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Biomedical subjects

B L Smith

Publications and source records attributed to B L Smith.

At least 109 records · Page 6Linked to original sources

Mesenteric angioplasty in the treatment of chronic intestinal ischemia.

PURPOSE: This study was undertaken to determine the safety and efficacy of percutaneous transluminal angioplasty (PTA) in the treatment of chronic mesenteric ischemia (CMI) in very high-risk surgical patients. METHODS: Twenty-four focal mesenteric stenoses treated from 1984 to 1994 by PTA in 19 patients with CMI were reviewed. All 19 patients were considered poor surgical candidates. Seventeen patients had classic symptoms of CMI, and two patients had atypical abdominal complaints. Vessels dilated included the superior mesenteric artery (18), celiac artery (3), inferior mesenteric artery (1), aorta-superior mesenteric artery vein graft (1), and aorta-splenic artery vein graft (1). Complete follow-up was possible in all patients, with the exception of one patient who had no symptoms when last seen 17 months after the procedure. RESULTS: PTA was technically successful in 18 of 19 patients (95%) and 23 of 24 stenoses (96%). The lone technical failure resulted in superior mesenteric artery dissection with thrombosis and bowel infarction; the patient died despite emergent laparotomy and revascularization (mortality rate, 5%). Complete symptomatic relief was attained in 15 patients (79%), with follow-up showing continued relief of symptoms for a mean of 39 months (range, 4 to 101 months). Partial symptomatic relief was attained in three patients. Recurrent symptoms developed in three patients (20%) at a mean interval of 28 months (range, 9 to 43 months). Repeat PTA performed in two patients provided good technical results and relief from clinical symptoms. One patient had a symptomatic axillary sheath hematoma that required surgical decompression. CONCLUSIONS: Mesenteric PTA is a valuable treatment option in patients who have CMI and are considered very high operative risks. The initial technical success rate is excellent, with the majority of patients having complete symptomatic improvement and continued relief of symptoms at short-term follow-up.

Aged↗

Lack of toxicity of a non-sporidesmin-producing strain of Pithomyces chartarum in cell culture and when dosed to lambs.

In New Zealand the fungus Pithomyces charturum normally produces sporidesmin, a mycotoxin, which is responsible for the hepatogenous photosensitisation disease known as facial eczema. Cultures from an isolate of P. charturum, which does not produce sporidesmin, were examined by cell culture and by dosing to lambs to determine whether other toxic metabolites were produced. Acute and long term toxicity studies were conducted with the toxic response being assessed by weight changes, postmortem and histological examination of tissues, blood biochemistry and haematology tests. An extract from a sporidesmin-producing isolate was highly toxic in cell culture, while extracts of the nonsporidesmin-producing isolate did not cause a cytotoxic response to HEp 2 cells. After dosing with a sporidesmin-producing isolate, lambs developed liver lesions and clinical signs of facial eczema. Serum biochemistry changes occurred which were consistent with sporidesmin poisoning. Lambs dosed with the nonsporidesmin-producing isolate, at the rate of thirty times the number of spores of the sporidesmin-producing isolate, showed no observable toxic effects. All organs were of normal appearance, and histological examination of tissues, blood biochemistry and haematology results showed no abnormal changes. Similarly, long term dosing of extracts of the nonsporidesmin-producing isolate, at a rate equivalent to 100,000 spores/g of grass, produced no indication of a toxic response. It was concluded that the nonsporidesmin-producing isolate of P. churtarum contained no toxic metabolites in significant concentration.

Journal Article↗

The eternal triangle across cultures. Oedipus, Hsueh, and Ganesa.

In this chapter we consider the cross-cultural relevance of the Oedipus complex by investigating three "oedipal" myths from three disparate cultures: Chinese, Indian, and European. Although all three myths concern the same mother-father-son triad, they stress different aspects and proscriptions. These are interpreted as reflecting the different values that are central to the respective cultures. The relationship between these values and child-rearing practices is discussed. We conclude that fundamental psychoanalytic concepts are relevant cross-culturally, although the content of the Oedipus complex may vary from society to society.

Adult↗

Signal transduction by the polymeric immunoglobulin receptor suggests a role in regulation of receptor transcytosis.

Many membrane traffic events that were previously thought to be constitutive recently have been found to be regulated by a variety of intracellular signaling pathways. The polymeric immunoglobulin receptor (pIgR) transcytoses dimeric IgA (dIgA) from the basolateral to the apical surface of polarized epithelial cells. Transcytosis is stimulated by binding of dIgA to the pIgR, indicating that the pIgR can transduce a signal to the cytoplasmic machinery responsible for membrane traffic. We report that dIgA binding to the pIgR causes activation of protein kinase C (PKC) and release of inositol 1,4,5-trisphosphate (IP3). The IP3 causes an elevation of intracellular Ca. Artificially activating PKC with phorbol myristate acetate or poisoning the calcium pump with thapsigargin stimulates transcytosis of pIgR, while the intracellular Ca chelator BAPTA-AM inhibits transcytosis. Our data suggest that ligand-induced signaling by the pIgR may regulate membrane traffic via well-known second messenger pathways involving PKC, IP3, and Ca. This may be a model of a general means by which membrane traffic is regulated by receptor-ligand interaction and signaling pathways.

Animals↗

Attitudes and opinions toward surgical research. A survey of surgical residents and their chairpersons.

OBJECTIVE: To learn more about how research in academic surgery is viewed by surgical residents and their chairpersons. SUMMARY BACKGROUND DATA: There is a general perception that a productive experience in a basic science laboratory is an important prerequisite for a successful career in academic surgery. METHODS: An anonymous mail survey of 189 surgical residents entering the laboratory and their chairpersons (n=81) was done. Questions included how a laboratory was chosen by the resident, the importance of a basic science laboratory experience as a prerequisite to an academic career, and the perceived goal or goals of the laboratory experience. Data were analyzed by chi square analysis. RESULTS: The response rate from each group was excellent (80% response for residents, 90% from chairpersons). Of the residents surveyed, 78% were men and 22% were women; 51% entered the laboratory after 2 years of clinical training and 34% after 3 years; 84% did their research at their home institution and 91% worked in a surgeon's laboratory; 51% were scheduled to be in the laboratory for 1 year, 41% for 2 years, and 7% for 3 years. Two thirds of the residents were salaried by the surgery department. Both residents (70%) and chairpersons (86%) felt that the best surgical journal was Annals of Surgery. Both groups ranked Science as the top basic science journal. Twenty-four percent of the residents felt their peers offered the best advice in choosing a laboratory compared to 0% of the chairpersons (p<0.01); chairpersons felt they themselves or the program director were better advisors (chairpersons, 44%, vs. residents, 27%; p<0.01). Chairpersons believed that the principal investigators' previous success with residents was the major factor in determining in which laboratory to work; the residents placed more value on their interest in the project. Eighty-nine percent of women requested to go into the laboratory versus 66% of men (p<0.05). Half of the chairpersons and residents believed the faculty felt pressure on them to get grants; however, 71% of postgraduate year (PGY) residents who were PGY3 sensed this pressure compared to 44% of the PGY2 residents (p<0.01). Being in debt did not adversely influence the decision of 77% of these residents to do research. The residents felt more so than did their chairpersons that basic science research was necessary to be a successful academic surgeon (p<0.01). CONCLUSIONS: Although there are some differences in opinions between surgical residents and surgical chairpersons about the value and purpose of basic science research, these differences should be embraced and serve to enhance openness and discussion. Overall, surgical residents viewed the research experience away from clinical surgery as a positive one. The main reason for going into the laboratory was because of a genuine interest in the scientific method and the academic mission.

Attitude of Health Personnel↗

Effects of road transport on indices of stress in horses.

Stress associated with road transport is believed to be a significant contributor to the pathogenesis of post transport respiratory disease in horses. To determine the effects of road transport on pulmonary function, pulmonary aerosol clearance rates were measured in 4 horses 24 h before, and immediately after, 24 h of road transport by delivering aerosolised 99mtechnetium-labelled diethylenetriaminepentacetate (99mTc-DTPA) to the lungs and monitoring its washout. Each horse was transported twice, once while the trailer was equipped with a leaf-spring suspension and bias-ply tyres (trailer's original equipment, smooth ride) and once while the trailer was equipped with a torsion-bar suspension and normal pressure radial tyres (rough ride) in order to generate different ride characteristics. Before transport, blood was drawn from each horse for haematology and measurement of serum cortisol concentration; 24 h rates of hay and water intake and faecal output were recorded for each horse. Horses were then transported, 2 at a time, over a 128 km circular route of predominantly rural freeways at a constant speed of 72 km/h for 24 h. Horses were rested by stopping the trailer every 3.75 h for 0.25 h. During transport, heart rates (continuous 1 min averages), rates of hay and water intake and rates of faecal output were measured. Ammonia (NH3) and carbon monoxide (CO) concentrations were measured within the trailer and temperatures (wet bulb [WB], dry bulb [DB] and black globe [BG]) within the trailer were recorded each minute. Immediately after each experiment blood was drawn for haematology and measurement of pulmonary aerosol clearance rates were measured. For control studies, horses were housed in their stalls while heart rates were measured for 24 h. Slopes calculated from the 99mTc-DTPA clearance curves for pretransport horses were not significantly different from post transport clearance slopes. Pretransport mean 99mTc-DTPA clearance half-lives (T50, left lung mean +/- s.d. 41.7 +/- 15.8 min, right lung 44.6 +/- 19.1 min) were not significantly different from post transport T50 (left lung 53.5 +/- 14.0 min, right lung 52.0 +/- 11.6 min). Heart rates during transport were not affected by suspension type or trip order (the horse's first or second transport experiment) and were not significantly different from stall controls after the first 120 min of the experiment. Horses had increased red blood cell count, packed cell volume, haemoglobin, plasma protein and cortisol concentrations, and decreased body weights immediately post transport, indicating slight dehydration. Water and hay intake rates were significantly lower during transport than pretransport. Temperatures within the trailer were highest in the midafternoon and lowest in the early morning hours, but all temperatures measured in the trailer were within the comfort zone for large homeotherms. Ammonia and CO concentrations in the trailer during the transport period were within acceptable limits for human exposure. However, respirable articulates in the atmosphere were elevated above safe concentrations for human exposure.

Aerosols↗

A longitudinal investigation of duration and temporal variability in children's speech production.

A number of cross-sectional, acoustic studies have found that young children's speech segments tend to be longer and more variable than those of older children and adults. However, very little longitudinal information of this nature is available that considers changes across time for individual children. The present investigation is a longitudinal analysis of several temporal characteristics of the speech of 12 children of various ages who were each seen twice, approximately 1 1/2 years apart. For the group, durations decreased on average from the initial to the follow-up recordings by approximately 10%, and temporal variability decreased by about 40%. For the individual children, however, it was found that some of them showed few, if any, changes in some of the temporal measurements made at the two different times, whereas others showed substantial differences. Younger children also did not necessarily show longer durations or greater variability than older children, nor did younger children always show greater changes across time than older children. Thus, although cross-sectional studies indicate that there is a general tendency when comparing groups for increased age to be associated with shorter durations and reduced variability, individual children may not evidence such patterns or changes across time.

Adolescent↗

Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease.

Aquaporin-1 (AQP1), located in proximal tubules (PT) and descending thin limbs of Henle (DTL), and aquaporin-2 (AQP2), located in collecting ducts (CD), are channels involved in water transport across renal tubule epithelia. Using antibodies against AQP1 and AQP2, we here show expression of AQP1 and AQP2 in normal human developing and adult kidneys and in autosomal dominant polycystic kidney disease (ADPKD). Unlike in rats, AQP1 and AQP2 are expressed early during human nephrogenesis (12-wk gestation). AQP1 was first seen in developing PT epithelia, predominantly in apical cell membranes, and, at 15 wk, was also detected in DTL. AQP2 was seen in apical cell membranes of the branching ureteric bud and CD system from 12 wk and throughout development. In adult normal kidneys, AQP1 was localized to apical and basolateral membrane domains of PT and DTL, whereas AQP2 was restricted to principal cells of CD. This distribution of AQP1 and AQP2 was also seen in early stage ADPKD, except that AQP1 was mostly located in the apical membrane region of expanded PT. In end-stage ADPKD, two-thirds of the cysts expressed either AQP1 or AQP2, but these two water channels were never colocalized in the same cyst. Western blot analysis showed maximal expression of AQP1 and AQP2 in normal adult kidneys, lower levels in fetal kidneys, and decreases associated with degree of cystic progression in ADPKD. These data 1) demonstrate specific, mutually exclusive localization of AQP1 and AQP2 in human fetal and adult kidneys; 2) show that both channels are expressed early during nephrogenesis; and 3) show that the mutual exclusivity of localization is maintained even into end-stage ADPKD.

Aging↗

Use of detergent to prevent initial responses to endotoxin in horses.

OBJECTIVE: To determine whether a detergent can prevent most of the early effects of i.v. infusion with Escherichia coli endotoxin (< 100 ng/kg of body weight) in horses: marked pulmonary hypertension, acute leukopenia, and fever. ANIMALS: 8 healthy adult horses (4 male, 4 female), 415 to 615 kg. DESIGN AND PROCEDURE: Control and detergent experiments were performed in each horse while it was awake but sedated. In control experiments, 10 to 100 ng of E coli endotoxin/kg was given. In detergent experiments, 100 mg of detergent/kg was given 1 hour before injecting endotoxin, similar to the control experiments. RESULTS: In control experiments, pulmonary arterial pressure increased transiently over 40 minutes by 33 +/- 8 mm of Hg (mean +/- SD; P < 0.001), then returned to baseline. Circulating leukocytes decreased to 47 +/- 19% (P < 0.02) of baseline by 1 hour after endotoxin, then increased above baseline by 6 hours. Rectal temperature increased by 0.7 +/- 0.4 C (P < 0.01). In detergent experiments, the increase in pulmonary arterial pressure was much less than that in the control experiments (8 +/- 7 mm of Hg; P < 0.001). Circulating leukocytes did not decrease, and the increase in rectal temperature after endotoxic was blocked. CONCLUSIONS: This attenuation of te response to endotoxin may occur because the normal steps in the response of pulmonary intravascular macrophages (ie, endocytosis of endotoxin and subsequent release of inflammatory mediators) are altered by the detergent. This low-technology, inexpensive, and safe treatment could be an important new clinical tool for veterinarians in combating endotoxemia.

Animals↗

Comparative toxicity of 2-hydroxy-3-alkyl-1,4-naphthoquinones in rats.

2-Hydroxy-1,4-naphthoquinone has previously been shown to cause severe haemolytic anaemia and renal tubular necrosis in animals. In order to establish if such toxic effects are common to other 2-hydroxynaphthoquinone derivatives, the short-term toxicity of a number of 2-hydroxy-3-alkyl-1,4-naphthoquinones has been compared in rats. 2-Hydroxy-3-methyl, 2-hydroxy-3-ethyl- and 2-hydroxy-3-propyl-1,4-naphthoquinone were found to cause both haemolysis and renal damage, although the severity of the changes provoked by these substances was much lower than those induced by the parent compound at an equivalent dose-level. Furthermore, the toxicity of the hydroxy-alkylnaphthoquinones decreased with increasing size of the alkyl substituent and no toxic changes were recorded in animals dosed with 2-hydroxy-3-butyl- or 2-hydroxy-3-pentyl-1,4-naphthoquinone. The relationship between the in vivo effects of these substances and previously reported data on their in vitro cytotoxicity is discussed in relation to the mechanism of toxicity of these and other naphthoquinone derivatives.

Animals↗

The influence of reduced dietary fat absorption induced by orlistat on the pharmacokinetics of digoxin in healthy volunteers.

To assess the influence of an orlistat-induced reduction in dietary fat absorption on the pharmacokinetics of digoxin, an open-label, placebo-controlled, randomized, two-way crossover study was performed in 12 healthy volunteers. Each subject received single 0.4-mg doses of digoxin (soft gelatin capsules) administered orally on the fourth day of orlistat (120 mg three times daily for 6 days) and placebo (three times daily for 6 days) treatment, separated by at least an 11-day washout period. Serial blood samples were collected before and at appropriate intervals after each digoxin dose to determine plasma concentrations of unchanged digoxin. The 90% confidence intervals for the ratio of geometric least-squares means (for Cmax, AUC0-48, AUC0-t, and AUC) and for the difference of arithmetic least-squares means (for tmax and lambda z) indicate that the pharmacokinetics of digoxin was not altered by treatment with orlistat. This results suggests that a approximately 30% reduction in dietary fat absorption will not change the efficacy of digoxin in cardiac patients.

Adolescent↗

Bracken fern (Pteridium spp.) carcinogenicity and human health--a brief review.

Bracken fern (Pteridium spp.), one of the most abundant plants on the planet, is well known to cause cancer naturally in sheep and cattle. It contains, in some locations, extremely high concentrations of ptaquiloside which almost certainly is its major carcinogen. Ptaquiloside is transferred through milk. There is epidemiological evidence that the bracken carcinogen, in special situations, may cause cancer in man. Ptaquiloside and its animal models of carcinogenesis also offer good tools for the study of cancer.

Animals↗

Toxicity of 2,3-dialkyl-1,4-naphthoquinones in rats: comparison with cytotoxicity in vitro.

The short-term toxicities of 2-methyl-1,4-naphthoquinone and a series of 2,3-dialkyl-1,4-naphthoquinones have been determined in rats and compared with their ability to cause oxidative damage to erythrocytes in vitro. In accord with previous results, 2-methyl-1,4-naphthoquinone caused marked oxidative damage to erythrocytes in vitro and haemolytic anaemia in rats. The dialkylnaphthoquinones were also haemolytic agents in vivo, with 2,3-dimethyl-1,4-naphthoquinone being particularly active. Unlike the monoalkyl derivative, however, these substances caused little or no damage to red cells in vitro. The in vivo toxicity of dialkylnaphthoquinones cannot, therefore, be predicted on the basis of in vitro cytotoxicity tests.

Anemia, Hemolytic↗

ABH and Colton blood group antigens on aquaporin-1, the human red cell water channel protein.

The recent identification of the red cell water transporter (AQP1) has led to the identification of the "aquaporins", a new class of membrane proteins which function as water-selective transport proteins and are involved in many physiological processes. Identification of the chromosomal localization of the corresponding gene led to the recognition that AQP1 is the structural basis of the Colton blood group antigens. Analysis of individuals with the Colton null phenotype led to the recognition that homozygosity for knockout mutations in the corresponding gene is exceedingly rare but is without a significant clinical phenotype, predicting a redundancy in expression of other aquaporin homologs. These studies demonstrate the importance which molecular studies in red cell blood group antigens may play in diverse areas of biomedical research. Moreover, they provide another example that blood group antigens may be polymorphisms in functionally important proteins on the red cell surface.

ABO Blood-Group System↗

Localization of small ovarian Sertoli-Leydig cell tumors by transvaginal sonography with color Doppler.

Color Doppler ultrasound is a non-invasive diagnostic modality that has been gaining popularity in the evaluation of gynecological tumors. It demonstrates blood flow in a visually familiar way, and facilitates detection of neovascularity in pelvic tumors. In this article we describe, for the first time, a case in which a small androgen-producing ovarian tumor was localized by color Doppler ultrasound after other non-invasive imaging techniques failed.

Adult↗

Benign and malignant breast lesions: differentiation with echo-planar MR imaging.

PURPOSE: To quantify dynamic enhancement of breast lesions with echo-planar and conventional magnetic resonance (MR) imaging, to correlate these data with histologic findings and vessel density, and to evaluate MATERIALS AND METHODS: Twenty female patients with 22 breast lesions underwent conventional and MR echo-planar imaging T1 values, change in gadopentetate dimeglumine concentration, and extraction-flow products were calculated with echo-planar imaging data and were correlated with histologic findings and microvessel density. RESULTS: T1 values of cancers were not statistically significantly shorter. Cancers had more rapid uptake and higher extraction-flow products (P < .02). Sensitivity was 86% and specificity was 93% for diagnosis of malignancy. Microvessel density was higher for malignant lesions (P < .02) with an overall positive (not statistically significant) correlation between extraction-flow product and microvessel density. CONCLUSION: Echo-planar imaging appears promising for quantification of breast lesion enhancement. Microvessel data indicate that tumor angiogenesis affects enhancement.

Adolescent↗