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Biomedical subjects

R Durham

Publications and source records attributed to R Durham.

16 recordsLinked to original sources
PubMed2001

Intraneuronal abeta-amyloid precedes development of amyloid plaques in Down syndrome.

CONTEXT: Down syndrome patients who live to middle age invariably develop the neuropathologic features of Alzheimer disease, providing a unique situation in which to study the early and sequential development of these changes. OBJECTIVE: To study the development of amyloid deposits, senile plaques, astrocytic and microglial reactions, and neurofibrillary tangles in the brains of young individuals (<30 years of age) with Down syndrome. METHODS: Histologic and immunocytochemical study of a series of autopsy brains (n = 14, from subjects aged 11 months to 56 years, with 9 subjects <30 years) examined at the Office of the Chief Medical Examiner of the State of Maryland and The Johns Hopkins Hospital. RESULTS: The principal observations included the presence of intraneuronal Abeta immunostaining in the hippocampus and cerebral cortex of very young Down syndrome patients (preceding the extracellular deposition of Abeta) and the formation of senile plaques and neurofibrillary tangles. CONCLUSIONS: We propose the following sequence of events in the development of neuropathologic changes of Alzheimer disease in Down syndrome: (1) intracellular accumulation of Abeta in neurons and astrocytes, (2) deposition of extracellular Abeta and formation of diffuse plaques, and (3) development of neuritic plaques and neurofibrillary tangles with activation of microglial cells.

Adolescent↗
PubMed2000

Recombinant humanized monoclonal antibody against CD18 (rhuMAb CD18) in traumatic hemorrhagic shock: results of a phase II clinical trial. Traumatic Shock Group.

BACKGROUND: Activated neutrophils have been shown to play a pivotal role in resuscitation injury after traumatic hemorrhagic shock. Blocking the adhesion of neutrophils with a recombinant humanized monoclonal antibody against CD18 (rhuMAb CD18) may reduce resuscitation injury but increase the risk of infection. This was a dose-finding phase II study to determine safety, pharmacokinetics, pharmacodynamics, and clinical outcome parameters for additional studies. METHODS: This was a prospective, placebo-controlled, randomized (3:1), double-blind phase II trial enrolling 116 blunt and penetrating trauma patients from 14 trauma centers over a 9-month period. Patients with hypotension (blood pressure < or =90 mm Hg) from hemorrhagic shock were given a single intravenous dose of rhuMAb CD18 or placebo. The three doses tested were 0.5, 1, and 2 mg/kg. The drug was administered within 4 hours of the hypotensive episode and no later than 6 hours from time of injury. Exclusion criteria included head injury resulting in Glasgow Coma Scale score less than 8 or a history of cardiopulmonary resuscitation in the trauma center. An independent Drug Safety and Monitoring Review Board periodically reviewed unblinded data for safety issues and to give approval for dose escalation. RESULTS: Minor and major infection rates in rhuMAb CD18 groups were comparable to placebo. There was no evidence of antibody formation against rhuMAb CD18. Linear PK was observed within the dose range studied. Duration of neutrophil binding was dose-dependent, with 2 mg/kg resulting in greater than 90% neutrophil CD18 receptor saturation for approximately 48 hours. The mortality was 6.7% (2 of 30) in the placebo group, 4.8% (1 of 21) in the 0.5-mg/kg group, 8.5% (4 of 47) in the 1-mg/kg group, and 0% (0 of 18) in the 2-mg/kg group. The study was not powered for efficacy, and none of the efficacy variables demonstrated statistical significance. Favorable trends were seen in the 2-mg/kg group as compared with placebo in median intensive care unit length of stay (5 vs. 9 days) and median time on ventilator (34 vs. 72 hours). CONCLUSIONS: A single 2-mg/kg dose of rhuMAb CD18 maintains greater than 90% saturation of neutrophil CD18 receptors for approximately 48 hours in patients with traumatic hemorrhagic shock undergoing resuscitation. There was no trend toward increased infection. A larger trial is needed to demonstrate the clinical efficacy of rhuMAb CD18, perhaps using more reliable endpoints.

Adult↗
PubMed1998

Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF): are we winning the battle?

The problems of inflammation and infection leading to organ dysfunction and failure continue to be the major problems after injury and operations and with intensive care for many diseases and problems. When SIRS goes to MODS and MOF, the mortality becomes high, ranging from 30-80% depending on the number of failed organs. In spite of this, there have been recent exciting discoveries and contributions to patient care. A reasonable question then is, are we making progress and if so, can we document it? Are the incidence and mortality of MOF decreasing? The literature comparing care over some years suggests a decrease in ICU mortality in patients with severe organ failure, a decrease in elective surgical mortality, and improvement in the results of care and outcome for trauma patients. Review of problems occurring in sick and injured patients indicates that certain problems are decreasing in frequency, such as renal failure and ARDS after trauma, stress gastrointestinal bleeding, and abdominal abscesses, and these should improve outcome. There are a number of exciting therapies that help certain patients but not everyone. These controversies challenge us to focus on where and when there are positive benefits. Risk factors for MOF are addressed to focus on early intervention. The possibilities of multiple therapeutic agents are described. Finally, we describe and emphasize our recommendation to strive to prevent MODS and SIRS.

Documentation↗
PubMed1995

Right ventricular end-diastolic volume as a measure of preload.

Right ventricular (RV) end-diastolic volume index (RVEDVI) measured by a modified thermodilution pulmonary artery catheter has been proposed as an improved measure of cardiac preload, compared with pulmonary capillary wedge pressure (PCWP). This study compared the correlation of RVEDVI and PCWP with cardiac index (CI) to determine which parameter better reflected ventricular preload. Modified thermodilution catheters were placed in 38 critically ill patients. Hemodynamic parameters were recorded in these patients at 2- to 4-hour intervals for 1 to 7 days. Complete data sets (1,008) were obtained. Regression analysis was performed comparing PCWP, RVEDVI, RV ejection fraction (RVEF) to CI in the entire group and in individual patients. Because mathematical coupling may exist between RVEDVI and CI, the correlation between these variables was corrected for mathematical coupling using the method described by Stratton. Simple regression analysis of data from all patients, uncorrected for mathematical coupling, yielded a significant correlation between CI and RVEDVI (r = 0.60, p < 0.0001), RVEF (r = 0.37, p < 0.0001), and PCWP (r = 0.01, p < 0.001). Correction for mathematical coupling between RVEDVI and CI resulted in a minor changes of the correlation coefficient to 0.56. In individual patients, a significant, uncorrected correlation (p < 0.05) was found between RVEDVI and CI in 27 of the 38 patients, whereas 11 patients had a significant correlation between PCWP and CI. RVEDVI correlated more closely with CI than did PCWP, even after correlation for mathematical coupling. In both the group as a whole and in individual patients, RVEDVI was a better indicator of cardiac preload.

Adolescent↗
PubMed1994

Computed tomography in the diagnosis of blunt thoracic injury.

BACKGROUND: Computed tomography (CT) is an important diagnostic modality in the evaluation of blunt head and abdominal injuries, but it has not been routinely used to evaluate blunt chest trauma. METHODS: One hundred seventy stable patients with blunt thoracic trauma were evaluated with chest x-ray (CXR), and subsequently by CT. RESULTS: Of a total of 131 fractures, 53% were identified on initial CXR, 39% on CT, and 26% were not seen on either study. Twenty-one pneumothoraces were seen on CT but not on CXR. Chest tubes were placed in 8 patients and 12 patients were observed without incident. One hemothorax identified by CT scan alone required treatment. Four of 6 diaphragmatic injuries were seen on CT and 2 on CXR. Parenchymal abnormalities were apparent in 189 lung fields on CT and in 66 lung fields on CXR. Most represented atelectasis and did not require treatment. Altogether, CT scanning resulted in changes in management for 11 patients (6%). CONCLUSIONS: Although CXR is less sensitive in detecting parenchymal and pleural injuries than CT, the majority of the injuries identified by CT alone are minor and require no treatment. CXR remains the primary modality for diagnostic evaluation of blunt thoracic trauma.

Adult↗
PubMed1994

Analysis of radiocontrast-induced nephropathy by dual-labeled radionuclide clearance.

RATIONALE AND OBJECTIVES: This study was devised to develop a method of measuring the acute effects of radiocontrast media on renal function and assessing the relationship of the dose of radiocontrast media infused with the incidence of radiocontrast-induced renal failure. In addition, the drug adenosine phosphate-magnesium chloride (ATP-MgCl2) was evaluated as a renoprotective agent. METHODS: Eighteen patients with pre-existing renal impairment, (serum creatinine greater than 133 mumol/L) were randomized to receive a continuous infusion of ATP-MgCl2 or placebo before and during a radiocontrast procedure. Subjects were monitored with daily serum creatinine and with radionuclide renal clearance studies at baseline, during, and 24 hours after the radiocontrast procedure. RESULTS: There was an initial deterioration in renal clearance in the entire study group (from 44.2 +/- 4.6 to 32.6 +/- 3.9 mL/min, P = .001) which was independent of the dose of radiocontrast infused. There was a persistent deterioration in renal clearance only in those who received greater than 135 mL of contrast media (from 48.6 +/- 7.8 to 37.1 +/- 3.9 mL/min, P = .05). There also was an increase in serum creatinine that persisted only in those subjects who received greater than 135 mL of contrast media (230 +/- 27 to 283 +/- 44 mumol/L, P = .01). CONCLUSION: Persistent deterioration in renal function after radiocontrast administration appears to be dose-dependent and is not prevented by the use of ATP-MgCl2. Radionuclide techniques are useful in monitoring acute changes in renal function during radiocontrast procedures and may be of value in assessing renal impairment in future intervention studies.

Acute Kidney Injury↗
PubMed1990

Management of gastric injuries.

The stomach, located in the intrathoracic portion of the abdomen, is well protected from injury. It has a thick wall that is easily mobilized and a rich blood supply that ensures rapid healing of wounds. Although the gastric contents may be contaminated by oral flora immediately after meals, in the resting state, the stomach has few, if any, endogenous organisms. All of these factors make morbidity and mortality associated with penetrating injuries low. In contrast, blunt injuries often cause extensive contamination of the peritoneal cavity with resultant high morbidity and mortality.

Humans↗
PubMed1977

The multiple techniques approach to behavioural psychotherapy: a retrospective evaluation of effectiveness and an examination of prognostic indicators.

A retrospective evaluation of the multiple techniques approach to behaviour therapy is described. The effectiveness of the approach seems to compare favourably with a single-technique approach as far as can be ascertained. The observed improvement can be attributed to some aspect of the treatment package and not to 'spontaneous remission' factors. A prospective trial would not seem valuable, providing the problems of replication can be solved. An examination of prognostic indicators reveals a range of variables associated with outcome. Amongst the diagnostic groups, the 'social phobics' and 'anxiety states' did poorly. A number of general adjustment variables also seemed important, particularly marriage, and social and vocational adjustment. The implications of these findings for the nature and deployment of services and briefly discussed.

Adult↗
PubMed1976

Personality and meditation.

The relationship of psychoticism, extraversion-introversion, and neuroticism to the practice of Transcendental Meditation was studied. Male meditators (n = 39) were more introverted and more neurotic than the normal population, whereas the female meditators (n = 27) had a higher mean psychoticism score. Over a 6-mo. period of meditation, the males (n = 24) became less neurotic; the degree to which they did so was related to the frequency of meditation. The implications of these findings are discussed.

Adult↗