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S E Smith

Publications and source records attributed to S E Smith.

At least 55 records · Page 3Linked to original sources
PubMed1997

Long-term beneficial effects of BW619C89 on neurological deficit, cognitive deficit and brain damage after middle cerebral artery occlusion in the rat.

4-Amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5-trichlorophenyl)pyrimidine (BW619C89) is a sodium channel antagonist which when administered parenterally reduces neurological deficit and infarct volume after middle cerebral artery occlusion in rats. We have investigated whether BW619C89 administered orally before middle cerebral artery occlusion is cerebroprotective when rats are assessed at one day after stroke, and whether cerebroprotection is long lasting and related to functional recovery. A cerebroprotective oral dose of BW619C89 (20 mg/kg) was used to determine whether reduction in infarct volume is long lasting and can be enhanced with continued therapy, and whether behavioural deficits occurring after middle cerebral artery occlusion such as disturbances in cognition and motor coordination are ameliorated by treatment with BW619C89. Rats received sham surgery or middle cerebral artery occlusion with a single treatment of BW619C89 (20 mg/kg) 1 h before middle cerebral artery occlusion, a double treatment group receiving 20 mg/kg BW619C89 1 h before and 10 mg/kg 5 h after middle cerebral artery occlusion, or continued treatment with BW619C89 for up to five days. Neurological deficit, assessed from days 1 to 21, and at 70 days after middle cerebral artery occlusion, was reduced to a similar extent in all three groups of rats treated with BW619C89, compared with vehicle-treated controls. At 70 days after middle cerebral artery occlusion, all groups performed at control level. Vehicle-treated rats were impaired in the Morris water maze and step-through passive avoidance paradigm five to eight weeks after middle cerebral artery occlusion, when neurological deficit was minimal. These deficits were partially alleviated, to a similar extent, by all of the three treatments with BW619C89. Total volumes of brain damage, assessed at 70 days after middle cerebral artery occlusion in Luxol Fast Blue- and Cresyl Violet-stained coronal sections, were reduced in all three groups of BW619C89-treated rats, to 46% in the single, 50% in the double and 58% in the continued treatment group, compared with vehicle-treated rats. Extent of brain damage correlated with extent of impairment of the rats in the water maze. These findings suggest that BW619C89 has long-lasting cerebroprotective effects with advantageous functional consequences after single oral administration in a rodent model of stroke. Prolonged treatment with BW619C89 did not significantly enhance the cerebroprotective effects. Deficits in performance of rats in the water maze and step-through passive avoidance tasks indicate sustained cognitive impairment after middle cerebral artery occlusion. The reductions in brain damage by BW619C89 correlated with significant long-term functional improvement.

Animals↗
PubMed1997

Caprine blastocyst formation following intracytoplasmic sperm injection and defined culture.

Experiments were undertaken to develop intracytoplasmic sperm injection (ICSI) to produce caprine embryos out of the normal breeding season. Oocytes were obtained from 2-6 mm ovarian follicles at slaughter. Selected oocytes with two to four layers of cumulus cells were incubated in 1 ml of H-TCM199 supplemented with 10 micrograms each of oFSH and bLH (NHPP, NIDDK, NICHD, USDA) and 20% fetal bovine serum (FBS) in a thermos (38.5 degrees C) for 4.5 h during transportation. Then, oocytes were transferred into 75 microliters of freshly prepared maturation medium under paraffin oil and a mixture of 5% O2, 5% CO2 and 90% N2. Approximately 26 h after recovery oocytes were denuded by incubation with hyaluronidase (100 IU/ml) and pipetting and held at 38.5 degrees C for 90 min. Spermatozoa frozen in egg yolk extender were thawed in a 37 degrees C water bath for 15 s. Motile fractions were selected by swim-up, then incubated for 90 min in TALP with 10 micrograms heparin/ml. Each oocyte was positioned with its first polar body at 6 or 12 o'clock by a holding pipette. Sperm (1 microliter) were added to 10 microliters medium containing 10% polyvinylpyrrolidone. A sperm cell was aspirated into a pipette, and then injected head-first into the cytoplasm of an oocyte maintained in H-TCM199 + 20% FBS at 37 degrees C. Injected oocytes were transferred to HM and, after 90 min, cultured in 50 microliters of BSA-free synthetic oviduct fluid plus polyvinyl alcohol, citrate and non-essential amino acids. Results demonstrate that caprine blastocysts can be produced outside the breeding season by the use of frozen-thawed semen and injection of sperm cells with broken tails into ova followed by culture in defined medium.

Animals↗
PubMed1997

Normotensive blood pressure in mice with a disrupted renin Ren-1d gene.

Renin is an aspartyl protease that is involved in the conversion of angiotensinogen to angitensin II and hence participates in the regulation of blood pressure. Mice are polymorphic for the number of renin genes with some strains harbouring two renin genes, Ren-1d and Ren-2. To study the role of renin Ren-1d in regulating cardiovascular homeostasis, mice with a disrupted Ren-1d gene were created. Analyses of kidney renin mRNA expression in Ren-1d-/-/Ren-2+/+ mice demonstrated that only Ren-2 transcripts were present. Mean arterial blood pressures of Ren-1d+/+/Ren-2+/+, Ren-1d+/-/Ren-2+/+ and Ren-1d-/-/Ren-2+/+ mice showed no significant differences. These observations demonstrate that the Ren-1d gene product is not essential for normal blood pressure maintenance under normal physiological conditions.

Animals↗
PubMed1997

The role of trophoblast interferons in the maintenance of early pregnancy in ruminants.

PROBLEM: Are the effects of ruminant trophoblast interferon-tau (IFN-tau) on uterine prostaglandin (PG) secretion a specific action of this cytokine and what are the effects of IFN-tau on expression of uterine genes not generally associated with pregnancy maintenance? METHODS: The effects of IFN-tau and IFN-alpha on bovine uterine explant and epithelial cell production of PGF2 alpha and PGE2 were determined in the presence and absence of oxytocin (OT). The effects of intrauterine administration of IFN-tau were determined on uterine expression of retinol-binding protein (RBP) and transforming growth factor-beta (TGF-beta) isoforms. RESULTS: IFN-tau attenuated uterine endometrial secretion of PGF2 alpha and PGE2 in vitro and diminish PG stimulation by OT. IFN-tau and IFN-alpha were observed to be equipotent. Intrauterine infusion of IFN-tau resulted in a significant decrease in steady-state RBP mRNA levels and expression of TGF-beta 1, 2, and 3 mRNA levels were lowest in IFN-tau treated animals. CONCLUSION: Negative regulation of gene expression may be a general strategy in IFN activity. This may explain the similar activities of IFN-tau and IFN-alpha on a broad variety of cell types, including ruminant uterine endometrium.

Animals↗
PubMed1997

Total hip arthroplasty performed with insertion of the femoral component with cement and the acetabular component without cement. Ten to thirteen-year results.

Fifty-two consecutive primary total hip arthroplasties were performed in forty-seven unselected patients by one surgeon. The prosthesis included a hemispherical porous-coated acetabular component, inserted without cement and with the use of screws through three peripheral flanges, and a femoral component, inserted with a so-called second-generation cementing technique. No patient was lost to radiographic follow-up, and the clinical result was known for all patients. The average age at the time of the index operation was fifty-seven years (range, twenty-nine to seventy-nine years). Four patients (four hips) who died were last examined less than ten years postoperatively (the minimum follow-up period for this study) and one hip was revised, leaving forty-seven non-revised hips in forty-two surviving patients who were followed for at least ten years. The duration of clinical follow-up of these forty-two patients averaged 12.3 years (range, 10.8 to 13.3 years), and the duration of radiographic follow-up averaged 12.1 years (range, 10.0 to 13.0 years). One (2 per cent) of the original fifty-two hips was revised for late recurrent dislocation, without loosening, 9.7 years after the index arthroplasty. The rate of dislocation was relatively high (13 per cent; seven hips), and we believed it to be related to the shallow-chamfer acetabular design combined with the small femoral head. At the time of the latest follow-up, no femoral component was loose. One (2 per cent) of the fifty-two acetabular components was loose according to radiographic criteria, but the hip functioned well (Harris hip score, 94 points) 12.4 years after the index arthroplasty. Pelvic osteolysis developed in one hip (2 per cent); femoral osteolysis, in eight (15 per cent); and distal femoral osteolysis, in three (6 per cent). The average Harris hip score for the forty-seven non-revised hips increased from 48 points (range, 26 to 63 points) preoperatively to 89 points (range, 67 to 100 points) at the time of the most recent follow-up. Forty (85 per cent) of the forty-seven hips had a good or excellent result, whereas five (11 per cent) had a fair result (score, 74 to 79 points) and two (4 per cent) had a poor result (score, 67 and 69 points). The hybrid primary total hip arthroplasty resulted in very good clinical function at ten to thirteen years, although the rate of dislocation was high.

Acetabulum↗
PubMed1996

cDNA cloning and expression of HIP, a novel cell surface heparan sulfate/heparin-binding protein of human uterine epithelial cells and cell lines.

Heparan sulfate proteoglycans and their corresponding binding sites have been suggested to play an important role during the initial attachment of murine blastocysts to uterine epithelium and human trophoblastic cell lines to uterine epithelial cell lines. Previous studies on RL95 cells, a human uterine epithelial cell line, had characterized a single class of cell surface heparin/heparan sulfate (HP/HS)-binding sites. Three major HP/HS-binding peptide fragments were isolated from cell surfaces by tryptic digestion, and partial amino-terminal amino acid sequence for each peptide fragment was obtained (Raboudi, N., Julian, J., Rohde, L. H., and Carson, D. D. (1992) J. Biol. Chem. 267, 11930-11939). In the current study, using approaches of reverse transcription-polymerase chain reaction and cDNA library screening, we have cloned and expressed a novel, cell surface HP/HS-binding protein, named HP/HS interacting protein (HIP), from RL95 cells. The full-length cDNA of HIP encodes a protein of 159 amino acids with a calculated molecular mass of 17,754 Da and pI of 11.75. Transfection of HIP full-length cDNA into NIH-3T3 cells demonstrated cell surface expression and a size similar to that of HIP expressed by human cells. Predicted amino acid sequence indicates that HIP lacks a membrane spanning region and has no consensus sites for glycosylation. Northern blot analysis detected a single transcript of 1.3 kilobases in both total RNA and poly(A+) RNA. Examination of human cell lines and normal tissues using both Northern blot and Western blot analyses revealed that HIP is expressed at different levels in a variety of human cell lines and normal tissues but absent in some cell lines and some cell types of normal tissues examined. HIP has relatively high homology (approximately 80% both at the levels of nucleotide and protein sequence) to a rodent ribosomal protein L29. Thus, members of the L29 family may be displayed on cell surfaces where they may participate in HP/HS binding events.

3T3 Cells↗
PubMed1996

Clinicopathologic factors and patient perceptions associated with surgical breast-conserving treatment.

BACKGROUND: Clinical studies have shown equivalent survival rates between breast-conserving surgery (BCS) and mastectomy in early breast cancer; however, rates for BCS remain low. The purpose of this study was to determine (a) the prevalence of BCS in a regional medical center, (b) clinicopathologic factors associated with BCS, and (c) patient perceptions of the treatment decision-making process. METHODS: We retrospectively reviewed 251 consecutive breast cancer cases during January 1990-December 1991; 77 patients were ineligible for BCS because of unfavorable pathology. We then interviewed 118 of the 160 women available for interview. RESULTS: BCS was performed in 31 of the eligible patients (18%). Multivariate analysis revealed that tumor size < 10 mm (p = 0.03) was the only significant predictive variable for BCS. Patient interviews revealed that 93% said their surgeon was the primary source of information regarding treatment options. Among 69% of the women whose surgeons reportedly recommended a particular option, 89% recommended mastectomy with 93% compliance, and 11% recommended BCS with 89% compliance. The BCS group more often obtained a second opinion (p = 0.04) and 60% said they made the decision themselves compared with only 37% of the mastectomy group (p = 0.05). CONCLUSION: Limiting BCS to women whose tumor size is < 10 mm is too restrictive; this excludes a large number of women who are clinically eligible for BCS. The surgical decision-making process for early-stage breast cancer is very much surgeon-driven, with a high degree of patient compliance.

Aged↗
PubMed1996

Chronic electroconvulsive shock enhances 5-HT2 receptor-mediated head shakes but not brain C-fos induction.

Chronic electroconvulsive shock (ECS), a widely used treatment for intractable depression, increases the density of 5-HT2A receptor binding sites and mRNA in rat frontal cortex. In contrast, this treatment appears to have no significant effect on 5-HT-stimulated phosphatidyl inositol turnover in rat brain. To investigate the effect of chronic ECS on the 5-HT2 receptor family further, we determined its effects on head shakes and c-fos expression in the rat in response to the 5-HT2A/2C receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane]. Chronic ECS (5 electroconvulsive shocks over 10 days, via earclips under halothane anaesthesia) caused a significant enhancement in the number of head shakes counted in a 30 min period after administration of 2 or 8 mg/kg DOI. In contrast, this treatment had no effect on Fos expression, induced by either dose of DOI, in any region of rat forebrain examined. Fos expression was low-to-undetectable in the brains of animals treated with chronic ECS followed by saline and sham ECS animals that had been treated identically, but with no administration of electrocurrent. Thus the lack of any change in PI turnover, following chronic ECS administration, appears to be mirrored by the failure of this treatment to alter 5-HT2 receptor-mediated Fos expression.

Amphetamines↗
PubMed1996

Anticonvulsant effects of 7-nitroindazole in rodents with reflex epilepsy may result from L-arginine accumulation or a reduction in nitric oxide or L-citrulline formation.

1. To investigate the role of nitric oxide in epilepsy we have studied the effects of agents which affect nitric oxide synthesis in sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone (GEP) rats. 2. The neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole (7-NI) is anticonvulsant in these models with ED50 values against clonic seizures in mg kg-1 i.p. (times following injection) of: 74 (+0.25 h), 120 (+1 h) in DAB/2 mice, and 56 (+0.25 h), 42 (+0.5 h), 36 (+1 h), 28 (+2 h), 38 (+4 h), 93 (+8 h) in GEP rats. 3. Therapeutic indices (locomotor deficit ED50/anticonvulsant ED50) for 7-NI are low, ranging from 0.6 to 1.1 at +0.25 h to +1 h after administration in GEP rats, but are more favourable at later times (1.6 at +2 h and 2.9 at +4 h). 4. The substrate for nitric oxide synthase, L-arginine (500-5000 mg kg-1, i.p. or 100-300 micrograms, i.c.v.) but not D-arginine (300 micrograms i.c.v.) is anticonvulsant in DBA/2 mice. L-Arginine (500-5000 mg kg-1, i.p. or 1800-6000 micrograms, i.c.v.) is a more potent anticonvulsant than D-arginine (1500-2500 mg kg-1, i.p. or 6000 micrograms, i.c.v.) in GEP rats. 5. In DBA/2 mice, L-arginine (30 micrograms i.c.v.) reverses the anticonvulsant effect of 7-NI (50 mg kg-1, i.p.). 6. In GEP rats, low dose L-arginine (25-50 mg kg-1, i.p.) but not D-arginine (50 mg kg-1, i.p.) reverses the anticonvulsant effect of low dose 7-NI (25 mg kg-1, i.p.). A higher dose of L-arginine (500 mg kg-1, i.p.) or 7-NI (50 mg kg-1, i.p.) produces summation of anticonvulsant effect. 7. The product for nitric oxide synthase, L-citrulline (250-831 micrograms i.c.v.), is convulsant in DBA/2 mice. 8. The anticonvulsant effect of the neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole, may therefore be mediated by L-arginine accumulation, as well as by a reduction in nitric oxide and L-citrulline formation in rodent models of reflex epilepsy.

Animals↗
PubMed1996

Interobserver reliability and intraobserver reproducibility of the modified Ficat classification system of osteonecrosis of the femoral head.

Anteroposterior and lateral plain radiographs of 116 osteonecrotic femoral heads were reviewed to assess the interobserver reliability and intraobserver reproducibility of the modified Ficat classification system. The radiographs were reviewed initially and then again six months later by three adult reconstructive surgeons, two general orthopaedic surgeons, two orthopaedic residents, and one musculoskeletal radiologist. All eight observers agreed on the classification of twenty hips (17 per cent) at both the first and the second review of the radiographs. Paired comparisons revealed a mean interobserver kappa reliability coefficient of 0.46 (range, 0.30 to 0.67) for the first review and 0.45 (range, 0.30 to 0.66) for the second. For all observers, the mean rate of perfect agreement between the first and the second review was 68 per cent (range, 56 to 80 per cent). The mean kappa value for intraobserver reproducibility was 0.59 (range, 0.44 [one of the residents] to 0.73 [one of the general orthopaedic surgeons]). No observer or pair of observers had excellent reproducibility or reliability (kappa > 0.75). The poor interobserver reliability and fair intraobserver reproducibility diminishes any meaningful comparison of studies in which the modified Ficat classification system has been used and illuminates the need for a more reliable and reproducible classification system.

Femur Head Necrosis↗
PubMed1995

Outcome of unoperated discogram-positive low back pain.

STUDY DESIGN: No previous discography study has addressed the nonoperative outcome of low back pain. OBJECTIVES: This study was undertaken to retrospectively analyze the outcome of patients with documented single-level discogenic pain who were considered candidates for surgery but did not receive it. SUMMARY OF BACKGROUND DATA: The natural history of "discogenic" low back pain is unknown, and its treatment is controversial. Although positive discography is viewed as a valid diagnostic technique, the results of fusion surgery are often disappointing. METHOD: Twenty-five individuals (16 women, 9 men) underwent comprehensive evaluation (examination, radiography, objective disability determination). Study criteria included incapacitating low back pain, single-level + morphologic + provocative discogram, no surgery, and a minimum follow-up period of 3 years. RESULTS: Average age of patients at discography was 43 years and at study was 48 years; level of involvement in 10 patients was L4-L5 and in 15 patients were L5-S1. The mean follow-up period was 4.9 years (range, 3.3-7.0 years). The condition of 17 (68%) patients improved, two (8%) stayed the same, and six (24%) worsened. Improved patients had a shorter history of low back pain (3.5 yr vs. 11.0 yr) and older age at onset (45 versus 33 yrs.) Psychiatric disease was present in 66.7% (4 of 6) patients whose conditions worsened. Eighty percent (12 of 15) of patients receiving workers' compensation improved. There was no correlation between disc level, gender, smoking, and outcome. CONCLUSIONS: Discogenic low back pain improved in patients without psychiatric disease. Older age at onset and shorter duration of low back pain were favorable indicators. These results are comparable with or better than those reported for surgical treatment of this condition.

Adult↗
PubMed1995

The gamma-aminobutyric acid uptake inhibitor, tiagabine, is anticonvulsant in two animal models of reflex epilepsy.

The effects of i.p. administration of the gamma-aminobutyric acid (GABA) uptake inhibitors R(-)N-(4,4-di(3-methylthien-2-yl)-but-3-enyl) nipecotic acid hydrochloride (tiagabine; molecular weight 412.0), (1-(2-(((diphenylmethylene)-amino)oxy)ethyl)-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid hydrochloride (NNC-711; molecular weight 386.9), and (+/-)-nipecotic acid (molecular weight 128.2) are compared with those of carbamazepine (molecular weight 236.3) on sound-induced seizures and locomotor performance in genetically epilepsy-prone (GEP) rats. The ED50 value against clonic seizures (in mumol kg-1 at the time of maximal anticonvulsant effect) for tiagabine was 23 (0.5 h), and for NNC-711 was 72 (1 h), and for carbamazepine was 98 (2 h). (+/-)-Nipecotic acid (0.4-15.6 mmol kg-1) was not anticonvulsant. High doses of NNC-711 (207-310 mumol kg-1) and of (+/-)-nipecotic acid (39-78 mmol kg-1) induced ataxia and myoclonic seizures 0.25-1 h. Tiagabine and carbamazepine did not induce myoclonic seizures and had similar therapeutic indices (locomotor deficit ED50/anticonvulsant ED50) ranging from 0.4 to 1.9. In Papio papio, we observed a reduction in photically induced myoclonic seizures with tiagabine (2.4 mumol kg-1 i.v.) accompanied with neurological impairment. Tiagabine has comparable anticonvulsant action to carbamazepine in rats and has anticonvulsant effects in non-human primates supporting the potential use of inhibitors of GABA uptake as therapy for epilepsy.

Acoustic Stimulation↗
PubMed1995

Allograft aortic valve replacement: long-term follow-up.

Aortic valve replacement using an allograft aortic valve has been performed on 804 patients. From December 1969 to May 1975, 124 patients received a nonviable allograft valve sterilized by incubation with low-dose antibiotics and stored for weeks by refrigeration at 4 degrees C (series 1). From June 1975 to January 1994, 680 patients received viable allograft valves, now cryopreserved early within 2 hours of collection from transplant recipient donors, 6 hours for multiorgan donor valves and 23 hours (mean) for autopsy valves from donor death. The 30-day mortality was 8.9% +/- 5% (95% confidence limits) for series I and 2.8% +/- 1% (95% confidence limits) for series II. Actuarial patient survival including hospital mortality at 15 years was 56% +/- 5% for series I and 62% +/- 5% for series II. The probability of a thromboembolic event was low, freedom at 15 years being 95% +/- 1% for patients receiving allografts with or without associated coronary bypass procedures and 81% +/- 5% for patients having allografts with other associated procedures (eg, mitral valve operations). Actuarial freedom from endocarditis was similar for the two series, 91% +/- 3% (series I) and 94% +/- 2% (series II) at 15 years. The freedom from valve incompetence, from reoperation for all causes, and from structural deterioration demonstrated clearly the inferiority of the 4 degrees C stored allograft valves. For structural deterioration as identified clinically, at reoperation and at death, freedom from this event at 15 years was 45% +/- 6% for series I and 80% +/- 5% for series II (p value for the difference is 0).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1995

Root replacement for all allograft aortic valves: preferred technique or too radical?

From November 1985 to January 1994, 146 patients have received a viable cryopreserved allograft for aortic root replacement. The follow-up was complete, with all events included to March 1st, 1994. The median age of patients was 49 years; 83.6% were male. Valve dysfunction (91 patients), primary aortic wall disease (45 patients), and a combination of both (10 patients) were the indications for aortic root replacement. The current operative mortality is 1.7% (three deaths in 172 patients to July 1st, 1994). Four late deaths have occurred, with an 8-year actuarial survival of 85% +/- 8% (95% confidence limits). Endocarditis (two events) and thromboembolism (four events) had a low incidence. Structural deterioration (three events) and reoperation for all causes (nine events) have constituted low morbidity and are compared with the results after non-root allograft implantation techniques. The clinical and echocardiographic evidence indicates that the immediate results of valve function with root replacement are superior. But no statistical difference between aortic root replacement and non-root procedures is apparent at 8 years, indicating that a longer follow-up is required before the answer to the question "preferred technique or too radical" can be answered.

Adolescent↗
PubMed1995

The Medtronic Intact xenograft: an analysis of 342 patients over a seven-year follow-up period.

Three hundred forty-two patients from December 1985 to January 1993 received 352 Medtronic Intact porcine xenograft valves (zero-pressure glutaraldehyde-fixed with toluidine blue anticalcification agent). The follow-up was 99.4% complete with a mean of 3.14 years (3 months to 7.9 years). The mean patient age was 64 years (range, 16 to 82 years) and the median age was 67 years. There were 14 aortic valve replacement patients (11.9%) and 62 mitral valve replacement patients (29.2%) who preoperatively were in New York Heart Association class IV to V. The hospital mortality was 8.4% +/- 2.9% (aortic valve replacement, 5.9%; mitral valve replacement, 9.4%; tricuspid valve replacement, 7.6%). Actuarial patient survival at 7 years was 65% +/- 5% (aortic valve replacement, 77% +/- 5%; mitral valve replacement, 63% +/- 5%). At 7 years, the freedom from thromboembolism was 74% +/- 4%, freedom from endocarditis 93% +/- 2%, and freedom from reoperation 90% +/- 3%. Reoperation was required for endocarditis (7 patients), periprosthetic leak (6), and 2 of 3 cases of structural deterioration. The actuarial freedom from structural deterioration at 5 years was 97% +/- 3%. The combined incidence of all important morbid valve-related events was analyzed with an actuarial freedom at 7 years of 63% +/- 3%. The durability of the Medtronic Intact is at least equal to that of other porcine bioprostheses. The relevant important time-frame of 7 to 12 years of follow-up has just begun, and possibly the reoperation rate for intrinsic value failure and the low incidence of calcification in the elderly patient may be showing improved characteristics of this valve. No stronger inferences are possible at this stage of the 7-year follow-up.

Actuarial Analysis↗
PubMed1995

Isolation and characterization of a 1 Mb region of 5q23.3-q31.2 surrounding the human lysyl oxidase gene.

Lysyl oxidase (EC 1.4.3.13) plays a pivotal role in the maintenance of tissue integrity in both the normal and pathological states. It is a member of a newly discovered gene family that exhibits a complex mode of regulation. To date the resources necessary to begin to address its regulation have not been assembled. In part, this reflects the instability of this region of the genome when cloned into cosmid vectors. The paucity of long range restriction endonuclease sites suitable for mapping this region of the genome has further hampered progress. To begin to address this issue 2 YAC clones of 920 kb and 245 kb that contain the human lysyl oxidase gene were isolated. Long range physical mapping revealed that the 245 kb clone was centrally located within the 920 kb clone. The corresponding map of this region is congruent with that observed in the human genome. Thus, these YACs faithfully represent this region of the human genome. The results of our cloning and mapping studies described in this communication should accelerate the advance of our understanding of this new connective tissue gene family.

Base Sequence↗
PubMed1995

Fetal pelvi-ureteric junction obstruction: predictors of outcome.

OBJECTIVE: To examine the relationship between pre-natal ultrasonographic findings typical of pelvi-ureteric junction (PUJ) obstruction and post-natal renal function in the affected kidney. PATIENTS AND METHODS: This retrospective study comprised 35 infants in whom pre-natal ultrasonography had identified a unilateral pattern of dilatation of the renal pelvis and calices typical of PUJ obstruction. In each case, the presence of unilateral hydronephrosis had been confirmed post-natally by ultrasonography, and differential function and drainage evaluated by isotope renography. The results of isotope renography were compared with the severity and timing of onset of the fetal hydronephrosis. RESULTS: Eleven kidneys (31%) appeared normal in the second trimester and dilatation only became apparent during the third trimester. Mean differential function in these kidneys was 48%. However, mean differential function was reduced (mean 38%) in those kidneys noted to be dilated between 16 and 24 weeks gestation. Differential function was loosely correlated with the severity of dilatation in early onset cases, i.e. the mean differential function was 42% for mild, 37% for moderate and 27% for severe dilatation. A considerable variation in differential function values was present in each group except for those with severe dilatation, which was a significant predictor of poor functional outcome when compared with mild and moderate dilatation combined (P < 0.01). CONCLUSION: Fetal PUJ obstruction is a heterogeneous condition permitting only broad predictions of functional outcome. Severe dilatation detected on second trimester imaging predicted significant loss of function. Mild and moderate degrees of dilatation were associated with a one in three risk of functional impairment in the obstructed kidney.

Dilatation, Pathologic↗