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Biomedical subjects

R Deutsch

Publications and source records attributed to R Deutsch.

At least 19 recordsLinked to original sources
PubMed2001

Human angiopoietin gene expression is a marker for severity of pulmonary hypertension in patients undergoing pulmonary thromboendarterectomy.

OBJECTIVE: A consistent pathologic feature seen in lungs of patients with pulmonary hypertension from thromboembolic disease is hyperplasia of the media of pulmonary arterioles. The molecular factors responsible for these vessel wall changes are unknown. Angiopoietin-1 is a gene responsible for the formation of the media of blood vessels in utero. We hypothesized that aberrant expression of the angiopoietin-1 gene in the adult lung would be a major contributing factor in the development of pulmonary hypertension. METHODS: From April 1999 to March 2000, a total of 35 patients (18 men, 17 women, mean age 52 years) with pulmonary hypertension and pulmonary vascular resistance ranging from 407 to 2006 dynes x sec x cm(-5) underwent pulmonary endarterectomy at our institution. Before cardiopulmonary bypass, lung biopsy specimens were taken from each patient. Biopsy specimens were also obtained from 10 patients (5 women, 5 men, mean age 55 years) undergoing lung resection for causes other than pulmonary hypertension. All specimens were blindly scored by a pathologist for degree of medial hyperplasia. Quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry were used to quantitate angiopoietin-1 messenger RNA and protein in each sample. RESULTS: Lung specimens from all patients with pulmonary hypertension demonstrated up-regulation of angiopoietin-1 at the messenger RNA level. The degree of angiopoietin-1 transcription was directly proportional to the preoperative pulmonary vascular resistance and medial wall hyperplasia/hypertrophy in each patient. By immunohistochemistry, angiopoietin-1 protein was confined to the media of pulmonary arterioles. Lung biopsy specimens from patients without pulmonary hypertension had no detectable expression of angiopoietin-1 at the messenger RNA or protein level. CONCLUSION: Angiopoietin-1, a gene responsible for vessel development in the embryonic lung, is up-regulated in the lung parenchyma of patients with pulmonary hypertension. The level of expression of angiopoietin-1 at messenger RNA and protein levels correlates to the severity of pulmonary hypertension in patients with thromboembolic disease and serves as a target for strategies to treat this disease.

Adult↗
PubMed2001

Shell osteochondral allografts of the knee: comparison of mr imaging findings and immunologic responses.

PURPOSE: To define the magnetic resonance (MR) imaging appearance of shell osteochondral allografts of the knee and compare the MR findings with antibody responses. MATERIALS AND METHODS: Thirty-six grafts were evaluated with a 1.5-T unit with T1-, intermediate-, and T2-weighted, and three-dimensional spoiled gradient-recalled MR imaging at 3, 6, 12, 24, and/or 36 months after surgery. Nineteen patients underwent imaging serially. Two osteoradiologists scored by consensus host marrow edema, thickness of graft-host interface, signal intensity of graft marrow, cyst formation, joint effusion, articular cartilage defects, and surface collapse. Patients were divided into antibody-positive (AP) (n = 11) and antibody-negative (AN) (n = 25) groups evenly distributed across the different time points on the basis of results of anti-human leukocyte antigen antibody screening. MR findings for the two groups were compared. RESULTS: AP patients demonstrated greater mean edema (P<.002), thicker interface (P<.03), and more abnormal graft marrow (P<.04) than AN patients, and they had a higher proportion of surface collapse (P<.03). CONCLUSION: Humoral immune responses were associated with more inflammation and less complete incorporation after allograft placement. MR imaging shows promise as a surrogate biomarker for success of shell osteochondral allograft implantation.

Adolescent↗
PubMed2001

Us of blunt abdominal trauma: importance of free pelvic fluid in women of reproductive age.

PURPOSE: To assess the importance of free fluid and to determine the accuracy of screening ultrasonography (US) in female patients of reproductive age with trauma. MATERIALS AND METHODS: US was performed in 1,047 patients, aged 10-60 years, to evaluate blunt trauma. Patients were retrospectively assigned to groups on the basis of presence and location of intraperitoneal free fluid. Injury and surgical injury rates were assessed by comparing US results with computed tomographic, repeat US, cystographic, peritoneal lavage, surgical, and/or autopsy findings in 144 patients and with final clinical outcome in 903. US scans were positive if fluid was outside the cul-de-sac or if suspicious parenchymal abnormalities were present. RESULTS: In 939 patients, no fluid was seen: Eight had injuries; three were surgical. In 56, anechoic fluid was isolated to the cul-de-sac: Two had injuries; one was surgical. In 26, fluid was isolated to the upper abdomen: Fifteen had injuries; five were surgical. In 22, fluid involved the pelvis and abdomen: Nineteen had injuries; 14 were surgical. In four, questionable fluid was isolated to the supravesical space. Patients with fluid in the cul-de-sac had similar injury and surgical injury rates as those with no fluid but had lower rates than those of patients with fluid elsewhere (P<.02 to P<.001). US screening had 89% sensitivity, 98% specificity, 97% accuracy, a 61% positive predictive value, and a 99% negative predictive value. CONCLUSION: In female patients of reproductive age with trauma, free fluid isolated to the cul-de-sac is likely physiologic; clinical follow-up should suffice. Patients with fluid elsewhere usually have clinically important injury and require further evaluation.

Abdominal Injuries↗
PubMed2000

Early expression of angiogenesis factors in acute myocardial ischemia and infarction.

BACKGROUND: When the myocardium is deprived of blood, a process of ischemia, infarction, and myocardial remodeling is initiated. Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator of vascular endothelial growth factor (VEGF) and is critical for initiating early cellular responses to hypoxia. We investigated the temporal and spatial patterns of expression of the alpha subunit of HIF-1 (HIF-1alpha) and VEGF in specimens of human heart tissue to elucidate the early molecular responses to myocardial hypoxia. METHODS: Ventricular-biopsy specimens from 37 patients undergoing coronary bypass surgery were collected. The specimens were examined by microscopy for evidence of ischemia, evolving infarction, or a normal histologic appearance. The specimens were also analyzed with the reverse-transcriptase polymerase chain reaction for HIF-1alpha and VEGF messenger RNA (mRNA) expression and by immunohistochemical analysis for the location of the HIF-1alpha and VEGF proteins. RESULTS: HIF-1alpha mRNA was detected in myocardial specimens with pathological evidence of acute ischemia (onset, <48 hours before surgery) or early infarction (onset, <24 hours before surgery). In contrast, VEGF transcripts were seen in specimens with evidence of acute ischemia or evolving infarction (onset, 24 to 120 hours before surgery). Patients with normal ventricles or evidence of infarction in the distant past had no detectable levels of either VEGF mRNA or HIF-1alpha mRNA. HIF-1alpha immunoreactivity was detected in the nuclei of myocytes and endothelial cells, whereas VEGF immunoreactivity was found in the cytoplasm of endothelial cells lining capillaries and arterioles. CONCLUSIONS: An increase in the level of HIF-1alpha is an early response to myocardial ischemia or infarction. This response defines, at a molecular level, one of the first adaptations of human myocardium to a deprivation of blood. HIF-1alpha is a useful temporal marker of acutely jeopardized myocardium.

Acute Disease↗
PubMed2000

Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury.

OBJECTIVES: To evaluate the effect of prolonged infusion of 3% hypertonic saline (514 mEq/L) and sustained hypernatremia on refractory intracranial hypertension in pediatric traumatic brain injury patients. DESIGN: A prospective study. SETTING: A 24-bed Pediatric Intensive Care Unit (Level III) at Children's Hospital. PATIENTS: We present ten children with increased intracranial pressure (ICP) resistant to conventional therapy (head elevation at 30 degrees, normothermia, sedation, paralysis and analgesia, osmolar therapy with mannitol, loop diuretic, external ventricular drainage in five patients), controlled hyperventilation (Pco2, 28-35 mm Hg), and barbiturate coma. We continuously monitored ICP, cerebral perfusion pressure (CPP), mean arterial pressure, central venous pressure, serum sodium concentrations, serum osmolarity, and serum creatinine. INTERVENTIONS: A continuous infusion of 3% saline on a sliding scale was used to achieve a target serum sodium level that would maintain ICP <20 mm Hg once the conventional therapy and barbiturate coma as outlined above failed to control intracranial hypertension. MEASUREMENTS AND MAIN RESULTS: The mean duration of treatment with 3% saline was 7.6 days (range, 4-18 days). The mean highest serum sodium was 170.7 mEq/L (range, 157-187 mEq/L). The mean highest serum osmolarity was 364.8 mosm/L (range, 330-431 mosm/L). The mean highest serum creatinine was 1.31 mg/dL (range, 0.4-5.0 mg/dL). There was a steady increase in serum sodium versus time zero that reached statistical significance at 24, 48, and 72 hrs (p < .01). There was a statistically significant decrease in ICP spike frequency at 6, 12, 24, 48, and 72 hrs (p < .01). There was a statistically significant increase in CPP versus time zero at 6, 12, 24, 48, and 72 hrs (p < .01). There was a statistically significant increase in serum osmolarity versus time zero at 12 hrs (p < .05) and at 24, 48, and 72 hrs (p < .01). Two patients developed acute renal failure and required continuous veno-venous hemodialysis; these were concurrent with an episode of sepsis and multisystem organ dysfunction. Both recovered full renal function with no electrolyte abnormalities at the time of discharge. CONCLUSION: An increase in serum sodium concentration significantly decreases ICP and increases CPP. Hypertonic saline is an effective agent to increase serum sodium concentrations. Sustained hypernatremia and hyperosmolarity are safely tolerated in pediatric patients with traumatic brain injury. Controlled trials are needed before recommendation of widespread use.

Acute Disease↗
PubMed2000

Predictors of patient response to pulmonary thromboendarterectomy.

OBJECTIVE: We sought to identify imaging features that help predict surgical success in patients undergoing thromboendarterectomy. MATERIALS AND METHODS: Thirty-nine consecutive patients who underwent pulmonary angiography and thromboendarterectomy during 1995 and 1996 were included. Thirty-four underwent helical CT angiography. Measurements of postoperative pulmonary vascular resistance were compared with preoperative imaging features and preoperative pulmonary vascular resistance. RESULTS: The best imaging indicators of a relatively high postoperative pulmonary vascular resistance were the extent of small vessel disease identified on CT angiograms as segments with abnormal perfusion but normal segmental arteries (p = 0.005) and the extent of central disease (p = 0.015). Combined with preoperative pulmonary vascular resistance, these features had a strong correlation with postoperative outcome (p = 0.0005). Segmental arterial disease seen on both conventional angiography and CT angiography correlated poorly with surgical outcome. CONCLUSION: In patients with chronic thromboembolic pulmonary hypertension, CT angiographic evidence of extensive central vessel disease and limited small vessel involvement indicates a favorable surgical outcome.

Adolescent↗
PubMed1999

Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study.

BACKGROUND: Children generally have low cholesterol and no clinical manifestations of atherosclerosis, but fatty-streak formation begins in fetuses and is greatly increased by maternal hypercholesterolaemia during pregnancy. In the FELIC study we assessed the evolution of such lesions during childhood. METHODS: Computer-assisted imaging was used to measure the area of the largest individual lesion and the cumulative lesion area per section in serial cross-sections through the entire aortic arch and abdominal aorta of 156 normocholesterolaemic children aged 1-13 years, who died of trauma and other causes. Children were classified by whether their mother had been normocholesterolaemic (n=97) or hypercholesterolaemic (n=59) during pregnancy. Atherosclerosis was correlated with 13 established or potential risk factors. Findings The largest fatty streaks in the aortic arch of children younger than 3 years of hypercholesterolaemic mothers were 64% smaller than those previously found in corresponding fetuses (p<0.0001), which suggests that fetal fatty streaks may regress after birth. In the two groups, lesion size in the aortic arch and abdominal aorta increased linearly with age (r=0.87-0.98). However, lesions progressed strikingly faster in children of hypercholesterolaemic mothers than in those of normocholesterolaemic mothers (p<0.0001). Conventional risk factors for atherosclerosis in children or mothers correlated with lesion size, but did not account for the faster progression of atherogenesis in normocholesterolaemic children of hypercholesterolaemic mothers. INTERPRETATION: Our results suggest that maternal hypercholesterolaemia during pregnancy induces changes in the fetal aorta that determine the long-term susceptibility of children to fatty-streak formation and subsequent atherosclerosis. If so, cholesterol-lowering interventions in hypercholesterolaemic mothers during pregnancy may decrease atherogenesis in children.

Adolescent↗
PubMed1998

Cerebrospinal fluid tau protein is not elevated in HIV-associated neurologic disease in humans. HIV Neurobehavioral Research Center Group (HNRC).

We measured the concentrations of the neuron-specific protein, tau, in the cerebrospinal fluid (CSF) of 32 neurologically characterized HIV-infected (HIVpos) subjects and nine matched seronegative (HIVneg) controls using a sensitive ELISA assay. Of 32 HIVpos subjects, nine had HIV-associated neurocognitive disorders, and nine had clinically diagnosed peripheral neuropathies. CSF tau levels in subjects with HIV-associated neurocognitive disorders were similar to those in HIVneg subjects (185 +/- 83 vs. 223 +/- 106 pg/ml; P = 57). CSF tau levels in HIVpos subjects with peripheral neuropathies did not differ from those without neuropathies (320 +/- 190 vs. 251 +/- 185; P = 23). In summary, CSF tau levels were not elevated in patients with HIV-associated neurologic disease.

AIDS Dementia Complex↗
PubMed1998

Resource-use analysis of a medical toxicology consultation service.

STUDY OBJECTIVE: To evaluate the impact of a medical toxicology consulting service (MTCS) on resource use and efficiency of care in patients hospitalized with a diagnosis of tricyclic antidepressant (TCA) poisoning. METHODS: We conducted a retrospective, case-controlled medical-records review at two urban tertiary care teaching hospitals. The study population comprised patients who presented to the emergency department with a diagnosis of TCA poisoning, in two phases. The first phase was longitudinal; we evaluated cases over 4 years before and after inception of an MTCS at one institution. In the second phase we compared consecutive cases of TCA poisoning treated at two urban teaching hospitals located within a mile of each other with similar patient populations, one with and one without MTCS backup. Inclusion criteria consisted of complete medical records, ingestion of first- and second-generation TCAs, and age greater than 16 years. Patients were excluded if history, physical examination, or laboratory analysis suggested that multiple substances had been ingested. Extensive demographic data were collected in each case. Clinical information obtained from each patient included admission vital signs, pupil size, QRS and corrected QT duration, and the presence of markers of severe TCA toxicity such as hypotension, seizures, pulmonary edema, respiratory insufficiency necessitating intubation, and the occurrence of antimuscarinic signs and symptoms. Information regarding treatment was also collected from each case, including laboratory tests, decontamination procedures, administration of sodium bicarbonate, and use of other medications and therapies. RESULTS: We identified a total of 88 patients in both phases of the study. Comparison groups were similar with respect to age, sex, presenting vital signs, presenting QRS and corrected QT duration, and incidence of recorded antimuscarinic signs, hypotension, seizures, and respiratory insufficiency requiring intubation. Total length of stay in a monitored hospital bed was also similar between groups. One fatality was recorded, but all other patients were discharged home or to a psychiatric facility. Patients seen by the MTCS consumed fewer health care resources in the form of less decontamination and fewer laboratory tests. CONCLUSION: The MTCS may provide a resource-efficient means of treating patients with TCA poisoning. A larger, multicenter study of a variety of poisoned patients should be undertaken to further investigate this issue.

Adolescent↗
PubMed1997

Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group.

OBJECTIVE: To determine if mortality is increased in individuals with human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders less severe than frank dementia. DESIGN: A prospective cohort study; median duration of follow-up was 2.4 years. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival times according to neurocognitive classification. SETTING: University-based research unit. PARTICIPANTS: A volunteer sample of 414 individuals seropositive for HIV-1. Subjects were classified at their baseline evaluation as neuropsychologically (NP) normal or abnormal (impaired in > or = 2 NP test domains). A subgroup of NP abnormal subjects met operational criteria for HIV-associated minor cognitive motor disorder; the remaining subjects were designated NP impaired. Subjects with frank dementia were excluded. MAIN OUTCOME MEASURE: Mortality. RESULTS: At the baseline evaluation, 256 (62%) of 414 subjects were designated normal; 109 (26%). NP impaired; and 49 (12%), minor cognitive motor disorder. One hundred six participants (26%) died during follow-up. Compared with the NP normal group, the unadjusted relative risk (RR) of death for all NP abnormal subjects (minor cognitive motor disorder and NP impaired) was significantly increased (RR, 1.7; 95% confidence interval [CI], 1.2-2.6; P < .005). After adjusting for concurrently measured predictors of survival (CD4 lymphocyte counts, Centers for Disease Control and Prevention HIV disease classification, hemoglobin concentration, and serum beta 2-microglobulin) in proportional hazards models, mortality for all NP abnormal subjects remained elevated (RR, 1.8; 95% CI, 1.2-2.8; P < .01). The elevation in mortality risk for subjects with minor cognitive motor disorder was statistically significant (RR, 2.2; 95% CI, 1.2-3.8; P < .01); for NP impaired subjects it was marginally significant (RR, 1.6; 95% CI, 1.0-2.8; P = .06). CONCLUSIONS: The HIV-infected individuals with NP impairment had a higher risk of dying than those without impairment. This was particularly true for those meeting syndromic diagnostic criteria.

Adult↗
PubMed1995

T-lymphocyte subsets in acute illness.

OBJECTIVES: To determine the range of T-lymphocyte subsets (CD4, CD8, and CD4/CD8 ratios) in acutely ill, hospitalized patients and to determine whether these concentrations correlate with illness severity, survival rate, or immunodepression. DESIGN: Cross-sectional study, comparing Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and the calculated, disease-specific, predicted mortality rate with T-lymphocyte subsets. SETTING: Urban county hospital intensive care unit (ICU), serving as the designated trauma center. PATIENTS: One hundred two consecutively admitted ICU patients (72 medical and 30 surgical). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient clinical data, APACHE II scores, and their associated predicted mortality rate were recorded. Blinded human immunodeficiency virus (HIV) and lymphocyte testing was performed on samples from all patients on ICU admission. Despite only three (2.9%) of 102 patients testing positive for HIV antibodies, 41% (42/102) of patients had CD4 concentrations of < 400 cells/microL, and 29% (29/102) had CD4 concentrations of < 300 cells/microL. Mean CD8 concentrations were even lower, compared with normal laboratory values, resulting in a slight increase in CD4/CD8 ratios, although 16% (16/102) of patients had a CD4/CD8 ratio of < 1. CD4 counts were linearly related to total lymphocyte concentrations (Pearson correlation coefficient = 0.948), but no relationship was found between total lymphocyte or lymphocyte subset counts and APACHE II score, predicted mortality rate, or survival rate. CONCLUSIONS: Acute illness alone, in the absence of HIV infection, can be associated with profound decreases of T-lymphocyte populations. This problem is unpredictable and does not correlate with severity of illness, predicted mortality rate, or actual mortality rate. No conclusions regarding HIV serostatus or survival can be made based on single measurements of T-cell concentrations in acutely ill hospitalized patients.

APACHE↗