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Biomedical subjects

C Clark

Publications and source records attributed to C Clark.

At least 91 records · Page 5Linked to original sources
PubMed1995

Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease.

In this clinical study the cerebrospinal fluid (CSF) level of a novel form of the beta-amyloid peptide (A beta) extending to position 42 (A beta 42) was determined in patients with Alzheimer's disease (AD) as well as controls. In addition to measurement of CSF A beta 42 levels, total A beta peptides, microtubule-associated protein tau, and apolipoprotein E (ApoE) genotype were also assessed. It is interesting that CSF A beta 42 levels were found to be significantly lower in AD patients relative to controls, whereas total A beta levels were not. A beta 42 has recently been shown to preferentially deposit in the brain tissue of patients with AD, suggesting that diminished clearance may account for its reduction in CSF. As previously reported, tau levels were increased in AD patients; however, neither A beta 42 nor tau levels were apparently influenced by the ApoE genotype.

Aged↗
PubMed1995

A controlled investigation of current and premorbid personality: characteristics of Parkinson's disease patients.

It has been suggested that before development of motor symptoms, Parkinson's disease (PD) patients with idiopathic display a specific cluster of personality traits consisting of increased rigidity, conscientiousness, industriousness, orderliness, and cautiousness. The idea of such a distinctive premorbid personality profile remains controversial. This hypothesis was reexamined using a methodology that expands on previous studies. Patients with idiopathic PD, probable Alzheimer's Disease (AD), and medical controls with nonneurological chronic progressive motor disorders were rated by a close relative on the NEO-Personality Inventory (PI) to compare current and premorbid personality profiles. For PD and control subjects, current and past self-ratings were also obtained. Results do not support the postulated distinctive PD personality either premorbidly or following onset of symptoms. Both in terms of the premorbid personality profile and perceived changes in personality post-dating the onset of illness, PD patients are similar to AD patients. Though not differing from medical controls premorbidly, after developing symptoms, PD patients were described as less extroverted; less exploratory and curious; and less organized, goal directed, and disciplined.

Age Factors↗
PubMed1995

Association of apolipoprotein epsilon 4 allele and neuropathologic findings in patients with dementia.

Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE epsilon 4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE epsilon 4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.

Aged↗
PubMed1995

Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest.

Human cytomegalovirus (HCMV) infection stimulates cellular DNA synthesis and causes chromosomal damage. Because such events likely affect cellular proliferation, we investigated the impact of HCMV infection on key components of the cell cycle. Early after infection, HCMV induced elevated levels of cyclin E, cyclin E-associated kinase activity, and two tumor suppressor proteins, p53 and the retinoblastoma gene product (Rb). The steady-state concentration of Rb continued to rise throughout the infection, with most of the protein remaining in the highly phosphorylated form. At early times, HCMV infection also induced cyclin B accumulation, which was associated with a significant increase in mitosis-promoting factor activity as the infection progresses. In contrast, the levels of cyclin A and cyclin A-associated kinase activity increased only at late times in the infection, and the kinetics were delayed relative to those for cyclins E and B. Analysis of the cellular DNA content in the infected cells by flow cytometry showed a progressive shift of the cells from the G1 to the S and G2/M phases of the cell cycle, leading to an accumulation of aneuploid cells at late times. We propose that these HCMV-mediated perturbations result in cell cycle arrest in G2/M.

Cell Cycle↗
PubMed1995

Ascertainment of myotonic dystrophy through cataract by selective screening.

Myotonic dystrophy (DM) almost always results from the expansion of an unstable (CTG)n repeat. The mutation can be detected directly. Affected patients with cataracts may have minimal additional signs of the disorder, but all are at risk of life threatening complications. We have studied the efficacy of detecting new families with myotonic dystrophy by selectively screening cataract patients. Selection criteria were: age under 60 with no obvious precipitating factor (except non-insulin dependent diabetes mellitus (NIDDM)); patients of any age with other signs suggestive of myotonic dystrophy detected by the ophthalmologist. Ninety-six patients were tested prospectively; 17 others under 55 were screened retrospectively. All patients were counselled by a clinical geneticist before testing. The patients' DNA was analysed using the DNA probe/restriction enzyme combinations GB2.6/EcoRI, KB1.4/BglI and polymerase chain reaction (PCR). Six patients have been found to have a mutation, three (3.1%) in the prospective group and three (17.6%) in the retrospective group. Three of these patients had minimal myotonic dystrophy and three had classical DM.

Adolescent↗
PubMed1995

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part IX. A prospective cliniconeuropathologic study of Parkinson's features in Alzheimer's disease.

Although extrapyramidal signs such as rigidity, bradykinesia, and postural impairment frequently occur in patients with Alzheimer's disease (AD), the correlation of these parkinsonian manifestations with the neuropathologic changes of Parkinson's disease (PD) has not been well established. Previous clinicopathologic studies addressing this issue have been largely retrospective or have consisted of relatively small numbers of cases. We examined the neuropathologic correlates of clinical parkinsonism in 78 cases with autopsy-confirmed AD prospectively enrolled in the Consortium to Establish a Registry for Alzheimer's Disease. Sixteen (20.5%) of the 78 AD cases showed concomitant PD pathology (AD/PD) as evidenced by the presence of nigral degeneration and Lewy bodies at any site. There were neocortical Lewy bodies in eight of these 16 cases. Two or more clinical manifestations of extrapyramidal dysfunction were present in eight (50.0%) of the 16 cases of AD/PD versus 11 (17.7%) of the 62 cases of AD alone (p < 0.01). Although semiquantitative ratings of the frequency of neuritic plaques showed no differences between the two groups, neurofibrillary tangles in the AD/PD group were less frequent in the midfrontal (p < 0.001) and superior temporal cortex (p < 0.05). These findings support previous reports that AD/PD cases are more likely to manifest extrapyramidal dysfunction and show plaque predominance at autopsy.

Aged↗
PubMed1995

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part XI. Clinical milestones in patients with Alzheimer's disease followed over 3 years.

The rate of cognitive decline, measured by psychometric testing, is widely used to track the progression of Alzheimer's disease (AD). As an alternative approach, we studied clinical measures as markers of the progression of dementia in 343 community-dwelling patients with probable AD enrolled in the multi-center Consortium to Establish a Registry for Alzheimer's Disease (CERAD) project. Subjects received standardized evaluations at entry and at annual follow-up. Decline on the Clinical Dementia Rating, loss of instrumental activities of daily living, failure to recall three words on the Mini-Mental State Examination (MMSE), and decline of the total MMSE score to below 10 were high-risk milestones, with cumulative frequencies exceeding 50% at 3 years. Loss of dressing and toileting activities occurred at intermediate rates, while loss of eating ability was rare. The risk of reaching clinical milestones and the annual rate of cognitive decline on the MMSE were directly correlated. Clinical milestones are useful indices of the progression of dementia in patients with AD.

Activities of Daily Living↗
PubMed1995

Spiritual care for the critically ill.

BACKGROUND: Spiritual well-being is the center of a healthy lifestyle and enables holistic integration of one's inner resources. However, the professional education process does not adequately provide socialization of nurses in the provision of spiritual care. Few studies exist that adequately address the spiritual aspect of nursing care. PURPOSE: To identify factors that contribute to providing spiritual care for patients in intensive care units. METHODS: A descriptive research design was used for this replication study conducted on a convenience sample of 63 patients in the critical care unit of a large midwestern military hospital. A trained interviewer asked each participant three open-ended questions regarding events that had created hope or meaning, created negative feeling, and could have contributed to hope or meaning. The interview took place 1 to 2 days after discharge from the intensive care unit. Predominant patterns were determined by content analysis. RESULTS: Three themes were identified as integral to the spiritual well-being of critical care patients: care providers, family/friends, and religion/faith. Nursing interventions identified for the three themes include establishing trusting relationships, providing in-depth spiritual assessment, conveying technical competence, and acting as facilitator among family, clergy, and other providers. CONCLUSIONS: We conclude that the key nursing interventions derived from this study include listening to patients' concerns and maintaining and conveying technical competence.

Adolescent↗
PubMed1994

Cloning, characterization, and expression of the murine cytomegalovirus homologue of the human cytomegalovirus 28-kDa matrix phosphoprotein (UL99).

We have identified, characterized, and expressed in bacteria and recombinant vaccinia viruses a protein which likely represents the murine cytomegalovirus (MCMV) homologue of the human cytomegalovirus (HCMV) 28-kDa matrix phosphoprotein, the product of the HCMV UL99 open reading frame (ORF). This protein, referred to as the MCMV UL99, is encoded by a 336-nucleotide ORF within the HindIII G fragment of MCMV strain Smith (K181). Using a DNA probe that corresponded to the amino terminus of the ORF, we detected a transcript of 4.8 kb at 8 hr and additional transcripts of 0.88, 2.4, and 5.7 kb at 24-48 hr postinfection (p.i.) of NIH 3T3 cells with MCMV. The smallest transcript is unspliced, initiates 235 nucleotides upstream from the start of the ORF, and utilizes a polyadenylation site located 62 nucleotides downstream from the end of the ORF. The ORF encodes a protein of 112 amino acids, with a predicted mass of 11.8 kDa. Comparison of the derived amino acid sequence with that of the HCMV UL99 gene product reveals 34.8% identity in an overlap of 66 amino acids. Within the amino acid sequence are at least two potential protein kinase C and one potential casein kinase II target motifs for phosphorylation. The ORF was cloned into the pGEX-KG prokaryotic expression vector and bacterially expressed protein was used to generate a specific rabbit antiserum against the protein. Western blotting of MCMV-infected NIH 3T3 cells showed that the ORF was expressed as a doublet of 16.3 and 15.2 kDa at 48 hr p.i. only in the absence of phosphonoacetic acid, thus demonstrating that this protein is a member of the true late gene class. The immunoreactive protein in MCMV-infected cells comigrated with that produced in cells infected with recombinant vaccinia virus containing the ORF. The protein appears to be part of the MCMV virion, is phosphorylated in vivo, and generates a strong humoral immune response following MCMV infection of BALB/c mice.

3T3 Cells↗
PubMed1994

Experimental investigation of the motions of the pumping diaphragm within a sac-type pneumatically driven ventricular assist device.

The motions of the pumping diaphragm within a sac-type pneumatically driven ventricular assist device (VAD) were monitored non-intrusively using a laser Doppler anemometer (LDA) working in the back-scattering mode. The interaction between the diaphragm and the flow, and the causative factors of the motions were investigated. The motions of a number of points on the diaphragm were determined by analysing the timing of interruption of the Doppler signals due to intrusion of the diaphragm on the LDA sampling volume. The position-time relationships for the identified diaphragm points were then interpolated into two-dimensional surfaces to reconstruct the moving patterns of the diaphragm at selected instants. The motion is strongly affected by the orientation of the device with respect to gravity due to hydrostatic pressure gradients on the liquid side, which are generally large compared with those associated with the fluid accelerations. Hence, during ejection, the part of the diaphragm experiencing the lowest hydrostatic pressure is always set in motion first, while during filling, the part with the highest hydrostatic pressure moves first. Consequences of these non-symmetrical motions on local flow behaviour are discussed, and methods of controlling diaphragm shape during pumping are outlined.

Acceleration↗
PubMed1994

Pressure development within a sac-type pneumatically driven ventricular assist device.

Intrinsic features of the pumping process of a pneumatically driven ventricular assist device (VAD) and the effects of different types of pneumatic drivers upon its performance were investigated in vitro by analysing the pressure distributions within the device and the motions of the prosthetic valves. It was found that the stretching of the flexible, elastic diaphragm in both late systole and diastole initiates a pressure oscillation which directly affects the timing of the pumping process. The timing was also found to be dependent on the length and stiffness of the cannulae which link the VAD to the model circulation system. During the stretch-induced oscillation in late systole, the VAD housing experiences partial collapse due to fluid momentum effects, which tends to increase the effective stroke volume of the device, and reduce the amplitude of the pressure oscillation. Reducing the rising (falling) rate of driving pressures (dpd/dt) may not necessarily reduce the maximum rate of change of the blood chamber pressure (dpch/dtmax) but may upset the stability of the pumping process. This is because a minimum dpch/dtmax exists, which is determined by the stretch-induced oscillation. In order to minimize dpch/dtmax and to provide the device with a stable working condition, dpd/dt should match the dpch/dtmax.

Algorithms↗
PubMed1994

Intelligence quotient profile in myotonic dystrophy, intergenerational deficit, and correlation with CTG amplification.

An abbreviated Wechsler Adult Intelligence Scale Revised (WAIS-R) was used to assess verbal and arithmetical cognitive performance in 55 subjects with myotonic dystrophy (DM), covering all grades of disease severity, and 31 controls at 50% risk of inheriting DM. Scaled scores from the assessment were converted into an intelligence quotient (IQ) estimation on each person. Significant IQ differences were found between: (1) all 55 DM subjects (mean 90.2, SD 16.1) and 31 controls (102.6, SD 9.4), with no sex differences in either group; (2) 15 affected parents (99.3, SD 12.2) and their affected children (88.1, SD 17.2), where significance was dependent on parental sex being female; and (3) 15 pairs of affected sibs (89.6, SD 13.2) and their normal sibs (100.2, SD 7.6). IQ steadily declined as (1) the age of onset of signs and symptoms decreased, and (2) the CTG expansion size increased. The correlation appeared to be more linear with age of onset. The correlation of IQ difference and CTG expansion difference in both the DM parent-child pairs and normal sib-affected sib pairs was poor, indicating that CTG expansion is not a reliable predictor of IQ either in individual persons or families. Further analysis of cognitive function in DM is required to clarify specific deficits characteristic of this patient group.

Adolescent↗
PubMed1994

Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients.

Decreases in gastric mucosal pH (pHi) are associated with splanchnic hypoxia in animals and with increased mortality in patients. In the present study we measured changes in gastric pHi with a tonometer in septic patients after a short-term infusion of dobutamine. These changes were compared with concurrent alterations in systemic O2 consumption (VO2) and arterial lactate. Twenty-one patients admitted sequentially to a medical intensive care unit with sepsis and gastric pHi < 7.32 were prospectively separated into a normal lactate group (< or = 2.2 mM; n = 10) and an elevated lactate group (> 2.2 mM; n = 11). Dobutamine HCl was infused intravenously at 5 micrograms/kg/min for approximately 3 h and then increased to 10 micrograms/kg/min. Measurements were obtained after each increase in the dose of dobutamine. Dobutamine infused at 10 micrograms/kg/min produced increases in O2 transport in both groups (p < 0.05) whereas systemic O2 consumption remained unchanged. These changes were accompanied by decreases in the arterial lactate concentration of the elevated lactate group (p < 0.01). Arterial lactate remained constant in the normal lactate group. Gastric pHi increased in both groups when dobutamine was infused at 5 micrograms/kg/min (p < 0.01), and then again at 10 micrograms/kg/min (p < 0.05). These results imply that regional tissue hypoxia, as characterized by a low gastric pHi, may be present in septic patients with normal arterial lactate concentration. Moreover, a rise in gastric pHi in response to increases in systemic O2 transport may be a better indicator of regional hypoxia in septic patients than related increases in systemic VO2.

Adult↗