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Biomedical subjects

D Strauss

Publications and source records attributed to D Strauss.

At least 19 recordsLinked to original sources

Centralisation of oesophagogastric cancer services: can specialist units deliver?

INTRODUCTION: Oesophagogastric cancer surgery is increasingly being performed in only centralised units. The aim of the study was to examine surgical outcomes and service delivery within a specialist unit. PATIENTS AND METHODS: The case notes of all patients undergoing attempted oesophagogastrectomy between January 2000 and May 2003 were identified from a prospective consultant database. RESULTS: A total of 187 patients (median age, 63 years; range, 29-83 years; M:F ratio, 3.9:1) underwent attempted oesophago-gastrectomy. Of these, 91% were seen within 2 weeks of referral and treatment was instituted after a mean of 31 days (range, 1-109 days). More patients underwent surgery (63%) than neoadjuvant therapy (56%) within 1 month of referral. The main indication for surgery was invasive malignancy in 166 patients (89%). The 30-day mortality was 0.5% (1 death) and in-hospital mortality was 1.1% (2 deaths). The median length of hospital stay was 14 days (range, 7-69 days). Significant postoperative morbidity included: pulmonary complications (36%), cardiovascular complications (16%), wound infection (13%) and clinically significant anastomotic leaks (7%). Of the study group, 28 patients (15%) were admitted to ICU with a median stay of 10 days (range, 1-44 days); this accounted for 0.9% of ICU bed availability. Twelve patients (6.4%) were returned to theatre, most commonly for bleeding. The 1-year survival rates were 78%. During 2002-2003, national waiting list targets for both hernia repair and cholecystectomy were achieved. CONCLUSIONS: Despite recent increases in workload, high volume specialist units can deliver an efficient and timely service with both good treatment outcomes and minimal impact upon elective surgical waiting lists and ICU provision.

Adult↗

A nuclear AAA-type ATPase (Rix7p) is required for biogenesis and nuclear export of 60S ribosomal subunits.

Ribosomal precursor particles are assembled in the nucleolus before export into the cytoplasm. Using a visual assay for nuclear accumulation of 60S subunits, we have isolated several conditional-lethal strains with defects in ribosomal export (rix mutants). Here we report the characterization of a mutation in an essential gene, RIX7, which encodes a novel member of the AAA ATPase superfamily. The rix7-1 temperature-sensitive allele carries a point mutation that causes defects in pre-rRNA processing, biogenesis of 60S ribosomal subunits, and their subsequent export into the cytoplasm. Rix7p, which associates with 60S ribosomal precursor particles, localizes throughout the nucleus in exponentially growing cells, but concentrates in the nucleolus in stationary phase cells. When cells resume growth upon shift to fresh medium, Rix7p-green fluorescent protein exhibits a transient perinuclear location. We propose that a nuclear AAA ATPase is required for restructuring nucleoplasmic 60S pre-ribosomal particles to make them competent for nuclear export.

Adenosine Triphosphatases↗

Long-term causes of death after traumatic brain injury.

OBJECTIVE: To determine which causes of death are more frequent in persons with traumatic brain injury (TBI), and by how much, compared with the general population. Our focus was the period beginning 1 yr after injury. DESIGN: Subjects were 2320 Californians with long-term mental disability after a TBI at age 10 yr or more, followed up between 1988 and 1997. The units of study were person-years, each linked to the subject's age, gender, level of ambulation, time since injury, and cause of death (if any) for the specific year. Observed numbers of cause-specific deaths were compared with numbers expected according to general population mortality rates. RESULTS: Mortality was higher between 1.0 and 5.0 yr postinjury than after 5.0 yr and was strongly related to reduced mobility. Death rates were elevated for circulatory diseases, respiratory diseases, choking/suffocation, and seizures, with seizure deaths being relatively frequent, even among the most ambulatory. CONCLUSIONS: Death rates for several causes are elevated in persons with long-term sequelae of TBI. The increased risk of choking/suffocation should be of interest to caregivers. Life expectancy seems to be reduced, even for patients who are fully ambulatory.

Activities of Daily Living↗

Classification of endocardial electrograms using adapted wavelet packets and neural networks.

The discrimination of ventricular tachycardias with 1:1 retrograde conduction from sinus tachycardia still remains a challenge for rate based algorithms commonly used in dual-chamber implantable cardioverter defibrillators. Morphology based analysis techniques for a classification of antegrade and retrograde atrial activation patterns can be used to cope with this problem. Here time-domain template matching techniques are known approaches. However, a time-domain representation of endocardial electrograms is not optimal for classification tasks as the dimensionality of the underlying signal space is high and features being irrelevant for a signal characterization are involved in the analysis. Therefore, the aim of this study is to develop an enhanced morphological analysis tool for a classification of antegrade and retrograde atrial activation by using a transform domain representation of endocardial electrograms. For this, we applied an adapted wavelet-packet decomposition to extract discriminating features in endocardial electrograms representing antegrade and retrograde activation patterns. Further, a feed-forward neural network was utilized to produce a classification based on the extracted information. In using our hybrid method, no false classification of the physiological and pathological cardiac state was made. It is concluded that the proposed classification scheme represents a highly efficient approach for a classification of antegrade and retrograde atrial activation.

Algorithms↗

Nuclear export of 60s ribosomal subunits depends on Xpo1p and requires a nuclear export sequence-containing factor, Nmd3p, that associates with the large subunit protein Rpl10p.

Nuclear export of ribosomes requires a subset of nucleoporins and the Ran system, but specific transport factors have not been identified. Using a large subunit reporter (Rpl25p-eGFP), we have isolated several temperature-sensitive ribosomal export (rix) mutants. One of these corresponds to the ribosomal protein Rpl10p, which interacts directly with Nmd3p, a conserved and essential protein associated with 60S subunits. We find that thermosensitive nmd3 mutants are impaired in large subunit export. Strikingly, Nmd3p shuttles between the nucleus and cytoplasm and is exported by the nuclear export receptor Xpo1p. Moreover, we show that export of 60S subunits is Xpo1p dependent. We conclude that nuclear export of 60S subunits requires the nuclear export sequence-containing nonribosomal protein Nmd3p, which directly binds to the large subunit protein Rpl10p.

Carrier Proteins↗

Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate.

Acyclovir resistance is not a recognized problem among neonates with perinatal herpes simplex virus (HSV) infection. A premature newborn with neurocutaneous HSV infection was treated for 21 days with acyclovir. Disseminated disease recurred 8 days later. A recurrent isolate was resistant to acyclovir and lacked thymidine kinase activity on the basis of a frameshift mutation in the thymidine kinase (tk) gene. Compared with the sensitive isolate obtained during primary infection, replication of the resistant isolate was reduced on primary and permanent cells and even further impaired on cells deleted for cellular tk. The resistant isolate lacked virulence in a murine model of genital infection. Acyclovir-resistant HSV-2 mutants can develop rapidly in neonatal infection and cause clinically significant disease, despite decreased replication in vitro and attenuated virulence in an animal model.

Acyclovir↗

Applied behavior management and acquired brain injury: approaches and assessment.

Individuals who have acquired brain injury (ABI) may express themselves through the use of challenging behaviors, such as aggression, withdrawal, disinhibition, and self-destructive behaviors. This article describes the effectiveness of behavior interventions derived from the assessment of behavior in a community-based setting. The premise is that behavior, no matter how difficult, has function, purpose, and meaning for the individual. A therapeutic model of behavior assessment is presented that bases its strength on behavior assessment and well-trained staff. A well-formulated behavior management plan is developed, reinforcing alternative behaviors teaching skills, and reducing unwanted behaviors. Through the use of data collection methods, the treatment team identifies variables related to unwanted behavior and outcomes of consequences as they relate to the behavior. Illustrated through a case study, the behavioral treatment model is defined through behavior identification, initial assessments, treatment approaches, and tracking outcomes.

Aggression↗

Comparative mortality of adults with traumatic brain injury in California, 1988--97.

We studied mortality rates of people with traumatic brain injury using the extensive California Department of Developmental Services database. The data provide mortality rates by age, gender, severity, cause, and associated conditions on 2629 subjects older than 15 years during 1988--97. Increased mortality was observed, particularly among patients with diminished mobility.

Adolescent↗

An analytic method for longitudinal mortality studies.

Our knowledge of mortality risks comes largely from longitudinal (cohort) studies. The most commonly used analytic tool is the Cox proportional hazards model for survival analysis. An alternative approach is a simple cross-sectional analysis of person-years. The key to the method is logistic regression, where the outcome variable is lived/died in the given year and the explanatory variables are age, sex, and other potential risk factors. This approach can be used to model any dichotomous outcome and has several important advantages over the more traditional survival analysis. As an example, we compare the two methods using a large data base of patients with spinal cord injury.

Adolescent↗

Causes of excess mortality in cerebral palsy.

It is well known that individuals with cerebral palsy (CP) are subject to higher mortality than the general population but the causes of this have not been systematically analysed. This study investigates mortality in a Californian population of 45,292 individuals with CP, 4028 of whom died during the 1986 to 1995 study period. The aims of this study were to identify diseases that may be causally linked with CP, and diseases whose diagnosis and/or treatment need improvement. Overall, the standardized mortality ratio (SMR) was 8.4. Mortality from breast cancer was three times that of the general population, suggesting poorer detection and/or treatment. The dramatic elevation of mortality due to brain cancer, especially in children (SMR=24), raises the possibility of a link between this and CP. Cause of death was non-specific in some individuals. Therefore, these SMRs are conservative. As expected, SMRs due to respiratory diseases were very high but, contrary to anecdotal reports, such diseases did not account for most deaths. High SMRs were also found for diseases of the circulatory and digestive systems. Finally, a marked elevation of deaths was due to external causes, including drowning and being hit by motor vehicles.

Adolescent↗

Inhibition of glutamine synthetase decreases proliferation of cultured rat intestinal epithelial cells.

The importance of glutamine synthetase (GS) for cell proliferation was examined in rat intestinal crypt cells (IEC-6) by inhibiting its activity with 10 mmol/L methionine sulfoximine (MS) at varying extracellular glutamine (Q) concentrations. In uninhibited cultures, cell number, protein, and DNA accumulation and synthesis showed a dependence on extracellular Q over a concentration range of 0.06 to 1.06 mmol/L, with apparent half-maximal responses of 0.46 mmol/L extracellular Q. In contrast, proliferation of GS-inhibited cultures required >/=1.06 mmol/L extracellular Q, with an apparent half-maximal response of 2 mmol/L. MS inhibited GS activity >97% in extracts of washed cells and appeared to be specific because its effects on proliferation were overcome by 4.06 mmol/L Q and were reversible. The increased dependence of IEC-6 cells on extracellular Q when GS was inhibited suggests that Q derived from GS (GS-Q) contributes importantly to cell proliferation at physiologic levels of extracellular Q (0.6 mmol/L). The unexpectedly high concentration of extracellular Q required to rescue maximal proliferation during GS-inhibition, relative to a reported Km for Q-transport into the cell, indicates that intracellular Q derived from the extracellular medium (exo-Q) is inefficiently utilized. In a previous study, we found that GS-protein and mRNA are concentrated in the proliferative crypt region of the small intestine in vivo, and predicted that GS activity is important for crypt cell proliferation. Here, we show that enzyme activity is important for cell proliferation at physiologic concentrations of Q in this cell culture model. Finally, we speculate that exo-Q and GS-Q are utilized differently in the cell.

Animals↗

Mortality of persons with developmental disabilities after transfer into community care: a 1996 update.

More than 2,000 persons with developmental disabilities have recently been transferred from California institutions into community care. Using data on 1,878 clients moved between April 1993 and December 1995, Strauss et al. (1998) found a corresponding increase in mortality rates. In the present report we update that study by analyzing 1996 data. There were 36 deaths, an 88% increase in risk-adjusted mortality over that expected in institutions, p < .01. We again found that persons transferred later were at higher risk than those moving earlier, even after adjustment for differences in risk profiles. In the highest functioning group, the community mortality rate was tripled. Death certificate information was also analyzed.

California↗

An extended Kaplan-Meier estimator and its applications.

We develop an extension of the Kaplan-Meier estimator for the case of multiple live states. The method can be used to construct prognostic charts for tracking individuals initially in a given condition. It is also the key component in constructing a longitudinal version of the multistate life table.

Adolescent↗

External causes of death among persons with developmental disability: the effect of residential placement.

The authors analyzed death rates from external causes (accidents, injuries, homicides, etc.) for persons with developmental disability in California. There were 520 such deaths during the 1981-1995 study period, based on 733,705 person-years of exposure; this represents all persons who received any services from the state. Compared with the general California population, persons with developmental disability were at lower risk of homicide, suicide, and poisonings (standardized mortality ratios, 0.31-0.68), but higher risk of pedestrian accidents, falls, fires, and, especially, drowning (standardized mortality ratio=6.22). A major focus of the study was comparisons between different residential settings. Persons in semi-independent living had significantly higher risk than did those in their family home or group homes, with homicides rates being three times higher and pedestrian accidents rates being doubled, while persons in institutions had much lower risks with respect to most causes. Of the 28 deaths due to drug and medication overdoses, 79 percent occurred in supported living or small-group homes. Avoidable deaths could be reduced by making direct care staff more aware of the risks and better trained in acute care, along with improved monitoring of special incidents.

Accidents↗

Psychobiological heterogeneity of familial and sporadic schizophrenia.

BACKGROUND: Although schizophrenia is presumed to be heterogeneous, there has been limited success distinguishing familial from sporadic cases. We used psychobiological measures to examine heterogeneity, as they may be closer to neurobiology than symptoms. Smooth pursuit eye movement quality (SPEM) and dichotic listening (DL) tests to tones and words were used to assess hemispheric laterality asymmetry. METHODS: Forty-six research unit patients participated in assessments of family history (FH) and physiological measures. FH was categorized by three exclusive groups: FH-1 patients had a chronic schizophrenia-related psychosis in a first-degree relative, FH-2 had it in second-degree relative, and FH-3 had no family member with a reoccurrence. RESULTS: Analysis of variance showed a significant group difference for SPEM and DL tones. SPEM was significantly worse in all three schizophrenia groups than for the normal comparison subjects. Among the schizophrenia groups, the nonfamilial group (FH-3) had the worst SPEM quality, FH-2 had intermediate quality, and FH-1 had the best quality. Conversely, only the nonfamilials (FH-3) had normal right hemispheric lateralization for tones, whereas familials did not, and FH-2 again had intermediate values. The lateralization quotient for DL words did not significantly differ among the groups. CONCLUSIONS: SPEM was affected most in sporadic, not familial schizophrenia, whereas dichotic listening was most affected in familial schizophrenia. This double dissociation supports the utility of the familial/sporadic distinction and suggests that etiological factors in different forms of schizophrenia may impact principally on distinct neurobiological substrates, despite similar patient phenomenology.

Adult↗

On Miettinen's multivariate confounder score.

Consider a regression model for the effect of a treatment on an outcome variable in the presence of potential confounders. It is common to test for main effects and interactions of the treatment variable; if the confounding variables are discrete, one might then compare the treatment groups within strata formed by suitable covariate patterns. An alternative, due to Miettinen, is to stratify according to a "multivariate confounder score" and test for treatment effects within strata. This test has been shown to be flawed, and the method appears largely to have fallen into disuse. Here we show that such stratification nevertheless provides a sound and often useful graphical comparison of treatment and control groups.

Child↗