Search PubMed⌕ Search

Biomedical subjects

S Alexander

Publications and source records attributed to S Alexander.

At least 55 records · Page 3Linked to original sources

A new, unique and simple method for ureteral implantation in kidney recipients with small, defunctionalized bladders.

BACKGROUND: Major, almost insurmountable, deterrents exist to the use of the small capacity, defunctionalized, nonneurogenic urinary bladder in renal transplantation, namely, the technical difficulty in performing a satisfactory ureteral implantation with conventional methods and the potential secondary problems with high grade ureteral reflux and obstruction. Alternatives are less than ideal and include transplantation into a bowel-augmented urinary bladder with intermittent self-catheterization, ileal conduit urinary diversion, or avoidance of transplantation and relegating the patient to life-long dialysis. METHODS: Eight consecutive patients (ages 13 months to 29 years) with small, defunctionalized urinary bladders underwent a new method of intravesical implantation of the transplant ureter. The mean capacity of these bladders was 18.5+/-13.1 ml (range 6 to 45 ml), with the bladders defunctionalized for a mean 81.6+/-24.3% of the patients' total lifetime. The technique involved placement of the transplant ureter into a shallow, mucosa-denuded, rectangular trough extending from a superiorly placed ureteral hiatus distally to the trigone. We hypothesized that the mucosal margins on the two lateral aspects of the rectangular trough would grow over the anterior surface of the ureter until they met the advancing mucosal edges from the contralateral side to form a natural neosubmucosal tunnel. RESULTS: Posttransplantation cystoscopic examination demonstrated bladder mucosal regeneration and growth over the ureter, confirming the spontaneous development of a good length neosubmucosal tunnel. All patients demonstrated no evidence of ureteral reflux or ureteral obstruction, whereas an immediate prior cohort of four consecutive patients with bladder capacities < or =30 ml showed that three of four had ureteral reflux (P=0.02) and four of four developed hydronephrosis (P=0.002). All urinary bladders in the present cohort enlarged to expected normal or nearnormal capacities. Serum creatinines were stable throughout the entire follow-up period, with the exception of one patient who had rejection episodes. Two patients had urinary tract infections posttransplantation, but there were no episodes of acute pyelonephritis. CONCLUSIONS: This novel technique for ureteral implantation successfully capitalizes on the regenerative potential of the bladder mucosa, resulting in a physiological, anatomically natural, and very effective neosubmucosal tunnel. It appears to guarantee success against both ureteral reflux and obstruction, no matter how small the urinary bladder, and offers no hindrance to enlarging the bladder to near normal capacity posttransplantation. The implantation technique is simple and safe, and its use should eliminate the reluctance to use these bladders. Moreover, this procedure offers a major incentive for the successful rehabilitation of small, defunctionalized, nonneurogenic bladders after kidney transplantation.

Adult↗

Branchio-oto-renal syndrome with generalized microdontia: case report.

Branchio-oto-renal syndrome, first defined in 1976, is an autosomal dominant disorder characterized by anomalies of the external, middle, and inner ear in association with preauricular sinuses, branchial cleft anomalies, and varying degrees of renal dysplasia, including aplasia. Less frequently expressed phenotypic abnormalities include lacrimal duct aplasia and stigmata of renal dysgenesis known as Potter facies. Although the precise incidence of the disorder is unknown, it may be more common than is generally appreciated, and it appears to be distinct from other autosomal dominant otobranchial syndromes. Moreover, not all features of the syndrome are expressed in all carriers of the gene. An unusual case of branchio-oto-renal syndrome with generalized microdontia of the permanent dentition is reported.

Branchio-Oto-Renal Syndrome↗

Classification differences and maternal mortality: a European study. MOMS Group. MOthers' Mortality and Severe morbidity.

OBJECTIVES: To compare the ways maternal deaths are classified in national statistical offices in Europe and to evaluate the ways classification affects published rates. METHODS: Data on pregnancy-associated deaths were collected in 13 European countries. Cases were classified by a European panel of experts into obstetric or non-obstetric causes. An ICD-9 code (International Classification of Diseases) was attributed to each case. These were compared to the codes given in each country. Correction indices were calculated, giving new estimates of maternal mortality rates. SUBJECTS: There were sufficient data to complete reclassification of 359 or 82% of the 437 cases for which data were collected. RESULTS: Compared with the statistical offices, the European panel attributed more deaths to obstetric causes. The overall number of deaths attributed to obstetric causes increased from 229 to 260. This change was substantial in three countries (P < 0.05) where statistical offices appeared to attribute fewer deaths to obstetric causes. In the other countries, no differences were detected. According to official published data, the aggregated maternal mortality rate for participating countries was 7.7 per 100,000 live births, but it increased to 8.7 after classification by the European panel (P < 0.001). CONCLUSION: The classification of pregnancy-associated deaths differs between European countries. These differences in coding contribute to variations in the reported numbers of maternal deaths and consequently affect maternal mortality rates. Differences in classification of death must be taken into account when comparing maternal mortality rates, as well as differences in obstetric care, underreporting of maternal deaths and other factors such as the age distribution of mothers.

Cause of Death↗

Perspectives in posterior vertical dimension: three case reports.

Using a powerful three dimensional perspective, it is possible to control the vertical components of bite opening appliances, which can prove to be valuable in design and application of functional appliances. Several cases are presented to illustrate this orthopedic technique.

Cephalometry↗

Correction of a Class III malocclusion with a four-way sagittal appliance: case report.

This case report demonstrates the treatment of a Class III malocclusion, in a twelve-year-old girl, using a unique combination of a removable functional appliance, the "four-way sagittal" appliance and fixed appliance therapy. Efficient and effective correction of malocclusion was attained, following use of the "four-way sagittal" appliance. This appliance was designed on the Denar Witzig articulator, a powerful instrument in providing the clinician with a three-dimensional perspective plus the ability of changing the location of the TMJ on the articulator. A significant increase in the maxillary length and maxillary width was achieved.

Cephalometry↗

Dental management of a pediatric patient with myelodysplastic syndrome.

Myelodysplastic syndrome in the pediatric population is an extremely rare-hematological disorder. An eleven-year-old girl with a remarkable, past medical history of myelodysplastic syndrome is presented. She was treated for a falling hematocrit and platelet count, with splenectomy as a lifesaving measure. The features of the syndrome and treatment options are described. The clinical protocol for the dental management of the pediatric patient with myelodysplastic syndrome is discussed.

Child↗

Investigations into the sterility of manually assembled extracorporeal circuits with vented reservoirs.

This study was designed to investigate the ability of an extracorporeal circuit (ECC) with a vented hard shell reservoir to remain sterile for a period of 72 h under dry conditions. The study was conducted in three phases. In Phase One: Two previously published methods for detecting contamination of the ECC were compared. A group of positive controls was collected by contaminating identical circuits with a known level of Enterobacter cloacae (ATTC: 13047) before initiating a regimen of "sample-dilute-sample" culturing. Negative controls for this phase were conducted by randomly sampling 1 L per manufacturer's lot of lactated ringers with each detection method. Culture results suggest that large volume filtration, but not small aliquot sampling, is sensitive to extremely low levels of contamination. No growth was detected in any negative control samples. In Phase Two: 19 ECC consisting of a membrane oxygenator, vented hardshell reservoir, arterial filter, and PVC tubing were removed from their sterile packages, assembled, and left unprotected in the moderate traffic environment of a research laboratory. The circuits were then primed with Lactated Ringer's solution. The prime solution was sampled for aerobic contamination by large volume filtration. None of the 19 samples detected contamination. In Phase Three: 43 ECC identical to the Phase Two circuits were assembled and left unprotected in the substerile pump room. The circuits were then primed, circulated, and cultured as in Phase Two. One of the 43 samples was discarded because of a recognized break in aseptic technique during sample collection. None of the remaining samples detected contamination. Mathematical calculations of binomial probabilities suggest that the chance of an open ECC developing a detectable level of contamination within 72 h of its dry assembly is insignificant.

Enterobacter cloacae↗

Successful transplantation of adult-sized kidneys into infants requires maintenance of high aortic blood flow.

BACKGROUND: Nationally, results of renal transplantation in infants are inferior to those in older children and adults. Within the infant group, best results are obtained with adult-sized kidneys (ASKs) rather than size-compatible pediatric kidneys. However, transplantation of ASKs into infants has an increased risk of acute tubular necrosis and graft loss from vascular thrombosis and primary nonfunction. The aim of this study was to define and understand the hemodynamic changes induced by ASK transplantation, so that outcomes of transplantation in infants can be improved. METHODS: Nine hemodynamically stable and optimally hydrated infants were studied under a controlled sedation with cine phase-contrast magnetic resonance at three time periods: before transplantation, 8-12 days after transplantation, and 4-6 months after transplantation. Cross-sectional images of both the infant aorta and the adult transplant renal artery were obtained and blood flow was quantitated. Renal volumes were also obtained, and expected renal artery blood flow based on early posttransplant volume was calculated. In addition, renal artery blood flow was determined in 10 in situ native adult kidneys prior to donor nephrectomy. Supplemental nasogastric or gastrostomy tube feeding was carried out during the blood flow study period to optimize intravascular volume. RESULTS: Mean infant aortic blood flows were 331+/-148 ml/min before transplantation, 761+/-272 ml/ min at 8-12 days after transplantation (P=0.0006 with pretransplant flow), and 665+/-138 ml/min at 4-6 months after transplantation (P=0.0001 with pretransplant flow). Mean transplanted renal artery flows were 385+/-158 ml/min at 8-12 days and 296+/-113 ml/min at 4-6 months after transplantation. Transplanted renal artery flows were less than prenephrectomy in situ donor renal artery blood flow (618+/-130 ml/min; P=0.02 and P=0.0003) and expected normal renal artery blood flow (666+/-87 ml/min; P=0.003 and P=0.001) at both 8-12 days and 4-6 months after transplantation. A 26% reduction in renal volume (P=0.003) occurred between the two postoperative time periods, and this paralleled the decrease in posttransplant renal artery flow. One-year graft and patient survival in the nine infants was 100%. The mean serum creatinine levels at 3, 6, and 12 months were 0.43+/-0.10, 0.48+/-0.15, and 0.49+/-0.16 mg/dl. CONCLUSIONS: This study is the first to quantitatively document the blood flow changes occurring after ASK transplantation in infants. There was a greater than two-fold increase in aortic blood flow after ASK transplantation, and this increase was sustained for at least 4 months and appeared to be driven by the blood flow demand of the ASK. However, actual posttransplant renal artery blood flow was significantly less than normal renal artery flow. Our study suggests that aggressive intravascular volume maintenance may be necessary to achieve and maintain optimum aortic blood flow, so as not to further compromise posttransplant renal artery flow and to avoid low-flow states that could induce acute tubular necrosis, vascular thrombosis, or primary nonfunction.

Adult↗

A mutation in repB, the dictyostelium homolog of the human xeroderma pigmentosum B gene, has increased sensitivity to UV-light but normal morphogenesis.

Nucleotide excision repair (NER) is an important cellular defense mechanism which protects the integrity of the genome by removing DNA damage caused by UV-light or chemical agents. In humans, defects in the NER pathway result in the disease xeroderma pigmentosum (XP) which is characterized by increased UV-sensitivity, with increased propensity for skin cancer, and an array of developmental abnormalities. Some XP patients exhibit, in addition, symptoms of Cockayne's syndrome (CS) and trichothiodystrophy (TTD), which are characterized by increased UV-sensitivity, without increased cancer incidence, and an array of developmental abnormalities. Some NER genes, including the DNA helicases XPB and XPD, have been shown to function in transcription as well as repair, by virtue of being an integral part of the transcription initiation factor TFIIH. This dual function may account for the above-mentioned wide pleiotropy of phenotypes associated with defects in NER genes, and may explain why some XP patients exhibit developmental abnormalities in addition to XP symptoms. To date, only five XPB patients with three different mutations in the XPB gene have been reported. One of these mutations is a C to A transversion at the splice site at the beginning of the last exon, which resulted in a frameshift throughout the last exon. This patient shows combined clinical symptoms of XP and CS. The recent cloning of the repB gene, the Dictyostelium discoideum homolog of XPB, allowed us to generate a similar C-terminal mutation in the Dictyostelium, in order to test whether the defect in this NER gene has an effect on growth or development. To this end, we have constructed a C-terminal deletion repB mutant in Dictyostelium. To avoid the possibility that a null mutant would be lethal, we used direct homologous recombination to create a 46 amino acid C-terminal deletion mutant. Indeed, we were unable to obtain mutants with a longer 95 amino acid deletion. The repB delta C46 mutants showed an increased sensitivity to UV-light, but a normal pattern of UV-induced expression of repair genes, and no immediately obvious defect in either growth rate or development. The results suggest that the associated developmental defects in the human XPB patients may be due to mutations in another gene.

Amino Acid Sequence↗

Rapid changes of nucleotide excision repair gene expression following UV-irradiation and cisplatin treatment of Dictyostelium discoideum.

Organisms use different mechanisms to detect and repair different types of DNA damage, and different species vary in their sensitivity to DNA damaging agents. The cellular slime mold Dictyostelium discoideum has long been recognized for its unusual resistance to UV and ionizing radiation. We have recently cloned three nucleotide excision repair (NER) genes from Dictyostelium , the rep B, D and E genes (the homologs of the human xeroderma pigmentosum group B, D and E genes, respectively). Each of these genes has a unique pattern of expression during the multicellular development of this organism. We have now examined the response of these genes to DNA damage. The rep B and D DNA helicase genes are rapidly and transiently induced in a dose dependent manner following exposure to both UV-light and the widely used chemotherapeutic agent cisplatin. Interestingly, the rep E mRNA level is repressed by UV but not by cisplatin, implying unique signal transduction pathways for recognizing and repairing different types of damage. Cells from all stages of growth and development display the same pattern of NER gene expression following exposure to UV-light. These results suggest that the response to UV is independent of DNA replication, and that all the factors necessary for rapid transcription of these NER genes are either stable throughout development, or are continuously synthesized. It is significant that the up-regulation of the rep B and D genes in response to UV and chemical damage has not been observed to occur in cells from other species. We suggest that this rapid expression of NER genes is at least in part responsible for the unusual resistance of Dictyostelium to DNA damage.

Animals↗

Perinatal outcomes in women with asthma during pregnancy.

OBJECTIVE: To determine whether adverse perinatal outcome is associated with asthma or asthma medication use during pregnancy. METHODS: A retrospective cohort study was conducted of women who resided in Halifax County, Nova Scotia, and delivered between 1991 and 1993. Asthmatic women were classified into three groups, according to medication usage: no medications, beta agonists only, and steroids with or without other asthma medications. Outcomes compared among asthmatic and nonasthmatic women included maternal complications (pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, and antepartum and postpartum hemorrhage) and neonatal outcomes (low birth weight, congenital malformations, hyperbilirubinemia, and respiratory distress syndrome). RESULTS: The cohort included 817 asthmatic women and 13,709 nonasthmatic women. Overall, the prevalence of pregnancies complicated by asthma increased from 4.8% in 1991 to 6.9% in 1993. Asthmatic women were at increased risk for antepartum and postpartum hemorrhage, independent of medication usage. Asthmatic women taking steroids were at increased risk for pregnancy-induced hypertension (odds ratio [OR] 1.7; 95% confidence interval [CI] 1.0, 2.9). The only significant difference in neonatal outcome between asthma medication groups and nonasthmatic women was of an increased risk of hyperbilirubinemia in infants of women taking steroids (OR 1.9; 95% CI 1.1, 3.4). CONCLUSION: Risk of antepartum and postpartum hemorrhage is increased in asthmatic women, independent of medication usage. The increased incidence of neonatal hyperbilirubinemia and the borderline increased risk of pregnancy-induced hypertension may be complications of steroid use or may be related to poorly controlled asthma.

Adult↗

Rhizopus microsporus in wooden tongue depressors: a major threat or minor inconvenience?

The investigation and management of an apparent outbreak of Rhizopus spp. in a London paediatric referral centre between September 1995 and April 1996 is described. The organism was identified in microbiological surveillance samples from 23 patients nursed in four hospital areas. Investigations revealed the presence of the organism in spatulae from all ward areas investigated and from closed boxed containers held in the central hospital stores obtained from a new supplier. In contrast, culture of spatulae from the initial supplier failed to yield any fungal isolates. The incident was reported to the Medical Device Agency (MDA), the Central Public Health Laboratory Service (CPHLS) and the Birmingham PHLS. A statement was prepared for the weekly Communicable Disease Report and a hazard warning issued by the MDA. The spatulae were withdrawn from use and the contract with the original supplier was re-established. This incident resulted in contamination of samples only and no patient involvement. It highlights the problems which may follow use of equipment for unintended purposes and the need for good manufacturing practice guidelines to be applied to non-sterile equipment used in direct patient care.

Child↗

Early onset of nephrotic syndrome after treatment with D-penicillamine in a patient with Wilson's disease.

Wilson's disease responds to a variety of treatments including D-penicillamine and trientene. Nephrotic syndrome is a late complication of D-penicillamine treatment. We report a pediatric patient with Wilson's disease who developed nephrotic syndrome 2 wk after beginning D-penicillamine. His nephrosis resolved and his disease is quiescent with trientene treatment.

Chelating Agents↗

A digital subtraction radiography investigation of upper first molar proximal bone density changes in adolescents.

The aim of this in vivo study was to investigate the ability of digital subtraction radiography to monitor changes in proximal bone density, adjacent to the upper first molars, in a group of adolescents using the Digora direct digital radiographic system to acquire images. For 57 adolescents, assessments of changes in probing attachment level at the mesio- and disto-buccal surfaces of both upper first molars and proximal crestal bone density using digital subtraction radiography were made. At the conclusion of this 21-month study attachment loss was identified in 34 (17%) of the 204 sites analysed. For sites with attachment loss a mean decrease in bone density equivalent to 5.51 mm3 aluminium (Al) was found compared to 2.96 mm3 Al for those without (p < 0.001). For the 17 subjects with attachment loss a mean equivalent to 4.66 mm3 Al was lost from the crestal bone compared with 2.56 mm3 Al for the 40 subjects without attachment loss (p < 0.01). The correlation between attachment loss and bone density changes was poor for both sites (r = 0.13), p = 0.067) and mean scores for subjects (r = 0.24, p = 0.069). A visual qualitative assessment of bone density change found that 70.6% of sites with attachment loss compared to 62.4% of those without had a decrease in crestal bone density. This study suggests that it is possible to monitor bone density changes in adolescents, with a developing dentition, using digital subtraction radiography. Further, it is suggested that conventional probing assessments of attachment level may underestimate the level of destructive periodontal disease in this age group.

Adolescent↗

CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo.

CCR5-utilizing (R5) and CXCR4-utilizing (X4) strains of human immunodeficiency virus type 1 (HIV-1) have been studied intensively in vitro, but the pathologic correlates of such differential tropism in vivo remain incompletely defined. In this study, X4 and R5 strains of HIV-1 were compared for tropism and pathogenesis in SCID-hu Thy/Liv mice, an in vivo model of human thymopoiesis. The X4 strain NL4-3 replicates quickly and extensively in thymocytes in the cortex and medulla, causing significant depletion. In contrast, the R5 strain Ba-L initially infects stromal cells including macrophages in the thymic medulla, without any obvious pathologic consequence. After a period of 3 to 4 weeks, Ba-L infection slowly spreads through the thymocyte populations, occasionally culminating in thymocyte depletion after week 6 of infection. During the entire time of infection, Ba-L did not mutate into variants capable of utilizing CXCR4. Therefore, X4 strains are highly cytopathic after infection of the human thymus. In contrast, infection with R5 strains of HIV-1 can result in a two-phase process in vivo, involving apparently nonpathogenic replication in medullary stromal cells followed by cytopathic replication in thymocytes.

Animals↗

Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins.

Intestinal ischemia-reperfusion (I-R) is associated with lung injury and the acute respiratory distress syndrome. The hypothesis of this study was that intestinal I-R activates circulating neutrophils to promote elastase-mediated lung injury. Isolated rat lungs were perfused with blood or plasma obtained after intestinal I-R, and lung neutrophil retention and injury and bronchoalveolar lavage (BAL) elastase were measured. Perfusion with I-R blood caused lung neutrophil accumulation and injury and increased BAL elastase. These effects were attenuated by the elastase inhibitor L-658758. Interference with neutrophil adherence before gut reperfusion blocked BAL elastase accumulation. The role of endothelial junction proteins (cadherins) in I-R-elicited lung damage was also evaluated. Activated human neutrophils proteolyzed cadherins in human umbilical vein endothelial cells. Furthermore, plasma of patients with acute respiratory distress syndrome contained soluble cadherin fragments. The results of this study suggest that the elastase released by systemically activated neutrophils contributes to lung neutrophil accumulation and pulmonary microvascular injury. Elastase-mediated proteolysis of endothelial cell cadherins may represent the mechanism through which lung microvascular integrity is disrupted after intestinal I-R.

Animals↗