The variable origin of the lateral circumflex femoral artery: a meta-analysis and proposal for a new classification system.

The lateral circumflex femoral artery (LCFA) is responsible for vascularisation of the head and neck of the femur, greater trochanter, vastus lateralis and the knee. The origin of the LCFA has been reported to vary significantly throughout the literature, with numerous branching patterns described and variable distances to the mid-inguinal point reported. The aim of this study was to determine the estimated population prevalence and pooled means of these anatomical characteristics, and review their associated clinical relevance. A search of the major electronic databases was performed to identify all articles reporting data on the origin of the lateral circumflex femoral artery and its distance to the mid-inguinal point. Additionally, an extensive search of the references of all relevant articles was performed. All data on origin, branching, and distance to mid-inguinal point was extracted and pooled into a meta-analysis. A total of 26 articles (n = 3731 lower limbs) were included in the meta-analysis. Lateral circumflex femoral artery most commonly originates from the deep femoral artery with a pooled prevalence of 76.1% (95% confidence interval 69.4-79.3). The deep femoral artery-derived lateral circumflex femoral artery was found to originate with a mean pooled distance of 51.06 mm (95% confidence interval 44.61-57.51 mm) from the mid-inguinal point. Subgroup analysis of both gender and limb side data were consistent with these findings. Due to variability in the lateral circumflex femoral artery's origin and distance to mid-inguinal point, anatomical knowledge is crucial for clinicians to avoid iatrogenic injuries when performing procedures in the femoral region, and thus radiographic assessment prior to surgery is recommended. Lastly, we propose a new classification system for origin of the lateral circumflex femoral artery.

An L-band monolithic InAs/InP quantum dot mode-locked laser with femtosecond pulses.

We have developed an InAs/InP quantum dot (QD) gain material using a double cap growth procedure and GaP sublayer to tune QDs into the L-band. By using it, a passive L-band mode-locked laser with pulse duration of 445 fs at the repetition rate of 46 GHz was demonstrated. The 3-dB linewidth of the RF spectrum is less than 100 KHz. The lasing threshold injection current is 24 mA with an external differential quantum efficiency of 22% and an average output power of 27 mW. The relationship between pulse duration and 3-dB spectral bandwidth as a function of injection current was investigated.

Gene expression analysis on sections of zebrafish regenerating fins reveals limitations in the whole-mount in situ hybridization method.

The caudal fin of adult zebrafish is used to study the molecular mechanisms that govern regeneration processes. Most reports of gene expression in regenerating caudal fins rely on in situ hybridization (ISH) on whole-mount samples followed by sectioning of the samples. In such reports, expression is mostly confined to cells other than those located between the dense collagenous structures that are the actinotrichia and lepidotrichia. Here, we re-examined the expression of genes by performing ISH directly on cryo-sections of regenerates. We detected expression of some of these genes in cell types that appeared to be non-expressing when ISH was performed on whole-mount samples. These results demonstrate that ISH reagents have a limited capacity to penetrate between the regenerating skeletal matrices and suggest that ISH performed directly on fin sections is a preferable method to study gene expression in fin regenerates.

Inhibition of BMP signaling during zebrafish fin regeneration disrupts fin growth and scleroblasts differentiation and function.

The zebrafish caudal fin provides a simple model to study molecular mechanisms of dermal bone regeneration. We previously showed that misexpression of Bone morphogenetic protein 2b (Bmp2b) induces ectopic bone formation within the regenerate. Here we show that in addition to bmp2b and bmp4 another family member, bmp6, is involved in fin regeneration. We further investigated the function of BMP signaling by ectopically expressing the BMP signaling inhibitor Chordin which caused: (1) inhibition of regenerate outgrowth due to a decrease of blastema cell proliferation and downregulation of msxb and msxC expression and (2) reduced bone matrix deposition resulting from a defect in the maturation and function of bone-secreting cells. We then identified targets of BMP signaling involved in regeneration of the bone of the fin rays. runx2a/b and their target col10a1 were downregulated following BMP signaling inhibition. Unexpectedly, the sox9a/b transcription factors responsible for chondrocyte differentiation were detected in the non-cartilaginous fin rays, sox9a and sox9b were not only differentially expressed but also differentially regulated since sox9a, but not sox9b, was downregulated in the absence of BMP signaling. Finally, this analysis revealed the surprising finding of the expression, in the fin regenerate, of several factors which are normally the signatures of chondrogenic elements during endochondral bone formation although fin rays form through dermal ossification, without a cartilage intermediate.

Weight loss in overweight patients maintained on atypical antipsychotic agents.

BACKGROUND: Weight gain and associated medical morbidity offset the reduction of extrapyramidal side effects associated with atypical antipsychotics. Efforts to control weight in antipsychotic-treated patients have yielded limited success. METHODS: We studied the impact of an intensive 24-week program of diet, exercise, and counseling in 17 chronically psychotic patients (10 women, seven men) who entered at high average body weight (105.0+/-18.4 kg) and body mass index (BMI) (36.6+/-4.6 kg/m(2)). A total of 12 subjects who completed the initial 24 weeks elected to participate in an additional 24-week, less intensive extension phase. RESULTS: By 24 weeks, weight-loss/patient averaged 6.0 kg (5.7%) and BMI decreased to 34.5 (by 5.7%). Blood pressure decreased from 130/83 to 116/74 (11% improvement), pulse fell slightly, and serum cholesterol and triglyceride concentrations changed nonsignificantly. With less intensive management for another 24 weeks, subjects regained minimal weight (0.43 kg). CONCLUSIONS: These findings add to the emerging view that weight gain is a major health problem associated with modern antipsychotic drugs and that labor-intensive weight-control efforts in patients requiring antipsychotic treatment yield clinically promising benefits. Improved treatments without weight-gain risk are needed.

Characterization of two new zebrafish members of the hedgehog family: atypical expression of a zebrafish indian hedgehog gene in skeletal elements of both endochondral and dermal origins.

We have characterized two new members of the Hedgehog (Hh) family in zebrafish, ihha and dhh, encoding for orthologues of the tetrapod Indian Hedgehog (Ihh) and Desert Hedgehog (Dhh) genes, respectively. Comparison of ihha and Type X collagen (col10a1) expression during skeletal development show that ihha transcripts are located in hypertrophic chondrocytes of cartilaginous elements of the craniofacial and fin endoskeleton. Surprisingly, col10a1 expression was also detected in cells forming intramembranous bones of the head and in flat cells surrounding cartilaginous structures. The expression of col10a1 in both endochondral and intramembranous bones reflects an atypical composition of the extracellular matrix of the zebrafish craniofacial skeleton. In addition, during fin ray regeneration, both ihha and col10a1 are detected in scleroblasts, osteoblast-like cells secreting the matrix of the dermal bone fin ray. The presence of cartilage markers suggests that the dermal fin ray possesses an intermediate phenotype between cartilage and bone.

Characterizing the frost sensitivity of black spruce photosynthesis during cold acclimation.

We used photosynthetic light response curves to measure and model the responses of two provenances of 3-year-old black spruce (Picea mariana (Mill.) BSP) seedlings to severe artificial frost treatments applied at 2-week intervals during cold acclimation. Black spruce seedlings responded to cold acclimation with long-term suppression of photosynthetic capacity (Amax) and apparent quantum-use efficiency (alpha'). Short-term reductions in both photosynthetic parameters following frost treatments were dependent on the extent of cold acclimation of the seedlings and the severity of the frost treatments. Large reductions in Amax in response to the frost treatments were observed in seedlings that had undergone little cold acclimation and these reductions were associated with an irreversible reduction in alpha'. Such seedlings recovered only partially during the subsequent 23 days, whereas seedlings in most other treatments showed complete recovery of Amax after 13 days. The impact of frost treatments on Amax and alpha' did not vary with seedling provenance. We propose an algorithm that predicts the combined effects of cold acclimation and severe freezing temperatures on the extent of the suppression of A(max) during autumn. The algorithm is based on (1) the maximum Amax observed during the growing season, (2) the accumulation of cold degree-days, based on a minimum nocturnal temperature < 5 degrees C, and (3) the severity of freezing temperatures during autumn. The parameters developed in the algorithm showed that cold acclimation of black spruce seedlings had a greater impact on the reduction of Amax in autumn than did the severe frost treatments. Mean Amax of seedlings subjected to artificial frosts showed a strong correlation with values predicted by the algorithm (r2 = 0.91).

Adjunctive agents in the management of chronic pain.

Chronic pain syndromes include cancer-related pain, postherpetic neuralgia, painful diabetic neuropathy, and central poststroke pain and are common in the elderly. Adjunctive (or adjuvant) analgesics, defined as drugs that do not contain acetaminophen and those not classified as nonsteroidal antiinflammatory or opioid agents, play a role in the management of chronic pain. The term "adjunctive" (or "adjuvant") is a misnomer as several of these agents may constitute first-line therapy for many chronic pain syndromes. Tricyclic antidepressants have formed the backbone of therapy for chronic neuropathic pain for years. However, the difficulty with using agents of this class, due to their clinically significant adverse-event potential, has led to the evaluation of other agents, most notably, the antiepileptic drugs. The most useful are gabapentin, carbamazepine, and lamotrigine. In selected patients, baclofen, mexiletine, and clonidine may be useful as well. Cancer-related pain may respond substantially to corticosteroids, and pain associated with bone metastases to parenteral bisphosphonates and strontium. Practitioners should consider these alternative agents when treating chronic pain.

Pet-assisted therapy in the nursing home setting: potential for zoonosis.

Pet-assisted therapy in the nursing home setting, as a vital component of the Eden Alternative or Human Habitat program, is gaining widespread recognition and implementation. Programs such as this help to improve the quality of life of nursing home residents by offsetting resident loneliness, helplessness, and boredom. However, use of companion animals (and, frequently, birds and fish) may be associated with the introduction of infectious entities that are normally uncommon in this setting (zoonosis). Examples include psittacosis, bartonellosis, toxocariasis, Capnocytophaga canimorsus, pasturellosis, Q fever, and leptospirosis, to name but a few. Hence vigilance for unusual clinical manifestations that may herald such diseases is necessary. In addition, prevention of such illnesses by routine veterinary screening of both resident and visiting companion animals is mandatory. Infection control policies and procedures geared toward management and prevention of zoonotic illnesses should be developed and implemented in all nursing homes offering pet-assisted therapy.

Pharmacokinetics and tolerability of extended-release clarithromycin.

BACKGROUND: Clarithromycin is a semisynthetic macrolide that exhibits broad-spectrum activity against gram-positive, gram-negative, and atypical respiratory tract and skin/skin structure pathogens, Mycobacterium species, and Helicobacter pylori. It is indicated for the treatment of a wide variety of respiratory and dermatologic infections in children and adults as well as prophylaxis and treatment of Mycobacterium avium complex infection and peptic ulcers due to H. pylori. OBJECTIVE: In this article, we review the results of 3 studies of the steady-state pharmacokinetic profiles of clarithromycin and 14(R)-hydroxy-clarithromycin after multiple oral once-daily doses of 500-mg extended-release (ER) clarithromycin tablets. We also review the drug tolerability in 2 phase III comparative clinical trials of immediate-release (IR) and ER clarithromycin conducted in adults with acute maxillary sinusitis (AMS) and acute exacerbation of chronic bronchitis (AECB). METHODS: In the 3 pharmacokinetic studies, multiple-dose regimens of clarithromycin IR (one 250-mg or 500-mg tablet twice daily) and clarithromycin ER (one or two 500-mg tablets once daily), administered to healthy male and female volunteers, were evaluated. The effect of administration in nonfasting versus fasting conditions was assessed as well. Tolerability information was collected from each adult patient enrolled in phase III efficacy studies conducted to support the application for US Food and Drug Administration approval for the treatment of AMS and AECB. Regimens evaluated were 500 mg IR clarithromycin tablets twice daily or 1000 mg (2 x 500 mg) ER clarithromycin tablets once daily for 7 days (AECB) or 14 days (AMS). RESULTS: Bioavailability of the ER clarithromyin tablet administered with food was equivalent to that of the reference IR tablet, based on area under the plasma concentration-time curve (AUC) for both parent compound and active metabolite. The bioavailability of the ER tablet was 30% lower (based on clarithromycin AUC) when administered under fasting versus nonfasting conditions. Compared with the IR tablet, administration of the ER tablet resulted in significantly lower (P < 0.05) clarithromycin peak plasma concentration (Cmax), delayed time to Cmax, and lower degree of concentration fluctuation, confirming its in vivo extended-release characteristics. The most frequently reported adverse events (AEs) in the phase III clinical trials were diarrhea, abnormal taste, and nausea and were generally mild or moderate. The incidence of AEs was comparable for the 2 formulations. The severity of gastrointestinal AEs was significantly less for the ER formulation than for the IR formulation (P = 0.018), as was the frequency of premature study discontinuation due to gastrointestinal AEs or abnormal taste (P = 0.004). CONCLUSIONS: The results from the 3 pharmacokinetic studies reviewed demonstrate the bioequivalence of the ER and IR formulations and support the use of this clarithromycin ER formulation in a once-daily dosing regimen in phase III clinical trials. The ER tablet should be taken with food to maximize bioavailability. The results of 2 phase III comparative clinical efficacy and safety trials of clarithromycin ER tablets versus IR tablets in AMS and AECB confirm the good tolerability of the ER formulation.

An update on the role of nitrofurans in the management of urinary tract infections.

There have been few recent reviews of the nitrofurans in the literature, and none include recently available data on the use of nitrofurazone (nitrofural) in the prevention of catheter-associated urinary tract infection (CAUTI). Nitrofurazone and nitrofurantoin are the only nitrofurans that have become established in clinical use in the 20th century. These 2 nitrofurans have remained clinically useful against a wide spectrum of gram-positive and gram-negative bacteria, including many strains of common urinary tract pathogens. Today, the primary use of nitrofurantoin is as an oral antibacterial treatment for genitourinary infections. Nitrofurazone is primarily used as a topical antibacterial agent in burns and skin grafts and recently was approved for the prophylaxis of CAUTI. The recent development of a nitrofurazone-impregnated catheter as a novel modality in the prevention of CAUTI reflects a renewed interest in the effectiveness of nitrofurans. In an era when concern about bacterial resistance to many anti-infective agents is growing, the nitrofurans have continued to be active against organisms that have developed resistance to antibacterials. The presence of multiple mechanisms of action for the nitrofurans might be expected to reduce the ability of bacteria to develop resistance. Considering that an emergence of resistance to the nitrofurans has not appreciably occurred after several decades of clinical use, the nitrofurans may be unique among common antibacterial agents in this regard.

Review of cefditoren, an advanced-generation, broad-spectrum oral cephalosporin.

BACKGROUND: Cefditoren is an advanced-generation, broad-spectrum cephalosporin antibiotic approved for the treatment of acute bacterial exacerbation of chronic bronchitis (AECB), group A beta-hemolytic streptococcal pharyngotonsillitis, and uncomplicated skin/skin structure infections in adult and adolescent patients. OBJECTIVE: This article briefly reviews the chemistry, antimicrobial activity, pharmacokinetics, efficacy, and safety of cefditoren. METHODS: Literature was identified by a MEDLINE search (January 1985 to October 2001) of the medical literature, review of the English-language literature, reference lists within these articles, as well as data presented at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. RESULTS: Cefditoren has a broad spectrum of activity against many gram-negative and gram-positive aerobes, including Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Cefditoren is stable to hydrolysis by many common beta-lactamases. Cefditoren is rapidly absorbed (time to peak plasma concentration, approximately 2-3 hours) from the gastrointestinal tract and is almost completely eliminated via renal clearance of unchanged drug. The terminal disposition half-life of the compound is approximately 0.8 to 1.3 hours. CONCLUSIONS: Cefditoren is effective in the management of AECB (in regimens of 400 mg twice daily for 10 days) and acute maxillary sinusitis, pharyngotonsillitis due to S pyogenes, and uncomplicated skin/skin structure infections (in regimens of 200 mg twice daily for 10 days). Cefditoren possesses broad activity against common pathogens of the respiratory tract and skin and is stable in the presence of numerous beta-lactamases. Its pharmacokinetic properties, in conjunction with in vitro susceptibility data, document the feasibility of twice-daily dosing.

Short-Course antimicrobial therapy for upper respiratory tract infections.

OBJECTIVE: This review examines the issues surrounding short-course antimicrobial therapy of group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis, acute (suppurative) otitis media, and acute sinusitis. BACKGROUND: Accumulating evidence suggests that short-course (ie, < or = 5 days) antimicrobial therapy may have equivalent or superior efficacy compared with traditional longer (10- to 14-day) therapies. RESULTS: In GABHS tonsillopharyngitis, short-course therapy with 6 days of amoxicillin, 4 or 5 days of various cephalosporins, and 5 days of azithromycin (10 mg/kg once daily on all 5 days in pediatric patients) are all reasonable alternatives to traditional 10-day penicillin therapy. In uncomplicated acute (suppurative) otitis media, single-dose intramuscular ceftriaxone or 3- to 5-day short-course oral antimicrobial therapy should be effective in > or = 80% of patients. However, more research is needed in children aged <2 years, since short-course therapy may not be successful in most patients in this population. In sinusitis, most short-course therapy data have involved acute maxillary disease in adult patients. Preliminary results are encouraging, but more study is needed, especially in children. CONCLUSIONS: Cost-containment in antimicrobial therapy should include consideration of short-course therapy in the management of upper respiratory tract infections.

Immediate-release oxybutynin versus tolterodine in detrusor overactivity: a population analysis.

We evaluated adherence to treatment with immediate-release (IR) oxybutynin (515 patients) and tolterodine (505 patients) for detrusor overactivity through retrospective analysis of a pharmacy claims database. Outcomes included percentage of patients continuing therapy for 6 months, medication possession ratios, and time to discontinuation of therapy. The proportion of patients continuing therapy for 6 months was statistically superior for tolterodine (32%) compared with IR oxybutynin (22%, p<0.001). Medication possession ratios were also superior for patients in the tolterodine group (medians 0.83 and 0.64, ranges 0.11-1.15 and 0.07-1.13, respectively, p<0.001). Oxybutynin was discontinued significantly earlier (mean 45 days) than tolterodine (mean 59 days, p<0.001) and was switched to another therapy more commonly than tolterodine (19% and 14%, respectively). Tolterodine was favored over oxybutynin for several measurements of patient adherence. However, less than one-third of patients continued therapy with either agent for 6 months. The clinical relevance of these differences is unknown.

Cefdinir: an expanded-spectrum oral cephalosporin.

OBJECTIVE: To review the antimicrobial activity, pharmacokinetics, clinical efficacy, and tolerability of cefdinir, an expanded-spectrum oral cephalosporin. DATA SOURCES: Literature was identified by a MEDLINE search (January 1983-November 1999) of the medical literature, review of English-language literature and bibliographies of these articles, and product information. STUDY SELECTION: Clinical efficacy data were selected from all published trials mentioning cefdinir. Additional information concerning in vitro susceptibility, safety, chemistry, and pharmacokinetic profile of cefdinir was also reviewed. DATA SYNTHESIS: Cefdinir, an oral expanded-spectrum cephalosporin, has a broad spectrum of activity against many gram-negative and -positive aerobic organisms, including Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Cefdinir is stable to hydrolysis by many common beta-lactamases. Cefdinir is rapidly absorbed from the gastrointestinal tract and is primarily eliminated via renal clearance of unchanged drug. The terminal disposition half-life of cefdinir is approximately 1.5 hours. Efficacy has been demonstrated in a number of clinical trials in adults and children with upper and lower respiratory tract infections (e.g., pharyngitis, sinusitis, acute otitis media, acute bronchitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia) and skin and skin-structure infections. The adverse event profile is similar to that of comparator agents. CONCLUSIONS: Cefdinir is a second-line alternative to first-line antimicrobial agents, with convenient once- or twice-daily dosing in the treatment of upper and lower respiratory tract infections and skin and skin-structure infections. Similar to other oral expanded-spectrum cephalosporins, cefdinir has activity against common pathogens of the respiratory tract and skin and is stable in the presence of many beta-lactamases. The clinical choice of an oral expanded-spectrum cephalosporin will be based on patient acceptance, frequency of administration, and cost.

Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin.

BACKGROUND: Oral second and third generation cephalosporins are undergoing continuing research and development in the arena of pediatric infectious disease in an attempt to fill voids created by existing agents in the quest for the "ideal" antimicrobial. This paper reviews the in vitro antimicrobial activity (pharmacodynamics) and pharmacokinetics of cefdinir, an extended spectrum oral cephalosporin, with an emphasis on those aspects relevant to the pediatric patient population. METHODS: A MEDLINE literature search was conducted for the years 1985 through 2000, identifying all English language papers examining the in vitro antimicrobial activity and human pharmacokinetics of cefdinir. Bibliographies of these papers were reviewed, as were relevant data on file with the manufacturer. DATA SYNTHESIS: Cefdinir exhibits broad range in vitro activity against Gram-positive and Gram-negative aerobes. It exhibits superior activity against Gram-positive aerobes, compared with drugs like cefixime, ceftibuten, cefuroxime and cefpodoxime. In addition it is stable to hydrolysis by many of the common betalactamases. The pharmacokinetic parameters of cefdinir in children are similar to those obtained in adults using similar milligram per m2 doses (300, 600 mg in adults = 7, 14 mg/kg in children, respectively). CONCLUSIONS: The pharmacodynamic and pharmacokinetic characteristics of cefdinir as described in this paper, as well as the results of the clinical trials program, support the use of this agent in the treatment of a wide variety of pediatric infectious diseases.

Micronized fenofibrate: a new fibric acid hypolipidemic agent.

OBJECTIVE: To review the efficacy and safety of fenofibrate in the management of hyperlipidemias. DATA SOURCES: A MEDLINE search (1974-October 1998), Current Contents search, additional references from article bibliographies, and the package insert from the manufacturer were used to identify data for evaluation. Studies evaluating fenofibrate (peer-reviewed publications, package insert data) were considered for inclusion. Abstracts and data on file with the manufacturer were not considered for inclusion. STUDY SELECTION: English-language literature was reviewed to evaluate the pharmacology, pharmacokinetics, clinical use, and tolerability of fenofibrate. Data from animals and in vitro systems were included only when necessary to explain the drug's pharmacology. DATA SYNTHESIS: Micronized fenofibrate is a fibric acid derivative approved by the Food and Drug Administration (FDA) in February 1998 for the treatment of types IV and V hyperlipidemia. Data from the peer-reviewed literature also support the use of fenofibrate in types IIa, IIb, and III hyperlipidemias. Micronized fenofibrate 67-201 mg/d is useful as monotherapy or as an adjunct to other hypolipidemics and dietary therapy. In placebo-controlled clinical trials, regular formulation fenofibrate 300-400 mg/d lowered serum triglyceride (TG) concentrations by 24-55%, total cholesterol by 9-25%, low-density lipoprotein cholesterol (LDL-C) concentrations by 6-35%, and raised high-density lipoprotein cholesterol (HDL-C) concentrations by 8-38%. Few comparative data exist regarding fenofibrate versus clofibrate and gemfibrozil. In noncomparative and comparative clinical trials, fenofibrate appeared to be well tolerated. The most common causally related adverse events were digestive, musculoskeletal, and dermatologic in nature. Concurrent use of fenofibrate and a hydroxymethylglutaryl-coenzyme A inhibitor may increase the risk of myopathy and/or rhabdomyolysis, although recent data suggest that concurrent use of fenofibrate with low-dose simvastatin or pravastatin is safe. Fenofibrate may enhance the effect of oral anticoagulants. CONCLUSIONS: Fenofibrate reduces serum TG, total cholesterol, and LDL-C, and raises HDL-C to clinically relevant degrees. Its spectrum of activity appears to exceed that recommended for types IV and V hyperlipidemia to encompass types IIa, IIb, and III hyperlipidemias as well. To this extent, it may be considered a broader-spectrum fibrate than is indicated by its FDA approval. Adverse effects of fenofibrate appear to be similar to those of other fibrates and require routine monitoring (clinical, liver function). Long-term safety data are readily available from drug registries in many countries where the product has been available for nearly two decades. Cost-effectiveness studies comparing fenofibrate with other hypolipidemics demonstrate benefits of fenofibrate over simvastatin in types IIa and IIb hyperlipidemia. The need for dosage titration of the micronized preparation from 67 mg/d upward to a final dose of 200 mg/d is also not supported by peer-reviewed literature (except in the case of renal impairment). Although preliminary data on plaque regression are encouraging, published clinical studies evaluating the impact of fenofibrate on cardiovascular morbidity and mortality are awaited. Micronized fenofibrate is worthy of formulary inclusion.

Tolterodine, a new antimuscarinic drug for treatment of bladder overactivity.

Tolterodine is a nonsubtype selective antimuscarinic agent recently approved as therapy in patients with overactive bladder with symptoms of urinary frequency, urgency, or urge incontinence. It acts by muscarinic receptor blockade in the bladder wall and detrusor muscle. Despite short terminal disposition half-lives of 2-3 and 3-4 hours for tolterodine and its active 5-hydroxy metabolite, respectively, twice/day dosing is effective due to the drug's prolonged pharmacodynamic effects. Dosage adjustment is recommended in the presence of hepatic impairment and during concurrent therapy with drugs that inhibit cytochrome P450 2D6 and 3A4 isozymes. Tolterodine significantly reduces clinically relevant end points such as number of micturitions and number of incontinence episodes/day. In general, it is superior to placebo and equivalent to oxybutynin in this regard. As might be expected from its pharmacologic profile, the principal adverse effects of the drug are anticholinergic. In clinical trials, tolterodine was tolerated significantly better than oxybutynin. Its relative merits as a first- or second-line agent for patients intolerant of oxybutynin are unclear. Until pharmacoeconomic analyses are conducted that clearly justify use of this more expensive agent, tolterodine is perhaps best reserved for patients who are intolerant of or fail oxybutynin therapy.

Substituted heterocyclic analogs as selective COX-2 inhibitors in the flosulide class.

Substituted heterocyclic analogs in the Flosulide class were investigated as potential selective cyclooxygenase-2 inhibitors. 6-(4-Ethyl-2-thiazolylthio)-5-methanesulfonamido-3H-isobe nzofuran-1-one 14 was found to be the optimal compound in the series with superior in vitro and in vivo activities.