Biomedical subjects

R S Smith

Publications and source records attributed to R S Smith.

At least 37 records · Page 2Linked to original sources

PubMed2000

The bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization.

Ocular neovascularization is the leading cause of blindness in developed countries and often causes rapid loss of vision in age-related macular degeneration. Acute visual loss is most often due to hemorrhage from new vessels that have extended from the choroid into the subretinal space. Growth of abnormal vessels beneath the retina in this condition is known as subretinal neovascularization (SRN). Age-related animal models of macular degeneration and SRN have not been described. Current animal models of SRN depend on chemical or physical stimuli to initiate growth of subretinal vessels. The genes responsible for age-related human macular degeneration with SRN have not been firmly identified. We report an angiogenic phenotype in Bst/+ mice that is age-related, clinically evident, and resembles human SRN. This represents a spontaneous, genetically determined model of SRN. Bst/+ mice offer the possibility of exploring the molecular mechanisms of SRN without the need for exogenous agents.

Aging↗

PubMed2000

Lop12, a mutation in mouse Crygd causing lens opacity similar to human Coppock cataract.

A new cataract mutation was discovered in an ongoing program to identify new mouse models of hereditary eye disease. Lens opacity 12 (Lop12) is a semidominant mutation that results in an irregular nuclear lens opacity similar to the human Coppock cataract. Lop12 is associated with a small nonrecombining segment that maps to mouse Chromosome 1 close to the eye lens obsolescence mutation (Cryge(Cat2-Elo)), a member of the gamma-crystallin gene cluster (Cryg). Using a systemic candidate gene approach to analyze the entire Cryg cluster, a G to A transition was found in exon 3 of Crygd associated with the Lop12 mutation and has been designated Crygd(Lop12). The mutation Crygd(Lop12) leads to the formation of an in-frame stop codon that produces a truncated protein of 156 amino acids. It is predicted that the defective gene product alters protein folding of the gamma-crystallin(s) and results in lens opacity.

Animals↗

PubMed2000

Retinal degeneration but not obesity is observed in null mutants of the tubby-like protein 1 gene.

The tub gene is a member of a small, well conserved neuronal gene family of unknown function. Mutations within this gene lead to early-onset blindness and deafness, as well as late-onset obesity and insulin resistance. To test the hypothesis that mutations within other members of this gene family would lead to similar phenotypes as observed in tubby mice, and hence have similar functional properties, we have generated null mutants of the tubby-like protein ( Tulp ) 1 gene by homologous recombination. Similarly to tubby mice, Tulp1 (-/-)mice exhibit an early-onset retinal degeneration with a progressive, rapid loss of photoreceptors, further supporting the notion that previously identified mutations within the human TULP1 gene are indeed causative of retinitis pigmentosa. However, in contrast to tubby mice, Tulp1 (-/-)mice exhibited normal hearing ability and, surprisingly, normal body weight despite the fact that both TUB and TULP1 are expressed in the same neurons within the hypothalamus in areas known to be involved in feeding behavior and energy homeo stasis. However, TUB and TULP1 show a distinctly different staining pattern in the nucleus of these neurons, perhaps explaining the difference in body weight between the Tulp1 (-/-)and tubby mutant mice.

Animals↗

PubMed2000

Ogilvie syndrome as a postoperative complication.

HYPOTHESIS: Ogilvie syndrome is a postoperative complication. DESIGN: Case series. SETTING: University-affiliated tertiary-care hospital. PATIENTS AND METHODS: The medical records of patients diagnosed as having Ogilvie syndrome after trauma or operation between 1989 and 1998 were reviewed. Medical charts were examined for history, treatment, cecal diameter, and outcome. MAIN OUTCOME MEASURES: Data were summarized in an attempt to identify patient populations at risk for Ogilvie syndrome. RESULTS: Ogilvie syndrome was diagnosed in 36 patients, 24 of whom were men. Average age at diagnosis was 68.9 years. Abdominal radiographs were obtained at time of diagnosis (mean cecal diameter, 13.4 cm; range, 8-20 cm). Operations preceding Ogilvie syndrome were orthopedic or spinal (n= 14), cardiothoracic (n= 12), abdominal (n= 5), and vascular (n= 2). Nonoperative trauma accounted for 3 cases. Coronary artery bypass grafting was the single most frequent procedure leading to Ogilvie syndrome (n=9 [25%]). Conservative treatment was successful in 52.8% of cases (n = 19). Twenty colonoscopic decompressions were performed on 13 patients, with an overall success rate of 77% (n= 10). Of the 3 patients in whom colonoscopic decompression failed, 2 died and 1 required operation. Five of the 36 patients required surgical intervention, with a mortality rate of 60% (n= 3). CONCLUSIONS: Previous studies have shown Ogilvie syndrome to occur most commonly after obstetrical/ gynecologic, abdominal/pelvic, and orthopedic procedures. Our data confirm that patients undergoing orthopedic and spinal procedures are at higher risk, but that the surgical procedure most commonly leading to Ogilvie syndrome was coronary artery bypass grafting. Cardiothoracic surgeons, orthopedic surgeons, and neurosurgeons should be cognizant of this complication in the patient whose abdomen becomes distended postoperatively. If recognized early and treated appropriately, pseudo-obstruction will resolve in most patients. If surgical intervention is required, the subsequent mortality rate is high.

Aged↗

PubMed2000

Need for urgent delivery after third-trimester amniocentesis.

OBJECTIVE: To estimate the risk of need for urgent delivery after third-trimester amniocentesis as currently done using ultrasound guidance to assess fetal lung maturity. METHODS: Ultrasound records of women scheduled for third-trimester amniocenteses to assess fetal lung maturity from February 1990 through October 1997 were reviewed for possible complications during or immediately after procedures. Collected data included gestational age, indication for the procedure, number of needle passes, transplacental passage, needle gauge, and fluid color. The primary outcome examined was procedure-related complications that required emergency delivery or the decision to deliver before completion of maturity studies. Infants who developed hyaline membrane disease leading to neonatal intensive care admission were also identified. RESULTS: During the 7 1/2-year study period, 962 amniocenteses were done to assess lung maturity. Complete data were not available for 49 cases. Of the remaining 913 procedures, 15 (1.6%) were unsuccessful (needle pass without collecting fluid). Forty-one infants were delivered spontaneously or by cesarean on the same day as the procedure. However, complications that required delivery were identified in only six cases, an incidence of 0.7% (95% confidence interval = 0.16, 1.24). Complications included fetal heart rate abnormalities (n = 3), placental bleeding (n = 1), abruptio placentae (n = 1), and uterine rupture (n = 1). Only one of six complications had a single needle pass with clear fluid collected. Hyaline membrane disease occurred in 14 neonates, including two with mature indices. CONCLUSION: Although complications that required urgent delivery after third-trimester amniocentesis are rare, the risks of the procedure should be carefully weighed against the benefits.

Amniocentesis↗

PubMed2000

Vasa previa: prenatal diagnosis, natural evolution, and clinical outcome.

OBJECTIVE: To describe the prenatal ultrasonographic diagnosis, natural evolution, and clinical outcomes of vasa previa in a large population at a single institution. METHODS: We attempted to view the internal cervical os of 93,874 women with second- and third-trimester pregnancies during an 8-year period. Echogenic parallel or circular lines near the cervix, seen by gray-scale ultrasonography, raised the possibility of vasa previa. Diagnosis was confirmed by Doppler and endovaginal studies if aberrant vessels over the internal cervical os were suspected. Abnormal placental morphology and velamentous cord insertion were documented if they were identified during prenatal scans. Ultrasonographic findings were correlated with clinical courses, perinatal outcomes, and placental pathology examinations. RESULTS: Eighteen cases of vasa previa were suspected at a mean (+/- standard deviation) gestational age of 26.0 +/- 6.3 weeks; the earliest diagnosis was at 15.6 weeks' gestation. Eight of those cases initially showed placental edge over the internal os and later developed vasa previa after the placenta "receded" from the cervix. Six women had mild vaginal bleeding at a mean gestational age of 31.3 weeks. Three women had normal late third-trimester scans and were allowed to have uncomplicated vaginal deliveries. The remaining subjects delivered by cesarean. There were two deaths (one fetal and one neonatal), and minor preterm complications slightly prolonged infant hospitalizations. One set of preterm twins needed neonatal transfusions. Pathology findings included ten cases of velamentous insertion and three cases each of bilobed placentas, succenturiate lobes, and marginal cord insertion. CONCLUSION: Vasa previa was detected in asymptomatic women as early as the second trimester. Perinatal outcome was generally favorable, although several infants had slightly extended newborn nursery admissions due to mild complications of prematurity.

Female↗

PubMed2000

Effect of varying the depth of heat application on the adaptability of gutta-percha during warm vertical compaction.

The purpose of this study was to compare the adaptability of gutta-percha after varying the depth of heat application in the obturation of a set of standard root canals. A split-tooth model was constructed using a human maxillary central incisor. The root canal was cleaned and shaped using a step-back preparation to a size #60 FlexOFile at the working length (WL). Five shallow depressions were produced on the root canal wall. Twenty obturations without sealer were performed for each technique (thermoplasticized injectable (TI), lateral condensation, and warm vertical compaction (WVC) with heat applications at 3, 4, 5, and 7 mm from the WL). After each obturation the model was separated and the mesial and distal sides of each obturation were examined and videotaped at x 32 magnification. The quality of the obturation was graded based on the replication to the WL, replication of the artificial depressions, surface adaptation, and homogenicity of the gutta-percha. The Kruskal-Wallis analysis and the Student-Newman-Keuls tests indicated that all the techniques were significantly different from each other (p < 0.05) except for the TI group versus the WVC group with the heat application to within 3 mm from the WL (p > 0.05). The TI technique was ranked best followed by the WVC with heat applications at 3, 4, 5, and 7 mm. The lateral condensation technique received the lowest ranking.

Analysis of Variance↗

PubMed2000

Family presence during trauma resuscitation: a survey of AAST and ENA members. American Association for the Surgery of Trauma. Emergency Nurses Association.

BACKGROUND: The Emergency Nurses Association (ENA) has formally resolved that family presence (FP) during resuscitation and invasive procedures (TR) is the right of the patient and is beneficial for both patients and family members. Furthermore, FP during TR has been implemented at several trauma centers. Because this policy is controversial, a survey was conducted to assess the opinions of members of the American Association for the Surgery of Trauma (AAST) and ENA in regard to FP. METHODS: A survey instrument regarding FP during TR was mailed to the AAST membership (n = 813) and a random sampling (10%) of ENA members (n = 2,988). Questions regarding membership (AAST vs. ENA), age, gender, years in practice, trauma experience, the patient's right to FP during the primary survey, secondary survey, and invasive procedures, the potential effects of FP on trauma team function, and medicolegal implications were included in the survey. Qualitative and quantitative variables were analyzed by analysis of variance and chi2 analysis, respectively. Responses to questions by using a Likert Scale for degree of agreement were analyzed by using the Kruskal-Wallis test. RESULTS: A total of 1,629 (AAST, n = 368; ENA, n = 1,261) surveys were returned (43.4% response). There were 44 surveys returned as undeliverable (1.2%). The members of the AAST were older, more likely to be male, had been in practice longer, and had greater trauma experience when compared with ENA members (p < 0.001). More AAST than ENA members (97.8% vs. 80.2%) believed that FP during all phases of TR was inappropriate (p < 0.001). Fewer AAST members believed that FP was a patient right when compared with ENA members (p < 0.0001). The AAST members were more likely to believe FP interfered with patient care and increased the stress of trauma team members (p < 0.0001). The majority of AAST and ENA members had experience with FP during TR (55.3 vs. 67.8%; p < 0.001). However, the impressions of their experiences were widely disparate, with 63.6% of ENA and only 17.5% of AAST members, indicating that the experience was beneficial (p < 0.001). CONCLUSION: Attitudes toward FP during TR are significantly different between AAST and ENA members. Because of these differences in opinion, implementation of an FP policy may create conflicts between trauma team members and may interfere with the effectiveness of the trauma team.

Adult↗

PubMed2000

Limited utility of routine drug screening in trauma patients.

BACKGROUND: Routine toxicology screening of seriously injured patients has become the standard of care in most trauma centers. However, the benefit of drug screening in acute trauma is unproven. We reviewed the impact of positive drug screening results on patient care within the first 3 days of treatment. METHODS: We retrospectively reviewed the charts of seriously injured patients admitted to an American College of Surgeons-certified level I trauma center over a 5-year period. Modifications of therapeutic regimens based on positive toxicology results were noted. Using current financial data, charges for toxicology were calculated. RESULTS: Between January 1, 1990, and December 31, 1995, 2,678 trauma patients had drug screening. Of these, 414 (15%) had detectable quantities of the following intoxicants: opiates, barbiturates, amphetamines, phencyclidine hydrochloride (PCP), cocaine, marijuana, or benzodiazepines. Review of all 401 available charts failed to identify any cases in which treatment was altered by a positive toxicology result. Hospital costs related to routine screening were $138,587, while charges to patients amounted to $538,278. CONCLUSIONS: Routine toxicology does not alter or improve the immediate care of the injured patient. Routine drug screening is expensive, and benefits were not easily documented. The policy of routine toxicology screening in trauma centers should be reevaluated.

Diagnostic Tests, Routine↗

PubMed2000

Retinal degeneration 6 (rd6): a new mouse model for human retinitis punctata albescens.

PURPOSE: To characterize the genetics and phenotype of a new mouse mutant with retinal degeneration, rd6, that is associated with extensive, scattered, small white retinal dots seen ophthalmoscopically. METHODS: The phenotype was characterized using ophthalmoscopy, fundus photography, electroretinography, light microscopy, immunocytochemistry, and electron microscopy. Genetic characterization and linkage analysis studies were performed using standard methods. RESULTS: The inheritance pattern of rd6 is autosomal recessive. Linkage analysis mapped rd6 to mouse Chromosome 9 approximately 24 cM from the centromere, suggesting that the human homolog may be on chromosome 11q23. Ophthalmoscopic examination of mice homozygous for rd6 revealed discrete subretinal spots oriented in a regular pattern across the retina. The retinal spots appeared by 8 to 10 weeks of age and persisted through advanced stages of retinal degeneration. Histologic examination revealed large cells in the subretinal space, typically juxtaposed to the retinal pigment epithelium. The white dots seen on fundus examination corresponded both in distribution and size to these large cells. By 3 months of age, the cells were filled with membranous profiles, lipofuscin-like material, and pigment. These cells reacted strongly with an antibody directed against a mouse macrophage-associated antigen. Photoreceptor cells progressively degenerated with age, and an abnormal electroretinogram was initially detected between 1 and 2 months of age. CONCLUSIONS: The fundi of mice homozygous for rd6 exhibit phenotypic similarities to the human flecked retinal disorder retinitis punctata albescens. Thus, rd6/rd6 mice may be a model for understanding the etiology of this or similar disorders. The relationship between the aberrant subretinal cells and the concomitant photoreceptor degeneration remains to be established.

Animals↗

PubMed2000

Spontaneous hepatic hemorrhage secondary to retained intraperitoneal gallstones.

We describe the first reported case of spontaneous hepatic hemorrhage as a result of retained gallstones in the region of Morison's pouch eroding into the liver parenchyma. The patient presented with acute right upper quadrant abdominal pain 7 months after laparoscopic cholecystectomy. She sustained an episode of limited spontaneous hepatic hemorrhage as noted by abdominal sonography, computerized tomography, and a 4-g/dL hemoglobin drop. Laparoscopic exploration revealed the source of hemorrhage to be an inflammatory source created by retained intraperitoneal gallstones.

Cholecystectomy↗

PubMed1999

Mouse fundus photography and angiography: a catalogue of normal and mutant phenotypes.

PURPOSE: Mice are an increasingly important tool in ophthalmic research. As a result of studying spontaneous and induced mutations, many new ocular diseases have been described in mice in recent years, including several degenerative retinal diseases that demonstrate progression with age. Clearly, documentation of progressive changes in clinical phenotype is an important facet of characterizing new mutations and for comparing them with human diseases. Despite these facts, there are few published photographs of mouse fundi. The small size of the mouse eye and the steep curvature of its structures have made it difficult to obtain high quality fundus photographs. The purpose of this work was to develop procedures for mouse fundus photography and angiography and to use these techniques to examine several new mouse strains with ocular abnormalities. METHODS: We have used a small animal fundus camera and condensing lens to develop a reliable technique for producing high quality fundus images of conscious albino and pigmented mice. The fundus camera also was utilized to develop a method for fluorescein angiography, which demonstrated the normal retinal vascular bed as well as abnormal vascular leakage. In addition, several mouse strains with previously unreported ocular abnormalities (including two with inherited optic nerve colobomas) and a catalogue of previously unpublished clinical images for various mutant mice are presented. RESULTS: Altogether, we provide clinical images for C57BL/6J, BALB/cByJ, retinal degeneration 1 (rd1), Rd2, rd3, rd7, achondroplasia, nervous, motor neuron degeneration, Purkinje cell degeneration, kidney and retinal defects, optic nerve coloboma 1, and two apparently multigenic optic nerve colobomas in a strain of mixed derivation (ONC) and the inbred CALB/Rk strain. CONCLUSIONS: Our photography procedure reliably produces high quality images of the mouse fundus. This permitted us to record progressive retinal changes over time in the same animal, allowed us to compare the phenotypes of newly discovered retinal mutants to existing mutants at other institutions and to potentially similar human conditions, and finally, permitted us to produce a catalogue of previously unpublished clinical phenotypes for various mutant mice.

Animals↗

PubMed1999

Identification of a missense mutation in the alphaA-crystallin gene of the lop18 mouse.

PURPOSE: The mouse lop18 (lens opacity 18) mutation causes a white cataract obvious at weaning age. It soon progresses to a large white nuclear cataract with mild cortical changes. The mutation maps to mouse Chromosome 17 in close linkage to the alphaA-crystallin (Crya) gene, which encodes one of the major vertebrate eye lens proteins. Here we report the identification of a missense mutation in the alphaA-crystallin gene of lop18/lop18 mutant mice. METHODS: PCR primers were designed based on the alphaA-crystallin gene sequence from GenBank and PCR products were sequenced. RESULTS: We have analysed the sequence of the alphaA-crystallin gene from the lop18/lop18 mouse and identified a missense mutation. This mutation is tightly associated with the cataract phenotype, as no recombination was detected in 112 meioses. CONCLUSIONS: Our results suggest that a missense mutation in the alphaA-crystallin gene is responsible for the lop18/lop18 phenotype and Cryalop18 should be used as a gene symbol for the lop18 mutation.

Animals↗

PubMed1999

Immunostimulation by plant polyphenols: a relationship between tumor necrosis factor-alpha production and tannin structure.

The ability of the naturally occurring tumoricidal ellagitannin coriariin A to stimulate secretion of both IL-1beta and TNF-alpha from human peripheral blood mononuclear cells has been demonstrated. Companion studies with the monomeric gallotannin beta-D-pentagalloylglucose and a synthesized dimeric gallotannin-ellagitannin hybrid suggest that TNF-alpha rather than IL-1beta is the causative agent in tannin-mediated antitumor action in vivo, in contrast to an ealier proposal.

Adjuvants, Immunologic↗

PubMed1999

Lens epithelial proliferation cataract in segmental trisomy involving mouse Chromosomes 4 and 17.

A dominant induced mutation in the mouse, tightly associated with a reciprocal chromosomal translocation between Chrs 4 and 17, causes abnormal head tossing and circling behavior (the translocation induced circling mutation, Tim). Affected mice develop an unusual anterior subcapsular cataract that appears after birth and is progressive. The most likely explanation for the phenotypic observations is that the translocation breakpoint disrupted a gene or its regulation. Although the Mos protooncogene is located close to the translocation breakpoint and transgenic mice that overexpress Mos demonstrate cataracts and circling behavior, there were no gross changes in the Mos gene or in its level of expression. The morphological changes observed in the lens resemble those seen in some human congenital cataract syndromes.

Animals↗

PubMed1999

Fetal cardiac asymmetry: a marker for congenital heart disease.

OBJECTIVE: To determine the sensitivity of prenatally detected fetal cardiac asymmetry as a sonographic marker for congenital heart disease. METHODS: The normal ratios of pulmonary artery to aorta diameters and of right ventricle to left ventricle diameters were derived from normal fetuses scanned at 17 weeks or more in a 65-month period. Cross-sectional diameters of cardiac ventricles and great arteries were measured at the level of the valves at the time of the scan. Fetuses with confirmed cardiac anomalies detected prenatally during the study were examined to identify how many had cardiac asymmetry, determined by abnormal ratios. RESULTS: Linear regression analysis of the group of 881 normal fetuses showed the normal pulmonary artery to aorta diameter ratio remained constant throughout pregnancy and the normal right ventricle to left ventricle ratio increased slightly with progressing gestational age. The 90% confidence intervals were 0.79, 1.24 for the right ventricle to left ventricle ratio and 0.84, 1.41 for the pulmonary artery to aorta ratio. Of the 73 fetuses with abnormal hearts, 66% had either ventricular or great artery asymmetry (at least one of the two ratios was abnormal). However, if no asymmetry was present, the cardiac defect was more likely to be a minor one. CONCLUSION: Cardiac asymmetry was present in two-thirds of fetuses with cardiac anomalies diagnosed prenatally. If cardiac asymmetry is found, a more thorough examination of the fetal heart is indicated.

Adult↗

PubMed1999

Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice.

Glaucomas are a major cause of blindness. Visual loss typically involves retinal ganglion cell death and optic nerve atrophy subsequent to a pathologic elevation of intraocular pressure (IOP). Some human glaucomas are associated with anterior segment abnormalities such as pigment dispersion syndrome (PDS) and iris atrophy with associated synechiae. The primary causes of these abnormalities are unknown, and their aetiology is poorly understood. We recently characterized a mouse strain (DBA/2J) that develops glaucoma subsequent to anterior segment changes including pigment dispersion and iris atrophy. Using crosses between mouse strains DBA/2J (D2) and C57BL/6J (B6), we now show there are two chromosomal regions that contribute to the anterior segment changes and glaucoma. Progeny homozygous for the D2 allele of one locus on chromosome 6 (called ipd) develop an iris pigment dispersion phenotype similar to human PDS. ipd resides on a region of mouse chromosome 6 with conserved synteny to a region of human chromosome 7q that is associated with human PDS. Progeny homozygous for the D2 allele of a different locus on chromosome 4 (called isa) develop an iris stromal atrophy phenotype (ISA). The Tyrpl gene is a candidate for isa and likely causes ISA via a mechanism involving pigment production. Progeny homozygous for the D2 alleles of both ipd and isa develop an earlier onset and more severe disease involving pigment dispersion and iris stromal atrophy.

Age Factors↗

PubMed1999

Double-outlet right ventricle: an antenatal diagnostic dilemma.

OBJECTIVE: The purpose of this study was to describe the antenatal ultrasonographic findings of fetuses with double-outlet right ventricle (DORV). DESIGN: The records were reviewed of all fetuses scanned in our ultrasound unit which were suspected of having DORV during a 6-year period ending in April 1996. A medical record search for all infants with a postnatal diagnosis of DORV was also undertaken to identify cases that were not detected antenatally. Records were examined to determine the accuracy of antenatal diagnosis and the reasons for diagnostic errors. Fetuses without follow-up were excluded. RESULTS: There were 20 fetuses with antenatally detected conotruncal defects that had DORV included in the differential diagnosis. Three fetuses were excluded, seven did not have DORV and ten were confirmed postnatally as having DORV. Two additional infants were found to have DORV from the medical record search, producing a total of 12 cases. Antenatal sonographic cardiac findings included malpositioned (overriding or transposed) great arteries (n = 11), ventricular septal defect (n = 11) and small pulmonary artery suggesting stenosis (n = 4). Confirmed postnatal cardiac findings that were missed antenatally included aortic coarctation (n = 2), right-sided aortic arch (n = 2) and pulmonary stenosis (n = 1). Seven of the 12 fetuses had extracardiac findings. Nine of the 12 fetuses tested had a normal karyotype. Eleven of the 12 infants were liveborn. Nine of these 11 survived the neonatal period and underwent surgical repair within the first year of life; two subsequently died. In total, seven fetuses survived and five did not. CONCLUSIONS: Most fetuses with DORV can be identified antenatally as having an abnormal heart. However, it is very difficult to distinguish this particular defect from other conotruncal abnormalities.

Diagnosis, Differential↗