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Biomedical subjects

D Rock

Publications and source records attributed to D Rock.

At least 19 recordsLinked to original sources

Laparoscopic mesh cruroplasty for large paraesophageal hernias.

BACKGROUND: Previous studies have shown that surgical repair of paraesophageal hernias is associated with a high recurrence rate, especially when a laparoscopic approach is used. Anatomic recurrence due to crura breakdown is a primary etiology, which has led us to employ prosthetic mesh reinforcement of large hiatal defects (> 5 cm) since 1996. We discuss the evolution of this approach and describe our current technique with limited outcomes in 52 consecutive patients during a 5-year period. METHODS: There were 31 males and 21 females, with a mean age of 57 years (range, 32-77 years) with symptomatic reflux and endoscopic or radiologic evidence of a large paraesophageal hernia. Utilizing a laparoscopic approach, the contents of the sac were reduced and the crura approximated with permanent interrupted sutures and a prosthetic mesh was secured over the repair as an on-lay reinforcement buttress. A Nissen (42) or Tilley (9) fundoplication was performed in all but 1 patient, and 18 patients (34%) required a wedge collis gastroplasty. Fifteen patients (28%) had a previous unsuccessful antireflux operation. RESULTS: There was no perioperative morbidity or mortality. Follow-up averaged 25 months (range, 7-60 months). Postoperative gastroscopy or barium swallow have been performed in 27 patients to date, with 11 experiencing foregut symptoms. There has been 1 recurrence (1.9%) and no prosthetic erosion. CONCLUSION: Early results suggest that prosthetic mesh cruroplasty may be effective in reducing recurrence after laparoscopic repair of large paraesophageal hernias, but long-term follow-up is required in all patients to determine the true incidence of anatomic recurrence and prosthetic erosion.

Adult↗

Linkage analysis of candidate regions using a composite neurocognitive phenotype correlated with schizophrenia.

As schizophrenia is genetically and clinically heterogeneous, systematic investigations are required to determine whether ICD-10 or DSM-IV categorical diagnoses identify a phenotype suitable and sufficient for genetic research, or whether correlated phenotypes incorporating neurocognitive performance and personality traits provide a phenotypic characterisation that accounts better for the underlying variation. We utilised a grade of membership (GoM) model (a mathematical typology developed for studies of complex biological systems) to integrate multiple cognitive and personality measurements into a limited number of composite graded traits (latent pure types) in a sample of 61 nuclear families comprising 80 subjects with ICD-10/DSM-IV schizophrenia or schizophrenia spectrum disorders and 138 nonpsychotic first-degree relatives. GoM probability scores, computed for all subjects, allowed individuals to be partly assigned to more than one pure type. Two distinct and contrasting neurocognitive phenotypes, one familial, associated with paranoid schizophrenia, and one sporadic, associated with nonparanoid schizophrenia, accounted for 74% of the affected subjects. Combining clinical diagnosis with GoM scores to stratify the entire sample into liability classes, and using variance component analysis (SOLAR), in addition to parametric and nonparametric multipoint linkage analysis, we explored candidate regions on chromosomes 6, 10 and 22. The results indicated suggestive linkage for the familial neurocognitive phenotype (multipoint MLS 2.6 under a low-penetrance model and MLS>3.0 under a high-penetrance model) to a 14 cM area on chromosome 6, including the entire HLA region. Results for chromosomes 10 and 22 were negative. The findings suggest that the familial neurocognitive phenotype may be a pleiotropic expression of genes underlying the susceptibility to paranoid schizophrenia. We conclude that use of composite neurocognitive and personality trait measurements as correlated phenotypes supplementing clinical diagnosis can help stratify the liability to schizophrenia across all members of families prior to linkage, allow the search for susceptibility genes to focus selectively on subsets of families at high genetic risk, and augment considerably the power of genetic analysis.

Adolescent↗

Positive and negative thought disorder and psychopathology in childhood among subjects with adulthood schizophrenia.

UNLABELLED: The New York High-Risk Project (NYHRP) is a longitudinal study of offspring of parents with schizophrenia or affective disorder and normal controls. Neuropsychological deficits had been observed at about age 9 in subjects with adulthood schizophrenia. We explored whether in these subjects, early signs of clinical schizophrenia-related symptoms, such as thought disorder or behavioral abnormalities, could also be observed. METHODS: We rated thought disorder and symptoms from videotaped interviews at age 9, using the Scale for the Assessment of Thought, Language and Communication (TLC), and the Mental Health Assessment Form (MHAF). With factor analyses we examined the structure of the ratings, and from interpretable factors, scales were assembled. MANOVAs were used to examine the effect of parental risk and adulthood psychiatric diagnosis (schizophrenia-related psychosis (SRP), major affective disorder (MAD), no disorder/other (NoDx/other)) as independent variables (IV) on thought disorder and symptoms as dependent variables. RESULTS: Global, positive and negative thought disorder, and negative symptoms were significantly higher in subjects with adulthood schizophrenia-related psychosis than both comparison groups. A significant interaction between the two IVs was effective with respect to positive thought disorder. This scale was particularly elevated among subjects with adulthood schizophrenia-related psychosis at parental risk for affective disorder (all of whom had adulthood schizoaffective disorder). CONCLUSIONS: We were able to show that global, negative and positive thought disorder and negative symptoms were present in subjects with adulthood schizophrenia already at mid-childhood, years before onset of psychosis. Further, we found a particularly high propensity to positive symptoms in subjects with adulthood schizophrenia who have also an affective component in their symptoms. This association, previously reported in acute schizophrenia, was here observed years before the first psychotic episode.

Adult↗

Inexpensive purification of P450 reductase and other proteins using 2',5'-adenosine diphosphate agarose affinity columns.

Two reductases, P450 oxidoreductase and P450Bm-3 reductase, were purified on a 2',5'-adenosine diphosphate solid support. Although the efficiency of these columns is well established, the cost of the resin and the eluting material 2'-adenosine can be prohibitive. Herein we show that the less costly 2',3'-adenosine monophosphate is an excellent eluting material.

Adenosine Diphosphate↗

HoNOS: is there any point in training clinicians?

This study examines the impact of training and clinical experience on the inter-rater reliability of the HoNOS. Following either standard or modified HoNOS training, two groups of registered mental health nurses (RMHNs) were tested for inter-rater reliability (IRR) using a standard case vignette. In addition, another group of nurses and two nonclinical comparison groups had their IRR tested using the same vignette but without receiving any HoNOS training. There was no significant difference between IRR scores post-training compared with the pre-training scores. This is the case whether the recommended or modified training programmes were used. In addition, there is no significant difference between nurses and the comparison group, characterized by nonclinical work experience in a mental health setting. All four groups achieved adequate IRR. Finally, the comparison group with no regular exposure to mental health patients but experience using rating scales are significantly less reliable than the other four groups. The results suggest two possible interpretations. The first is that the HoNOS scales are so well designed that only familiarity with psychiatric patients and no experience with rating scales is sufficient to achieve adequate IRR even without training. Alternatively, the use of written vignettes does not provide a valid measure of HoNOS IRR.

Clinical Competence↗

Auditory sensory memory in schizophrenia: inadequate trace formation?

This study explored duration mismatch negativity reductions observed in individuals with schizophrenia, in particular, the relationship to behavioural measures of temporal discrimination and two event-related potential (ERP) components occurring during the first phase of auditory sensory memory. Twenty-two patients with a DSM-IV and ICD-10 diagnosis of schizophrenia and 25 healthy comparison volunteers participated in a behavioural and an ERP testing session. Both groups performed equivalently on behavioural estimates of filled interval duration discrimination and gap detection. In contrast, electrophysiological measures revealed a significant reduction in patients' duration mismatch negativity and a significant difference in patients for the pattern of N100 facilitation over short stimulus onset asynchronies. Whilst behavioural results indicate intact temporal processing of filled intervals and equal temporal resolution limits in schizophrenia, both ERP measures indicated differences in auditory processing that may be traced to activity occurring during the first 250 ms. Results highlight the possibility of abnormalities in the process of auditory trace formation and temporal summation in schizophrenia.

Acoustic Stimulation↗

Duration and frequency mismatch negativity in schizophrenia.

OBJECTIVES: The aim of the present study was to elucidate the reasons for apparent inconsistencies in the schizophrenia literature with respect to the mismatch negativity (MMN) waveform of the event-related potential (ERP). While most previous research has shown that MMN is reduced in schizophrenia, there are a small number of studies reporting that frequency MMN is not reduced. METHODS: We recorded ERPs to auditory stimuli with different frequencies and durations from patients with schizophrenia (N = 14) and control subjects (N = 17) of similar age and sex. MMNs to small but discriminable frequency deviants were contrasted with large frequency deviants and duration deviants. RESULTS: Only the MMN to duration deviants was significantly reduced in patients, although there was evidence of a similar trend for large frequency deviants. CONCLUSIONS: The results together with a review of the frequency MMN literature suggest that there are 3 variables which are important in determining whether patients exhibit a reduced MMN to frequency deviants: deviant probability, degree of deviance and interstimulus interval. The results also indicated that patients with schizophrenia may have particular deficits in processing the temporal properties of auditory stimuli. This finding has implications for the pathophysiology of the disorder as time-dependent processing is reliant on the integrity of an extensive network of brain areas consisting of auditory cortex, areas of pre-frontal cortex, the basal ganglia and cerebellum.

Acoustic Stimulation↗

Does drawing up technique influence patients' perception of pain at the injection site?

Traditionally nurses have used one of two drawing up techniques for the administration of intramuscular (i.m.) injections. In the first, the injectable is drawn up using one needle, which is then discarded before administration using a new needle. Alternatively, the injectable is drawn up and administered without changing the needle. Advocates of the two-needle technique suggest that this method reduces pain at the injection site. In the present study, 70 subjects completed an independently validated pain scale following administration of an i.m. depot neuroleptic. The conclusion, that there is a significant reduction in injection site pain, using the two-needle technique, is not supported by the data obtained in this study.

Analysis of Variance↗

Phenotypic markers as risk factors in schizophrenia: neurocognitive functions.

OBJECTIVE: To review the literature on neurocognitive measures as risk markers for schizophrenia and to present data from the Perth family study of schizophrenia. Of all the risk markers that have been identified, the most promising are deficits in sustained attention. METHOD: Inclusion in the review was determined by whether the research addressed a number of key questions: methods of assessing sustained attention; evidence of sustained attention deficits in patients and first-degree relatives including children; the importance of attentional dysfunction in the schizophrenic process and functional outcome; and the biological basis of sustained attention deficits. RESULTS: Sustained attention deficits are evident in both patients and a proportion of their first-degree relatives, a finding replicated in preliminary data from the Perth family study. The literature suggests that the attention deficit is a stable enduring trait that is independent of clinical state. The neural basis of the deficit may be a functional disconnection between prefrontal and parietal cortex. Attention impairment is an important predictor of functional outcome in patients and the development of social dysfunction in adulthood in the at-risk offspring of patients. However, sustained attention deficits that are measured in childhood results in an unacceptable high false-positive rate (21%) when predicting which at-risk offspring of parents with schizophrenia will develop a schizophrenia spectrum disorder, although the overall classification accuracy (78%) is impressive. CONCLUSIONS: The main findings are that sustained attention deficits are important risk markers for schizophrenia but need to be supplemented by other neurocognitive risk markers to improve predictive accuracy.

Adult↗

The New York High-Risk Project: comorbidity for axis I disorders is preceded by childhood behavioral disturbance.

The relationship between childhood behavioral disturbance and comorbidity for adult psychiatric disorders has not been sufficiently investigated. Subjects of this report (N = 185) were offspring of parents with schizophrenia or affective disorder and of normal parents from the New York High-Risk Project. Data on childhood behavior at the mean age of 9.5 years were obtained in a parent interview at initial assessment in 1971-72. Adulthood outcomes were assessed through standardized interviews, and lifetime axis I diagnoses were based on Research Diagnostic Criteria. Subjects with comorbidity for axis I disorders exhibited significantly more behavioral problems as children, compared with those who developed either one or no psychiatric disorder in adulthood. This association was not biased by gender or parental diagnosis of psychiatric disorder. The findings emphasize that psychiatric comorbidity can be traced back to childhood and underline the importance of longitudinal observations in psychiatric research.

Adult↗

Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project.

OBJECTIVE: Childhood neurobehavioral deficits in offspring of schizophrenic, affectively ill, and psychiatrically normal parents were evaluated as predictors of schizophrenia-related psychoses in adulthood. METHOD: The offspring were tested with neurobehavioral measures at 7-12 years of age and assessed in mid-adulthood for axis I diagnoses. The relationships of childhood deficits in attention, verbal memory, and gross motor skills to adulthood schizophrenia-related psychoses were examined in separate path analyses by using logistic regression equations. Sensitivity and specificity were determined for each of the childhood dysfunctions. RESULTS: For the offspring of schizophrenic parents, childhood deficits in verbal memory, gross motor skills, and attention identified 83%, 75%, and 58%, respectively, of the subjects with schizophrenia-related psychoses; 50% were identified by all three variables combined. False positive rates in subjects who did not develop schizophrenia-related psychoses ranged from 18% for those with deficits in attention during childhood to 28% for those with deficits in memory. The three variables had low deficit rates in the offspring of the other two parental groups and were not associated with other psychiatric disorders in any group. CONCLUSIONS: Schizophrenia-related psychoses in adulthood are distinguished in subjects at risk for schizophrenia by childhood deficits in verbal memory, gross motor skills, and attention. The findings suggest that deficits in these variables are relatively specific to schizophrenia risk and may be indicators of the genetic liability to schizophrenia.

Adolescent↗

Relationship between childhood behavioral disturbance and later schizophrenia in the New York High-Risk Project.

OBJECTIVE: An association between childhood behavioral disturbance and adulthood schizophrenia has been seen previously in retrospective or follow-back studies and in prospective studies. The authors examined the relationship between childhood behavioral problems and adulthood schizophrenia-related psychoses. Because a high rate of childhood behavioral problems is known to be associated with adult substance abuse, these analyses controlled for substance abuse. METHOD: The subjects of this investigation (N = 185) were offspring of parents with schizophrenia or affective disorder and of normal parents from the New York High-Risk Project (sample A). Data on childhood behavioral problems were obtained in a parent interview at initial assessment in 1971-1972. Adulthood outcomes (schizophrenia-related psychoses, affective disorders, anxiety disorders, substance abuse) were based on lifetime axis I diagnoses according to the Research Diagnostic Criteria. RESULTS: Substance abuse had a significant interaction with the clinical outcome groups. In subjects without substance abuse, those with schizophrenia-related psychoses had exhibited significantly more behavioral problems as children than had adult offspring with affective or anxiety disorder or with substance abuse only or no disorder. CONCLUSIONS: These results support the view that schizophrenia-related psychoses can be followed back to early behavioral disturbances. The confounding effects of substance abuse should be statistically controlled in studies of longitudinal associations between childhood behavioral disturbance and axis I outcomes.

Adult↗

The New York High-Risk Project: social and general intelligence in children at risk for schizophrenia.

UNLABELLED: Social deficits, as well as low performance on intelligence tests, are known early symptoms of schizophrenia. We studied whether impairment of social intelligence can be detected before the outbreak of the disorder. In the New York High-Risk Project, children at risk for schizophrenia (HRSz) or affective disorder (HRAff) and a normal control group (NC) were studied over the past 26 years. The children are now in mid-adulthood, with known psychiatric outcomes. Developmental and clinical data from childhood can now be related to adulthood diagnoses. We compared mean WISC (or WISC-R) and WAIS (or WAIS-R) scores from childhood and adolescence, and change of IQ, between the risk groups, as well as between the adulthood outcomes. We were specifically interested in the development of social intelligence (the Picture Arrangement and Comprehension subtests). We used logistic regression analyses to generate a model predicting adulthood schizophrenia. RESULTS: IQ at age 9,7 was lower in children with HRSz than with HRAff. Adulthood schizophrenia, compared with major depressive disorder and no psychiatric diagnosis could not be related conclusively to low IQ. This may be a result of the study design, since children with IQ below 70 or behavioral problems were not eligible as study subjects. There was no evidence of lower scores or more decline in social intelligence related to age or group membership (risk or outcome). Subtest-Scatter, a nondirectional measure of the differences between all subtests and Vocabulary, reflecting a lesser difference between crystallized and fluid intelligence, was identified as a significant predictor of adulthood schizophrenia, in the whole group as well as in the HRSz group alone.

Adolescent↗

The New York High-Risk Project: attention, anhedonia and social outcome.

In the New York High-Risk Project we have followed two samples of subjects (Sample A and Sample B) at risk for schizophrenic or affective disorders and low-risk controls from childhood to adulthood, in an attempt to identify early predictors of later psychopathology. We administered a large number of cognitive, psychometric and other types of measures to both samples as possible psychopathology predictors, including an index of attentional deviance assessed in childhood, the Physical Anhedonia Scale in adolescence, and three measures of social outcome in adulthood ('Suspicious Solitude', 'Social Insecurity', and 'Lack of Empathy'), derived from the Personality Disorders Examination. In the analysis of the combined samples, parental diagnostic group, gender, attentional deviance in childhood, and physical anhedonia in adolescence were used to predict three measures of social outcome in adulthood. While only physical anhedonia was directly related to all three social outcome measures, with the strongest relationship to Suspicious Solitude, attention deviance successfully predicted two of the three outcomes. Subjects at risk for affective disorder did not show increased levels of attention deviance, physical anhedonia, or social dysfunction, relative to the normal control subjects. Attention deviance appears to be a key neurobiological indicator and physical anhedonia appears to be a potentiating factor mediating the relationship between risk for schizophrenia and later social dysfunction.

Adolescent↗

The bovine herpesvirus type 1 UL3.5 open reading frame encodes a virion structural protein.

The bovine herpesvirus type 1 (BHV-1) open reading frame (ORF) UL3.5 is similar to ORFs found in pseudorabies virus, infectious laryngotracheitis virus, equine herpesvirus type 1, and varicella zoster virus, but clearly absent from herpes simplex virus. The published sequence for this ORF predicts a 126-amino-acid (13.2 kDa) protein product with an isoelectric point of 12.3. We confirmed the UL3.5 sequence, expressed the ORF as a glutathione-S-transferase fusion protein, and made rabbit antibodies against the purified fusion protein. The antiserum detected a 13-kDa protein in Western blots of MDBK cells infected with BHV-1, but not with other herpesviruses or uninfected cells. The BHV-1 UL3.5 protein was characterized as a component of the virion envelope or tegument because it was expressed as a late protein, it was present in the cytoplasm but not the nucleus of infected cells, and it was removed from purified virions by detergent extraction.

Animals↗

The New York High-Risk Project. Prevalence and comorbidity of axis I disorders in offspring of schizophrenic parents at 25-year follow-up.

BACKGROUND: The New York High-Risk Project is a study of offspring of patients with schizophrenia (HRSz group) or affective illness (HRAff group) and psychiatrically normal parents (NC group) observed prospectively from childhood to adulthood. We herein present lifetime prevalence and comorbidity rates of Axis I disorders in subjects and their siblings from sample A of the project. METHODS: Schedule for Affective Disorders and Schizophrenia-Lifetime Version interviews conducted with the offspring in adulthood were used to obtain diagnoses of Axis I disorders. RESULTS: Schizophrenia and unspecified psychoses occurred only in the HRSz group. However, schizoaffective and psychotic affective disorders occurred equally in the HRSz and HRAff groups. Total rates of psychosis in these groups were significantly higher than in the NC group. All groups had similar rates of nonpsychotic affective and substance abuse disorders. The HRAff group, however, had significantly more total affective illness than the NC group and tended to have more anxiety disorders than the other groups. Comorbidity rates in the HRSz and HRAff groups were nearly twice those of the NC group. CONCLUSIONS: The familial liabilities to schizophrenia and affective disorders show specificities and commonalities, differing markedly from each other in their expression of some disorders and sharing others. Patterns of comorbidity are generally, although not entirely, similar to these liabilities.

Adolescent↗