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Significant Clinical Problem (significant + clinical_problem)
Selected AbstractsRectal Absorption of Lamotrigine Compressed TabletsEPILEPSIA, Issue 7 2000Angela K. Birnbaum Summary: Purpose: Interruption of oral drug administration poses a significant clinical problem for antiepileptic drugs that have no parenteral formulation. If a drug is absorbed rectally, rectal administration can be a useful alternative when the oral route of administration is not possible. The purpose of this study was to compare the single-dose pharmacokinetics of la-motrigine (LTG) compressed tablets after rectal and oral administration in healthy volunteers. Methods: A single LTG compressed tablet (100 mg) was administered orally and rectally to 12 volunteers in this single-dose, two-period, crossover study with a 2-week washout between doses. For rectal administration, tablets were crushed and suspended in 10 mL of water. Plasma samples were collected from 0 to 120 hr after each dose and analyzed for LTG by an HPLC method developed for this investigation. Results: LTG plasma concentrations were lower after rectal administration versus oral administration. The average area under the curve was 28.90 ± 9.5 ,g/mL/hr after rectal administration and 51.71 ± 19.2 ,g/mL/hr after oral administration. The average maximum LTG concentration was 0.53 ± 0.14 ,g/mL after rectal administration and 1.45 ± 0.35 ,g/mL after oral administration. The relative bioavailability for LTG compressed tablets was 0.63 ± 0.33 for rectal administration. There were no drug-related rashes or serious side effects. Conclusions: LTG suspension prepared from LTG compressed tablets is absorbed rectally, although not to the same extent or rate as when given orally. [source] A review of gastrointestinal foreign bodiesINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2006A. A. Ayantunde Summary Gastrointestinal tract (GIT) foreign bodies represent a significant clinical problem in the Emergency Department, causing a high degree of financial burden, morbidity and mortality. A large variety of foreign bodies are accidentally ingested or inserted into the GIT in different age groups. This a retrospective review of 38 patients who presented to the Emergency Department with GIT foreign bodies between January 2001 and December 2004. Computer database and case note search of patients' personal data, nature of the foreign objects and mode of entry to the GIT were recorded. There were 30 males and eight females (M : F ratio of 3.75:1) with an age range of 10 months to 87 years (median age 25.5 years). Foreign body ingestion/insertion was accidental in 14 patients, deliberate in 11, for anal erotism in 11 and as a result of assault in two cases. The median time before presentation was 12 h, and the mean length of hospital stay was 1.7 days. Treatment was conservative in 15 patients; five patients had gastroscopic retrieval; 15 patients underwent examination under anaesthetic, retrieval and proctosigmoidoscopy and three patients underwent laparotomy for impacted foreign bodies. GIT foreign body ingestion or insertion is common; however, majority of cases can be successfully managed conservatively. [source] Review article: visceral hypersensitivity in irritable bowel syndrome: molecular mechanisms and therapeutic agentsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009A. AKBAR Summary Background, Although development of visceral pain is an important defensive mechanism, hypersensitivity results in a significant clinical problem and is likely to be one of the major factors involved in the pathogenesis of abdominal and chest pain in functional bowel disorders (FBDs). Understanding of the molecular mechanisms involved in peripheral sensitization of visceral nociceptors has advanced as a result of the experimental studies, especially in animal models, which have led to knowledge and identification of key mediators and receptors. Aim, To provide a comprehensive review focused on the peripheral mechanisms believed to be responsible for sensitization and potential molecular targets for a disorder which is common, distressing and has sub-optimal treatment options. Methods, Literature review using Ovid and Pubmed from 1966. Results, There is substantial interest in the development of new drugs for treatment of FBDs in the background of advances in understanding the molecular and physiological mechanisms of visceral hypersensitivity. The potential drug targets include TPRV1, ASICs, voltage-gated sodium channels, ATP, PAR-2, cannabinoid, prostaglandin, tachykinin and 5HT3 receptors. Conclusion, It is anticipated that with advancing molecular understanding of the basis of visceral hypersensitivity, the next decade will see accelerated development of new molecules for treatment of functional bowel diseases. [source] The Problem of Stent Thrombosis Associated With Drug-Eluting Stents and the Optimal Duration of Dual Antiplatelet TherapyPREVENTIVE CARDIOLOGY, Issue 2 2009Susana Ayyanathan MD Drug-eluting stents have significantly reduced the problem of restenosis, but there is an association between drug-eluting stents and stent thrombosis that can be a significant clinical problem resulting in myocardial infarction or death. The risk for stent thrombosis increases in certain clinical situations and has been reduced through the use of dual antiplatelet therapy for prolonged periods. Until new therapies are developed, it is essential that patients who have had drug-eluting stents implanted continue with dual-antiplatelet therapy for at least 1 year and possibly for an indefinite period. [source] C3H/HeJ Mouse Model for Spontaneous Chronic Otitis Media,THE LARYNGOSCOPE, Issue 7 2006Carol J. MacArthur MD Abstract Objectives/Hypothesis: Chronic otitis media is a significant clinical problem. Understanding the mechanisms of chronic otitis media is critical for its control. However, little is known of these processes as a result of lack of animal models of spontaneous otitis media. The C3H/HeJ mouse has a single amino acid substitution in its toll-like receptor 4 (TLR4), making it insensitive to endotoxin. As a result, these mice cannot clear Gram-negative bacteria. The chronically inflamed middle ear in this animal provides us the opportunity to study spontaneous chronic otitis media. Study Design and Methods: Otoscopy and auditory brain response (ABR) evaluation of C3H/HeJ mice at 3, 5, 7, 9, and 11 months were carried out under sedation. At 12 months of age, mice were killed and histologic analysis of the middle ear, inner ear, and eustachian tube was carried out. Results: Tympanic membrane visualization and ABR thresholds in 7- to 8-month-old C3H/HeJ mice showed that approximately half developed middle and inner ear disease spontaneously. The significant elevation of thresholds suggested a sensorineural component in addition to the conductive loss. Middle and inner ear histology showed some degree of middle and inner ear inflammation in half the mice, paralleling the ABR data. Conclusions: The histopathologic changes reported here in the C3H/HeJ mouse model of chronic otitis media have been reported in human chronic otitis media. This spontaneous model of chronic otitis media will be valuable for the characterization of middle and inner ear inflammatory disease processes that are induced by middle ear infections. [source] Prevention of white spot lesions in orthodontic practice: a contemporary reviewAUSTRALIAN DENTAL JOURNAL, Issue 4 2006TR Sudjalim Abstract The development of white spot demineralization associated with fixed appliance orthodontic treatment is a significant clinical problem. Both established and experimental methods for prevention of such lesions in day-to-day clinical practice are presented and discussed. [source] Role of coordinated molecular alterations in the development of androgen-independent prostate cancer: an in vitro model that corroborates clinical observationsBJU INTERNATIONAL, Issue 1 2006YAN SHI OBJECTIVE To investigate the role of potential downstream targets of HER-2/neu, including the cell-cycle regulator p27, proliferation-associated protein Ki-67, apoptosis inhibitor Bcl-2, and signal-transduction molecule Akt (which is associated with cell survival), as the development of androgen-independent prostate cancer (AIPC) in patients who are initially responsive to androgen-ablation therapy (AAT) is a significant clinical problem. PATIENTS AND METHODS Earlier studies showed that high levels of HER-2/neu tyrosine kinase receptor expression as assessed by immunohistochemistry were significantly associated with the development of AIPC, and we hypothesised that HER-2/neu overexpression provides an alternative proliferative stimulus upon androgen depletion. We established a unique clinical model system, comprising patients who received no AAT, or who had preoperative AAT, or those with advanced tumours resistant to AAT. To test our hypothesis in vitro, we stably transfected full-length HER-2/neu cDNA in androgen-responsive LNCaP cells and examined the effects of HER-2/neu overexpression on cell proliferation, apoptosis, androgen-receptor activation, and Akt phosphorylation upon androgen deprivation by using immunohistochemistry and Western blot technique. RESULTS p27 expression was initially induced on exposure to AAT, and significantly decreased in AIPC (P < 0.001). There was also a significant increase in the Ki-67 index in AIPC (P = 0.001). Elevated Bcl-2 expression was closely associated with AAT (P = 0.002), suggesting that Bcl-2 expression is induced on initial exposure to AAT. Further, Bcl-2 expression was highest in hormone-resistant cancers (P < 0.001). Using the HER-2/neu transfected cell-line model, we confirmed the mechanistic basis of the clinical observations which elucidate the pathway leading to HER-2/neu-mediated androgen independence. On androgen deprivation, the HER-2/neu transfected cells had higher proliferation rates, lower G1 arrest, inhibited p27 up-regulation, a lower apoptotic index, and higher Bcl-2, prostate-specific antigen and phosphorylated Akt expression than the mock-transfected LNCaP cells. CONCLUSION This study suggests that prostate cancer cells undergo a series of coordinated changes after exposure to AAT, which eventually result in the development of androgen independence. Further, in support of previous results, it appears that a major factor in this process is the induction of HER-2/neu overexpression, which occurs after initial exposure to AAT. HER-2/neu may contribute to the development of androgen independence through: (i) maintaining cell proliferation; (ii) inhibiting apoptosis; and/or (iii) inducing AR activation in a ligand-independent fashion. These effects may be mediated, at least in part, through activation of the PI3K/Akt pathway. [source] Prospective study of open preperitoneal mesh repair for recurrent inguinal hernia,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2002M. Kurzer Background: Recurrent inguinal hernia presents a significant clinical problem with high re-recurrence and complication rates, particularly when an anterior approach is used. This study evaluated the open preperitoneal approach for repair of recurrent inguinal hernia. Methods: This was a prospective cohort study of 101 consecutive patients with 114 recurrent inguinal hernias. All were operated on using an open preperitoneal technique and prosthetic mesh by the method of Stoppa or Wantz. Follow-up was at 2,6 weeks, 15 and between 42 and 54 months. Results: There were no major complications. There was one infection and one case of retention of urine. There were no testicular complications. There were five recurrences, all within 6 months of operation, four of which were among the first 20 cases. Modifications to the original technique were made, and one recurrence occurred in the remaining 81 patients (1 per cent) or 106 hernias (1 per cent). Conclusion: Preperitoneal mesh repair gives results far superior to those of the commonly used anterior approach. It is safer and easier to learn than laparoscopic repair and is the procedure of choice for complex multirecurrent inguinal hernia. © 2002 British Journal of Surgery Society Ltd [source] Prevalence and prediction of re-experiencing and avoidance after elective surgical abortion: a prospective studyCLINICAL PSYCHOLOGY AND PSYCHOTHERAPY (AN INTERNATIONAL JOURNAL OF THEORY & PRACTICE), Issue 6 2008Arnold A. P. van Emmerik Objective: This study investigated short-term re-experiencing and avoidance after elective surgical abortion. In addition, it was prospectively investigated whether peritraumatic dissociation and pre-abortion dissociative tendencies and alexithymia predict re-experiencing and avoidance. Method: In a prospective observational design, Dutch-speaking women presenting for first trimester elective surgical abortion completed self-report measures for dissociative tendency and alexithymia. Peritraumatic dissociation was measured immediately post-abortion. Re-experiencing and avoidance were measured 2 months post-abortion. Results: Participants reported moderately elevated levels of re-experiencing and avoidance that exceeded a clinical cut-off point for 19.4% of the participants. Peritraumatic dissociation predicted intrusion and avoidance at 2 months. In addition, avoidance was predicted by the alexithymic aspect of difficulty describing feelings. Conclusions: Re-experiencing and avoidance after elective surgical abortion represent a significant clinical problem that is predicted by peritraumatic dissociation and alexithymia. Psychological screening and intervention might be a useful adjunct to elective abortion procedures.,Copyright © 2008 John Wiley & Sons, Ltd. [source] | ||||||||||