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Biomedical subjects

G Gupta

Publications and source records attributed to G Gupta.

At least 19 recordsLinked to original sources

Comparison of military and civilian reporting rates for smallpox vaccine adverse events.

INTRODUCTION: US smallpox vaccination (SMA) started most recently in December 2002. Military and civilian personnel report adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS), a surveillance system that relies on spontaneous reports. Although reported rates of probable myo/pericarditis after SMA in the literature are similar between military personnel and civilian healthcare workers, some civilian AE reporting rates after SMA appeared higher than those in the military. OBJECTIVE: Determine if SMA-associated reporting rates are different in civilians than in the military, considering age, sex, seriousness, and expectedness of the AE, as well as self-reporting. METHODS: Numerators were SMA reports in VAERS from 12/12/02 to 3/1/04. Limitations of VAERS include underreporting and lack of diagnostic confirmation. Denominators were number of military and civilian vaccinees. RESULTS: Reporting rates stratified by age and sex of serious and non-serious AEs were significantly higher in civilian than military personnel ages <55 years (rate ratios 4-27). These rate ratios decreased with increasing age. CONCLUSIONS: Reporting rates in VAERS differed significantly and substantially in civilians compared to military personnel <55 years of age. Differences in stimulated passive surveillance systems, and AE reporting practices, including the 'threshold' for reporting most likely explain these findings. These results suggest that in the case of smallpox vaccine AEs, there may be systematic differences in reporting completeness between the civilian and military sectors, and that passive surveillance data should be interpreted with caution.

Adult↗

Novel disulphide esters of carbothioic acid as potent, non-detergent spermicides with low toxicity to Lactobacillus and HeLa cells in vitro.

BACKGROUND: The design, synthesis, characterization and evaluation of a novel series of non-detergent spermicides has led to the discovery of two unique molecules (DSE-36 and DSE-37) that were approximately 25 times more potent spermicides than nonoxynol-9 (N-9). METHODS: Normal human spermatozoa were used to assess the spermicidal activity (Sander-Cramer Assay), the effect on sperm-membrane integrity [hypo-osmotic swelling test (HOST)], supravital staining and scanning electron microscopy (SEM) and the induction of apoptosis [fluorescein isothiocyanate (FITC) Annexin-V and JC-1 labelling using flow cytometry] by the new class of compounds. HeLa and Lactobacillus cultures were used to assess the cytotoxicity of compounds and their compatibility to normal vaginal flora, respectively. RESULTS: Compounds DSE-36 and DSE-37 exhibited a strong spermicidal activity [minimum effective concentration (MEC) = 0.002%], which was approximately 25 times more potent than that of N-9 and Sapindus saponins (MEC = 0.05%). As compared with surfactants, DSE-36 and DSE-37 were found to be safer at MEC towards the growth and survival of Lactobacilli and HeLa cells in vitro and to have a milder effect on sperm plasma membrane. At EC(50) both induced apoptosis in sperm cells as characterized by increased labelling with Annexin-V and decreased polarization of sperm mitochondria. CONCLUSION: Preliminary studies have revealed that in sharp contrast to the non-specific surfactant action of N-9, DSE-36 and DSE-37 have a highly potent, mechanism-based, detrimental action on human sperm. The unique ability of these non-detergent molecules to selectively kill sperm and spare Lactobacilli and HeLa cells at MEC values much lower than that required for N-9 indicates their potential as superior ingredients for formulation into microbicidal contraceptives.

Cell Survival↗

Intraindividual, right-left comparison of topical methyl aminolaevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratoses: a multicentre, randomized controlled study.

BACKGROUND: Actinic keratosis (AK), the most common premalignant skin condition, can represent a management challenge. Treatment should not only be effective, but also well tolerated and allow for good cosmesis on typical sun-exposed highly visible body sites. OBJECTIVES: The primary objective was to compare the lesion response and subject preference for topical methyl aminolaevulinate (MAL)-photodynamic therapy (PDT) vs. cryotherapy for the treatment of AK. METHODS: In this 24-week, multicentre, randomized, intraindividual (right-left) study, subjects received both one treatment session of MAL-PDT and a double freeze-thaw cryotherapy; the treatments were randomly allocated to either side of the face/scalp. Lesions with a noncomplete response were retreated after 12 weeks. The primary assessments were the subject's overall preference and lesion response at week 24. Secondary assessments included lesion response at week 12, cosmetic outcome, subject and investigator cosmetic outcome preference at week 24, and investigator overall preference at week 24. Skin discomfort and adverse events were also evaluated. RESULTS: In total, 119 subjects with 1,501 lesions were included in the study. At week 12, treatment with MAL-PDT resulted in a significantly larger rate of cured lesions relative to cryotherapy (percentage lesion reduction from baseline: 86.9% vs. 76.2%; P < 0.001). At week 24, both treatment groups showed a high rate of cured lesions (89.1% for MAL-PDT vs. 86.1% for cryotherapy; P = 0.20; 95% confidence interval: -1.62 to 7.67). Results for subject and investigator preferences as well as cosmetic outcome favoured MAL-PDT. Both treatment regimens were safe and well tolerated. CONCLUSIONS: The present study shows that, when treated with both MAL-PDT and cryotherapy, subjects significantly prefer MAL-PDT treatment for AK. MAL-PDT is an attractive treatment option for AK, with comparable efficacy and superior cosmetic outcomes compared with double freeze-thaw cryotherapy.

Aged↗

Management of basal cell carcinoma by surveyed dermatologists in Scotland.

BACKGROUND: The British Association of Dermatologists (BAD) has produced guidelines for management of basal cell carcinoma (BCC) in the UK. OBJECTIVES: Our primary objectives were to assess the management of BCCs in Scotland and to compare it with BAD guidelines. Our secondary objectives were to audit waiting times and referral patterns. METHODS: In phase I of the audit, dermatologists in 14 centres across Scotland prospectively registered demographic and clinical data of all lesions suspected to be BCCs over a 6-week period between October and December 2000. In phase II, details of management of these lesions were evaluated by case note review. RESULTS: Of the 48 consultant dermatologists contacted, 42 took part in the survey. There were 524 clinically suspected BCCs seen in 470 patients; 164 lesions in 146 patients showed pathology other than BCC and were excluded from analysis, thus leaving 360 lesions available for analysis. There was wide variation in waiting times among Scottish dermatology centres. BCCs were equally distributed between the sexes, and lesions most commonly presented in those aged 71-80 years. A diagnostic biopsy was taken in 22% of lesions, and the rest were treated definitively after a clinical diagnosis of BCC, of which 90% were confirmed on histology. Nodulocystic lesions were the most common type of tumour, comprising 48% of lesions, and most BCCs were located on the head and neck region. Correlation of the histological type of BCC and treatment received showed that nodulocystic and morpheic BCCs were managed as recommended. There were more superficial BCCs treated with surgical excision than expected (22 of 34 lesions). Four of 21 recurrent tumours and 9 of 81 tumours on high-risk areas of the face were managed with curettage and cautery or cryotherapy, rather than surgical excision. Of the 297 excised tumours, 25 (9%) were incompletely excised. All the high-risk tumours and incompletely excised tumours were offered follow-up in the dermatology clinics. CONCLUSIONS: In general, BCCs are managed according to BAD guidelines in Scotland, but waiting times vary considerably.

Adult↗

Discovery of substituted isoxazolecarbaldehydes as potent spermicides, acrosin inhibitors and mild anti-fungal agents.

BACKGROUND: The continued endeavour to design novel, non-detergent molecules that can be useful as topical, prophylactic contraceptives has led to the discovery of substituted isoxazolecarbaldehydes as a new class of compounds exhibiting both spermicidal and acrosin inhibitory activities simultaneously. METHODS: Normal human semen samples were used to detect the spermicidal and acrosin inhibitory activities of the new compounds. Lactobacillus, HeLa and Candida cultures were used to determine the safety of compounds towards normal vaginal flora, their cytotoxicity and anti-fungal activity. Supravital staining and the hypo-osmotic swelling test (HOST) were used to detect the effect on sperm membrane integrity. Nonoxynol-9 (N-9) was used as a reference standard. RESULTS: The 5- and 3-substituted isoxazolecarbaldehydes showed significant spermicidal [minimum effective concentration (MEC)=0.005-2.5%] and acrosin inhibitory (IC50=3.9-58 x 10(-4) mol/l) activities in several molecules along with weak fungicidal activity against Candida albicans. Lineweaver-Burk and Dixon plot analysis of a representative structure showed non-competitive inhibition of human acrosin enzyme, and the most potent acrosin inhibitors also considerably diminished the induction of the acrosome reaction by Ca2+ ionophore. Some compounds were found to be significantly safer than N-9 towards Lactobacillus acidophilus in vitro at their respective spermicidal MECs. In the cytotoxicity assay, the IC50 of these compounds towards the HeLa cell line was of the same order as N-9 (0.9-0.1 mmol/l); however, in contrast, the compounds exhibited only a moderate effect on sperm membrane integrity. CONCLUSIONS: This study indicates that 5- and 3-substituted isoxazolecarbaldehydes are 'first generation' multifunctional, spermicidal molecules that hold promise for development as topical contraceptives with useful associated activities that can add considerably to their effectiveness, safety and prophylaxis.

Acrosin↗

"Bomb explosion on the Nis express" - lessons from a major incident, Kosovo 16 Feb 2001.

On Friday 16 February 2001, terrorists detonated a bomb under a civilian coach travelling from Nis in Serbia to Gracanica in Kosovo. 10 people were killed at the scene. 13 casualties were treated in the British KFOR hospital (Reynolds Hospital) in Pristina. Another 8 casualties were evacuated to the American KFOR hospital at Camp Bondsteel. The incident provided a unique opportunity for co-operation between British, American, Russian, German and French KFOR hospitals, as well as with Serbian clinicians and forensic pathologists. This article analyses the medical management of this major incident, identifies the lessons to be learned from it, and also provides enough detail for teaching scenarios.

Adolescent↗

The management of non-melanoma skin cancer.

Non-melanoma skin cancer is an increasingly common problem with a diversity of aetiologies as well as treatments. This article describes the clinical sub-groups and discusses potential management strategies as determined by best clinical practice and patients' individual needs.

Administration, Topical↗

Mechanism of action of some acrylophenones, quinolines and dithiocarbamate as potent, non-detergent spermicidal agents.

Some suitably substituted acrylophenones, quinolines and dithiocarbamate were synthesized as new generation, non-detergent spermicides and were studied for their mechanism of action in comparison with various known spermicides belonging to several different classes of chemical compound. Nonoxynol-9, benzalkonium chloride, Sapindus saponins, verapamil, emetine and tartaric acid were used as reference molecules to study the effect of new spermicides on human sperm motility parameters (using computer-assisted semen analyzer), plasma membrane integrity, lipid peroxidation and defense system against reactive oxygen species (ROS). Results have indicated that sperm plasma membrane remains the primary site of action of most of the spermicides, though the effect may be predominantly on the physiological integrity rather than the structural integrity in case of the new compounds. Lipid peroxidation may play an important role in disrupting sperm membrane physiology that may or may not be accompanied with a detrimental effect on the defense system of the human spermatozoa against the ROS.

Acrylates↗

Effect of spermicides on Lactobacillus acidophilus in vitro-nonoxynol-9 vs. Sapindus saponins.

Saponins extracted from the fruit pericarp of Sapindus mukorosii were tested for their bactericidal/bacteriostatic property against Lactobacillus acidophilus. Nonoxynol-9 was used as a reference compound for the comparison of activity. Lactobacillus colonies were grown on specific medium (Rogosa SL agar) containing different concentrations of saponins and nonoxynol-9 in an atmosphere of 5% CO2/95% air at 37 degrees C for 72 h. The number and size of colonies were recorded at the end of the experiment and compared with controls. Results indicated that nearly 90% of Lactobacillus colonies with minor reduction in size thrived at 0.05% concentration of saponins whereas only 18% of colonies with approximately 75% reduction in size grew in dishes containing 0.05% nonoxynol-9. At higher concentrations of saponins, there was a gradual, dose-dependent reduction in the number and size of colonies and at 2.5% concentration there was an approximately 55% reduction in the number and 60% reduction in the size of surviving colonies. No lactobacillus colonies, however, grew in dishes containing 0.1% and higher concentrations of nonoxynol-9. The studies indicate that Sapindus saponins as compared to nonoxynol-9 are far less toxic to lactobacillus species and therefore saponins containing spermicidal preparations are likely to be more vaginal-friendly than equivalent nonoxynol-9 preparations.

In Vitro Techniques↗

Erythrodermic syringotropic cutaneous T-cell lymphoma.

Syringotropic cutaneous T-cell lymphoma (CTCL) is a rare localized variant of CTCL, characterized histologically by eccrine gland and ductal hyperplasia surrounded by a dense syringotropic lymphocytic infiltrate. Previously reported only in men, we describe the first woman with syringotropic CTCL. Unusually, she presented with erythroderma, cutaneous nodules, poikilodermatous patches, widespread alopecia and lymphadenopathy.

Alopecia↗

Comparison of potassium titanyl phosphate vascular laser and hyfrecator in the treatment of vascular spiders and cherry angiomas.

Patients with vascular spiders and angiomas, especially on exposed sites, demonstrate considerable psychological morbidity and therefore request treatment. Traditionally, electrosurgical modalities have been used to treat such lesions, but more recently lasers have been introduced. This open study assesses the efficacy of these two treatment modalities, scoring patients' preference and psychological morbidity before and after treatment. All patients had two vascular spiders or angiomas. One lesion was randomized for treatment with the hyfrecator, whilst the other lesion was treated with the potassium titanyl phosphate (KTP) vascular laser. The end-point of the study was either clearance of lesions or a maximum of three treatments at 2-month intervals. In this first comparative study, we demonstrate that both therapeutic modalities were effective in treating these lesions and in significantly reducing the post-treatment psychological morbidity score. However, on average, only one treatment with the KTP laser was required to achieve clearance compared with two treatments with the hyfrecator. This would result in less clinic visits. In addition, patients favoured the KTP laser because of the lack of side-effects. Both the KTP vascular laser and the hyfrecator were able to clear vascular spiders and angiomas, but the KTP laser was superior as fewer treatment episodes were required and patients preferred this treatment modality because of the lack of side-effects.

Adolescent↗

Plantar warts treated with an immune response modifier: a report of two cases.

Viral warts are the most common disease of the skin and are caused by human papillomavirus (HPV). Plantar warts, a manifestation of infection by HPV-1, -2 and -4, tend to be smoother and flatter than common warts and can also be painful when pressure is applied. A variety of local treatments, including topical salicyclic acid, cryotherapy, topical 5-fluorouracil, intralesional interferons and photodynamic therapy, are available to treat plantar warts. Here we report two cases of plantar warts, which had been previously treated without success. Total clearance of the warts was observed in both cases after treatment with imiquimod 5% cream over a period of 12 weeks. No evidence of local skin reactions was observed in either case during the treatment period. Recurrent lesions were not evident in the follow-up period for each patient.

Adjuvants, Immunologic↗

Microsomal acetoxy drug: protein transacetylase of placenta: part 1. Characterization of DAMC: GST transacetylase.

We have earlier established in tissues of several mammalian animal species the existence of a novel membrane bound enzyme termed 7,8-diacetoxy-4-methylcoumarin (DAMC): protein transacetylase (TAase) that possibly transfers acetyl groups from the model acetoxy drug (DAMC) to certain enzyme protein viz. glutathione S-transferase (GST), cytochrome P-450 and NADPH cytochrome C reductase leading to the drastic modulation of their catalytic activities. We have in this report extended the studies to human tissue and characterized TAase from placenta. For this purpose placental microsomes were preincubated with DAMC along with the receptor protein (cytosolic GST) followed by the addition of the substrates of GST in order to quantify the catalytic activity of GST, the extent of inhibition of GST served as a measure of TAase. Placental TAase was also found to irreversibly activate NADPH cytochrome C reductase by DAMC. Placental enzyme activated the reductase even at very low concentration of DAMC. Iodoacetamide nearly abolished the placental TAase suggesting the presence of active thiol group in the enzyme and the TAase demonstrated hyperbolic kinetics. Kinetic constants obtained by varying the concentrations of either of the substrates DAMC or cytosolic GST characterized TAase catalysed reaction as the bimolecular reaction. Further studies are in progress to delineate the physiological importance of TAase in placenta.

Acetyltransferases↗

Phi-LOG: a domain specific language for solving phylogenetic inference problems.

Domain experts think and reason at a high level of abstraction when they solve problems in their domain of expertise. We present the design and motivation behind a domain specific language called Phi-LOG to enable biologists (domain experts) to program solutions to phylogenetic inference problems at a very high level of abstraction. The implementation infrastructure (interpreter, compiler, debugger) for the DSL is automatically obtained through a software engineering framework based on Denotational Semantics and Logic Programming.

Computer Simulation↗