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At least 361 records · Page 20Linked to original sources
PubMed2002

Thiazolidinediones in the treatment of type 2 diabetes.

In the last few years there has been an explosion of research that has improved our understanding of the pathogenesis of Type 2 diabetes mellitus (DM-2) and has led to the development of new oral antidiabetic drugs. Thiazolidinediones (TZDs) are the newest of these antidiabetic agents. TZDs are insulin sensitisers that depend on the presence of insulin for their action. They target insulin resistance, which is thought to play a central role in DM-2 and the associated metabolic syndrome characterised by central obesity, hypertension, dyslipidemia and hypercoagulability, all leading to increased cardiovascular morbidity and mortality. As a result, TZDs have the potential to improve other conditions associated with the metabolic syndrome, in addition to their glycaemic action. TZDs act by activating peroxisome proliferator-activated receptor (PPAR) phi a nuclear receptor implicated not only in lipid and glucose metabolism but other physiological functions as well. TZDs may have wide clinical applications beyond DM-2, as they can potentially be used to treat other conditions associated with insulin resistance and PPAR-phi receptors, such as impaired glucose tolerance, polycystic ovarian syndrome and HIV lipodystrophy.

Diabetes Mellitus, Type 2↗
PubMed2006

Genotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilities.

2-Amino-4,6-dinitrobenzoic acid (2-A-4,6-DNBA), 4-amino-2,6-dinitrobenzoic acid (4-A-2,6-DNBA), 2,4,6-trinitrobenzoic acid (2,4,6-TNBA), 2-amino-4, 6-dinitrobenzylalcohol (2-A-4,6-DNBAlc), 4-amino-2,6-dinitrobenzylalcohol (4-A-2,6-DNBAlc), 2,4-dinitrotoluol-5-sulfonic acid (2,4-DNT-5-SA), 2,4-dinitrotoluol-3-sulfonic acid (2,4-DNT-3-SA), and 2, 4-dinitrobenzoic acid (2,4-DNBA) are derivatives of nitro-explosives that have been detected in groundwater close to munitions facilities. In the present study, the genotoxicity of these compounds was evaluated in Salmonella/microsome assays (in strains TA100 and TA98, with and without S9 and in TA98NR without S9), in chromosomal aberration (CA) tests with Chinese hamster fibroblasts (V79), and in micronucleus (MN) assays with human hepatoma (HepG2) cells. All compounds except the sulfonic acids were positive in the bacterial mutagenicity tests, with 2,4,6-TNBA producing the strongest response (8023 revertants/micromol in TA98 without S9 activation). 2-A-4,6-DNBA was a direct acting mutagen in TA98, but negative in TA100. The other positive compounds were approximately 1-3 orders of magnitude less mutagenic than 2,4,6-TNBA in TA98 and in TA100; relatively strong effects ( approximately 50-400 revertants/micromol) were produced by the benzylacohols in the two indicator strains. With the exception of 2,4-DNBA, the mutagenic responses were lower in the nitroreductase-deficient strain TA98NR than in the parental strain. 2,4-DNBA produced a marginally positive response in the V79-cell CA assay; the other substances were devoid of activity. Only the benzoic acids were tested for MN induction in HepG2 cells, and all produced positive responses. As in the bacterial assays, the strongest effect was seen with 2,4,6-TNBA (significant induction at >or=1.9 microM). 4-A-2,6-DNBA was positive at 432 microM; the weakest effect was observed with 2,4,-DNBA (positive at >or=920 microM). The differences in the sensitivity of the indicator cells to these agents can be explained by differences in the activities of enzymes involved in the activation of the compounds. The strong responses produced by some of the compounds in the human-derived cells suggest that environmental exposure to these breakdown products of nitro-explosives may pose a cancer risk in man.

Animals↗
PubMed2006

Bacteriology of war wounds at the time of injury.

Bacterial contamination of war wounds occurs either at the time of injury or during the course of therapy. Characterization of the bacteria recovered at the time of initial trauma could influence the selection of empiric antimicrobial agents used to prevent infection. In the spring of 2004, U.S. military casualties who presented to the 31st Combat Support Hospital in Baghdad, Iraq, with acute traumatic injuries resulting in open wounds underwent aerobic culture of their wounds to identify the bacteria colonizing the wounds. Forty-nine casualties with 61 separate wounds were evaluated. Wounds were located predominantly in the upper and lower extremities and were primarily from improvised explosive devices or mortars. Thirty wounds (49%) had bacteria recovered on culture, with 40 bacteria identified. Eighteen casualties (20 wounds) had undergone field medical therapy (irrigation and/or antimicrobial treatment); six of these had nine bacterial isolates on culture. Of the 41 wounds from 31 patients who had received no previous therapy, 24 grew 31 bacteria. Gram-positive bacteria (93%), mostly skin-commensal bacteria, were the predominant organisms identified. Only three Gram-negative bacteria were detected, none of which were characterized as broadly resistant to antimicrobial agents. The only resistant bacteria recovered were two isolates of methicillin-resistant Staphylococcus aureus (MRSA). Our assessment of war wound bacterioly soon after injury reveals a predominance of Gram-positive organisms of low virulence and pathogenicity. The presence of MRSA in wounds likely reflects the increasing incidence of community-acquired MRSA bacteria. These data suggest that the use of broad-spectrum antibiotics with efficacy against more resistant, Gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter spp., is unnecessary in early wound management.

Anti-Bacterial Agents↗
PubMed2003

Influenza vaccination and antiviral therapy: is there a role for concurrent administration in the institutionalised elderly?

Influenza vaccination is estimated to be 50-68% efficacious in preventing pneumonia, hospitalisation or death in nursing home residents. Large culture-proven outbreaks may occur despite high resident vaccination rates. There is, therefore, a significant role for concurrent administration of influenza vaccination and antiviral therapy. The use of antiviral treatment and chemoprophylaxis requires community reporting of viral isolates, and contingency plans for rapid case identification and application of antiviral therapy. Clinicians must react quickly to control a highly infectious seasonal pathogen that may strike as an explosive outbreak. This situation is unique in geriatric practice. Current antiviral treatment should be administered within 48 hours of symptom onset, and is more efficacious if administered within 12 hours. In the case of an explosive institutional outbreak, a 1-day delay in prophylaxis may allow infection of many residents with a potentially fatal illness. Influenza must be differentiated from other respiratory viruses or syndromes. Grouped rapid diagnostic tests can aid laboratory confirmation. Antiviral agents include the M(2) inhibitors, amantadine and rimantadine, active against influenza A, and the neuraminidase inhibitors, zanamivir and oseltamivir, active against influenza A and B. In our experience, influenza B illness is as severe as influenza A. All agents have similar efficacy as treatment and prophylaxis against sensitive strains. When M(2) inhibitors are used simultaneously within an enclosed space (i.e. household or nursing home) as both treatment and prophylaxis, resistant strains may emerge that limit prophylactic efficacy. When M(2) inhibitors are administered to suspected cases (residents or staff) in institutions, precautions against secretion are especially important to diminish the risk of transmission of resistant virus. Rimantadine has been shown to have significantly fewer CNS adverse events compared with amantadine. Amantadine and oseltamivir require dosage adjustment in those with renal impairment. Oseltamivir, rimantadine and amantadine are administered by mouth, while zanamivir is administered by oral inhalation in a lactose powder. The labelling advises caution in the use of zanamivir in those with underlying airway disease. Pooled analysis of studies in patients given zanamivir indicate that individuals over the age of 50 years (at high risk for complications) and those severely symptomatic at presentation, tend to benefit most from early treatment. Neuraminidase inhibitors also diminish the need for antibacterials to treat secondary complications. An institutional programme to control influenza should include vaccination, and contingency plans for clinical surveillance, specimen processing and the rapid application of antiviral treatment and prophylaxis.

Aged↗
PubMedDate not supplied

Study of sterilizing effectivity of different ethylene oxide gaseous mixtures using CFCs and HCFCs (Oxyfume 12R and 2002R).

The use of ethylene oxide as a sterilizing agent has been frequently practiced, especially taking into account the huge variety of medical devices produced with heat sensitive materials. Mixtures of ethylene oxide and inert gases have been widely adopted in order to decrease the undesirable flammable and explosive properties of ethylene oxide. This article provides a study regarding the sterilizing effectiveness of two ethylene oxide blends: Oxyfume 2002R (using HCFCs 22 and 124) and Oxyfume 12R (using CFC 12), at different temperatures (45, 55, and 65 degrees C). To accomplish this procedure, sub-lethal challenges were performed (0, 3, 6, 9, 12, and 15 minutes) using biological indicators (obtained in the laboratory) made of Bacillus subtilis var. niger ATCC 9372. The sterilizing efficacy of both mixtures was equivalent at the gas concentration of 600 mg/L. The influence of higher temperatures was thus proved.

Antisepsis↗
PubMed1996

Too much of a good thing. Maternal and infant hyperlactation syndromes.

Milk stasis, blocked ducts, inflammatory or infectious mastitis, and breast abscess represent the spectrum of maternal hyperlactation syndrome. Management includes decreasing the rate of milk synthesis, improving milk removal out of the breast, and antibiotic therapy for ascending lactiferous duct infections and mastitis. Thriving infants who choke and splutter at the breast, feed frequently, are colicky, and have explosive, watery bowel movements have infant hyperlactation syndrome and are managed by decreasing quantity and increasing quality of breast milk drunk.

Anti-Bacterial Agents↗
PubMed1992

Update on chemical peels.

The area of chemical peeling has seen an explosion of growth and interest in the last 5 years. The use of peeling for the therapy of pigmentary dyschromias, actinic keratoses and rhytides, depressed scarring, and in selected cases, irradiation dermatitis, is amplified by the discovery of new wounding agents and new variations in technique. Appropriate growth in the objective evaluation of these agents and techniques is dependent on the demonstrative histology and the sharing of knowledge of both excellent results and significant complications in the dermatologic surgical literature.

Chemexfoliation↗
PubMed1995

Effects of heparin and hirudin on thrombin generation and platelet aggregation after intrinsic activation of platelet rich plasma.

The effects of unfractionated heparin (UH) and recombinant hirudin (rH) on prothrombin activation, free thrombin generation, and platelet aggregation induced by endogenously generated thrombin after intrinsic activation of platelet rich plasma were compared. Free thrombin generation and platelet aggregation were assessed simultaneously by delaying fibrinogen polymerisation with GPRP. UH more effectively inhibited prothrombin activation and free thrombin generation than rH. Increasing concentrations of rH had hardly any effect on the peak amount of free thrombin, while in the presence of 400 nM UH only traces of free thrombin were detected. Comparison of TAT and THC (thrombin-hirudin complex) generated until the onset of platelet aggregation on a molar basis showed that much more thrombin was inactivated in the presence of rH than in plasma containing UH. The explosive generation of free thrombin in hirudinized plasmas was accompanied by a markedly steeper aggregation curve as compared to heparinized plasmas. The generation of thromboxane B2 was markedly delayed in the presence of UH but not influenced in the presence of rH. Our results suggest that UH is more effective than rH in inhibiting prothrombin activation after intrinsic activation of platelet rich plasma, while rH prevents clotting more by direct inactivation of already generated thrombin. The inability of even high concentrations of rH to prevent the explosive generation of free thrombin might contribute to the observed inefficiency of rH to inhibit platelet aggregation.

Blood Platelets↗
PubMed1997

[Arbovirus infections. From virus, mosquitoes, animals and humans].

Arboviruses occur throughout the world in plants and animals: reptiles, birds and mammals including man. These relatively recent RNA-containing viruses have great evolutionary potential and are a major cause of epidemics. Arboviruses exhibit a dual life cycle involving continual transmission to and from the vertebrate host and arthropod vector which ingests or inoculates the agent during blood meals. Agents belong to many different viral families and represent an important source of emerging diseases. Because of the mode of transmission is vectorial, spread can enhanced by man-made changes in the ecosystem. This risk is often underestimated. The population explosion provides a great opportunity for the progression of these arboviruses.

Animals↗
PubMed1986

Surgical management of severe intractable postvagotomy diarrhoea.

Experience with the surgical management of 23 patients with postvagotomy diarrhoea is outlined. The most common pre-operative abnormalities are rapid gastric emptying (14/23) and fast small bowel transit (23/23). Three patients were found to have steatorrhoea due to organic disease. Peptic ulcer surgery performed at a young age (means = 29 years, range 21-37) appears to be the only identifiable risk factor. The results of medical treatment with bile salt binding agents were disappointing in the long term. In 10 out of 13 patients treated with antiperistaltic segments, the procedure had to be reversed because of episodes of severe postprandial colic, intestinal obstruction and bacterial overgrowth. A good result with relief of the explosive diarrhoea was obtained by the distal onlay reversed ileal graft in six out of seven patients. This procedure creates a passive non-propulsive segment, and has no undesirable sequelae. It should be considered in those patients in whom the diarrhoea is not controlled by conservative measures.

Diarrhea↗
PubMed2003

Liquid chromatography/mass spectrometric analysis of explosives: RDX adduct ions.

In liquid chromatography/mass spectrometry (LC/MS) of 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX), attachment of an anion to the analyte molecule is the major way of producing characteristic ions under electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) conditions. The formation of RDX cluster ions in LC/MS and the origin of the clustering agents have been studied. In order to determine whether the clustering anions originate from self-decomposition of RDX in the source or from impurities in the mobile phase, isotopically labeled RDX ((13)C(3)-RDX and (15)N(6)-RDX) and isotopically labeled glycolic acid, acetic acid, ammonium formate and formaldehyde have been used in order to establish the composition and formation route of RDX adduct ions produced in ESI and APCI sources. The results showed that, in ESI, self-decomposition of RDX plays no role in adduct ion formation; rather, RDX clusters with formate, acetate, hydroxyacetate, and chloride anions present in the mobile phase as impurities at ppm levels. In APCI, part of the RDX molecules decompose yielding NO(2) (-) species which in turn cluster with a second RDX molecule producing abundant [M+NO(2)](-) cluster ions.

Journal Article↗
PubMed2006

Historical approaches to post-combat disorders.

Almost every major war in the last century involving western nations has seen combatants diagnosed with a form of post-combat disorder. Some took a psychological form (exhaustion, combat fatigue, combat stress reaction and post-traumatic stress disorder), while others were characterized by medically unexplained symptoms (soldier's heart, effort syndrome, shell shock, non-ulcer dyspepsia, effects of Agent Orange and Gulf War Syndrome). Although many of these disorders have common symptoms, the explanations attached to them showed considerable diversity often reflected in the labels themselves. These causal hypotheses ranged from the effects of climate, compressive forces released by shell explosions, side effects of vaccinations, changes in diet, toxic effects of organophosphates, oil-well fires or depleted-uranium munitions. Military history suggests that these disorders, which coexisted in the civilian population, reflected popular health fears and emerged in the gaps left by the advance of medical science. While the current Iraq conflict has yet to produce a syndrome typified by medically unexplained symptoms, it is unlikely that we have seen the last of post-combat disorders as past experience suggests that they have the capacity to catch both military planners and doctors by surprise.

Combat Disorders↗
PubMed2006

Molecular imaging in cancer.

Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumor is located in the body, but also to visualize the expression and activity of specific molecules (e.g., proteases and protein kinases) and biological processes (e.g., apoptosis, angiogenesis, and metastasis) that influence tumor behavior and/or response to therapy. This information is expected to have a major impact on cancer detection, individualized treatment, and drug development, as well as our understanding of how cancer arises.

Animals↗
PubMed2002

A localised outbreak of Vibrio cholerae O139 in Kolkata, West Bengal.

BACKGROUND & OBJECTIVES: An explosive outbreak of diarrhoeal disease which occurred in the Baishnabghata, Patuli area of Kolkata Municipal Corporation during September 28 to October 12, 2000, was investigated by a team from the National Institute of Cholera and Enteric Diseases, Kolkata, to identify the causative agent and determine the antimicrobial susceptibility pattern. METHODS: Clinical and epidemiological data were collected from domiciliary cases and also from patients attending two medical camps that had been set up for the purpose. Stool and water samples were collected for isolation of diarrhoeagenic pathogens. RESULTS: A total of 710 cases of diarrhoea occurred with an attack rate of 7.1 per cent; majority were adults. All 6 faecal samples and 2 water samples collected, were positive for Vibrio cholerae O139. The strains were uniformly (100%) susceptible to the commonly used drugs for cholera such as tetracycline, norfloxacin, ciprofloxacin, co-trimoxazole and nalidixic acid but resistant (100%) to furazolidone and ampicillin. INTERPRETATION & CONCLUSION: This is the first localised outbreak of V. cholerae O139 in Kolkata since the devastating epidemic in 1992. Extensive chlorination of all water sources resulted in a dramatic decline of the outbreak. The appearance of resistance in V. cholerae O139 to furazolidone is a matter of great concern since this drug is used for the treatment of cholera in children and pregnant women.

Cholera↗
PubMed1997

Psychopharmacologic treatment of pathologic aggression.

Several drugs are apparently effective in treating pathologic anger and aggression. Because many of the studies on aggressive populations allowed the use of concomitant medications, it is unclear whether the efficacy of each drug in a particular population is dependent on the presence of other medications, such as antipsychotic agents. Finally, one needs to be circumspect in inferring efficacy of a particular drug in aggressive patients with neuropsychiatric conditions other than the ones in which some efficacy has been established. Lithium appears to be an effective treatment of aggression among nonepileptic prison inmates, mentally retarded and handicapped patients, and among conduct-disordered children with explosive behavior. Certainly, lithium would be the treatment of choice in bipolar patients with excessive irritability and anger outbursts, and it has been shown to be effective in this population. Anticonvulsant medications are the treatment of choice for patients with outbursts of rage and abnormal EEG findings. The efficacy of these drugs in patients without a seizure disorder, however, remains to be established, with the exception perhaps of valproate and carbamazepine. In fact, dyphenylhydantoin did not appear to be effective in treating aggressive behavior in children with temper tantrums and was found to be effective in only a prison population. There is some evidence for the efficacy of carbamazepine and valproate in treating pathologic aggression in patients with dementia, organic brain syndrome, psychosis, and personality disorders. As Yudofsky et al point out in their review of the literature, although traditional antipsychotic drugs have been used widely to treat aggression, there is little evidence for their effectiveness in treating aggression beyond their sedative effect in agitated patients or their antiaggressive effect among patients whose aggression is related to active psychosis. Antipsychotic agents appear to be effective in treating psychotic aggressive patients, conduct-disordered children, and mentally retarded patients, with only modest effects in the management of pathologic aggression in patients with dementia. Furthermore, at least in one study, these drugs were found to be associated with increased aggressiveness in mentally retarded subjects. On the other hand, atypical antipsychotic agents (i.e., clozapine, risperidone, and olanzapine) may be more effective than traditional antipsychotic drugs in aggressive and violent populations, as they have shown efficacy in patients with dementia, brain injury, mental retardation, and personality disorders. Similarly, benzodiazepines can reduce agitation and irritability in elderly and demented populations, but they also can induce behavioral disinhibition. Therefore, one should be careful in using this class of drugs in patients with pathologic aggression. Beta-blockers appear to be effective in many different neuropsychiatric conditions. These drugs seem effective in reducing violent and assaultive behavior in patients with dementia, brain injury, schizophrenia, mental retardation, and organic brain syndrome. As pointed out by Campbell et al in their review of the literature, however, systematic research is lacking, and little is known about the efficacy and safety of beta-blockers in children and adolescents with pathologic aggression. Although widely used in the management of pathologic aggression, the use of this class of drugs has been limited partially by marked hypotension and bradycardia, which are side effects common at the higher doses. The usefulness of the antihypertensive drug clonidine in the treatment of pathologic aggression has not been assessed adequately, and only marginal benefits were observed with this drug in irritable autistic and conduct disorder children. Psychostimulants seem to be effective in reducing aggressiveness in brain-injured patients as well as in violent adolescents with oppositional or conduct disorders, particu

Adrenergic beta-Antagonists↗
PubMed1999

Oligonucleotide Therapeutics--IBC Sixth International Conference. 3-5 May 1999, La Jolla, CA, USA.

A wide array of strategies was presented for exploiting antisense oligonucleotides (AS ONs). Vitravene (ISIS Pharmaceuticals Inc), a first-generation phosphorothioate (PS) oligodeoxynucelotide (ODN) has been approved for use in the US and European markets for the treatment of CMV retinitis. A number of pharmaceutical companies introduced numerous compounds in both phase I and pivotal phase II clinical trials, for treatment of a wide range of diseases, including cancer, inflammation and viral agents. Advances in AS ON delivery were also described, including topical and oral routes of administration. New chemical modifications incorporated into second-generation oligonucleotides demonstrated superior potency and duration of action in a number of preclinical models. Finally, in response to the explosion in new genomic sequence information generated by the Human Genome Project, a number of companies are combining bioinformatics with high-throughput screening (HTS) to rapidly discover new drug targets. As a result, there was much excitement exhibited by researchers attending this meeting and a strong feeling that this new drug paradigm is delivering on its initial promise.

Journal Article↗
PubMed1993

Detection of liquid injection using an atmospheric pressure ionization radiofrequency plasma source.

An atmospheric pressure rf plasma source which operates in a variety of different buffer gases has been developed as an ionization method for organic samples introduced by liquid injection into atmospheric pressure ionization mass spectrometry (API/MS). The rf source can operate in He at < 1 W of load power at 165 kHz. It can also be sustained in Ar, N2, air, and CO2 at a load power of < 15 W. In most cases studied, the protonated molecule, MH+, is observed with little or no fragmentation even under the relatively high current conditions of the discharge. However, using increasingly higher acceleration voltages between the skimmers in the differentially pumped region between atmospheric pressure and high vacuum, one can induce fragmentation via collision-induced dissociation. This can be assisted in these experiments via the use of a heavy buffer gas. The detection limits achieved for rf/API plasma detection are typically in the low femtomole region for small organic molecules including neurotransmitters, PTH-amino acids, steroids, drugs, pesticides, and explosives. The detection can be performed with quantitation over at least 4 orders of magnitude.

Air Ionization↗