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Biomedical subjects

E Shaffer

Publications and source records attributed to E Shaffer.

17 recordsLinked to original sources
PubMed2003

Acalculous biliary pain: new concepts for an old entity.

Biliary pain is commonly reported in household surveys with the presumed cause being gallstones. When gallstones are absent or other abnormalities as a potential cause of similar pain do not exist, a different approach is necessary. Although trans-abdominal ultrasound can detect stones down to 3-5 mm, the advent of endoscopic ultrasound provides an even better definition for microlithiasis of < 3 mm. Duodenal aspiration of bile can further detect cholesterol microlithiasis or bilirubin granules, another potential source of biliary-type pain and perhaps even pancreatitis. Only in this way can acalculous gallbladder disease be clearly defined. The percentage of cholecystokinin-stimulated gallbladder emptying has been reputed to be the most sensitive diagnostic test for 'biliary dyskinesia', but abnormality of gallbladder emptying can be due to a smooth muscle defect of the gallbladder itself or heightened tone in the sphincter of Oddi. The value of surgical intervention has not been clearly established. The advent of laparoscopic cholecystectomy, however, has increased the number of patients with acalculous biliary disease who undergo surgery. Surgery is best done using impaired gallbladder emptying as the criterion for operation with improved outcome. Often, following cholecystectomy, biliary pain does not resolve the so-called 'post cholecystectomy syndrome'. Absence of the gallbladder as a pressure reservoir leaves the sphincter of Oddi as the prime determinant of bile duct pressure. Sphincter of Oddi dysfunction also exists in patients with an intact biliary tract and may become evident following cholecystectomy. Biliary manometry has clarified who might benefit from sphincterotomy. Choledochoscintigraphy is a non-invasive preliminary test. Advent of visceral hypersensitivity and better definition of this entity has shown, that in some of these patients with type III sphincter of Oddi, dysfunction appears to reside in duodenal hyperalgesia. It is clear that improved criteria are required to perform gallbladder emptying and better techniques to detect visceral hypersensitivity. Nonetheless, functional biliary pain in the absence of gallstone disease is a definite entity and a challenge for clinicians.

Acalculous Cholecystitis↗
PubMed2001

The cardiovascular actions of omapatrilat in spontaneously hypertensive rats.

Omapatrilat is a newly developed vasopeptidase inhibitor that inhibits both angiotensin-converting enzyme (ACE) and neutral endopeptidase and has potent antihypertensive efficacy. However, the specific effect of omapatrilat on cardiac function and left ventricular hypertrophy with hypertension remains controversial. Therefore, we investigated the effect of omapatrilat on blood pressure, cardiac hypertrophy, and cardiac function in spontaneously hypertensive rats (SHR). Studies were performed in SHR that received vehicle (n = 9), omapatrilat (n = 10), or fosinopril (ACE inhibitor, n = 7) by daily gavage for 56 days. Systolic blood pressure (SBP) and mean blood pressure (MBP) were measured by tail plethysmography. Left ventricular fractional shortening and left ventricular mass were measured by echocardiography at day 56. Omapatrilat and fosinopril significantly decreased SBP and MBP from day 1 through day 56, and omapatrilat markedly reduced SBP and MBP compared with fosinopril from day 21 to day 56. Although both omapatrilat and fosinopril decreased left ventricular mass and left ventricular mass-to-body weight ratio with increased LV fractional shortening, omapatrilat had a more potent effect on the reduction of left ventricular mass and improvement of cardiac function. This study shows that in SHR, omapatrilat mediated a potent and stable antihypertensive effect and a reduction in left ventricular mass with improvement of cardiac function, compared with ACE inhibition alone.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Three-dimensional imaging of aortic arch anomalies in infants and children with intravascular ultrasound catheters from a transesophageal approach.

Aortic arch anomalies usually require surgical intervention preceded by precise anatomic definition. We studied 20 patients to evaluate the feasibility and accuracy of using intravascular ultrasound catheters from a transesophageal approach with 3-dimensional image reconstruction for the diagnosis of aortic arch anomalies in infants and children. All patients had transthoracic echocardiograms and/or angiograms or magnetic resonance imaging. A 12.5-MHz intravascular ultrasound catheter was positioned in the esophagus and withdrawn by using an electrocardiogram and a respiratory gated pullback device to acquire the mediastinal images. All patients with arch anomalies underwent surgical repair. Reconstructed images were analyzed in the "anyplane" mode and with surface rendering. Intravascular ultrasound 3-dimensional imaging was successfully accomplished without complications. Anatomy was correctly identified in all patients by both blinded and unblinded observers, thus confirming the sensitivity and accuracy of the technique. We foresee this new technique to be useful as an adjunctive imaging modality applicable at the bedside or in the cardiac imaging laboratory.

Aorta, Thoracic↗
PubMed1993

Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide.

We studied the efficacy of low-dose nitric oxide inhalation in nine consecutive patients with severe persistent pulmonary hypertension of the newborn (PPHN) who were candidates for extracorporeal membrane oxygenation (ECMO). All patients had marked hypoxemia despite aggressive ventilator management and echocardiographic evidence of pulmonary hypertension. Associated diagnoses included meconium aspiration syndrome (3 patients), sepsis (3 patients), and congenital diaphragmatic hernia (2 patients). Infants were initially treated with inhaled nitric oxide at 20 ppm for 4 hours and then at 6 ppm for 20 hours. In all infants, oxygenation promptly improved (arterial/alveolar oxygen ratio, 0.077 +/- 0.016 at baseline vs 0.193 +/- 0.030 at 4 hours; p < 0.001) without a decrease in systemic blood pressure. Sustained improvement in oxygenation was achieved in eight patients treated with inhaled nitric oxide for 24 hours at 6 ppm (arterial/alveolar oxygen ratio, 0.270 +/- 0.053 at 24 hours; p < 0.001 vs baseline). One patient with overwhelming sepsis had an initial improvement of oxygenation with nitric oxide but required ECMO for multiorgan and cardiac dysfunction. We conclude that low doses of nitric oxide cause sustained clinical improvement in severe PPHN and may reduce the need for ECMO. However, immediate availability of ECMO is important in selected cases of PPHN complicated by severe systemic hemodynamic collapse.

Acute Disease↗
PubMed1993

Expression pattern of metalloproteinases and their inhibitors changes with the progression of human sporadic colorectal neoplasia.

Several studies have implicated the extracellular matrix-degrading metalloproteinases (MMPs) as essential agents in tumor cell invasion and metastasis. In the present study, we have investigated the patterns of expression of a number of MMPs and their specific tissue inhibitors (TIMP-1 and TIMP-2) in human colonic tissue samples that represent various stages of progression from adenomas showing different degrees of dysplasia to adenocarcinomas. We assessed levels of mRNA by Northern blot analysis and the results were measured semiquantitatively by densitometry. In total, we analyzed nine adenomas of varying size and with varying degrees of dysplasia, three adenomas with adenocarcinoma (malignant polyps), and five adenocarcinomas. Although expression of MMP and TIMP mRNA was highly intercorrelated, transcripts for stromelysin 3 and TIMP-2 (high) showed the strongest relation to the neoplastic process. Detection of stromelysin 3 mRNA accompanied a diagnosis of severe dysplasia or malignancy, whereas levels of TIMP-2 (high) mRNA transcripts permitted finer distinctions on the neoplastic continuum. These data indicate changes within extracellular matrix acquired during the process of malignant transformation of human sporadic colorectal neoplasia.

Adolescent↗
PubMed1992

Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn.

We studied the effects of inhaled nitric oxide (NO) in 9 newborn infants with severe persistent pulmonary hypertension (PPHN) who were candidates for extracorporeal membrane oxygenation treatment. With low doses of NO (10-20 ppm) all showed rapid improvement in oxygenation without reduction of systemic blood pressure. In 6 infants treated with inhaled NO for 24 h, clinical improvement was sustained at 6 ppm.

Administration, Inhalation↗
PubMed1990

Influence of protein concentration on platelet 3H-imipramine binding.

1. The effects of protein concentration in the assay mixture on platelet 3H-imipramine binding were studied in normal controls. 2. Increasing protein concentrations (76-926 micrograms/ml) were found to alter estimates of binding affinity (Kd) but not the number of binding sites (Bmax). 3. Increasing Kd estimates were protein dependent at concentrations in excess of ca. 200 micrograms/ml but were not protein dependent at lower concentrations. 4. A comparison of the present results with previous reports suggests that widespread interlaboratory differences in reported Bmax values for normal controls cannot be attributed to differences in the protein content of incubated samples. Rather these differences may be due to the inclusion of non-membrane protein in the assayed material.

Blood Platelets↗
PubMed1990

Relationship between 3H-imipramine binding, 14C-serotonin uptake, and the surface area of blood platelets.

1. The relationship between 14C-serotonin uptake, 3H-imipramine binding and surface area was studied in blood platelets. 2. Platelet rich plasma from 5 normal subjects was divided into 5 size subfractions by differential centrifugation and the total surface areas computed from platelet size profiles. 3. Linear relationships were found between both uptake and binding as a function of surface area regardless of platelet size. 4. The results suggest that platelet heterogeneity may contribute to the variability of uptake measurements which are commonly expressed on a per platelet basis. In contrast, the importance of heterogeneity to binding measurements, which are expressed per unit protein, may have been previously overestimated.

Biological Transport↗
PubMed1989

Midazolam in upper gastrointestinal endoscopy: a single-blind dose-finding study.

Midazolam is a water soluble benzodiazepine with potent sedative and amnestic properties. Sixty unpremedicated patients who were to undergo upper endoscopy for diagnostic purposes were enrolled in an open, non-randomized study to assess the efficacy of 4 increasing dosages of midazolam (0.05, 0.10, 0.15 and 0.20 mg/kg). Efficacy measures included Trieger test (psychomotor drawing), presence of anterograde amnesia, patient rating (PR) of the sedation, evidence of inflammation at the site of the injection and physician's global assessment (PGA). The 4 patient groups were similar in age, sex and ASA class. Eight of the 15 patients who received the 0.05 mg/kg and 1 patient each in the 0.10 mg/kg and 0.15 mg/kg group were considered to be treatment failures and required supplemental diazepam. PR (excellent-good) was constant for all doses throughout. Nearly all patients had anterograde amnesia. Deterioration in the Trieger test results was associated with increasing dose (ANOVA, p less than 0.05). There were no significant changes in vital signs. Signs of phlebitis were noted in two patients who received both diazepam and midazolam. PGA rating rose from 26.7% (0.05 mg/kg) to 80.0% (0.20 mg/kg) (p less than 0.01). Few adverse effects (unrelated to dosage) were noted. Midazolam is a well tolerated benzodiazepine which provides satisfactory sedation for endoscopy. If no premedication is given, there are no benefits to be gained from using a dose greater than 0.10 mg/kg.

Adult↗
PubMed1988

Obstruction to left coronary artery blood flow secondary to obliteration of the coronary ostium in supravalvular aortic stenosis.

Supravalvular aortic stenosis is characterized by obstruction of the left ventricular outflow tract distal to the aortic valve, and may result in diminished coronary artery blood flow. This report describes the cases of 2 patients in whom obstruction to left coronary artery flow was caused by obliteration of the coronary ostium itself. This mechanism differs from the more commonly recognized cause--valve leaflet adhesion to the obstructing ridge of aortic tissue. The coronary artery obstruction found in these 2 patients required direct enlargement of the left coronary ostium in both. This mechanism of impaired coronary artery flow deserves emphasis, as traditional methods of extended patch aortoplasty may fail to relieve the coronary ostial narrowing.

Aorta↗
PubMed1979

Intestinal absorption of bile salts: immature development in the neonate.

The intestinal absorption of sodium taurocholate was studied in fetuses, neonates, infants, children, and adults. Absorption rates were measured in vitro in everted rings of jejunum and ileum. Mucosal accumulation of 3H-taurocholate against a concentration gradient was consistently demonstrated in rings of ileum from adults, children, and infants older than 8 months, whereas fetal and neonatal ileal mucosal concentrations were not significantly above those in the incubation medium after exposure of the mucosa to 0.003, 0.03, and 0.3 mM taurocholate. There were no significant differences in mucosal uptake of taurocholate by perinatal jejunal and ileal rings. Incubations of mucosa from older infants, children, and adults in 0.3 mM taurocholate exhibited saturation phenomena. It is concluded that the ileal mechanism for active transport of taurocholate is undeveloped in the fetus and newborn infant. It is probable that the enterohepatic circulation of bile salt during the perinatal period is limited to that fraction of bile salt absorbed passively. The results suggest that losses of bile salt from the immature intestine may contribute to the steatorrhea and so-called diarrhea of newborn infants.

Aged↗