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PubMed2001

Comparison of the efficacy of extended-release clarithromycin tablets and amoxicillin/clavulanate tablets in the treatment of acute exacerbation of chronic bronchitis.

BACKGROUND: Clarithromycin has established efficacy and safety in the treatment of respiratory infections. OBJECTIVE: This study examined the efficacy and safety of a new extended-release formulation of clarithromycin compared with amoxicillin/clavulanate in the treatment of acute exacerbation of chronic bronchitis (AECB). METHODS: This phase IIIB, multicenter, randomized, parallel-group, investigator-blinded study in patients with AECB and productive cough with purulent sputum compared treatment with extended-release clarithromycin (two 500-mg tablets once daily for 7 days) and amoxicillin/clavulanate (one 875-mg tablet twice daily for 10 days). Assessments were performed before treatment, between study days 10 and 12 (or within 48 hours after premature discontinuation), and between study days 17 and 21 (test of cure). RESULTS: Of 287 patients randomized and treated, 270 were clinically evaluable (137 clarithromycin, 133 amoxicillin/clavulanate). Treatment groups were well matched in terms of demographic characteristics, medical condition, and history. Among clinically evaluable patients at test of cure, 85% and 87% of clarithromycin- and amoxicillin/clavulanate-treated patients, respectively, demonstrated clinical cure (as defined in 1998 draft US Food and Drug Administration guidelines); among clinically and bacteriologically evaluable patients, 92% versus 89%, respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were similar in the 2 groups (88% clarithromycin, 89% amoxicillin/clavulanate). Rates of premature discontinuation of study drug for any reason differed between treatments: 3% (4/142) of clarithromycin-treated patients versus 12% (17/145) of amoxicillin/clavulanate-treated patients (P = 0.005). One percent (2/142) and 6% (8/145) of the respective treatment groups discontinued study drug because of adverse events. Adverse events generally occurred with a similar frequency in the 2 groups; however, taste alteration was more common with clarithromycin (9/142 [6%]) than with amoxicillin/clavulanate (1/145 [1%]; P = 0.01). Mean severity scores for gastrointestinal adverse events showed a significant difference between groups (1.16 for clarithromycin-treated patients and 1.58 for amoxicillin/clavulanate-treated patients: P = 0.016). CONCLUSIONS: The results of this study demonstrate the clinical and bacteriologic equivalence and improved gastrointestinal tolerability of a 7-day course of once-daily extended-release clarithromycin relative to a 10-day course of twice-daily amoxicillin/clavulanate in the treatment of AECB.

Acute Disease↗

PubMedDate not supplied

Pharmacologic and clinical comparison of cefaclor in immediate-release capsule and extended-release tablet forms.

A new controlled-delivery, extended-release 500-mg formulation of cefaclor that is administered twice daily may improve patient compliance compared with the older, immediate-release 250-mg formulation that is administered three times daily. When the extended-release tablet is administered with food, peak plasma cefaclor concentrations are achieved about 2.5 hours after the dose compared with about 1 hour after a dose with the immediate-release capsule. However, the two formulations have an equivalent extent of absorption and equivalent pharmacokinetics after absorption. Cefaclor has retained its excellent in vitro activity against the pathogens most commonly associated with acute exacerbations of chronic bronchitis, namely, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Clinical trials show similar efficacy of the two formulations in patients with acute exacerbations of chronic bronchitis caused by these organisms, but for this indication a 7-day regimen may be used with the extended-release 500-mg formulation compared with a 10-day dosing regimen with the 250-mg capsule. The shorter course of treatment with the new formulation may also improve patient compliance.

Bronchitis↗

PubMed1979

Complications associated with extended wear of soft contact lenses.

The major complications with extended wear lenses are due to hypoxia and lens deposits. Certain patients tend to deposit proteins and lipids on the lens surface with daily wear and at a greater frequency during prolonged wear. A build-up of these deposits can be associated with decreased vision, conjunctival irritation, and giant papillary conjunctivitis. Frequent lens cleaning and the frequent use of concomitant topical artificial tears will hopefully reduce the incidence of lens deposits and their complications. Superficial circumlimbal vascularization occurs in a large percentage of patients who have worn lenses for weeks at a time. Corneal edema, ocular irritation, and decreased vision are also the hallmarks of a decreased oxygen supply to the cornea. A thin-loose-fitting lens will increase the percentage of patients who are able to successfully use extended wear lenses by increasing the amount of oxygen available to the cornea. Cessation or reduction in duration of lens wear will decrease the frequency and severity of this complication. Conjunctival and corneal infections are real risks; lens loss, breakage, deformation, or discoloration also occur during extended wear.

Calcium↗

PubMed1983

Myopic extended wear with the Hydrocurve II soft contact lens.

One thousand ninety-nine patients were fitted by 42 investigators with a Hydrocurve II-55% contact lens for myopia extended wear. Five hundred thirty-three patients (48%) have successfully worn the lenses for 3 1/2 years. The major reasons for discontinuing extended wear were due to lack of interest or discontinuance of follow-up visits. Ninety-eight percent of all patients achieved a corrected acuity of better or equal to 20/30; 84% achieved an acuity better than or equal to 20/20. There was no permanent change in visual acuity in any patient during the study. Ocular complications forced 6.4% of patients to discontinue the study. It is clear from the results of this study that myopic extended wear is highly successful.

Adolescent↗

PubMed2002

Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression?

BACKGROUND: Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment. A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension. METHOD: Fifty outpatient volunteers aged 18-65 from Seattle and Portland with moderate-marked depression received fluoxetine (20 mg) doubled at 6 weeks if needed; half took clonazepam (0.5 mg) and half took an identical placebo, 1 or 2 tablets adjusted during the first 2 weeks, until a 3-week taper at 3 months. RESULTS: No serious adverse events and no special problems with sedation or discontinuation were noted. Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D (t=2.03, df=48, P<0.05) and CGI-I (32 vs. 4% responders, P<0.03, Fisher Exact Test) but not otherwise. Cotherapy was effective in reducing insomnia but not anxiety or core symptoms (low mood, suicidality, reduced interest). The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76% after 8 weeks compared to 16 weeks for monotherapy. LIMITATIONS: Small sample size (N=50) limited power and rendered conclusions tentative. CONCLUSIONS: Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed outpatients: it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase. Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated.

Administration, Oral↗

PubMed2002

Dopamine- and cyclic AMP-regulated phosphoprotein-immunoreactive neurons activated by acute stress are innervated by fiber terminals immunopositive for pituitary adenylate cyclase-activating polypeptide in the extended amygdala in the rat.

The bed nuclei of the stria terminalis (BST) and the central nucleus of the amygdala are highly heterogeneous structures, which form one functional unit, the so-called extended amygdala. Several studies described increased c-fos expression following acute stress in this brain area, confirming its central role in the modulation/regulation of stress responses. The oval nucleus of the BST and the central amygdala exhibit a dense network of pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive (ir) fiber terminals. In addition, several dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive neurons were also observed here. Because the extended amygdala plays an important role in the central autonomic regulation during stress and the distribution of PACAP-ir and that of DARPP-32-ir nervous structures overlap, the aims of this study were to investigate the possible activation of DARPP-32-ir neurons following acute systemic stress and to demonstrate synaptic interactions between DARPP-32-ir neurons and fiber terminals immunopositive for PACAP.In summary, this study provided morphological evidence that acute stress resulted in the activation of DARPP-32 neurons, which were innervated by PACAP-ir neuronal structures in the extended amygdala. Furthermore, interaction between neuropeptides/neurotransmitters and phosphoproteins was also demonstrated.

Amygdala↗

PubMed2000

The DNA-binding domain of the gene regulatory protein AreA extends beyond the minimal zinc-finger region conserved between GATA proteins.

The AreA protein of Aspergillus nidulans regulates the activity of over 100 genes involved in the utilisation of nitrogen, and has a limited region of homology with the vertebrate family of GATA proteins around a zinc finger (Zf) motif. A 66 amino acid (a.a.) residue fragment (Zf(66)) corresponding to the zinc finger, a 91 a.a fragment (Zf(91)) containing an additional 25 a.a. at the C-terminus, and a much larger 728 a.a. sequence (3'EX) corresponding to the 3'exon have been over-expressed as fusion proteins in E. coli and purified. The DNA-protein complexes formed by these proteins have been examined by gel retardation analysis. The 91 a.a. protein forms a discrete shifted species with a GATA-containing DNA fragment with high affinity (K(d)=0.15 nM), whereas the 66 a.a. protein has very low ( approximately microM) affinity for the same sequence. The results show that the region of AreA required for high affinity DNA binding extends beyond the zinc finger motif that is homologous to GATA-1, requiring in addition a region within the 25 a.a. sequence C-terminal to the zinc finger. Using hydroxyl radical and ethylation interference footprinting, the minimal Zinc finger protein (Zf(66)) shows no appreciable interference effects whereas Zf(91) shows much stronger interference effects, identical to those of the larger protein. These effects extend over sequences up to two nucleotides either side of the GATA site, and indicate contacts additional to those observed in the three-dimensional structure of the complex of the minimal zinc-finger protein with DNA. We suggest that these additional contacts are responsible for the enhanced DNA binding affinity of the extended zinc-finger protein Zf(91).

Amino Acid Sequence↗

PubMed2001

Extending Fitts' law to a three-dimensional pointing task.

An attempt was made to extend Fitts' law to a three-dimensional movement (pointing) task to enhance its predictive performance in this domain. An experiment was conducted in which 10 subjects performed three-dimensional pointing movements under the manipulation of target size, distance to target and direction to target. As expected, the duration of these three-dimensional movements was rather variable and affected markedly by direction to target. As a result, the variance in the movement times produced was not satisfactorily explained by the conventional Fitts' model. The conventional model was extended by incorporating a directional parameter into the model. The extended model was shown to better fit the data than the conventional Fitts' model, both in terms of r(2) and the standard error of the residual between the measured movement time and the value predicted by model fit.

Adult↗

PubMed1999

Extended recombinant bacterial ghost system.

Controlled expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts from a variety of bacteria are used as non-living candidate vaccines. In the recombinant ghost system, foreign proteins are attached on the inside of the inner membrane as fusions with specific anchor sequences. Ghosts have a sealed periplasmic space and the export of proteins into this space vastly extends the capacity of ghosts or recombinant ghosts to function as carriers of foreign antigens. In addition, S-layer proteins forming shell-like self assembly structures can be expressed in candidate vaccine strains prior to E-mediated lysis. Such recombinant S-layer proteins carrying foreign epitopes further extend the possibilities of ghosts as carriers of foreign epitopes. As ghosts have inherent adjuvant properties, they can be used as adjuvants in combination with subunit vaccines. Subunits or other ligands can also be coupled to matrixes like dextran which are used to fill the internal lumen of ghosts. Oral, aerogenic or parenteral immunization of experimental animals with recombinant ghosts induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in this production. This fact explains the superior quality of ghosts when compared to other inactivated vaccines. The endotoxic component of the outer membrane does not limit the use of ghosts as vaccine candidates but triggers the release of several potent immunoregulatory cytokines. As carriers, there is no limitation in the size of foreign antigens that can be inserted in the membrane and the capacity of all spaces including the membranes, peri-plasma and internal lumen of the ghosts can be fully utilized. This extended recombinant ghost system represents a new strategy for adjuvant free combination vaccines.

Adjuvants, Immunologic↗

PubMed2005

Using an image-extended relational database to support content-based image retrieval in a PACS.

This paper presents a new Picture Archiving and Communication System (PACS), called cbPACS, which has content-based image retrieval capabilities. The cbPACS answers range and k-nearest- neighbor similarity queries, employing a relational database manager extended to support images. The images are compared through their features, which are extracted by an image-processing module and stored in the extended relational database. The database extensions were developed aiming at efficiently answering similarity queries by taking advantage of specialized indexing methods. The main concept supporting the extensions is the definition, inside the relational manager, of distance functions based on features extracted from the images. An extension to the SQL language enables the construction of an interpreter that intercepts the extended commands and translates them to standard SQL, allowing any relational database server to be used. By now, the system implemented works on features based on color distribution of the images through normalized histograms as well as metric histograms. Metric histograms are invariant regarding scale, translation and rotation of images and also to brightness transformations. The cbPACS is prepared to integrate new image features, based on texture and shape of the main objects in the image.

Information Storage and Retrieval↗

PubMed1997

Extended temporal bone resection for squamous cell carcinoma.

OBJECTIVE: The aim of this study was to assess the surgical results of a series of patients from this unit who underwent extended temporal bone resection for recurrent squamous cell carcinoma as a salvage procedure. DESIGN: The surgical records of 15 patients were analyzed in detail. Each patient had salvage surgery in the form of an extended temporal bone resection with supraomohyoid block dissection, dural grafting, and free microvascular forearm or scalp rotation flap repair for recurrent squamous cell carcinoma in a radical mastoid cavity. RESULTS: Radical surgery yielded a 47% 5-year survival. Twenty-nine percent of the survivors had temporal lobe involvement that necessitated a partial excision of the temporal lobe of the brain. Histologic evidence of local lymph node involvement in the supraomohyoid neck dissection was present in 13% of cases. Those who died did so in the first postoperative year. All those with poorly differentiated tumors died. The survivors had well or moderately differentiated tumors. CONCLUSIONS: Radiotherapy alone or partial temporal bone resection, most commonly a radical mastoidectomy with or without preoperative or postoperative radiotherapy is used by the majority of otolaryngologists in treating squamous cell carcinoma of the temporal bone. The 5-year survival rate after this treatment remains depressingly low and the prognosis gloomy, particularly for advanced tumors. The findings in this series of extended temporal bone resections as salvage surgery in recurrent disease is encouraging, and radical surgery combined with radiotherapy from the outset may give much better 5-year survival figures in the future than the conventional partial temporal bone resection and radiotherapy.

Adult↗

PubMed1998

An outbreak of extended-spectrum, beta-lactamase-producing Salmonella senftenberg in a burns ward.

A strain of Salmonella senftenberg resistant to ceftazidime, gentamicin, chloramphenicol and ciprofloxacin was isolated from burn wounds of eight patients on a burns ward of a hospital in Delhi, India. The organism, which had probably been spread from patient to patient on staff hands, produced the extended-spectrum beta-lactamase SHV-5 and the aminoglycoside-modifying enzymes AAC(3)II + AAC(6'). The strain was not isolated from stool cultures of any of the patients or staff, apart from the index patient who had a history of diarrhoea and fever before admission. The outbreak ended in three weeks, after the implementation of strict handwashing. This is the first report of SHV-5 beta-lactamase in Salmonella spp. and also the first report of SHV-5 in India. The extended-spectrum beta-lactamases that have been reported in Salmonella spp. now include the Group 2 be enzymes SHV-2, SHV-5, TEM-3, TEM-25, TEM-27, CTX-M2, PER-1 and PER-2, and the Group 1 enzymes DHA-1 and CMY-2. The types of extended-spectrum beta-lactamases produced by salmonellas, their association with aminoglycoside resistance and their geographical distribution are now similar to those seen in klebsiella. Increasing antibiotic resistance in these organisms is reducing therapeutic options for the treatment of invasive disease.

Adolescent↗

PubMed1996

Late increase in acetaminophen concentration after overdose of Tylenol Extended Relief.

We report a case demonstrating a late increase in acetaminophen concentration after ingestion of Tylenol Extended Relief (extended-release acetaminophen; McNeil Consumer Products) along with drugs known to slow gastrointestinal motility. Coingestants that slow gastrointestinal motility are known to affect the interpretation of serum drug concentrations. However, this case illustrates potentially significant differences between extended-release and immediate-release acetaminophen and demonstrates an exception to the current manufacturer recommendation for the use of the Rumack-Matthew nomogram in this setting.

Acetaminophen↗

PubMedDate not supplied

Modified uvulopalatopharyngoplasty: The extended uvulopalatal flap.

OBJECTIVE: To investigate the surgical outcomes of a modified uvulopalatopharyngoplasty-extended uvulopalatal flap in the treatment of obstructive sleep apnea. MATERIAL AND METHODS: Thirty-three consecutive patients with obstructive sleep apnea underwent extended uvulopalatal flap that consisted of bilateral tonsillectomy, dissection and removal of submucosal adipose tissue of the soft palate and supratonsillar area; imbrication; and reposition of the denuded uvulopalatal flap. Variables of polysomnography included the respiratory disturbance index, snoring index, and minimal oxygen saturation. Surgical success was defined as achieving the postoperative respiratory disturbance index to less than 20 events per hour and a greater than 50% reduction of the preoperative respiratory disturbance index. RESULTS: Six months after operation, 27 patients (81.8%) responded successfully. The mean respiratory disturbance index decreased from 41.6 +/- 28.2 to 12.5 +/- 18.1(P <.0001), and the mean minimal oxygen saturation and snoring index improved significantly (P <.0001). The postoperative sequelae were mild with 3% of occasional nasal regurgitation. CONCLUSIONS: The results in this series revealed that extended uvulopalatal flap improves obstructive sleep apnea with minimal adverse effect in selected patients, and this technique suggests a role of fat dissecting in the palatal surgery for obstructive sleep apnea.

Adult↗

PubMed2001

Neuronal cell lines expressing PC5, but not PC1 or PC2, process Pro-CCK into glycine-extended CCK 12 and 22.

Endocrine tumor cells in culture and in vitro cleavage assays have shown that PC1 and PC2 are capable of processing pro-CCK into smaller, intermediate and final, bioactive forms. Similar studies have shown that PC5 has the ability to process a number of propeptides. Here, we use GT1-7 (mouse hypothalamic) and SK-N-MC and SK-N-SH (human neuroblastoma) tumor cell lines to study the ability of PC5 to process pro-CCK. RT-PCR and Western blot analysis showed that the cells express PC5 mRNA and protein, but not PC1 or PC2. They were engineered to stably overexpress CCK and cell media was analyzed for pro-CCK expression and cleavage of the prohormone. Radioimmunoassays showed that pro-CCK was expressed, but no amidated CCK was detected. Lack of production of amidated CCK may be due to the lack of the appropriate carboxypeptidase and amidating enzymes. Production of glycine-extended CCK processing products was evaluated by treatment of media with carboxypeptidase B followed by analysis with a CCK Gly RIA. Glycine-extended forms of the peptide were found in the media. The predominant forms co-eluted with CCK 12 Gly and CCK 22 Gly on gel filtration chromatography. The results demonstrate that these cell lines which express PC5 and not PC1 or PC2 have the ability to process pro-CCK into intermediate, glycine-extended forms more closely resembling pro-CCK products in intestine than in brain.

Animals↗

PubMed1998

Identification of glycine-extended CCK peptides in endocrine cells and modulation of CCK amide and CCK Gly content and secretion from endocrine tumor cells by an inhibitor of amidation.

Immunoreactive glycine-extended CCK peptides are found in normal mouse cerebral cortex and are very abundant in some CCK expressing endocrine tumor cells in culture. The glycine-extended forms in mouse cortex and in cell lines mirror their respective amidated forms. Mouse cerebral cortex, mouse AtT20 and rat WE cells produce mainly CCK 8 amide and CCK 8 Gly. In contrast, mouse intestinal STC-1 cells produce CCK 22 and CCK 8 amide along with forms of CCK Gly which are slightly larger than their respective amidated forms. The CCK 8 Gly-like peptide from AtT20 cells, after desulfation, co-eluted on HPLC with unsulfated CCK 8 Gly. Addition of copper and ascorbate to culture medium of WE cells caused a small increase in secretion of amidated CCK, without changing cellular levels of this peptide. Treatment with the amidation inhibitor diethyldithiocarbamate greatly decreased cellular content and secretion of CCK amide while it increased cellular content and secretion of CCK Gly. These results provide further evidence that glycine-extended CCK peptides are the immediate precursors of amidated CCK peptides.

Amides↗

PubMed1998

Perception of the social support role of the extended family network by some Nigerians with schizophrenia and affective disorders.

Enquiries into patients' perception of psychosocial support from families should help objectively to identify the strengths and needs of families with sick members, in order to enhance management. The aim of this study was to identify the categories of relatives in the extended family whom a sample of Nigerian psychiatric patients perceived as having provided material, social and emotional support, and the factors associated with these perceptions. 123 schizophrenics and 31 patients with major affective disorders attending out-patient clinics were interviewed. Using operational definitions of family member (i.e. tendency to confide in and expect support from a relative), it appears that the size of extended family network that was mostly relied upon for support was five, including parents, full siblings, uncles/aunts, first cousins and in-laws. There were no significant differences in summary scores of family size and social support between the two illness groups. Age and duration of illness were significantly negatively correlated with perception of supports. The size of family network with whom patients interacted was predicted by tendency to confide in members, and emotional support. The findings indicate that the presumed support of the extended family should not negate the need to strengthen the resources of the nuclear family, in order to provide a focus for attraction and deployment of materials needed for the effective care of patients.

Adolescent↗

PubMed1999

Extended culture of multipotent hematopoietic progenitors without cytokine augmentation in a novel three-dimensional device.

The ability to culture multipotent hematopoietic progenitor cells for extended periods is of practical importance to both clinical and research efforts involving these cells. Conventional techniques for the extended culture of hematopoietic progenitor cells (HPCs) have proven largely ineffective in sustaining these cells and preserving their multipotency over protracted periods. To overcome barriers to extended HPC culture, numerous alternative approaches, including cytokine augmentation and co-culture with bone marrow stroma, have been explored to enhance HPC maintenance but have generally yielded mixed results. The present study examined the ability of a novel, three-dimensional, tantalum-coated porous biomaterial (TCPB) to support HPC maintenance and multipotency in long-term cultures to which no exogenous cytokines have been added. As a follow-up to previously published short-term HPC cultures in TCPB, we examined the maintenance, phenotype and multipotency of HPCs cultured for up to 6 weeks in the TCPB matrix compared to control systems, including fibronectin-coated plastic, bone marrow stroma cocultures and other three-dimensional materials. These studies indicated that TCPB supports the maintenance of immature progenitors for up to 6 weeks in the absence of supplemented cytokines. Further, the results demonstrate that the TCPB matrix facilitates and enhances HPC maintenance and leads to a 1.5-fold expansion of HPC numbers following 1 week in culture and a 6.7-fold increase in colony-forming ability following 6 weeks in culture in the absence of exogenous cytokines. Under the same conditions, control systems were less able to support progenitor viability and multipotency. These findings point to new approaches that may improve the in vitro preservation of progenitors and may have important implications in clinical areas such as progenitor expansion, bone marrow transplantation and gene therapy.

Biocompatible Materials↗