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PubMed2006

Pyridoxine-dependent seizures in Dutch patients: diagnosis by elevated urinary alpha-aminoadipic semialdehyde levels.

BACKGROUND: Pyridoxine-dependent seizures (PDS) is a rare, autosomal recessively inherited disorder. Recently alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was identified as a major cause of PDS, which causes accumulation of both alpha-AASA and pipecolic acid (PA) in body fluids. METHODS: We studied urinary and plasma alpha-AASA and PA levels in 12 Dutch clinically diagnosed patients with PDS. RESULTS: Alpha-AASA was elevated in both urine and plasma in 10 patients. In these patients plasma PA levels were also elevated but urinary PA levels were normal. DISCUSSION: In all patients with clinically definite PDS, and in most patients with probable or possible PDS, the clinical diagnosis of PDS could be confirmed at the metabolite level. Non-invasive urinary screening for alpha-AASA accumulation provides a reliable tool to diagnose PDS and can save these patients from the classical and potentially dangerous pyridoxine withdrawal test to prove PDS.

Aldehyde Dehydrogenase↗
PubMed2006

Power Doppler sonography monitoring of synovial perfusion at the wrist joints in patients with rheumatoid arthritis treated with adalimumab.

OBJECTIVE: To use power Doppler sonography (PDS) to evaluate changes in synovial perfusion induced by adalimumab in the wrist joints of patients with rheumatoid arthritis. METHODS: 48 wrists of 24 patients (18 women and 6 men) were examined. Despite prior treatment with disease-modifying antirheumatic drugs, including methotrexate, patients with clinically active rheumatoid arthritis were recruited in two rheumatological centres to receive 40 mg adalimumab subcutaneously every other week. Clinical, laboratory and PDS assessments were carried out at 0, 2, 6 and 12 weeks. Clinical and laboratory measurements of disease activity included physician's global assessment of disease activity, erythrocyte sedimentation rate and serum levels of C reactive protein. The Disease Activity Score for 28 joints (DAS28) was calculated. PDS signal was scored from 0 to 3 according to the overall expression of PDS findings at the wrists. RESULTS: A significant reduction in both clinical (p<0.001) and PDS findings (p<0.001) was found at all follow-up examinations. A tendency to positive correlation (Spearman's r = 0.382; p = 0.067) was shown between reduction in PDS score and improvement in DAS28 at week 2 examination. CONCLUSION: PDS detected a rapid and significant reduction in synovial perfusion at the wrist joints of patients with rheumatoid arthritis receiving adalimumab. Ongoing follow-up will provide further information regarding the persistence of considerable reduction in PDS signal score and its correlation with DAS28.

Adalimumab↗
PubMed2002

Differential diagnosis between Pendred and pseudo-Pendred syndromes: clinical, radiologic, and molecular studies.

The disease gene for Pendred syndrome has been recently characterized and named PDS. It codes for a transmembrane protein called pendrin, which is highly expressed at the apical surface of the thyroid cell and functions as a transporter of chloride and iodide. Pendrin is also expressed at the inner ear level, where it appears to be involved in the maintenance of the endolymph homeostasis in the membranous labyrinth, and in the kidney, where it mediates chloride-formate exchange and bicarbonate secretion. Mutations in the PDS gene and the consequent impaired function of pendrin leads to the classic phenotype of Pendred syndrome, i.e. dyshormonogenic goiter and congenital sensorineural hearing loss. In the present study, we performed a detailed clinical, radiologic, and molecular analysis of six families presenting with clinical diagnosis of Pendred syndrome. In two families a homozygous pattern for PDS mutations was found, whereas the affected members of the other four families were compound heterozygotes. One family did not harbor PDS mutations. Among the four novel mutations described, one is a transversion in exon 2 (84C>A), leading to the substitution S28R. Two other novel mutations lie in exon 4 (398T>A) and in exon 16 (1790T>C), leading to the substitutions S133T and L597S, respectively. The fourth novel mutation (1614+1G>A) is located in the first base pair of intron 14, probably affecting the splicing of the PDS gene. Clinically, all patients had goiter with positive perchlorate test, hypothyroidism, and severe or profound sensorineural hearing loss. In all the individuals harboring PDS mutations, but not in the family without PDS mutations, inner ear malformations, such as enlargement of the vestibular aqueduct and of the endolymphatic duct and sac, were documented. The pseudo-Pendred phenotype exhibited by the family without PDS mutations is likely caused by an autoimmune thyroid disease associated with a sensorineural hearing loss of different origin.

Adolescent↗
PubMed2004

Pancreatic duct strictures: identifying risk of malignancy.

BACKGROUND: This study aimed to define PDS characteristics that predict malignancy and would thus invoke further diagnostic evaluation or aggressive treatment. METHODS: 355 cases of PDS were diagnosed by ERCP during a 7-year period at a single institution. A retrospective review identified clinical/demographic patient data and ERCP results. RESULTS: 218 (61%) patients with a PDS were found to have an isolated PDS. Twelve percent of isolated PDS and 79% of CBD stricture-associated PDS were malignant. The sensitivity and specificity for the double duct sign for malignancy were 77% and 80% respectively, and the positive predictive value was 65%. Predictors of malignancy were statistically similar for both isolated PDS and those associated with a CBD stricture. Univariate predictors of malignancy included stricture location in the pancreatic head/neck, jaundice, and patient age. Predictors of benign disease included a history of pancreatitis, the presence of multiple strictures, pancreatic duct stones, pseudocyst, pancreas divisum anatomy, irregular side branches, and irregular pancreatic duct morphology. Less than 1% of patients with either pancreas divisum anatomy, pancreatic duct stones, or pancreatic pseudocyst had malignancy. Using malignancy as the dependent variable, multivariate factors included in the final prognostic equation were history of pancreatitis (odds ratio 0.009 with history of pancreatitis), stricture location in the head or neck (odds ratio 42) and irregular pancreatic duct side branches (odds ratio 0.05 with irregular branches). CONCLUSIONS: This study demonstrates that certain characteristics of PDS can predict the subset of patients who have an increased risk of cancer.

Algorithms↗
PubMed2001

Expression pattern of the pendrin and sodium/iodide symporter genes in human thyroid carcinoma cell lines and human thyroid tumors.

OBJECTIVE: In the present study we analyzed the pattern of pendrin (PDS) and sodium/iodide symporter (NIS) gene expression in some thyroid carcinoma cell lines and a series of thyroid tumoral tissues. METHODS: Total RNA was extracted from all cell lines and from 53 tissues, and gene expression was examined by RT-PCR. Semiquantitative 'multiplex' RT-PCR was used to assess variations in PDS gene expression among various thyroid pathologies. Pendrin expression was determined in the thyroid cell lines by Western blot analysis. RESULTS: PDS mRNA was expressed in all the cells investigated; conversely, NIS mRNA was detectable only in the B-CPAP cells. Pendrin protein was expressed in B-CPAP and WRO cell lines, reduced in FRO and absent in ARO cells. PDS gene expression was not detected in 5 of 25 differentiated thyroid carcinomas (DTC) while NIS gene was not expressed in six carcinomas. A concordance expression of both PDS and NIS transcripts was found in 20 DTC. In contrast, 2 neoplastic thyroid tissues carrying undetectable PDS mRNA maintained NIS transcript, and 3 thyroid carcinomas negative for NIS mRNA retained the expression of PDS gene. A semiquantitative analysis showed that the mean PDS mRNA levels were significantly decreased in DTC tissues. CONCLUSIONS: Our data demonstrate that pendrin expression: (i) is present in the more differentiated thyroid carcinoma cell lines studied; (ii) is reduced or absent in DTC tissues; (iii) may not correlate with the NIS expression. These alterations may contribute to the loss of iodine concentration ability detected in thyroid tumors.

Adenocarcinoma, Follicular↗
PubMed1996

Power Doppler versus color Doppler imaging in renal allograft evaluation.

The purpose of this study was to evaluate the impact of PDS compared to conventional CDI in the followup of 72 renal allograft patients. Renal allograft vascularization, assessed by PDS and CDI, was scored from 0 to 4, where 0 was the cortical "blush" and 4 was residual central perfusion. These scores were correlated with the resistive index, serum creatinine levels, hematocrit, and, in 35 cases, biopsy results. PDS scores of renal perfusion were one grade lower than CDI scores in 59 of 72 patients and two grades lower in two of 72 patients. A statistically significant correlation was found between PDS scores and the RI (r2 = 0.6, P < 0.05). However, no significant correlation was found between PDS scores and creatinine levels or hematocrit values. PDS scores are not related to histologic findings in renal allograft dysfunction. Overall, five biopsy-related arteriovenous fistulas were detected, two of which were missed on the initial PDS examination. In conclusion, PDS provides more complete visualization of the renal allograft vessel tree than CDI. However, biopsy-related arteriovenous fistulas are better seen by CDI.

Biopsy↗
PubMedDate not supplied

Case study. When outsourcing goes awry ... seven experts discuss how the outsourcing crisis could have been avoided.

Grant Newman, chief executive officer of Regional Medical Center, expected the worst from the meeting that was scheduled to begin in less than an hour. The anesthesiologists were at the end of their rope, and the hospital's surgeons and obstetricians were pretty riled up, too. Eighteen months earlier, Newman had made the decision to outsource RMC's anesthesia services, and he had signed a contract with Physicians Development Services, a contract management company. As is typical in these arrangements, the anesthesiologists would be independent contractors with PDS while PDS would be under contract with RMC. Legally, therefore, there would be no agreement of any sort between the anesthesiologists and the hospital where they worked. At the time, PDS seemed a good fit. It had a reputation for providing high-quality physicians both on a permanent basis and for temporary assignments. Unfortunately, however, PDS was undercapitalized and chronically mismanaged. PDS's paychecks to the anesthesiologists began arriving late and then bounced several times over a three-month period. In addition, the contract between the anesthesiologists and PDS had expired three months earlier, and the anesthesiologists were providing services without a contract. Newman knew that he had no legal right to interfere with the contract between PDS and the anesthesia group unless PDS breached the contract with RMC. But Newman felt that the future viability of the hospital would be seriously compromised if he allowed an exodus to occur even for a single day. What can Newman do to resolve this conflict? Seven experts consider how the hospital's outsourcing crisis could have been avoided.

Anesthesia Department, Hospital↗
PubMed1999

The inheritance of the pigment dispersion syndrome in blacks.

PURPOSE: Evidence has indicated that pigment dispersion syndrome (PDS) is inherited as an autosomal dominant disorder in white patients, often with a high degree of penetrance. Because heredity patterns in blacks are unknown, an investigation was carried out to study inheritance of PDS in this population. METHODS: Six unrelated black adults (5 women, 1 man, age range 43-60 years) with PDS were identified from a primary eye care population at an inner city teaching clinic in Chicago, Illinois. Nineteen first-degree relatives (all siblings or children; age range 18-52 years) of these patients subsequently underwent thorough eye examination to look for signs of PDS. RESULTS: Among the relatives, two (12%) showed evidence of the condition (these two patients belonged to different families): one was a 42-year-old daughter of a 60-year-old proband, and the other was the 49-year-old sister of a 47-year-old proband. Both exhibited definite signs of PDS in one eye only. CONCLUSION: Evidence of expression of PDS among family members of black probands with PDS is provided. Incomplete penetrance of PDS among the black pedigrees may be suggested by these data.

Adolescent↗
PubMed1975

[A comparison of paying patients in private practice and in public dental service--found from the Harstad-study 1974].

Since 1950, the Public Dental Service (PDS) has gradually been developed in Norway. In addition to rendering free and systematic treatment to children aged 6--17 years, which has priority, the PDS also offers treatment to other categories of patients at fixed fees, generally lower than those in private practice. The purpose of the present study was to elucidate the impact made by PDS on the dental treatment pattern within one particular area (the district of Harstad with a population of approximately 29,000). Furthermore, the study included a description of the clientele in the PDS, excluding the "free clientele" aged 6--17, in relation to that treated in private practice. During a limited period in February--March 1974, all the 9 dentists in the PDS treating "paying clientele" and all the 9 private practitioners in the district, filled in a questionnaire by each patient visit (course of treatment) (Fig. 1). In addition to the information on social and demographic characteristics, data were also collected on dental treatment pattern, the treatment presently rendered, and the presence of teeth and possible dentures (Fig. 1). Four--fifths of the visits made by "paying clientele" were made in private practice, only one--fifth in the PDS. In private practice, rural people, women and people of young age were underrepresented. Children under 6 years of age comprised 3% of the clientele in private practice and 9% in the PDS. No significant difference was found between the two types of practice regarding the social class composition of the clientele. Dental status as measured by the occurrence of teeth and dentures was generally poorer among the PDS patients, seemingly due to the overweight of rural people and of those with an irregular or occasional treatment pattern. Totally 40% of all visits were made by regular treatment attenders. 20% of the services delivered were prophylaxes and/or periodontics, 56% were conservative and/or endodontic treatments. The introduction of the FDS in the district some 10--15 years ago has conceivably contributed to an overall increase in the demand for dental services, and to an improvement of denial treatment patterns. During this period, the number of public dentists has increased from 2--3 to a total of 12. Correspondingly, the number of private practitioners has increased from 5 to 9, of whom 2 work part time. The treatment attendance of some population subgroups is, however, still lagging behind: rural people, small children and persons over 50 years of age, and particularly people belonging to lower socio-economic brackets.

Adolescent↗
PubMed2003

[Chemical synthesis of biodegradable poly-para-dioxanone and its application for mandibular fracture fixation].

OBJECTIVE: To observe mandibular fracture healing after synthesized bioabsorable poly-para-dioxanone (PDS) ligature fixation. METHODS: Para-dioxanone monomer was prepared by chemical reactions of metallic sodium, ethylene glycol and other raw materials. PDS was synthesized by polymerizing the purified para-dioxanone in the presence of catalyst under the conditions of negative pressure and certain temperature. PDS ligature was obtained by processing the polymer into small granules, drying and melt-extruding through a spinnerette. Eighteen adult male New Zealand rabbits were assigned randomly into two groups. After mandibular fracture models were created, reductions of the artificial fractures were accomplished by means of transosseous PDS ligatures on each of 12 rabbits in experimental group. While the other six rabbits without any internal fixation were set as control. Schedules for killing were arranged to give postoperative samples at two-week interval till 12th week. RESULTS: Radiographical and histological examinations demonstrated that all fractures fixed with PDS ligatures healed without any complication. Periosteal and cartilaginous osteogenesis was observed in newly formed external callus. In contrast, bone fragment migration and the consequent nonunion occurred in the control group. PDS ligature degraded and absorbed without interference with osseous union and healing. The tensile strength reduction of PDS ligature was prior to its absorption in vivo. CONCLUSION: The synthesized PDS is a colorless, flexible, themoplastic and monofilament fiber, which can be sterilized by ethylene oxide embalmment without serious loss of tensile strength. It seems that the application of this macromolecular material in internal fixation is of great worth for further study.

Absorbable Implants↗
PubMed2004

Ultrasonographic study of Achilles tendon and plantar fascia in chondrocalcinosis.

OBJECTIVE: To investigate by high frequency grey-scale ultrasonography (US) and power Doppler sonography (PDS) the modality and frequency of involvement of the Achilles tendon and plantar fascia in chondrocalcinosis (CC), and to correlate these findings with clinical complaints and radiographic evidence. METHODS: The heels of 57 consecutive patients with CC were evaluated by US, PDS, and radiography. One control group of 50 consecutive patients with osteoarthritis (OA) without signs of CC was studied in the same way. A second control group of 50 healthy subjects underwent only US/PDS examination. All subjects also underwent clinical assessment. RESULTS: US revealed Achilles tendon calcifications in 57.9% of those with CC, but none in the control groups. Plantar fascia calcifications were observed in 15.8% of CC and in 2% of OA cases, but not in healthy controls. US showed no significant difference in postero-inferior and inferior calcaneal enthesophytosis between subjects with CC (59.6% and 61.4%, respectively) and those with OA (46% and 44%, respectively). Such alterations were also present, in lower percentages, in the healthy controls. Posterior and inferior calcaneal erosions were absent in all groups. Achilles enthesopathy was found in 22.8% of patients with CC (14.9% of heels, with vascular signals in 11.4% of heels on PDS). Deep retrocalcaneal bursitis was found in 10.5% of patients with CC (7% of heels, with vascular signals in 5.2% of heels on PDS). Plantar fasciitis was found in 40.3% of patients with CC (36% of heels, with vascular signals in 2.6% of heels on PDS) and in 14% of OA patients, but not in healthy controls. No significant correlation was found between talalgia or sex of patients and presence of calcifications. A significant correlation was observed between talalgia and Achilles enthesopathy (r = 0.78, p < 0.0001), deep retrocalcaneal bursitis (r = 0.7, p < 0.0001), and plantar fasciitis (r = 0.31, p < 0.001). A significant correlation between talalgia and vascular signals on PDS was observed in Achilles enthesopathy (r = 0.91, p < 0.0001) and deep retrocalcaneal bursitis (r = 0.65, p < 0.0001). The presence of vascular signals on PDS was significantly associated with the presence of tendinous and bursal grey-scale US alterations. Achilles tendon calcifications were 39% sensitive, 100% specific, and 77% accurate for the presence of CC, whereas plantar fascia calcifications were 15% sensitive, 98% specific, and 54% accurate. Excellent agreement was found between US and radiography in detecting Achilles tendon calcifications (k = 0.86), plantar fascia calcifications (k = 0.77), postero-inferior enthesophytosis (k = 0.90), and inferior enthesophytosis (k = 0.83). CONCLUSION: Calcaneal tendon calcifications are frequent and asymptomatic findings in patients with CC, and they have a high specificity for this disease. US shows high agreement with radiography in depicting calcifications and enthesophytosis. Inflammatory changes of the calcaneal soft tissues are frequently observed by US and PDS in patients with chondrocalcinosis.

Achilles Tendon↗
PubMed2006

[Patients suffered from enlarged vestibular aqueduct syndrome in Chifeng deaf and dumb school detected by Pendred's syndrome gene hot spot mutation screening].

OBJECTIVE: To investigate the incidence of hot spot mutation of PDS gene by genetic screening testing method in Chifeng City, Inner Mongolia. The feasibility and effectiveness of genetic screening method in finding enlarged vestibular aqueduct syndrome were confirmed by temporal bone CT scan. METHODS: DNA were extracted from peripheral blood of 141 students of Chifeng Deaf and Dumb school. PDS IVS7-2 A-G mutation, the most common PDS mutation in Chinese population, was analyzed by direct sequencing for PDS exon 7, exon 8 with intron 7. The individuals found with homozygous or heterozygous PDS IVS7-2 A-G mutation were given further temporal CT scan, ultrasound scan of thyroid and thyroid hormone assays. The results of PDS genetic screening and temporal bone CT scan were compared with each other. RESULTS: The sequencing results revealed twenty cases carrying PDS IVS7-2 A-G mutation, of whom nine cases were homozygous mutation and eleven cases were heterozygous mutation. Eighteen cases underwent temporal bone CT scan except two cases that left the school due to other health problem. Sixteen cases were confirmed to be enlarged vestibular aqueduct syndrome (EVAS) by CT scan and the shape and function of thyroid were clinically normal by ultrasound scan of thyroid and thyroid hormone assays, respectively. CONCLUSIONS: The patients suffered from EVAS can be diagnosed by the screening for the PDS hot spot mutation which has unique advantage in epidemiologic study in large scale deaf population. The preliminary data of this study suggested relatively high incidence of EVAS in Chifeng area.

Adolescent↗
PubMed1986

Control theory applied to neural networks illuminates synaptic basis of interictal epileptiform activity.

A brief historical account is presented of the formulation of two hypotheses that have been proposed to explain the mechanisms underlying the paroxysmal depolarizing shift (PDS) in experimental epilepsy. The two hypotheses are called the giant EPSP hypothesis and the endogenous burst hypothesis. The giant EPSP hypothesis states that the PDS (the intracellular correlate of the interictal discharge) is comprised of a larger-than-normal-strength excitatory synaptic input, whereas the endogenous burst hypothesis states that the PDS is an endogenous burst triggered by an excitatory postsynaptic potential of normal strength. Two sets of four experimentally testable predictions, which were derived from these two hypotheses for the PDS, are presented. These predictions describe the expected behavior of the PDS in response to changes in membrane potential and under conditions of voltage clamping. With the advent of single-electrode current- and voltage-clamp techniques and improved intracellular recording conditions, the testing of these predictions has become possible. Experiments are described in which each of the predictions from the two hypotheses were tested. The results strongly support the giant EPSP hypothesis and are not easily reconciled with the endogenous burst hypothesis. Because the PDS is a network-driven event, it is important to understand the properties of the neuronal network responsible for the genesis of the PDS. Others have proposed that there are three necessary conditions for epileptiform activity in any neuronal network: endogenous bursting, disinhibition, and recurrent excitatory synapses. Using control theory as a frame of reference, we argue that it is premature to raise these three phenomena to the level of general theoretical requirements for interictal activity. Insufficient quantitative information exists about the properties of neurons, synapses, and connectivity patterns in any cortical neuronal network to conclude that the three preposed requirements are necessary and sufficient general conditions for epileptiform activity. Because all of the key predictions of the giant EPSP hypothesis have now been experimentally verified, we conclude that the PDS is a large, network-driven EPSP. The current challenge to neurophysiologists is to describe is detail the properties of neurons and synapses in a cortical neuronal network and then to evaluate the relative contributions of network and individual neuronal properties to the expression of interictal epileptiform activity.

Animals↗
PubMed1996

[Clinical evaluation of power Doppler sonography for the diagnosis of hepatocellular carcinoma].

We compared power Doppler sonography (PDS) with conventional color Doppler sonography (CDS) in the visualization of intratumoral blood flow of hepatocellular carcinoma (HCC) and evaluated the usefulness of PDS for assessing of the effects of TAE with Lipiodol and anticancer agents (Lp-TAE) and for the diagnosis of recurrence of HCC after Lp-TAE. The ability of PDS and CDS to visualize intratumoral blood flow was compared in 36 patients with HCC, and the usefulness of PDS for the diagnosis of HCC was evaluated. Also, in 17 patients with HCC who underwent Lp-TAE, the usefulness of PDS for evaluating the therapeutic effects of Lp-TAE and the diagnosis of recurrence after Lp-TAE was examined. The ability of PDS to visualize intratumoral blood flow and delineate tortuous and meandering intratumoral vasculature was superior to that of CDS. The effects of Lp-TAE could be evaluated and recurrence detected accurately and easily by PDS on the basis of residual intratumoral blood flow and the appearance of new blood flow. PDS is expected to achieve widespread acceptance as a useful imaging modality for the diagnosis of HCC, assessment of therapeutic effects of TAE, and detection of recurrence of HCC after TAE.

Carcinoma, Hepatocellular↗
PubMed1996

Personality disorders predict onset of Axis I disorders and impaired functioning among homosexual men with and at risk of HIV infection.

BACKGROUND: A longitudinal study was conducted to investigate whether personality disorders (PDs) increase risk for the development of future Axis I disorders and serious functional impairment among human immunodeficiency virus (HIV)-seropositive and HIV-seronegative homosexual men. METHOD: Baseline assessments of PDs, Axis I disorders and symptoms, and Global Assessments of Functioning were conducted with a community sample of 107 (66 HIV-positive and 41 HIV-negative) homosexual men participating in a longitudinal study with semiannual interviews over 3 years. RESULTS: Logistic regression analysis indicated that PDs predicted onset of subsequent Axis I disorders after controlling for both HIV status and lifetime Axis I history (adjusted odds ratio, 4.31; P=.01; 95% confidence interval, 1.39 to 13.32). Of the 21 participants with PDs, 16 (76%) were subsequently diagnosed with Axis I disorders on at least one occasion. By contrast, only 36 (42%) of the 86 participants without PDs were subsequently diagnosed with Axis I disorders. Further, 33% of the participants with PDs, in comparison with only 8% of those without PDs, were assigned Global Assessments of Functioning scores of 50 or lower, indicating serious impairment during the postbaseline study period (adjusted odds ratio, 5.70; P<.005; 95% confidence interval, 1.66 to 19.53). CONCLUSION: Personality disorders may contribute to increased risk for onset of Axis I disorders and serious impairment among homosexual men regardless of HIV serologic status.

Adult↗
PubMed2004

Co-occurrence of 12-month alcohol and drug use disorders and personality disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

BACKGROUND: Very little information is available on the co-occurrence of different personality disorders (PDs) and alcohol and drug use disorders in the US population. OBJECTIVE: To present national data on sex differences in the co-occurrence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol and drug use disorders and 7 of the 10 DSM-IV PDs. DESIGN: Face-to-face interviews conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43 093). SETTING: The United States and the District of Columbia, including Alaska and Hawaii. PARTICIPANTS: Household and group-quarters residents, aged 18 years and older. RESULTS: Among individuals with a current alcohol use disorder, 28.6% (95% confidence interval [CI], 26.7-30.6) had at least 1 PD, whereas 47.7% (95% CI, 43.9-51.6) of those with a current drug use disorder had at least 1 PD. Further, 16.4% (95% CI, 15.1-17.6) of individuals with at least 1 PD had a current alcohol use disorder and 6.5% (95% CI, 5.7-7.3) had a current drug use disorder. Associations between PDs and alcohol and drug use disorders were overwhelmingly positive and significant (P <.05). Overall, alcohol use disorders were most strongly related to antisocial (odds ratio [OR], 4.8; 95% CI, 4.1-5.6), histrionic (OR, 4.7; 95% CI, 3.8-5.8), and dependent (OR, 3.0; 95% CI, 1.9-4.8) PDs. Drug use disorders also were more highly associated with antisocial (OR, 11.8; 95% CI, 9.7-14.3), histrionic (OR, 8.0; 95% CI, 6.0-10.7), and dependent (OR, 11.6; 95% CI, 7.1-19.1) PDs. Associations between obsessive-compulsive, histrionic, schizoid, and antisocial PDs and specific alcohol and drug use disorders were significantly stronger (P <.04) among women than men, whereas the association between dependent PD and drug dependence was significantly greater (P <.04) among men than women. CONCLUSIONS: The co-occurrence of PDs with alcohol and drug use disorders is pervasive in the US population. Results highlight the need for further research on the underlying structure of these disorders and the treatment implications of these disorders when comorbid.

Adolescent↗
PubMed2006

Problem-solving ability and comorbid personality disorders in depressed outpatients.

Major depressive disorder (MDD) is associated with poor problem-solving abilities. In addition, certain personality disorders (PDs) that are common among patients with MDD are also associated with limited problem-solving skills. Attempts to understand the relationship between PDs and problem solving can be complicated by the presence of acute MDD. Our objective in this study was to investigate the relationships between PDs, problem-solving skills, and response to treatment among outpatients with MDD. We enrolled 312 outpatients with MDD in an open, fixed-dose, 8-week fluoxetine trial. PD diagnoses were ascertained via structured clinical interview before and after fluoxetine treatment. Subjects completed the Problem-Solving Inventory (PSI) at both time points. We used analyses of covariance (ANCOVAs) to assess relationships between PD diagnoses and PSI scores prior to treatment. Subjects were divided into three groups: those with PD diagnoses that remained stable after fluoxetine treatment (N=91), those who no longer met PD criteria after fluoxetine treatment (N=119), and those who did not meet criteria for a PD at any time point in the study (N=95). We used multiple chi(2) analyses to compare rates of MDD response and remission between the three PD groups. ANCOVA was also used to compare posttreatment PSI scores between PD groups. Prior to fluoxetine treatment, patients with avoidant, dependent, narcissistic, and borderline PDs reported significantly worse problem-solving ability than did patients without any PDs. Only subjects with dependent PD remained associated with poorer baseline problem-solving reports after the effects of baseline depression severity were controlled. Patients with stable PD diagnoses had significantly lower rates of MDD remission. Across PD groups, problem solving improved as MDD improved. No significant differences in posttreatment problem-solving were found between PD groups after controlling for baseline depression severity, baseline PSI score, and response to treatment. Treatment with fluoxetine is less likely to lead to remission of MDD in patients with stable PDs. More study is needed to investigate causal links between PDs, problem solving, and MDD treatment response.

Adult↗
PubMed1991

Bicuculline-induced epileptogenesis in the human neocortex maintained in vitro.

Intracellular and extracellular recordings were made from human neocortical slices of the temporal lobe maintained in vitro. The slices were treated with bicuculline methiodide to reduce synaptic inhibition mediated by tha gamma-aminobutyric acid A (GABAA) receptor. Spontaneously occurring epileptiform activity was never observed in over 60 slices examined. All epileptiform discharges were elicited by single-shock stimuli delivered in the underlying white matter or within the cortical layers. Intracellularly, the stimulus-induced epileptiform discharge resembled the paroxysmal depolarization shift (PDS). This potential was observed in neurons located between 200 and 2200 microns from the pia. It was characterized by a 100-1800 ms long depolarization which triggered burst firing of action potentials, and was at times followed by an afterdischarge. Simultaneous intracellular and extracellular recordings showed that each PDS was reflected by the synchronous discharge of a neuronal aggregate. The voltage behaviour of the PDS and its preceding EPSP was analyzed in cells that were injected with the lidocaine derivative QX-314. The amplitudes of the PDS depolarizing envelope measured at its peak and during its falling phase both behaved as a monotonic function of the membrane potential by increasing in amplitude during hyperpolarization. In addition, the PDS peak amplitude showed a much greater rate of increase than the early EPSP peak amplitude, thus suggesting that the synaptic conductance underlying the PDS was much greater. Perfusion of the neocortical slices with the N-Methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-phosphonovaleric acid (APV) reduced both the duration and the amplitude of the paroxysmal field discharge in a dose related fashion. The effects of APV were reflected intracellularly by an attenuation of the PDS's late phase and a blockade of the afterdischarge. Similar findings were also obtained by using the NMDA receptor antagonist 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid. These data indicate that reduction or blockade of the GABAA receptor is sufficient to elicit epileptiform discharges in the human neocortex maintained in vitro. Mechanisms dependent upon the NMDA receptor contribute to this type of epileptiform response mainly by prolonging the stimulus-induced depolarizing potential and the associated burst of firing.

2-Amino-5-phosphonovalerate↗