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Biomedical subjects

S Ritchie

Publications and source records attributed to S Ritchie.

At least 37 records · Page 2Linked to original sources
PubMed1998

The human c-Src proto-oncogene promoter contains multiple targets for triplex-forming oligonucleotides.

The overexpression and activation of the human c-Src proto-oncogene is closely associated with cancer of the colon and breast. Characterization of the 5' region of the c-Src gene revealed that the promoter is very GC rich, regulated by the Sp family of transcription factors, and contains four perfect homopolypurine/homopolypyrimidine tracts (Pu:Py tracts). These Pu:Py tracts (TC1, TC1.1, TC2, and TC3) are located near or overlap critical Spl binding sites required for full activation of the gene. Triplex-forming oligonucleotides (TFOs) can be targeted to such sequences with high affinity to form intermolecular triple-helical DNA and modulate transcriptional activity. We therefore designed a series of antiparallel purine-based TFOs and measured their ability to form triplexes with the c-Src promoter Pu:Py tracts using comigration, bandshift, and chemical footprint techniques. With one interesting exception, all of the TFOs were found to bind with specificity and high affinity (67 nM-28 nM) to their target sequences at physiologic pH. These results indicate that the c-Src gene can successfully form stable triplexes under physiologic conditions and is, therefore, an excellent candidate for triplex-mediated transcriptional downregulation.

Base Composition↗
PubMed1998

Domestic Aedes aegypti breeding site surveillance: limitations of remote sensing as a predictive surveillance tool.

This project tested aerial photography as a surveillance tool in identifying residential premises at high risk of Aedes aegypti breeding by extending the use of a recently developed, ground-based, rapid assessment technique, the modified Premise Condition Index (PCI2). During 1995, we inspected 360 premises in Townsville, Australia for Ae. aegypti breeding, and PCI2 scores were recorded. The PCI2 values were also estimated from 1:3,000 color and infrared aerial photograph interpretation for the same premises. We found that shade levels can be accurately identified from both color and infrared images, and the PCI2 can be accurately identified from infrared photographs. Yard conditions, however, cannot be accurately identified from either aerial photograph type. The airborne PCI2 did not significantly correlate with breeding measures, and logistic regression further demonstrated that neither aerial photograph type allows the accurate prediction of Ae. aegypti breeding risk. Therefore, the ability of low-level aerial photography to enhance Ae. aegypti breeding site surveillance is at present limited, with ground surveillance remaining our most reliable tool for identifying the probability of Ae. aegypti breeding in the residential environment.

Aedes↗
PubMed1997

An audit of in-patients aged 18-65 in acute psychiatric wards who are inappropriately placed three months after admission.

OBJECTIVE: To identify acute psychiatric patients considered inappropriately placed three months after admission and expedite a more suitable placement by improving liaison with social work. DESIGN: A survey established the point prevalence of inappropriately placed patients. Changes in usual practice were implemented with the identification of a named social worker for each ward and the introduction of a 'contact sheet' which updated the progress of these patients monthly. A repeat survey one year later assessed the impact of these changes. SETTING: Gartnavel Royal Hospital, Greater Glasgow Community and Mental Health NHS Trust. SUBJECTS: Patients aged 18-65 in the acute psychiatric wards who were resident beyond three months. RESULTS: Use of the contact sheet and improved liaison with a named social worker did not shorten the length of stay of the inappropriately placed patients. Conversely, their mean value for in-patient weeks on the dates surveyed increased from 41.8 in 1994 to 64.7 in 1995. (p = 0.05, 95% confidence intervals from -1 to 42. The length of stay of patients who were still considered to be appropriately placed beyond three months after admission decreased from a mean of 47.7 to 31.9 weeks. (p > 0.5, 95% confidence intervals from -16 to 16). By 1995 the mean length of stay was significantly greater for inappropriately placed patients (p = 0.008, 95% confidence intervals from 10 to 47). CONCLUSIONS: Improved liaison with social work at an operational level was not sufficient to solve the problem of inappropriately placed patients on acute wards. Additional factors such as limited access to rehabilitation placements and patients having complex physical or behavioural problems made placement elsewhere difficult. Such patients with unmet needs place increasing strain on acute psychiatric beds. A reappraisal of current services is required.

Adolescent↗
PubMed1996

The significance of anticardiolipin antibodies in patients with lupus nephritis.

The objective of this study was to determine whether anticardiolipin antibodies (ACL) in SLE patients are associated with a specific pattern of lupus nephritis and/or with renal microvascular changes. Patients with SLE, followed prospectively between June 1991-May 1994 at The Wellesley Hospital Lupus Clinic, who underwent a renal biopsy were included. The ACL was measured by the ELISA according to international standardized method. Renal biopsy morphology was assessed using the WHO criteria for the classification of lupus nephritis. Renal vascular changes included glomerular hyaline thrombi, intimal fibrosis and intraluminal thrombi of renal arterioles. There were 23 SLE patients. The mean age at diagnosis of SLE was 28.2 years and the mean disease duration was 6.3 years. Of these 10 (43%) had high levels of ACL. No difference in the frequency of severe nephritis (Class III and IV) was identified amongst patients with and without ACL. Mesangial nephritis was more common in patients with ACL 40% vs 0, p = 0.02). Glomerular hyaline thrombi occurred in 3 (13%) patients. None of them had positive ACL. Renal vascular lesions included intimal proliferation in 4 (ACL + , 1) occluded lumens by thrombi in 2 (ACL + 1). Our data indicate that the development of glomerular and/or microvascular changes is not related to the presence of ACL.

Adolescent↗
PubMed1995

A controlled trial of cyclosporine in patients with progressive membranous nephropathy. Canadian Glomerulonephritis Study Group.

A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein diet (< or = 0.9 g/kg) and followed closely for 12 months (Part 1). Patients at high risk of progression based on an absolute loss in creatinine clearance (CCr) of > or = 8 ml/min and persistent nephrotic range proteinuria (Pr) were selected and randomly assigned to either (D) (N = 9) or (P) (N = 8) for 12 months (Part 2). No differences in the two groups were noted at entry. After 12 months, the improvement in CCr slope in ml/min/month was significantly greater in the D patients (D + 2.1 vs. P + 0.5, mean difference 1.6; 95% CI 0.3 to 3.0, P < 0.02). This improvement was maintained in six of eight D (75%) over a mean follow-up period of 21 months. Daily Pr also improved with D (by month 3, D - 4.5 g/day vs. P + 0.7 g/day, P = 0.02) and was sustained in six of eight (75%) D patients. When Pr was expressed as a function of their concurrent CCr, the D versus P patients' time to halving was faster (P = 0.02) and absolute number higher (4/9 D vs 0/8 P). In the D group a trend towards worse hypertension and an increase in the number of transient rises in serum creatinine were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Familial Dandy-Walker malformation associated with macrocephaly, facial anomalies, developmental delay, and brain stem dysgenesis: prenatal diagnosis and postnatal outcome in brothers. A new syndrome?

Brothers are reported with an apparently new constellation of manifestations including Dandy-Walker complex (DWC), migrational brain disorder, macrocephaly, and facial anomalies. The first brother presented at birth, the second was detected prenatally with DWC and the pregnancy terminated. Fetal brain histopathology showed DWC associated with brainstem dysgenesis. Inheritance is likely autosomal or X-linked recessive. An extensive review of the differential diagnosis of DWC is provided.

Adult↗
PubMed1994

Long-term benefits of angiotensin-converting enzyme inhibitor therapy in patients with severe immunoglobulin a nephropathy: a comparison to patients receiving treatment with other antihypertensive agents and to patients receiving no therapy.

Of 531 cases of immunoglobulin A nephropathy in the Toronto Glomerulonephritis Registry, 115 were determined by retrospective analysis to have proteinuria > or = 1 g/d. These patients have been followed a minimum of 3 months (range, 3 to 121 months). Monitoring in the registry included routine blood pressure estimates and renal function status by serum creatinine, creatinine clearance, and proteinuria. These patients were grouped and examined retrospectively into three categories (1) hypertensive on angiotensin-converting enzyme (ACE) inhibitor therapy (ACEi), (2) hypertensive on other medication, and (3) no hypertension (NT). Despite comparable renal function abnormalities, the 27 ACEi patients, when compared with the 55 patients receiving other medication, experienced a significantly slower rate of decline in renal function as measured by slope of creatinine clearance (-0.4 mL/min/mo v-1.0 mL/min/mo; P = 0.007), longer time to a loss of one third of baseline creatinine clearance (P = 0.004), and a higher percentage of remission in proteinuria (18.5% v 1.8%; P = 0.003). A subsequent comparison was made between the NT and ACEi groups and, despite a much lower initial serum creatinine, less severe pathology, and a longer observation period in the NT group, both the rate of decline of creatinine clearance (-0.5 mL/min/mo v -0.4 mL/min/mo; P = 0.9) and the percentage of patients progressing to renal failure (21.2% v 18.5; P = 0.8) were not different. The remission rate of proteinuria was superior in the ACEi-treated group compared with the NT group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Motor development, infantile reactions and postural responses of preterm, at-risk infants.

Eighty-nine low-birthweight, preterm infants were enrolled in a longitudinal study to describe motor development, infantile reactions and postural responses during the first chronological year of life and to determine the relationship between these behaviors. There was a clear trend from prevalence of primitive patterns, such as the asymmetric tonic neck reflex, towards a prevalence of mature postural reactions such as the Landau, righting and protective extension reflexes. Statistical analysis suggested that a relationship exists between infantile patterns, automatic postural reactions and motor development that is similar to that accepted as normal in term infant development, when allowance is made for preterm birth. Correlations were also obtained between integration of the tonic labyrinthine response and the presence of the asymmetric tonic neck pattern at the time of hospital discharge and later achievement of motor milestones. These relationships warrant further investigation.

Female↗
PubMed1993

Clinical variability within Brachmann-de Lange syndrome: a proposed classification system.

Seven patients, including two sibs, with the Brachmann-de Lange syndrome (BDLS) are presented as representative of the different types of BDLS in a proposed classification system. Type I ("classic") patients have the characteristic facial and skeletal changes of BDLS using the criteria in the diagnostic index of Preus and Rex. Type I is distinguished from the other subtypes by prenatal growth deficiency (< 2.5 S.D. below mean for gestation) becoming more severe postnatally (< 3.5 S.D. below the mean), moderate to profound psychomotor retardation, and major malformations which result in severe disability or death. Type II ("mild") BDLS patients have similar facial and minor skeletal abnormalities to those seen in type I; however, these changes may develop with time or may be partially expressed. Patients with type II BDLS are distinguished from those with other types by mild to borderline psychomotor retardation, less severe pre- and postnatal growth deficiency, and the absence of (or loss severe) major malformations. Behavioral problems can be a significant clinical problem in type II BDLS. Type III ("phenocopies") BDLS includes patients who have phenotypic manifestations of BDLS which are causally related to chromosomal aneuploidies or teratogenic exposures.

Adolescent↗
PubMed1993

Trisomy 4 in a fetus with cyclopia and other anomalies.

We report on an 18-week fetus with cyclopia, alobar holoprosencephaly, complex congenital heart defect, anal atresia, oligosyndactyly, cystic hygroma, and skeletal abnormalities with trisomy 4. Structural anomalies were detected on routine ultrasound of the pregnancy of a 17-year-old G3 P1 TAB1 woman with sickle cell trait. Trisomy 4 conceptuses usually miscarry in the first trimester. We are aware of no other reports of a fetus with trisomy 4 and cyclopia. Causal association of chromosome abnormalities and holoprosencephaly sequence may be more apparent in embryos and early fetuses than term fetuses because of poor viability of affected conceptuses.

Abnormalities, Multiple↗
PubMed1990

Pigmented lesions of the retinal pigment epithelium and familial adenomatous polyposis.

Bilateral pigmented fundus lesions were found in 65 out of 72 patients with familial adenomatous polyposis, an additional five patients having unilateral lesions. With a family history of familial adenomatous polyposis, the occurrence of multiple bilateral fundus lesions indicates the presence of the abnormal gene, as does the occurrence of oval pigmented lesions with surrounding pale haloes. The absence of pigmented fundus lesions does not exclude the abnormal genotype, while the presence of occasional pigmented spots can be found in an appreciable percentage of the population. Ocular examination would, however, appear to be valuable in screening those at risk, with a positive yield in most carriers of the gene for familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1990

The significance of the anti-class I antibody response. I. Clinical and pathologic features of anti-class I-mediated rejection.

In renal transplantation, preformed cytotoxic antibody against donor HLA class I antigens causes hyperacute rejection of renal allografts, but its pathogenic significance when it develops in the posttransplant period is unknown. In the present studies we describe the clinical and pathologic features of patients with rejection associated with anti-class I. In the course of 400 consecutive cadaveric renal transplants, 7 patients were identified who had antibody against donor class I HLA antigens in association with atypical but distinctive patterns of rejection. All 7 were presensitized. In 3 patients, the transplant had been inadvertently performed with a positive donor-specific T cell crossmatch. In the remaining 4, the T cell crossmatch on current sera was negative but became positive posttransplant. The clinical picture was deterioration of graft function with rapid onset of oliguria, apparently due to acute tubular necrosis, but with persistence of blood flow demonstrable by radioisotope scan studies. Renal histology showed that the typical lesions observed in cell-mediated rejection, such as tubulitis and interstitial infiltration, were absent. Granular complement deposition (6), polymorphonuclear infiltration (6), and endothelial injury in the microvasculature (6) were common, and mononuclear infiltrates were absent (2) or not prominent (4). In 3 patients the glomerular changes resembled a picture of hemolytic uremic syndrome, with capillary fibrin thrombi and widening of the subendothelial space. IgG staining was negative. The pathologic features suggest that anti-class I antibody appearing or persisting in the early posttransplant period injures the endothelium of the microvasculature, with the clinical presentation different from that of hyperacute rejection. Particularly in sensitized patients, rapid deterioration in function, leading to a picture of acute tubular necrosis, with pathologic features of endothelial injury in the microcirculation, should suggest the diagnosis of anti-class I-mediated rejection.

Adult↗
PubMed1989

A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy.

We conducted a prospective randomized study in which patients with biopsy-confirmed idiopathic membranous nephropathy were assigned to receive either a six-month course of prednisone given on alternate days (45 mg per square meter of body-surface area; n = 81) or no specific treatment (n = 77). The mean duration of follow-up was 48 months. Patients in the prednisone group (median age, 46 years) entered with a mean disease duration of 15 months, a median creatinine clearance of 1.2 ml per second per 1.73 m2 (range, 0.25 to 2.6), and a median rate of urinary protein excretion of 6.8 g per day (0.3 to 26). The annual change in the corrected creatinine clearance at six months did not differ between the prednisone group and the control group (0.10 vs. 0.06 ml per second; P = 0.8), or at the last follow-up evaluation (-0.07 vs. -0.02 ml per second; P = 0.2; 95 percent confidence interval on the difference, -0.03 to 0.13). The proportion of patients with complete remission of proteinuria was also similar in the groups at 6 and 12 months and after a mean of 48 months. Outcomes were similar in the two groups with respect to progression to renal failure (3 vs. 4 patients), death (3 vs. 1 patient), complete remission of proteinuria at 36 months (16 vs. 19 patients), and a decline of 25 percent or more in the creatinine clearance at 60 months (32 vs. 25 percent of patients). A multivariate analysis, which adjusted for differences at entry in sex distribution, urinary protein excretion, and creatinine concentration, as well as other prognostic variables, failed to provide an explanation for the lack of effect of prednisone. We conclude that a six-month course of therapy in which prednisone is given on alternate days is of no benefit to patients with idiopathic membranous nephropathy.

Adolescent↗
PubMed1989

Prenatal diagnosis of Opitz (BBB) syndrome in the second trimester by ultrasound detection of hypospadias and hypertelorism.

Prenatal diagnosis in a kindred with the Opitz (BBB) syndrome is presented. The inheritance is consistent with either autosomal dominant inheritance with sex limited expression or X-linked inheritance. The abnormalities in the kindred consist of hypertelorism, hypospadias, ambiguous genitalia, urocolic fistula, imperforate anus, mental retardation, diaphragmatic hernia, and malrotation with volvulus. A male fetus at 19 weeks was found by ultrasound to have hypertelorism and hypospadias with a small phallus consistent with the syndrome. The diagnosis was confirmed by pathologic examination after pregnancy termination. This is the first report of prenatal diagnosis of Opitz syndrome by ultrasonographic demonstration of hypertelorism and hypospadias in the second trimester.

Adult↗