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PubMed1995

Inhibitory mechanisms in epileptiform activity induced by low magnesium.

In rat hippocampal slices epileptiform activity was induced by superfusion with Mg(2+)-free artificial cerebrospinal fluid (ACSF). Paroxysmal depolarization shifts (PDS) were evoked by electrical stimulation of Schaffer collaterals. To investigate the afterpotentials that follow PDS, intracellular recordings were made from CA1 pyramidal cells. The experiments revealed that several components are engaged in the generation of PDS afterpotentials in Mg(2+)-free ACSF. A long lasting component which determined the overall duration of the PDS afterhyperpolarization was blocked by intracellular application of ethylenebis(oxonitrilo)-tetraacetate (EGTA); concomitantly, the afterhyperpolarizations following depolarizing current injections were blocked. This indicated that the long lasting component was due to a slow Ca(2+)-activated K+ current. The block of Ca(2+)-activated K+ current uncovered a depolarizing PDS afterpotential with an N-shaped voltage dependence, suggesting that this depolarizing afterpotential component may be due to an N-methyl D-aspartate (NMDA) conductance. Intracellular injection of Cl- revealed that the PDS were followed by Cl- currents lasting about 500 ms. This component could be blocked by application of bicuculline suggesting that it is due to a synaptically GABA-mediated (i.e. gamma-aminobutyric acid) Cl- current. A comparison of PDS afterpotentials in Mg(2+)-free ACSF and those in other models of epileptiform activity suggests that similar sequences of inhibitory components are activated in spite of different pharmacological alterations of membrane conductances which induce the epileptiform discharges.

Animals↗
PubMed1995

Progression of motor and cognitive impairment in Parkinson's disease.

We performed a longitudinal study (mean follow-up 86.7 months) to evaluate motor and mental deterioration in patients with Parkinson's disease. Of the original 91 patients, only 61 could be re-examined 7 years later and 11 of these had become demented (PD-Dems). PD-Dems were older with worse motor and, obviously, cognitive performance than non-demented parkinsonian patients (PDs). A global cognitive decay index (DI) was calculated for each patient. Based on this, non-demented PDs were further split into 38 stable parkinsonian patients (S-PDs) with DI-30% to +30%, and 10 deteriorated but non-demented parkinsonian patients (D-PDs) with a DI worse than -30% (as had PD-Dems). D-PDs were older and had greater motor impairment than S-PDs but did not differ from PD-Dems on these measures. D-PDs and PD-Dems deteriorated especially in attention, visuospatial and executive ability tests. Ageing seems to be the main predictive factor for mental deterioration.

Adult↗
PubMed2003

Synthesis and in vitro properties of prednisolone 21-sulfate sodium as a colon-specific prodrug of prednisolone.

Colon-specific delivery of glucocorticoids is highly desirable for the efficient treatment of inflammatory bowel disease. We synthesized prednisolone 21-sulfate sodium (PDS) as a colon-specific prodrug of prednisolone (PD) and investigated its properties using rats as test animals. We expected that introduction of sulfate ester as a sodium salt might increase the hydrophilicity and restrict the absorption in the GI tract. If PDS is stable and nonabsorbable in the upper intestine, it will be delivered to the colon as an intact form, where it hydrolyze by the sulfatase to release PD. Compared with PD, the solubility of PDS increased and the apparent partition coefficient decreased greatly. PDS was stable on incubation with pH 1.2 and 6.8 buffer solutions and with the contents of the stomach and small intestine. On incubation with the cecal contents, PDS decreased to 9.6% of the dose in 10 h producing PD. The amount of PD increased to give a maximum 54% of the dose and decreased. As a control, when PD was incubated with the cecal contents, it decreased to 29% of the dose in 8 h, which implied that reduction of PD proceeded under such conditions. These results suggested that hydrolysis of PDS took place to produce and accumulate PD, which decreased by reduction as the incubation period extended. Our results suggested that PDS can be a promising colon-specific prodrug of PD, and sulfate ester group might serve as a potential colon-specific promoiety, especially for the drugs which are resistant to reduction in the colon.

Administration, Oral↗
PubMed2004

Plasmodesmata in Arabidopsis thaliana suspension cells.

A current challenge in plant biology is to identify the structural and functional components of plasmodesmata (PDs). The use of plant tissue as a source material for plasmodesmal characterisation has had limited success, so we have explored the frequency and features of PDs occurring in suspension cell cultures of Arabidopsis thaliana. This material has the advantages of homogeneity, quantity, and ease of disruption. Using light and electron microscopy and immunostaining for callose and calreticulin, we showed that suspension cells laid down abundant PDs in division walls, and that vestiges of these structures were retained as half PDs even when the cell-to-cell contacts were disrupted during culture growth. Although callose was a reliable marker for PD distribution, which was deposited in an organised collar around the neck of PDs, it was not abundant in unstressed cells. Calreticulin and the chemical stain 3,3'-dihexyloxacarbocyanine iodide also provided useful markers when monitoring PDs in cell wall preparations by light microscopy. Purified cell walls were shown to be virtually free of contamination from cytoplasmic components, except for the presence of small amounts of cortical endoplasmic reticulum attached to PDs. Hence, clean cell walls from A. thaliana suspension cells provide a valuable resource for a proteomic approach to the analysis of plasmodesmal components.

Arabidopsis↗
PubMed2003

Localization and functional studies of pendrin in the mouse inner ear provide insight about the etiology of deafness in pendred syndrome.

Immunolocalization studies of mouse cochlea and vestibular end-organ were performed to study the expression pattern of pendrin, the protein encoded by the Pendred syndrome gene (PDS), in the inner ear. The protein was restricted to the areas composed of specialized epithelial cells thought to play a key role in regulating the composition and resorption of endolymph. In the cochlea, pendrin was abundant in the apical membrane of cells in the spiral prominence and outer sulcus cells (along with their root processes). In the vestibular end-organ, pendrin was found in the transitional cells of the cristae ampullaris, utriculi, and sacculi as well as in the apical membrane of cells in the endolymphatic sac. Pds-knockout (Pds-/-) mice were found to lack pendrin immunoreactivity in all of these locations. Histological studies revealed that the stria vascularis in Pds-/- mice was only two-thirds the thickness seen in wild-type mice, with the strial marginal cells showing irregular shapes and sizes. Functional studies were also performed to examine the role of pendrin in endolymph homeostasis. Using double-barreled electrodes placed in both the cochlea and the utricle, the endocochlear potential and endolymph potassium concentration were measured in wild-type and Pds-/- mice. Consistent with the altered strial morphology, the endocochlear potential in Pds-/- mice was near zero and did not change during anoxia. On the other hand, the endolymphatic potassium concentration in Pds-/- mice was near normal in the cochlea and utricle. Together, these results suggest that pendrin serves a key role in the functioning of the basal and/or intermediate cells of the stria vascularis to maintain the endocochlear potential, but not in the potassium secretory function of the marginal cells.

Animals↗
PubMed1988

Prostacyclin synthesis by endothelial cells from human umbilical veins: effect of cumulative population doublings.

There is a wide range of reported values for prostacyclin (PGI2) synthesis by cultured endothelial cells from human umbilical veins (HUVE). Part of this variation may be due to differences in isolation and culture conditions, but part may be due to previously unstudied variation in the number of population doublings (PDs) which the cells have undergone in vitro. Attention is now shifting to arachidonic acid (AA) metabolism by cells from adult human vessels and these cells may require increased PDs to obtain confluent cultures for testing. Therefore, we have examined the effect of number of cell population doublings as well as number of subcultivations on PGI2 synthesis using HUVE as a model system. Primary and first subcultivation cultures inoculated at high density, so that PDs at confluence were less than 4, synthesized 10 times as much PGI2 as the same isolates inoculated at low density with PDs greater than 4. Isolates inoculated and subcultivated so that the PDs at confluence after the fourth subcultivation were less than 6, showed 50% less PGI2 synthesis between the primary and first subcultivation and between the first and second subcultivations. Isolates with less than 4 PDs after the fourth subcultivation were carried further to determine the effect of extensive subcultivation. Four of six isolates showed a sudden increase in PGI2 synthesis which occurred between subcultivations 5 and 12 (PDs 4-6). These results demonstrate that AA metabolism is markedly affected by growth in culture and serial subcultivation.

Calcimycin↗
PubMed1983

Shortening of the in vitro lifespan of human diploid fibroblasts exposed to hyperbaric oxygen.

Serially cultivated WI-38 cells were exposed to 50 atm of oxygen for one hour at each passage after they reached 31 population doublings (PDs). They phased out at 51 PDs while the untreated and nitrogen-exposed cells at 56 PDs. The early-passage cells were found to be resistant to 50 atm of oxygen. The in vitro lifespan of WI-38 cells remained unchanged on less than eight exposures given before 46 PDs, and shortened in proportion to the number of extra exposures given after 46 PDs in addition to the seven exposures. For TIG-1 cells treated doubly with oxygen at late passages, modal cell volume began to increase at 54 PDs, and for the nitrogen-treated cells at 59 PDs. The in vitro aging of late-passage human cells exposed to hyperbaric oxygen seems to be accelerated.

Cell Survival↗
PubMed2005

Biodegradable polydioxanone and poly(l/d)lactide implants: an experimental study on peri-implant tissue response.

Several implants for orbital wall fracture treatment are available at the present, but they have drawbacks: resorption, risk for migration and foreign body reaction. Alloplastic resorbable implants would be advantageous: no removal operation and no donor side morbidity. The purpose of this study was to evaluate the foreign body reaction, capsule formation and mechanical properties of two bioresorbable implants. PDS and SR-P(L/DL)LA mesh sheet (70/30) with solid frame (96/4) implants (SR-P(L/DL)LA 70,96) were placed into subcutaneous tissue of 24 rats. Immunohistochemistry was used to evaluate reactivity for Tn-C, alpha-actin, type I and III collagens and two mononuclear cells: T-cells and monocyte/ macrophage. GPC, DSC and SEM were performed. Student's t-test or nonparametric Kruskall-Wallis test were used for statistical analysis. Histology of peri-implant capsule exhibited an inner cell-rich zone and an outer connective tissue zone around both materials. Tn-C reactivity was high in the inner and alpha-actin in the outer zone. At the end of the study, the difference of type I collagen versus type III collagen reactivity in inner zone was statistically significant (P<0.0001) as was the difference of type I collagen versus type III collagen reactivity in outer zone (P<0.0001). Immunohistochemistry did not reveal any statistical differences of T-cell and monocyte/macrophage reactivity around PDS versus SR-P(L/DL)LA 70,96 implants, nor any differences as a function of time. PDS were deformed totally after 2 months. SR-P(L/DL)LA 70,96 implants were only slightly deformed during the follow up of 7 months. PDS degraded rapidly in SEM observation. Particles were detaching from surface. SEM observation revealed that polylactide implant was degrading from the surface and the inner porous core became visible. The degradation came visible at 7 months. There were cracks in perpendicular direction towards to the long axis of the filaments. M(w) of PDS decreased fast compared to the polylactide implant. Foreign body reaction was minimal to both materials but continued throughout the whole observation period. Mechanically PDS was poor, it looses its shape totally within 2 months. It cannot be recommended for orbital wall reconstruction. New mesh sheet-frame structure (SR-P(L/DL)LA 70,96) approved to be mechanically adequate for orbital wall reconstruction. It seems not to possess intrinsic memory and retains its shape. The resorption time is significantly longer compared to PDS and is comparable to other studied P(L/DL)LA copolymers. Thus, the new polylactide copolymer implant may support the orbital contents long enough to give way to bone growth over the wall defect.

Absorbable Implants↗
PubMed2006

Methods for effective real-time RT-PCR analysis of virus-induced gene silencing.

We applied real-time RT-PCR to the analysis of Tobacco rattle virus (TRV)-mediated virus-induced gene silencing (VIGS) of the phytoene desaturase (PDS) gene in Nicotiana benthamiana and tomato. Using a combination of direct measurement and mathematical assessment, we evaluated three plant genes, ubiquitin (ubi3), elongation factor-1 alpha (EF-1), and actin, for use as internal reference transcripts and found that EF-1 and ubi3 were least variable under our experimental conditions. Primer sets designed to amplify the 5' or 3' regions of endogenous PDS transcripts in tomato yielded similar reductions in transcript levels indicating a uniform VIGS-mediated degradation of target RNA. By measuring the ratio of the abundance of the PDS insert transcript to the TRV coat protein RNA, we established that the PDS insert within TRV was stable in both hosts. VIGS in N. benthamiana resulted in complete photo-bleaching of all foliar tissue compared to chimeric bleaching in tomato. PDS transcript levels were decreased eleven- and seven-fold in photobleached leaves of N. benthamiana and tomato, respectively, while sampling tomato leaflets on the basis of age rather than visible bleaching resulted in only a 17% reduction in PDS coupled with a large leaf-to-leaf variation. There was a significant inverse relationship (r2=76%, P=0.01) between the relative abundance of CP RNA and the amount of PDS transcript in rTRV::tPDS-infected tomato suggesting that virus spread and accumulation are required precursors for successful VIGS in this host.

Gene Silencing↗
PubMed1996

Prospective, randomized evaluation of midline fascial closure in gastric bariatric operations.

BACKGROUND: Severe obesity is cited as a major risk factor for fascial wound dehisence and late incisional hernia after major abdominal surgery. The purpose of this study was to prospectively compare two methods of closure of the linea alba after gastric restrictive operations performed for treatment of morbid obesity. METHODS: During a 6-year period 229 patients were randomized to have closure of the midline fascia using either a double-stranded #1 PDS suture placed in a continuous fashion or #1 Ethibond suture placed using an interrupted figure-eight technique. RESULTS: Two of 109 patients who had closure with Ethibond suffered an acute dehiscence of the midline fascia vs no cases of fascial dehiscence in the PDS group. There were no wound infections in either group. There were 20 late incisional hernias (18%) in the Ethibond group vs 11 late hernias (10%) in the PDS group (P < or = 0.04). Mean postoperative follow-up time for all patients was 29.4 months. The cost of suture material and the time required to completely close the linea alba were also calculated for each group. The mean closure time in the Ethibond group was 13.3 vs 9.1 minutes in the PDS group (P < 0.0001). Although the cost per suture pack of #1 PDS was $4.63 vs $1.76 per pack for #1 Ethibond, the mean cost of sutures per patient was $4.81 for PDS vs $11.09 for Ethibond. CONCLUSIONS: We conclude that #1 PDS placed in a continuous fashion provides a more secure and cost-effective closure of the midline fascia in morbidly obese patients than #1 Ethibond placed using an interrupted figure-eight technique.

Adult↗
PubMedDate not supplied

[Use of antidepressant drugs in schizophrenic patients with depression].

INTRODUCTION: Depression is common in people with schizophrenia and is associated with substantial morbidity explaining also the considerable attention and recognition of this entity as suggested by the inclusion of the post-psychotic depression in DSM IV and ICD 10. The prevalence of this disorder varies according to the type of approach used (range between 7% to 75%). Prescription of antidepressants plus antipsychotic treatment is frequent in clinical practice (11 to 43%). BACKGROUND: Pharmacokinetic and metabolic interactions have been identified. The cytochrome P450 has been identified as being implicated in the metabolism of most psychotropics, mainly through the CYP1A2, CYP2C19, CYP2D6, CYP3A4 isoenzymes. Tricyclic antidepressants are likely to increase chlorpromazine plasma levels. Similarly, antipsychotics such as perphenazine, chlorpromazine or haloperidol can increase antidepressant plasma levels, through the inhibition of CYP 450 isoenzymes (CYP2D6). Most of the Specific Serotonin Recapture Inhibitors (SSRIs) are likely to inhibit one or several CYP450 isoenzymes. The inhibition is moderate to marked for CYP1A2 (fluvoxamine and fluoxetine), CYP2C19 (fluoxetine, fluvoxamine and sertraline), CYP2D6 (paroxetine, fluoxetine and sertraline), and CYP3A4 (fluvoxamine, fluoxetine and sertraline). In the US, one-fourth of psychiatrists report the use of depression-rating scales in schizophrenic patients. Non specific scales (Hamilton Depression Rating Scale or Beck Depression Inventory) are the most commonly used in spite of the fact that these scales do not allow the distinction of depressive from negative symptoms in schizophrenic patients. LITERATURE FINDINGS: Due to these limitations, more specific assessment tools for depressive symptoms in schizophrenia are required. Two specific scales for assessing depressive symptoms in schizophrenic patients have been constructed and validated. The Calgary Depression Scale (CDS) is a nine item scale, each item scored from 0 to 3. This scale was derived from the HDRS and the Present State Examination. Factor analysis showed that the CDS is unidimensional, has high internal consistency, and significant strong correlation with scores on the HDRS, Beck and BPRS depression scales. The CDS has been validated in different languages (Brazilian, Danish, French...). It has been shown that there is no overlap between negative or extrapyramidal and depressive symptoms assessed by the PDS in schizophrenic patients. The Psychotic Depression Scale (PDS) is a 32 item scale derived from the HDRS, PANSS, CPRS and AMDP, each item being rated from 0 to 7. A principal component analysis of the PDS items using a Varimax rotation disclosed 8 orthogonal components that account for 71% of the variance. These components involved the following dimensions : depressive mood, inhibition, vegetative signs, paranoid signs, strangeness of thought, inverse vegetative signs, guilt feelings and cognitive signs. The analysis revealed that the 'depressive mood' factor of the PDS was correlated with the 'depressive' factor and was slightly correlated with the cognitive factor of the PANSS. This first factor was not correlated with either the "negative" factor of the PANSS, or the Positive or Excitement factor of the PANSS. Hence, this PDS, factor distinguished depressive signs from negative symptoms. Due to their metrologic properties, specific scales should be preferred. However, only one open trial (of an antipsychotic) and two double blind controlled trials (one comparison of 2 antipsychotics and one comparison of an cholinesterase inhibitor versus placebo) have been published using the CDS. Likewise, only one double blind controlled trial using the PDS (comparison of 2 antipsychotics) has been published. No study of the effect of antidepressants in depressed schizophrenic patients has been published, using either the CDS or the PDS assessment criteria. DISCUSSION: These specific scales are rarely used in clinical practice. Only about 1% of the US psychiatrists reported the use of the Calgary Depression Scale. Several open clinical trials have assessed the efficacy of antidepressant agents added to antipsychotic in patients with schizophrenia. They have produced inconsistent results but have suffered from methodological limits (short duration of the studies, non homogeneous inclusion criteria, heterogeneous assessment methods...). Due to the lack of a reference drug, double blind placebo-controlled trial are necessary. A recent meta-analysis has been performed on results of trials that have investigated the clinical efficacy of antidepressant medication (either tricyclics, SSRIs or others) in the treatment of depression in schizophrenic patients. In a subset of 5 trials (209 patients), the proportion improved in the antidepressant group was 26% (95% CI 10 to 42) higher than in the placebo group. The estimated number needed to treat was 4. In a subgroup of 6 studies (267 patients), the standardized mean difference on the HDRS score was -0.27 (95% CI - 0.7 to -0.2). There was no evidence that antidepressant treatment induced a deterioration of psychotic symptoms in these trials. CONCLUSION: The results provide weak evidence for the efficacy of antidepressants in patients with schizophrenia and depression. Today, the only SSRI tested in the treatment of depression in schizophrenic patients is sertraline. One study led to positive results. Since the meta-analysis, one additional study has been performed comparing sertraline to placebo. No difference between the 2 treatment groups was demonstrated but the power of the trial was rather low. Further research is required to determine the best approach towards treating depression in patients with schizophrenia, with clinical trials performed for longer periods, using appropriate assessment criteria such as depressive symptoms and quality of life.

Antidepressive Agents↗
PubMed1999

Eye movements and spatial working memory in Parkinson's disease.

Mechanisms of spatial working memory and eye movement control were investigated in eight mild to moderate Parkinson's disease patients (PDs). Subjects were presented with a sequence of four targets which had to be memorized and then recalled by moving their eyes to fixate the four locations in the correct order. Two variations on this procedure were used in which either a different sequence of lights was presented on each trial, or an identical sequence of lights was repeated on each trial. In both conditions subjects made memory-guided eye movements in the dark, without any visual cues to eye movement accuracy or the locations of the previously illuminated lights. Analysis of the amplitude of the primary eye movement and final eye position for each step in the sequence showed that PDs made several discrete saccadic eye movements of reduced amplitude before reaching the final eye position (multi-stepping). When a novel target sequence had to be memorized on each trial, the final eye position reached by PDs for each location was also found to undershoot relative to controls. In contrast, when an identical sequence of targets was repeated on each trial, PDs' final eye position was found to be normal, although primary movement amplitudes were still reduced. PDs showed no multi-stepping and normal final eye position gain under conditions for which the target lights in the sequence were illuminated during movement execution. PDs also made an increased proportion of overt errors in target sequence recall. Parallel neuropsychological testing in PDs and controls revealed that error rates in the sequential memory-guided saccade task were significantly correlated with performance in a task thought to be sensitive to spatial working memory dysfunction. The findings suggest that short-term spatial memory representations are disrupted in the early stages of PD.

Aged↗
PubMed1997

Load to failure of common meniscal repair techniques: effects of suture technique and suture material.

Success of meniscal repair with early or immediate motion depends on the ability of the suture fixation to withstand the loads applied. Vertical and horizontal mattress suture techniques were tested using 2-0 Ethibond, and 0-PDS and 1-PDS sutures (Ethicon, Somerville, NJ). Mulberry knot technique was tested with 0-PDS and 1-PDS sutures. Twenty menisci (60 sutures) were tested for each suture material. Sutures were placed 3 to 4 mm from the peripheral edge of the meniscus with double barreled cannulas for vertical and horizontal mattress techniques or a spinal needle for the mulberry knot technique, reproducing clinical techniques of meniscal repair. Mechanical testing of suture fixation was performed to failure at a rate of 10 mm/min on a MTS material testing system (MTS Systems Corp, Minneapolis, MN). Suture pullouts were reported as the load displacement to failure from the inner fragment only, because clinical failure would ensue should a suture pull through the inner fragment of a tear. Vertical mattress technique with 1-PDS suture had significantly greater load to failure than any other combination (P < .05). Analysis of variance showed that the vertical mattress technique had statistically superior pullout strength (P < .0001) compared with the horizontal mattress and mulberry knot techniques, which were statistically similar. There were significant differences (P < .0001) between suture types, with 1-PDS proving best compared with 0-PDS, which was stronger than 2-0 Ethibond. Selection of suture material had the greatest impact on vertical mattress load to failure and was not important to the strength of the other techniques.

Analysis of Variance↗
PubMed2000

Co-occurrence of Axis I and Axis II disorders in substance abusers.

OBJECTIVE: This study examined the co-occurrence of anxiety/mood and personality disorders (PDs) in substance abusers, the impact of anxiety/ mood disorders on the symptom profiles of PDs, and the impact of anxiety/mood disorders and PDs on pre-treatment status. METHOD: Current anxiety/mood disorders and PDs and pre-treatment status were assessed using semi-structured interviews in 370 treated substance abusers. RESULTS: Anxiety/mood disorders and PDs frequently co-occurred, with the overall pattern of associations being non-specific. The strongest associations were of social phobia with avoidant and schizotypal PD, and of major depression with borderline PD. However, symptom profiles of PDs were not associated with anxiety/mood disorders. Finally, anxiety/mood disorders and PDs were both independently and differentially associated with poor pre-treatment characteristics. CONCLUSION: The findings suggest the clinical importance of obtaining both Axis I and Axis II diagnoses in treated substance abusers, and highlight the distinctiveness of the Axis I and Axis II disorders.

Adult↗
PubMed1997

Physical, psychiatric and social characteristics of the temporomandibular disorder pain dysfunction syndrome: the relationship of mental disorders to presentation.

OBJECTIVE: To investigate the physical and psychosocial characteristics and to identify the prevalence of mental disorders in pain dysfunction syndrome (PDS). DESIGN AND SETTING: New referrals to temporomandibular disorder clinics at Manchester Dental Hospital and diagnosed with PDS. METHODS: Patients were assessed with a range of socio-demographic, dental and psychosocial measures including a psychiatric interview. Patients with PDS and a mental disorder were compared with those without a mental disorder. RESULTS: 97 patients were included; 32 (33%) had a mental disorder. There were no significant differences between those with and those without a mental disorder on any of the objective dental measures. Those with a mental disorder complained of more pain associated with PDS. They reported more anxiety and depression and also more physical symptoms unrelated to the PDS for which they had sought help and received more treatments. CONCLUSIONS: Psychosocial factors contribute to the presentation and possibly causation of PDS in the third of patients seen in a hospital setting who have a mental disorder. This factors should be considered when managing patients with PDS.

Adolescent↗
PubMed1998

Outbreak of sterile peritonitis among continuous cycling peritoneal dialysis patients.

BACKGROUND: Approximately 30,000 patients receive peritoneal dialysis in the United States. In August 1996, several dialysis centers from different states reported sterile peritonitis among CCPD patients using sterile peritoneal dialysis solution (PDS) from a single manufacturer. The manufacturer recalled 53 lots of PDS that had passed established industry guidelines and Food and Drug Administration (FDA) approved quality control tests [including endotoxin levels <0.5 endotoxin units (EU)/ml], but had pre-sterilization bacterial colony counts >1 cfu/ml. METHODS: At one outpatient dialysis center, Hospital of the University of Pennsylvania (HUP), we conducted a retrospective cohort study of all CCPD patients treated during July 15 to August 30, 1996. A case-patient was defined as any HUP patient with culture-negative peritoneal fluid with a white blood cell count >100/mm3, cloudy peritoneal fluid, and/or abdominal pain. PDS and tubing were cultured for bacteria and assayed for endotoxin. RESULTS: Overall, 14 of 28 patients had sterile peritonitis. The only risk factor identified was exposure to > or =1 lot of recalled PDS (14 of 22 vs. 0/6, P = 0.02); the more recalled lots received, the higher the attack rate (P = 0.0001). Five of 47 PDS bags had detectable endotoxin; recalled lots were more likely to have measurable endotoxin than nonrecalled lots (5/19 vs. 0/17, P = 0.05). When case-patients resumed CCPD using PDS from non-recalled lots, no further cases were reported. CONCLUSIONS: Our results suggest that this outbreak was caused by intrinsic PDS contamination with endotoxin. Pre-sterilization colony counts may be an important quality control indicator for CCPD fluids in conjunction with endotoxin levels.

Adult↗
PubMed2006

[Categorical versus dimensional classification of personality disorders: are dimensional models the future?].

The classification of personality disorders (PD) according to ICD-10 and DSM-IV has been critisized for several reasons. For example, those who have attempted to validate the presence of a non-arbitrary distinction between normal and abnormal personality functioning have suggested that no such distinction exists. Furthermore, PDs frequently co-occur with a number of Axis-I conditions and other Axis-II disorders leading to multiple diagnoses. Therefore, many have suggested classifying PDs dimensionally, rather than categorically. However, there are only a few studies that have investigated the applicability of these models with respect to PDs, and most of these studies used the Big Five. In this study we investigated the applicability of the Seven-Factor model of temperament and character for the classification of PDs. Our results show that the Seven-Factor model discriminates well between PDs and healthy controls, as well as between PDs and Axis-I disorders. We discuss our findings and present a modified scheme to diagnose PDs.

Algorithms↗
PubMed1978

Mediation of pinocytosis in cultured arterial smooth muscle and endothelial cells by platelet-derived growth factor.

Pinocytosis was measured in monkey aortic smooth muscle cells (SMC), bovine aortic endothelial cells, and Swiss 3T3 cells in culture as cellular uptake of [U-(14)C]sucrose and horseradish peroxidase (HRP) from the tissue culture medium. Monkey arterial SMC and Swiss 3T3 cells were maintained in a quiescent state of growth at low cells density in medium containing 5 percent monkey plasma-derived serum (PDS). Replacement of PDS with 5 percent monkey whole blood serum (WBS) from the same donor, or addition to PDS of partially purified platelet-derived growth factor(s) (PF), resulted in a marked stimulation of pinocytosis as well as of cellular proliferation. In SMC, enhancement of the rate of pinocytosis occurred 4-6 h after exposure to WBS or PF, and the rate was up to twofold higher than the rate in medium containing PDS. In contrast, [(3)H]thymidine uptake by SMC did not increase until 12-16 h after exposure to PF. In endothelial cells the presence of PF or WBS did not enhance either the rate of pinocytosis or the rate of proliferation over that in PDS. Thus, endothelial cells did not become quiescent at subconfluent densities in PDS but maintained rates of proliferation and pinocytosis that were equivalent to those in WBS. By autoradiography, the fraction of labeled nuclei in SMC cultures 24 h after change of medium increased from 0.061 +/- 0.004 in quiescent cultures to 0.313 +/- 0.028 after exposure to WBS or PF. In contrast, labeling indices of endothelial cells were similar for cultures grown in PDS, WBS, or PF at any single time point after change of medium. These findings suggest that the rate of pinocytosis maybe be coupled in some fashion to growth regulation, which may be mediated in part by specific growth factors, such as that derived from the thrombocyte.

Animals↗