Biomedical subjects
Publications and source records attributed to C Hall.
A case of myxoedema due to Hashimoto's thyroiditis associated with a significant increase in serum creatinine is reported. Thyroid hormone replacement therapy resulted in normalization of the serum biochemistry within 1 month.
In 22 newborn piglets we studied the effect of hypovolemia or hypoxemia on hemodynamics and regional blood flow after instillation of porcine surfactant. Surfactant deficiency was obtained by repeated lung lavage, and blood flow measurements were carried out using radioactive microspheres. Three groups of piglets were studied, controls (n = 8), hypovolemia (n = 7), and hypoxemia (n = 7). Three to five minutes after instillation of surfactant, mean arterial blood pressure decreased significantly in all three groups with a mean decrease (+/- SD) of 31(+/- 12), 33(+/- 9), and 29(+/- 9) mm Hg, respectively (p < 0.01 in all three groups). Systemic vascular resistance decreased significantly in all three groups immediately after surfactant instillation (p < 0.01) and returned to presurfactant level after 60 min. Blood flow did not change after surfactant instillation in any of the three groups, in neither skin, muscle, pancreas, brain, nor retina. In liver, kidney, intestine, and choroidea there was a decrease in blood flow immediately after instillation with return to presur-factant levels within 60 min. Hypoxemia or hypovolemia before surfactant instillation did not increase the hemodynamic instability. The decrease in mean arterial blood pressure was caused by a vasodilation and not by a reduced cardiac output.
The Culture-Free Self-Esteem Inventory (CFSEI-2) was administered to 7 groups of children: 84 White Catholic school students from a New Orleans suburb, 78 White rural public school students from Virginia, 62 Hispanic Migrant student from Florida, 90 Aboriginal and White students from an isolated Canadian community, 199 African American students attending an inner city school, 60 Hispanic and White international students from Venezuela, and 61 Innuit students from isolated community in Labrador. The four elder groups also wrote three words to describe themselves (the Adjective Generation Technique [AGT]). Significant differences in responding between groups were found on all CFSEI-2 scales and for AGT favorability means. Although several possible reasons for these results are discussed, we conclude that the CFSEI-2 is not culture-free. Recommendations are: change the title of the test to avoid misrepresentation, limit test usage to elementary school children, develop an adolescent version with age appropriate language, and construct local norms before using the CFSEI-2 to make decisions about a child's self-esteem. To determine relevance of scores, a team of professionals and lay persons should review items from this or any test given to children who may be different from the normative or standardization group.
In diabetic patients, several factors contribute to volume expansion and have to be counteracted by humoral and neuronal feedback control systems. We investigated N-terminal proatrial natriuretic factor (ANF1-98) and digoxin-like immunoreactive factor (DLIF), which are two counteracting hormones, and their interrelationship, with additional consideration given to autonomic nervous function in diabetic patients. ANF1-98 and DLIF were measured in 64 diabetic patients. Autonomic nervous function was assessed using nine autonomic nervous function tests. The patients were subdivided into two groups, one with four or more (group 1) and one with less than four abnormal results in autonomic function tests (group 2). Compared with group 2, group 1 demonstrated detectable DLIF levels less often (17.2 vs. 45.7, P = 0.0195) and increased levels of ANF1-98 (mean +/- SEM: 850.0 +/- 108.8 vs. 554.8 +/- 45.9 pmol/L, P = 0.0099). However, the groups did not differ in blood pressure, daily sodium, and daily potassium excretion. The number of abnormal autonomic function tests correlated significantly with ANF1-98 (P = 0.0002). In patients with detectable DLIF, DLIF correlated with ANF1-98 (P = 0.0080). These results demonstrate close interactions between the autonomic nervous system and the two natriuretic hormones. In patients with autonomic nervous dysfunction, higher levels of ANF may possibly compensate for the lack of the natriuretic DLIF to counteract hypertension and chronic volume expansion.
To determine the relationship between neuroanatomic and neuropsychological changes in both asymptomatic and symptomatic HIV-1-infected individuals, we conducted a longitudinal study of 47 HIV-infected individuals, 15 of whom were asymptomatic and 32 of whom had either AIDS-related complex or AIDS. To measure neuroanatomic change over a 30-month period, we conducted quantitative MRI measures of bicaudate/brain ratio (BCR) and bifrontal/ brain ratio. A comparison of change over time between BCR and neuropsychological performance showed a correlation between increase in atrophy and worsening in certain cognitive functions. The correlation held for both asymptomatic and symptomatic groups, with more pronounced changes in the symptomatic group.
In a pilot open-labeled study 10 subjects with AIDS dementia complex (ADC) were treated with didanosine. Only half of the subjects were able to complete the trial as a result of side effects. Five subjects exhibited improved performance on neuropsychological testing, but the mean change in performance in this small group was not statistically significant. The study suggests that this drug may have some value in ADC patients unable to tolerate other therapies, but that further study is needed to establish this firmly.
We have theorized a direct relationship between viral burden and deleterious effects on the central nervous systems. It was hypothesized that HIV+ individuals would manifest poorer neuropsychological functioning after increased viral load. To address this, we compared viral burden to neuropsychological performance in subjects who participated in ACTG 116-118. Plasma samples and neuropsychological assessments completed at the same time were available for 64 observations on 21 subjects. Subjects who had a viral peak of over 1000 TCID per ml were classified as high viral load, those who did not as low viral load. Mean performances of the high viral load subjects were poorer, even though baseline performances were slightly poorer in the low viral load group. Mean post-viral peak performances were poorer than pre-viral peak performances. Declines in neuropsychological performance were found significantly more often in the high viral load group. These findings support the viral load hypothesis.
Our aim was to determine whether the use of room air or 100% oxygen has different effects on the peripheral circulation during resuscitation from severe hypoxemia. Twenty-four piglets, 2-to 5-days old, were anesthetized with pentobarbital and randomized to control (n = 5, surgery only) or hypoxemia. Hypoxemia (FiO2 = 0.08) was continued until base excess reached - 20 mml/L. Resuscitation was then performed with 21% (n = 10) or 100% O2 (n = 9) for 25 min followed by 21% O2 in both groups. Regional blood flow was measured with radioactive microspheres. Both hypoxic groups showed marked hyperemia during resuscitation in cardiac and skeletal muscle, a moderate hyperemia in intestine and pancreas while kidneys, liver, spleen and skin showed no hyperemic response. There were no significant differences between the two treatment groups in blood flow to any organ. Arterial oxygen content was significantly higher in the 100% O2 group than in the 21% O2 at 5 and 20 min after onset of resuscitation (11.6 +/- 0.7 and 11.2 +/- 0.6 vs 8.6 +/- 0.3 and 8.7 +/- 0.3 ml/100 ml, p < 0.01). Oxygen delivery was, however, significantly higher in the 100% O2 group than in the 21% O2 group only to the intestine and pancreas at 5 min of resuscitation. We conclude that resuscitation with 21% or 100% oxygen produces similar changes in peripheral blood flow in this porcine model of neonatal hypoxemia.
OBJECTIVE: Pelvic floor weakness may allow prolapse of the bowel into the rectogenital space, forming an enterocele. Enteroceles are believed to obstruct defecation by rectal compression and are therefore considered an abnormal finding on evacuation proctography. With a technique combine evacuation proctography and peritoneography, we prospectively studied constipated patients to reveal the pelvic peritoneal recesses during evacuation and to determine if enterocele actually impairs rectal emptying. SUBJECTS AND METHODS: Fifty constipated patients were studied prospectively, Using 20 ml of water-soluble contrast medium, we performed peritoneography, then evacuation protography with 120 ml of intrarectal paste. Lateral evacuation and posteroanterior stress views were analyzed by computerized video capture. Anatomic features and functional measurements of rectal emptying were noted. Posteroanterior views were compared with views in 31 subjects undergoing peritoneography for investigation of groin pain. RESULTS: Technical failure in three patients left 47 for analysis. A deep rectogenital pouch was seen in 36 patients (77%). Of these, 12 (58%) contained viscera that formed an enterocele, but the remaining 15 patients (42%) showed no visceral filling. Most pouches were apparent only during straining (31 cases, 86%). Peritoneal descent was greater than in controls (p < .0001), of whom only three had small rectogenital pouches. Patients with enterocele were compared with those who had a rectogenital pouch but no visceral filling and those who had no pouch. Standard anatomic measurements by evacuation proctography were not significantly different, but patients with enterocele evacuated more rapidly (p = .008) and completely (p = .021) than did the other two groups. CONCLUSION: Combined evacuation proctography and peritoneography is a new technique to diagnose pelvic hernias that occur during evacuation. This technique has shown that a deep rectogenital pouch is common in constipated patients and that just over half such pouches fill with viscera. However, because an enterocele does not impair rectal evacuation, this proctographic finding should be interpreted with caution.
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BACKGROUND: A gradual accommodation to increasing exercise loads has been recommended for exercise testing in denervated posttransplantation heart recipients. However, how the exercise protocol influence the hemodynamic, gas exchange, and hormonal response to exercise in this not been studied. METHODS: Nine heart transplant recipients tests incremental maximal bicycle ergometry tests in random order. Exercise stages of 1 and 3 minute durations were compared with matched work rate increments ranging between 30 and 40 W. Expiratory gas was measured continuously and arterial blood was sampled at each of the matched work rates. RESULTS: Total exercise duration was 6.4 +/- and 15.3 +/- 0.7 minutes for the 1-minute and 3-minute protocols, respectively. Maximal workload was significantly higher during the 1-minute versus the 3-minute protocol (238 +/- 9 versus 200 +/- 11 W, p < 0.001), but maximal oxygen uptake was not significantly different (25.5 +/- 1.1 versus 26.5 +/- 1.2 ml. min-1.kg-1). Hemodynamic, metabolic, and some hormonal parameters showed marked differences between the two protocols, with significantly higher responses observed during the 3-minute protocol for heart rate, ventilation, lactate, atrial natriuretic factor, and growth hormone. Catecholamine (epinephrine and norepinephrine) and insulin responses did not differ between the two tests. If expressed as a relative exercise intensity (percentage of maximal oxygen uptake) no differences in hormonal responses were observed between the two protocols, except for growth hormone response which remained higher during the 3-minute protocol. CONCLUSIONS: Although maximal oxygen uptake was independent of the exercise protocol in these heart transplant recipients, the exercise protocol has a major influence on the hormonal and metabolic response. The delayed response observed for oxygen uptake and hormonal responses suggests a significant physiologic lag time during the more rapidly incremental protocol. These differences should be taken into account when exercise is used as a method to evaluate the heart transplant recipient.
In this study, two factors that could affect fetal drug exposure were examined: 1) the extent of elimination of drug delivered to the fetal liver from the placenta via the umbilical vein; and 2) the degree to which there is preferential distribution of drug in umbilical venous blood to the fetal upper body, as is the case with oxygen and other endogenous substances. Studies were conducted with the histamine H1 antagonist, diphenhydramine (DPHM), in chronically instrumented nonpregnant and pregnant sheep (115-138 days gestation). Hepatic presystemic DPHM elimination was assessed using simultaneous and separate administration of DPHM and stable isotope labeled DPHM ([2H10]DPHM) via the umbilical vein (test route) and abdominal inferior vena cava (control route) in fetal lambs by either bolus injection (N = 6) or 90-min infusion (N = 5), and in nonpregnant sheep (N = 5), by simultaneous and separate bolus injections of the two forms of the drug via the mesenteric vein (test route) and abdominal inferior vena cava (control route). With the bolus injection protocol, hepatic presystemic elimination was estimated by the ratio of the area under the arterial drug concentration vs. time curve for the test and control routes of drug administration, whereas with the fetal infusion study it was calculated as the difference in fetal DPHM clearance values for the test and control routes of administration. To test for isotope effects in the disposition of [2H10]DPHM in the ewe or fetus, both DPHM and [2H10]DPHM were simultaneously injected via the inferior vena cava; however, no isotope effects were noted. In the ewe, there was extensive (93.2 +/- 1.4%) presystemic elimination of DPHM (F 0.068 +/- 0.014). However, in the fetus, this did not occur with bolus drug injection (F = 1.10 +/- 0.07), nor were there differences in the fetal DPHM clearance values estimated from the tarsal and umbilical venous infusions. During the latter experiments, DPHM levels were higher in the femoral artery than in carotid artery, with both umbilical venous and inferior vena caval drug infusion, and this was opposite of the differences in the concentrations of glucose, lactate, and oxygen between these two vessels. Thus, there is extensive hepatic presystemic elimination of DPHM in adult sheep, but no evidence for this phenomenon in the fetus. Furthermore, the preferential distribution of umbilical venous blood to the upper body of the fetal lamb does not result in higher drug levels in ascending aortic blood.
OBJECTIVE: To study pulmonary perfusion after long term intravenous lipid-based total parenteral nutrition (TPN). DESIGN: Open experimental study. SETTING: Teaching hospital, Norway. MATERIAL: 31 pigs. INTERVENTIONS: Infusion of TPN alone, TPN + pellets, or Ringer's solution alone through central venous catheters for 7 weeks. OUTCOME MEASURES: Haemodynamic variables during a standardised volume load, and measurement of plasma N-terminal pro-atrial natriuretic factor (ANF). RESULTS: Mean pulmonary artery pressure (PAP) was 12.9 (6.1) to 20.1 (3.0) mmHg in response to the volume load in control animals compared with 15.8 (8.5) to 25.4 (5.8) (p < 0.05) mmHg in those given TPN alone and 22.8 (10.3) (p < 0.05) to 28.0 (6.4) (p < 0.05) mmHg in those given TPN and pellets. Pulmonary vascular resistance index was also increased after TPN, but the plasma N-terminal pro-ANF concentration did not increase during infusion of TPN. CONCLUSION: Long term TPN caused moderate pulmonary hypertension, but not longstanding right-sided congestion.
In six chronically instrumented fetal lambs, hind-limb skin, bone, and muscle comprised 22.5 +/- 1.3, 35.3 +/- 1.6, and 42.3 +/- 1.1% of total limb weight, respectively. As estimated using radionuclide-labeled microspheres, blood flow to these tissues averaged 30.4 +/- 4.9, 30.1 +/- 3.3, and 14.0 +/- 3.1 mL.min-1.100 g-1, respectively, and they received 29.5 +/- 3.3, 45.3 +/- 3.6, and 25.2 +/- 4.5% of total limb blood flow. Thus, muscle has a lower blood flow in relation to its weight in comparison with the other tissues, while bone receives the largest fraction of hind-limb blood flow. The higher perfusion rate to bone may by due to a high rate of hematopoiesis in late gestation, whereas muscle flow may be lower than that reported immediately after birth because of limited limb movement and lack of shivering thermogenesis. There were no significant differences in tissue weights between the limb in which femoral arterial and lateral tarsal venous catheters were implanted (nonstudy limb) and the leg that had smaller diameter catheters placed in the pudendoepigastric artery and vein (study limb). However, nonstudy limb blood flow was 13.4 +/- 1.8% less than in the study limb, although the flow distribution to hind-limb tissues was not different between the two limbs. This suggests that the longer, larger diameter catheters inserted into the nonstudy limb had an adverse effect on hind-limb blood flow but not on overall limb growth or blood flow distribution. More attention should be paid to the effects of chronic fetal vascular catheterization on the tissues or organs normally perfused by the catheterized vessel.
OBJECTIVES: The aim of the present study was to examine the relation between the plasma levels of the atrial peptide N-terminal proatrial natriuretic factor (proANF) measured during the 1st 12 h after myocardial infarction and 1-year mortality. BACKGROUND: The atrial peptides atrial natriuretic factor and N-terminal proANF are released from cardiac atria secondary to increased atrial pressures. The plasma levels of both peptides have been found to be related to long-term prognosis when measured in the subacute phase of myocardial infarction. METHODS: The study was of a retrospective case-control design studying patients enrolled in the Thrombolysis in Myocardial Infarction (TIMI) II trial. Seventy-six patients who died within the 1st year of enrollment in the trial were matched with another 76 patients who survived. N-terminal proANF was analyzed by radioimmunoassay at enrollment (no later than 4 h after the start of chest pain) and at 50 min, 5 h and 8 h after enrollment. RESULTS: At all studied time points the peptide levels were significantly higher in the case group than in the control group. At 8 h after enrollment, an N-terminal proANF value above a cutoff point of 1,500 pmol/liter was associated with an odds ratio for death of 3.9. CONCLUSIONS: The plasma level of N-terminal proANF, when measured during the 1st 12 h after the onset of chest pain, is related to 1-year mortality after myocardial infarction. Together with previous findings, these results suggest that N-terminal proANF measurements represent a valuable supplement to currently used prognostic indicators after myocardial infarction.
A number of "target" proteins for the Rho family of small GTP-binding proteins have now been identified, including the protein kinases ACK and p65PAK (Manser, E., Leung, T., Salihuddin, H., Zhao, Z.-S., and Lim, L. (1994) Nature 367, 40-46). The purified serine/threonine kinase p65PAK has been shown to be directly activated by GTP-Rac1 or GTP-Cdc42. Here we report the cDNA sequence encoding a new brain-enriched PAK isoform beta-PAK, which shares 79% amino acid identity with the previously described alpha-isoform. Their mRNAs are differentially expressed in the brain, with alpha-PAK mRNA being particularly abundant in motor-associated regions. In vitro translation products of the alpha- and beta-PAK cDNAs exhibited relative molecular masses of 68,000 and 65,000, respectively, by SDS-polyacrylamide analysis. A specific beta-PAK peptide sequence was obtained from rat brain-purified p65PAK. Recombinant alpha- and beta-PAKs exhibited an increase in kinase activity mediated by GTP-p21 induced autophosphorylation. Cdc42 was a more potent activator in vitro of alpha-PAK kinase, and the fully activated enzyme is 300 times more active than the unphosphorylated form. Interestingly the down-regulation in the binding of p21s to recombinant beta-PAK and brain p65PAK, which is observed upon kinase activation does not occur with recombinant alpha-PAK.
Atrial stretch results in myocyte release of the prohormone atrial natriuretic factor (1-126). The N-terminal (1-98) fragment, proatrial natriuretic factor (proANF) is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply due to in vitro stability. This study was undertaken to evaluate the relation between proANF and routinely available measures of clinical status. ProANF was sampled from 202 patients (median age 68 years [range 15 to 85], 77% men) recruited from an active outpatient heart failure clinic. Patients were subgrouped according to New York Heart Association functional class, radionuclide ejection fraction (EF), echocardiographic left ventricular (LV) end-diastolic diameter, and Doppler-determined systolic pulmonary arterial pressure. The median proANF (pmol/L) values for patients in New York Heart Association classes I, II, III, IV were 725, 1,527, 1,750, and 5,172, respectively. The proANF value for the group with EF > 40% was 1,534 versus 1,993 for EF < or = 40% (p < 0.05). The value for the group with LV diameter < 60 mm ws 838 versus 1,751 for LV diameter > or = 60 mm (p < 0.01). The value for the group with systolic pulmonary artery pressure < 45 mm Hg was 1,241 versus 2,660 for systolic pulmonary artery pressure > or = 45 mm Hg (p < 0.01). ProANF correlated better than the other variables with New York Heart Association functional class and was more closely associated with noninvasive measurements than New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)