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Biomedical subjects

R M Lewis

Publications and source records attributed to R M Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Increased urinary excretion of endothelin during hypothermic perfusion preservation in kidneys subjected to preretrieval warm ischemic injury.

The purpose of the study was two-fold: 1) to determine whether endothelin (ET) levels could be detected in the ureteral effluent during hypothermic perfusion preservation (HPP) and; 2) to determine whether preretrieval warm ischemic (WI) injury is associated with increased ureteral excretion of ET. In situ pre-WI injury was induced in Lewis rats (n=10) by a 30-min extrinsic occlusion of the suprarenal aorta. The left kidney underwent 16 hr of HPP, and ureteral effluent (UE) from ischemic and control kidneys (n=10) was collected over 16 hr of HPP. The UE ET concentration and total ET excretion over 16 hr of HPP were significantly higher in kidneys subjected to pre-WI injury compared with nonischemic controls. Kidneys subjected to pre-WI injury can be distinguished from nonischemic control kidneys during HPP by a significantly higher concentration of ET in the UE and a higher overall excretion of ET during HPP.

Animals↗
PubMed1999

Identification of kidneys subjected to preretrieval warm ischemic injury by simultaneous monitoring of glomerular filtration and perfusate flow during hypothermic perfusion preservation.

BACKGROUND: Historically, ex vivo physiological evaluation of cadaveric renal allografts has been limited to assessing perfusate flow (PF) during hypothermic perfusion preservation (HPP). Using a small animal model, we have previously described a method for continuous monitoring of glomerular filtration rate (GFR) during HPP. Our study was undertaken to determine if monitoring GFR and PF during HPP distinguished kidneys subjected to preretrieval warm ischemic (WI) injury more reliably than PF alone. METHODS: In situ WI was induced in Lewis rats (n=10) by extrinsic occlusion of the suprarenal aorta for 30 min. After in situ cold perfusion and retrieval, the left kidney underwent 16 hr of HPP. Nonischemic (NI) control kidneys (n=10) were retrieved in the absence of suprarenal aortic occlusion. Longitudinal changes in PF, GFR, and filtration fraction (FF) during HPP were compared in WI versus NI kidneys (FF=GFR/PF x 100%). RESULTS: PF remained the same in both cohorts throughout HPP. GFR, however, increased to a significantly greater degree in WI versus NI kidneys during the first 4 hr of HPP (713+/-401 vs. 26+/-23%, respectively) (P<0.05). The increase in FF at 4 hr was 1203+/-696% in the WI kidneys versus 83+/-46% in the NI controls (P<0.05). CONCLUSIONS: In contrast to PF alone, measurement of both PF and GFR distinguished kidneys subjected to pre-WI from NI controls. The data provide a means to determine if monitoring of both GFR and PF during HPP will predict short- and long-term renal allograft function more reliably than PF alone.

Animals↗
PubMed1999

Differences in bioavailability between oral cyclosporine formulations in maintenance renal transplant patients.

Previous studies of healthy volunteers and small numbers of transplant recipients have suggested that the oral solution formulation of Sandimmune (cyclosporine [CsA]; Sandoz Pharmaceuticals, East Hanover, NJ) is bioequivalent to the soft gelatin capsule (SGC) formulation. However, there is conflicting evidence as to whether the two formulations are bioequivalent in all patients; to date, there are no published studies that explicitly address their bioequivalence in patients. We conducted a randomized, open-label, two-sequence, two-period, crossover study. Of 20 maintenance renal transplant recipients shown by a screening pharmacokinetic (PK) profile to be poor absorbers of CsA, half were randomized to receive first the SGC formulation and half the oral solution formulation for a period of 7 days. Each patient then underwent a 12-hour PK profile on the last day of the assigned formulation before a crossover to receive the other formulation and repeat the 7-day treatment and PK profile cycle. The results showed that peak and total exposure to CsA was greater with the SGC formulation. The SGC-oral solution ratios indicated an average 38% greater peak and 11% greater total exposure for the SGC formulation (P < 0.01 and P = 0.09, respectively). Trough levels were more similar between formulations, with SGC showing an average of 5% greater troughs (P > 0.10). In our selected population of malabsorbers, the SGC formulation made a difference in drug exposure.

Administration, Oral↗
PubMed1999

Fatal visceral and neural sarcocystosis in dogs.

This paper describes acute visceral and neural sarcocystosis in four dogs. One animal was simultaneously infected with distemper virus, and another with Blastomyces dermatitidis. Schizonts and merozoites of Sarcocystis canis were found in the lesions. 1999 W.B. Saunders and Company Ltd.

Animals↗
PubMed1999

Effects of maternal captopril treatment on growth, blood glucose and plasma insulin in the fetal spontaneously hypertensive rat.

In the spontaneously hypertensive rat (SHR) fetal growth and metabolism are abnormal. It has been speculated that maternal hypertension may be the cause of these abnormalities. Captopril treatment, which reduces maternal blood pressure, during pregnancy and lactation, is reported to have a beneficial effect postnatally, normalizing the blood pressure of offspring in the SHR. In the present study, the effects of maternal captopril treatment on fetal growth and plasma metabolites were investigated in the fetuses of two rat strains (SHR and Wistar-Kyoto (WKY)), in order to determine whether normalizing maternal blood pressure also normalized abnormalities in fetal growth and metabolism. On fetal Day 20, SHR fetuses were lighter and placentae were heavier than for the corresponding WKY. Captopril had no effect on fetal weight in the SHR, but decreased it in the WKY. There was no effect of captopril on placental weight. Fetal plasma insulin levels were higher in the SHR than in the WKY and were decreased by captopril treatment in both strains. Fetal blood glucose was elevated and fetal blood lactate was decreased in captopril-treated litters from both strains. Captopril had no effect on fetal plasma IGF-1 but fetal plasma IGF-2 levels were lower in the captopril-treated SHR than in the captopril-treated WKY. These findings suggest that maternal captopril treatment decreases insulin secretion in the fetal rat. High levels of fetal plasma insulin suggest that the SHR fetus is insulin resistant. Fetal insulin levels may contribute to the adverse consequences of gestational captopril treatment observed in many species. The differences in the effect of captopril on the two strains suggest that there are underlying endocrine differences in the SHR.

Animals↗
PubMed1998

Glucocorticoid activity in the fetal spontaneously hypertensive rat.

Fetal exposure to high concentrations of corticosteroids in the rat is associated with elevated blood pressure in postnatal life. In this study we have investigated indicators of corticosteroid activity in fetal spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in order to determine whether fetal corticosteroid exposure is increased in the SHR. Placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity, which prevents maternal steroids from crossing the placenta, was not impaired in the SHR. Concentrations of amniotic fluid corticosterone were significantly decreased in the SHR compared with the WKY at fetal Day 20, but were not significantly different on fetal Days 16 or 22. This suggests that rather than increased exposure to corticosteroids in the SHR fetus corticosteroid exposure may be reduced. Expression of lung surfactant protein A (Sp-A), a gene induced in late gestation by corticosteroids, was decreased in the SHR. In addition, differences in amniotic fluid electrolyte concentrations were observed which may reflect delayed renal maturation in the fetal SHR. These data suggest that the SHR fetus is exposed to low concentrations of corticosteroids and that the late gestation rise in fetal corticosteroid may be delayed in the SHR.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Fetal rat lung epithelium has a functional growth hormone receptor coupled to tyrosine kinase activity and insulin-like growth factor binding protein-2 production.

Although growth hormone (GH) receptor (GHR) mRNA and protein are present in fetal tissues such as the lung, there is little evidence that GH mediates growth in the fetus. We have identified functional responses to GH in fetal rat lung epithelia and suggest a possible role for GHR in the developing lung. GHR mRNA in lung extracts was high before birth at day 16 of gestation (16f), decreased to low levels at day 22f but increased again after birth. At day 20f GHR mRNA levels were higher in lung than in liver, whereas growth hormone binding protein mRNA levels were approximately equal in lung and liver. Stimulation of primary cell cultures of day 19f lung epithelia with GH caused increased tyrosine phosphorylation in specific proteins, demonstrating functional GHR. Lung fibroblasts isolated at the same time did not respond to GH. Ligand and Northern blot analysis of the epithelial cultures revealed that GH stimulation increased insulin-like growth factor binding protein-2 (IGFBP-2) activity and mRNA. These experiments demonstrate the functional activity of GHR, specifically in fetal lung epithelium. We suggest that one role for GH in vivo may be indirectly to modify insulin-like growth factor activity in the developing fetal lung by increasing IGFBP-2.

Animals↗
PubMed1997

The teaching of cardiopulmonary resuscitation in schools in Hampshire.

In order to maximise the number of potential providers of cardiopulmonary resuscitation (CPR) in the community, it has been suggested that a programme of basic life support (BLS) training should be included within the school curriculum. Using a questionnaire sent to 275 schools in south east Hampshire (representing 71,716 pupils), we discovered that BLS was taught at only 26% of schools which replied. The age at which teaching commenced ranged from 7-16 years (mode = 10 years). We estimated that almost 5000 children might currently be trained annually in these schools. Consequently, each year approximately 40% of children in south east Hampshire schools might be exposed to BLS training. On average, schools offering BLS tuition were larger, had more teaching staff and employed a higher proportion of staff who were themselves BLS providers. The majority of BLS teaching was undertaken by school staff (50.9% of schools) and members of the Red Cross, The St. John Ambulance Brigade or statutory ambulance service (30.9%). One school utilised members of the local fire brigade. Only one school offering BLS training to its pupils did not have a staff member trained in CPR.

Adolescent↗
PubMed1997

Morphologic, immunohistochemical, and ultrastructural characterization of a distinctive renal lesion in dogs putatively associated with Borrelia burgdorferi infection: 49 cases (1987-1992).

A distinctive renal lesion consisting of glomerulonephritis, diffuse tubular necrosis with regeneration, and interstitial inflammation was found in 49 biopsy/necropsy cases obtained from 1987 to 1992. This lesion is manifested clinically as a rapidly progressive glomerular disease that was uniformly fatal. Immune-mediated membranoproliferative glomerulonephritis predominated (43/49, 88%). Membranous glomerulonephritis (5/49, 10%) and amyloidosis (1/49, 2%) were also noted. Subendothelial deposits, IgG, IgM, and C3 were present along glomerular basement membranes. IgA was absent. The exact cause of the tubular necrosis is unknown. Affected dogs were significantly younger (5.6 +/- 2.6 years) than dogs with other forms of glomerulonephritis (7.1 +/- 3.6 years) and amyloidosis (7.8 +/- 3.5 years) both in the studied population for the same period and in the reported canine population. Labrador and Golden retrievers were 6.4 and 4.9 times more likely, respectively, to develop this lesion. This is the first report of a breed predilection for spontaneous canine glomerulonephritis. Previous reports have associated this lesion with Borrelia burgdorferi exposure. All dogs in this study were from Lyme disease-endemic areas. Of 18 dogs serologically tested, all were positive for exposure. Silver stain examination of kidneys revealed rare spirochetes, suggesting that the presence of spirochetes in the kidney is apparently unrelated to lesion development. The role of vaccination in development of the renal lesion is undetermined. The association of this histologically and clinically unique lesion, Lyme nephritis, with Borrelia burgdorferi infection is significant because it is the only fatal form of canine Lyme borreliosis.

Age Factors↗
PubMed1997

Perinatal growth disturbance in the spontaneously hypertensive rat.

Disproportionate fetal and placental growth are associated with the development of hypertension in the rat and human. Here we report differences in fetal, neonatal, and placental growth, and in metabolism and endocrinology, between the spontaneously hypertensive rat (SHR), a genetic model for human essential hypertension, and the control Wistar-Kyoto (WKY) strain. Gestation in SHR (23 d) was longer than in WKY by 20 h. Body weights were lower in the SHR from fetal d 16 to 20 and on postnatal d 15. However, on fetal d 22 and postnatal d 1, there was no significant difference in body weight between SHR and WKY. SHR placentas were larger than those of WKY at d 20, and by term there was a difference of 30% (p < 0.01). Other indices of disproportionate growth were hypertrophy of the fetal heart and kidney and decreased ponderal index in the SHR neonate. Blood glucose in SHR fetuses was lower than in WKY fetuses (p < 0.05), whereas blood lactate was higher (p < 0.05) and fetal hematocrit was reduced (p < 0.001). These findings suggest undernutrition and placental insufficiency may occur in SHR fetuses. Plasma IGF-II was increased on the last day of gestation in both strains, whereas IGF-I was unaltered. Fetal liver IGFBP-2 mRNA and plasma IGFBP-2 levels were reduced in SHR on fetal d 20 and 22 (p < 0.01). Differences in growth and endocrine and metabolic parameters suggest abnormal perinatal physiology in the SHR, which may influence the later development of hypertension.

Animals↗
PubMed1996

The Eph kinase ligand AL-1 is expressed by rostral muscles and inhibits outgrowth from caudal neurons.

In the peripheral nervous system, neurons derived from specific rostrocaudal levels of the neuraxis selectively synapse on targets that arise from corresponding body positions. To identify molecules involved in such position-dependent connectivity, we used subtractive hybridization to isolate genes selectively expressed in rostral or caudal skeletal muscle. One mRNA that was more abundant in neck than in hindlimb muscles encoded the mouse ortholog of human AL-1 and chick RAGS, membrane-associated ligands of Eph tyrosine kinases that have recently been implicated in cortical axon fasciculation and retinotectal connectivity, respectively. We show here that mouse AL-1 is expressed in discrete regions of the central and peripheral nervous systems and in a subset of developing skeletal muscles. The abundance of AL-1 RNA in immortalized myogenic cell lines derived from rostral muscles is higher than in caudally derived lines, suggesting that levels are heritably maintained. Growth of neurites from cultured sensory ganglia and spinal cords is specifically inhibited by cells expressing AL-1, suggesting that this molecule could serve to guide peripheral axons. The inhibitory effects of AL-1 are position dependent, such that axons derived from caudal (lumbar) ganglia are more affected than those derived from rostral (cervical) ganglia. Together, these results support the notion that Eph kinases and their ligands regulate topographically appropriate neural connectivity in the peripheral nervous system, as well as in the central nervous system.

Amino Acid Sequence↗
PubMed1996

Ewe fertility in the STAR accelerated lambing system.

Effects of environmental factors such as ewe age, season of exposure, and time from lambing to exposure on fertility were evaluated using records on 1,084 Dorset ewes in the STAR accelerated lambing system. The STAR program consisted of five 30-d concurrent breeding and lambing periods per year beginning on January 1, March 15, May 27, August 8, and October 20. Fertility in the flock changed in a cyclic and predictable fashion during the year. Changes in prolificacy were less consistent but also tended to show cyclic variation. Matings that occurred within the typical breeding season (August, October, and January) were more fertile than those occurring in March and June. However, fertility also varied with the age of the ewe and the time since the ewe's last lambing. Except in June, fertility at the first postpartum mating increased as ewes aged. In March and June matings, adult ewes that had just weaned lambs were less fertile than ewes that had failed to conceive in the previous season and therefore had longer postpartum intervals. However, in October and January, ewes that had just weaned lambs were more fertile. A matrix of expected pregnancy rates, or probabilities of fertility, was constructed using a mixed GLM to describe the combined effect of season, ewe age, and time since lambing on ewe fertility in accelerated lambing.

Aging↗
PubMed1995

Molecular cloning of a novel laminin chain, alpha 5, and widespread expression in adult mouse tissues.

We have identified a fifth member of the alpha subfamily of vertebrate laminin chains. Sequence analysis revealed a close relationship of alpha 5 to the only known Drosophila alpha chain, suggesting that the ancestral alpha gene was more similar to alpha 5 than to alpha 1-4. Analysis of RNA expression showed that alpha 5 is widely expressed in adult tissues, with highest levels in lung, heart, and kidney. Our results suggest that alpha 5 may be a major laminin chain of adult basal laminae.

Amino Acid Sequence↗
PubMed1995

Adenocarcinoma of the cervix in a renal transplant patient.

Treatment of cervical carcinoma in a renal transplant patient with a single pelvic kidney presents several management dilemmas. Standard treatment modalities are complicated by the patient's immunosuppressed state and the location of the transplanted kidney in the standard pelvic field, as well as other surgical risks. No information on the best approach to this clinical situation is available in the English language literature. We present this case to discuss factors considered in selecting a treatment plan and possible reasons for the rapid recurrence and demise of this patient.

Adenocarcinoma↗
PubMed1995

An immunohistochemical study of three equine pulmonary granular cell tumors.

Granular cell tumor (GCT) is a morphologic designation for tumors of varied histogenesis. Most GCTs in human beings are derived from Schwann cells, and rat meningeal GCTs are believed to originate in the neural crest. Three equine pulmonary GCTs from aged horses were studied immunohistochemically with primary antibodies directed against vimentin, cytokeratins (AE1/AE3), S-100, Leu 7, desmin, and neuron-specific enolase (NSE) using a steptavidin-biotin procedure. All three tumors stained similarly with strong and diffuse staining of neoplastic cells for vimentin and S-100 and negative staining with all other antibodies. On the basis of the immunohistochemical results and the previously described histologic and ultrastructural characteristics, equine pulmonary GCT is designated as neural crest and possibly Schwann cell derived, similar to GCT in rats and human beings.

Animals↗
PubMed1995

Long-term use of cyclosporine A does not adversely impact on clinical outcomes following renal transplantation.

The present review summarizes thirteen selected studies addressing the impact of cyclosporin A (CsA) on long-term outcomes following successful renal transplantation. Together, the data reflect the clinical courses of over 4,000 CsA-treated renal allograft recipients followed from one to ten years from the time of transplantation. Seven of the studies provided historical control data from more than 10,000 patients treated with azathioprine and prednisone. Graft survival beyond one year in CsA-treated recipients was consistently as good as or better than that achieved in the pre-CsA era. Underscoring the graft survival data, severe forms of the afferent arteriolopathy described as pathognomonic for 'CsA nephropathy' have become very uncommon and highly unlikely to be a cause of early or late graft loss. Retrospective analyses of longitudinal changes in aggregate serum creatinine concentrations did not demonstrate any differences in the long-term rate of attrition of allograft function between CsA- and non-CsA-treated patients. Similarly, prospective studies of serial glomerular filtrate rates did not reflect accelerating loss of function in association with long-term CsA use. CsA may be used for up to 10 years following successful renal transplantation without jeopardizing clinical outcomes. Graft arteriopathy (that is, chronic rejection), not progressive nephrotoxicity, is the dominant obstacle to achieving more uniformly successful long-term graft survival in the CsA era.

Animals↗
PubMed1994

Rheumatoid arthritis.

Much has been learned about the interactions of immunologic events and the development of musculoskeletal disease. Much more needs to be learned. The partnership of astute clinicians and investigators will enhance this learning process and eventually benefit the health and well being of our patients, and perhaps, humankind.

Animals↗