plates sprayed with the active ingredient. Chlorine (1%) was the only disinfectant with the ability to cause a rapid inactivation of all five strains. Phenol (5%) was equally effective against Candida species; however, a number of A. ochraceus conidia were able to survive this treatment for up to 1 h. Benzalkonium chloride (0.5%) and cetrimide (0.5%) were also able to disinfect the three Candida species rapidly; however, these two quaternary ammonium compounds were relatively ineffective against A. ochraceus. In spray experiments, quaternary ammonium compounds had a fungicidal activity against Candida species and were fungistatic against A. ochraceus conidia. All five fungal strains were able to resist 0.5% sodium dodecyl sulfate, present either in the suspension solution or on the sprayed plate. Of the two pharmaceutical antifungal products tested, bifonazole (1%) were essentially ineffective against all five strains. Terbinafine (1%) had a fungicidal activity against A. ochraceus and C. parapsilosis. In suspension experiments, an exposure to 0.01% terbinafine required a contact period of 1 h for a complete inactivation of A. ochraceus conidia and an onset of fungicidal effect on C. parapsilosis yeast cells. Terbinafine was only moderately effective against C. albicans and was completely ineffective against C. krusei.

Antifungal Agents↗
PubMed2002

Alternate week and combination itraconazole and terbinafine therapy for chromoblastomycosis caused by Fonsecaea pedrosoi in Brazil.

Patients with long-standing chromoblastomycosis may respond poorly to standard treatments such as amphotericin B, oral antifungals, surgical measures or thermotherapy. The objective of this study was to determine the potential of alternate week and combination therapy with itraconazole and terbinafine in the treatment of poorly responsive, or non-responsive, chromoblastomycosis. Four patients with longstanding chromoblastomycosis (8-23 years) caused by Fonsecaea pedrosoi had responded poorly to standard therapies including monotherapy with the oral antifungal agents. In order to try and improve the response to oral itraconazole and terbinafine, alternate week or combination therapy with itraconazole and terbinafine was initiated. Bloodwork including complete blood count and liver function tests were performed every 3-8 weeks to ensure patient safety. Reduction or resolution of lesions of chromoblastomycosis was noted with alternate week or combination treatment using oral itraconazole and terbinafine. Three of four patients experienced no clinical side-effects; the third reported mild, transient gastric discomfort which responded to antacids. Bloodwork generally remained within normal limits throughout the entire course of treatment with no clinically significant changes. The combination therapy was considered effective in treating the poorly responsive chromoblastomycosis of all four patients. Some success with alternative week therapy was also noted in one patient. The favorable response and lack of significant adverse effects suggests that these regimens may be an option for some patients with chromoblastomycosis.

Adult↗
PubMed2002

Arachnomyces kanei (anamorph Onychocola kanei) sp. nov., from human nails.

Five isolates of a slow-growing cycloheximide resistant hyphomycetous fungus were obtained from nail specimens and investigated for their relationship to Onychocola canadensis (teleomorph Arachnomyces nodosetosus), a known agent of onychomycosis. In one patient diagnosed with superficial white onychomycosis, etiology was confirmed by a nail sample showing atypical filaments in direct microscopy, and by a follow-up specimen yielding cultures of the same fungus. A case of mixed infection with Aspergillus sydowii was also confirmed after examination of cultures grown from three successive microscopic-positive hallux nail specimens. For other isolates, etiological significance could not be confirmed by repeat sampling or results of direct microscopy were negative or unknown. Mating experiments yielded setose ascomata containing smooth oblate ascospores typical of Arachnomyces species. Phylogenetic analysis of ITS 2 region sequences support the conspecificity of the isolates and their placement within the genus. A. kanei sp. nov. (anamorph O. kanei sp. nov.) is described.

Aged↗
PubMed2002

Effect of hypothermia on brain tissue oxygenation in patients with severe head injury.

BACKGROUND: There is renewed interest in the use of induced hypothermia as a method of neuroprotection both intraoperatively and in the intensive care management of severe brain injury. In this study we have investigated the effects of hypothermia on brain tissue oxygenation in patients with severe head injury. METHODS: Thirty patients with severe head injury (Glasgow coma score <8) were monitored with a multimodal sensor inserted into the brain which measures tissue PO2, PCO2, pH and temperature in addition to routine monitoring. Patients were cooled to a minimum of 33 degrees C when clinically indicated. RESULTS: For all 30 patients brain and systemic temperature correlated well (r=0.96). Brain temperature was consistently higher than systemic temperature by 0.41 +/- 0.26 degrees C (confidence limits). Brain tissue PO2 decreased with hypothermia, with a significant reduction below 35 degrees C (P<0.05). CONCLUSIONS: These results emphasize the advantage of measuring brain temperature directly, and suggest that decreasing brain temperature below 35 degrees C may impair brain tissue oxygenation.

Adolescent↗
PubMed2002

Regression of solid tumour using laser and 5-aminolevulinic acid in mice.

Solid tumour reducing effect in Swiss albino mice induced with Dalton's Lymphoma Ascites tumour cells (DLA) and Ehrlich Ascites tumour cells (EA) was determined with the application of He-Ne and Nd:YAG lasers along with the photosensitising agent 5-Aminolevulinic acid (ALA). The experiment was designed with six groups and each group consisted of six animals. Animals in Groups I-III were injected with DLA cell lines and Groups IV-VI were injected with EA cell lines (1 x 10(6) in 0.1ml saline) subcutaneously in the right hind limb of mice to induce solid tumours. The tumour was further treated with photosensitiser induced laser therapy. The hyperthermic effect of Nd:YAG laser on tumour reduction was also evaluated. The results of the study suggest that the combination of He-Ne laser and 1 W Nd:YAG laser along with the photosensitiser 5-Aminolevulinic acid is a very effective therapeutic method for the treatment of tumour of DLA and EA cell lines. It is clear from the results that this mode of therapy very well depends on the type of tumour that has to be treated.

Aminolevulinic Acid↗
PubMed2002

Adenosine induced PR jump on surface ECG to differentiate atrioventricular nodal re-entrant tachycardia from concealed accessory pathway mediated tachycardia: a bedside test.

OBJECTIVE: To evaluate the efficacy of single dose intravenous adenosine in differentiating atrioventricular nodal re-entrant tachycardia (AVNRT) from concealed pathway mediated atrioventricular re-entrant tachycardia (AVRT) using surface ECG at the bedside. METHOD: 12 mg of adenosine was administered to 97 consecutive patients who had documented narrow QRS tachycardia without manifest pre-excitation. The test was labelled positive for AVNRT if surface ECG recordings showed signs of dual atrioventricular (AV) node physiology-namely, PR jump or AV nodal echo. The diagnostic value of this test was evaluated by electrophysiological study as the yardstick. RESULTS: The adenosine test was positive for AVNRT in 48 patients (adenosine induced PR jump in 48, AV nodal echo in 3) and negative in 49 patients. On electrophysiological study, 62 patients had AVNRT and 35 had concealed pathway mediated AVRT. Thus, the test had a sensitivity of 74% and specificity of 94%. The positive predictive value was 96% and the negative predictive value was 67%. CONCLUSION: Single dose (12 mg) intravenous adenosine administered during sinus rhythm can identify dual AV node physiology on surface ECG recording at the bedside. A positive adenosine test identified by a PR jump can differentiate AVNRT from AVRT with a high specificity and positive predictive accuracy.

Adenosine↗
PubMed2002

Increases in GABA concentrations during cerebral ischaemia: a microdialysis study of extracellular amino acids.

OBJECTIVES: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably gamma-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage. METHODS: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping. RESULTS: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005). CONCLUSIONS: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.

Adolescent↗
PubMed2002

Topical metronidazole for rosacea.

Rosacea is relatively common, typically occurring in individuals of Northern European and Celtic origin between 30 and 50 years of age. It is more common in women, but may be more severe in men. Currently there is no cure available for rosacea, but it can be controlled with topical and oral drug therapy. Topical metronidazole 1% cream is approved by the US FDA for the treatment of inflammatory lesions (papules and pustules) and erythema associated with rosacea. This treatment option is effective, safe and well tolerated.

Administration, Topical↗
PubMed2002

Infrasellar craniopharyngioma mimicking a clival chordoma: a case report.

An unusual case of entirely infrasellar craniopharyngioma mimicking a clival chordoma is described. Only 22 cases of craniopharyngioma with nasopharyngeal extension have been reported in the literature. Of the reported cases, most were primarily intracranial with secondary downward extension; only two were thought to originate from an infrasellar location. The present case is another example of an entirely infrasellar craniopharyngioma, with extensive clival destruction, mimicking a clival chordoma. Relevant literature on the subject is reviewed.

Adult↗
PubMed2002

Itraconazole (Sporanox®) for vulvovaginal candidiasis.

Vulvovaginal candidiasis is a common occurrence among women over 25 years of age. The likelihood of developing infection increases with pregnancy, the use of oral contraceptives or antibiotics, or immune disorders. However, in many cases, the etiology of the disorder is unknown. Sobel1 suggests that some cases of reinfection may actually be cases of relapse, due to either inadequate testing methods, which result in false-negative results after treatment, or to ineffective treatments. Misdiagnosis of the causative organism may also result in ineffective treatment. The most common causal Candida species is C. albicans. However, other, less easily eradicated species may also be involved.

Antifungal Agents↗
PubMed2002

Itraconazole (Sporanox®) for seborrheic dermatitis.

Seborrheic dermatitis is a common superficial dermatosis, characterized by red, flaking areas of the skin, which may in some cases be covered with yellowish flakes. The most commonly affected areas are the nasolabial folds, ears, eyebrows, scalp and chest. While seborrheic dermatitis may be easy to recognize clinically, the variability of the lesions in both appearance and location may complicate the diagnosis. Seborrheic dermatitis has been described as resembling psoriasis (in which case, the condition may be called "sebopsoriasis") and, when affecting the eyes or ears, has also been described as blepharitis and otitis, respectively. Seborrheic dermatitis tends to be chronic, though seasonal variation is common, with lesions worsening in the dry, winter months.

Antifungal Agents↗