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Biomedical subjects

A Hart

Publications and source records attributed to A Hart.

At least 19 recordsLinked to original sources
PubMed1996

Gestational pyelonephritis--associated Escherichia coli isolates represent a nonrandom, closely related population.

OBJECTIVE: A select group of Escherichia coli strains known as uropathogenic cause pyelonephritis in nonpregnant individuals. We investigated whether Escherichia coli from gestational pyelonephritis represent a random population or possess common uropathogenic characteristics. STUDY DESIGN: Repetitive element sequence-based polymerase chain reaction, plasmid profiles, hemolysin, and O serotypes were assayed from Escherichia coli isolates of 57 pregnant patients with acute pyelonephritis at different gestational ages. RESULTS: The majority of the first trimester isolates fell primarily into repetitive element sequence-based patterns 1 and 3 and O6, O15, and O75 serotypes. Second-trimester isolates had multiple patterns with high-frequency repetitive element sequence-based polymerase chain reaction 1 and 5 and an unknown (OX) serotype. Pattern 3, predominantly O75 serotype, was found primarily among third-trimester isolates. CONCLUSION: It is likely that Escherichia coli associated with acute pyelonephritis during different trimesters of pregnancy represents nonrandom closely related isolates, and some of these strains may be characteristic in pregnant patients only.

Base Sequence↗
PubMed1995

Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck.

We evaluated the prognostic significance of overexpression of cyclin D1 in 47 patients with surgically resected squamous cell carcinomas of the head and neck. Overexpression of cyclin D1 was detected immunohistochemically using an affinity-purified polyclonal antibody directed against the carboxyl-terminal part of the cyclin D1 protein, applied to formalin-fixed, paraffin-embedded tissue sections. Overexpression of cyclin D1 was found in 30 of 47 head and neck squamous cell carcinoma (HNSCC) cases and was associated with a more rapid and frequent recurrence of disease (P = 0.027). There was a 5-year disease-free interval of 47% for HNSCC patients with a strong overexpression of cyclin D1 and of 80% for cyclin D1-negative HNSCC patients. Overexpression of cyclin D1 was also associated with a shortened overall survival of these patients (P = 0.0095), with a 5-year survival of 60% for the cyclin D1 strongly positive cases and of 83% for cyclin D1-negative cases. Overexpression of cyclin D1 appears to indicate poor prognosis in operable HNSCC.

Adult↗
PubMed1995

Prognostic factors for survival after breast conserving therapy for stage I and II breast cancer. The role of local recurrence.

Risk factors for local recurrence (LR) in a univariate analysis had a significant correlation with survival. Local and distant failure could not be regarded as independent events. We undertook a multivariate survival analysis to study the relation between LR and survival. In a retrospective study of 1026 patients treated with tumorectomy, axillary dissection and radiotherapy, factors associated with disease-specific survival (DSS) were analysed. Actuarial estimates for DSS are 91% at 5 years and 86% at 10 years. The multivariate analysis revealed five factors: clinical stage, number of affected axillary nodes, histological grade, degree of tubule formation and left-sided primary tumour. Controlling for these factors, LR appeared to be significantly correlated with DSS. The hazard rate of DSS was estimated to increase by a factor 8.8 (95% confidence interval 4.6-16.8) upon occurrence of a LR. Local recurrence per se, apart from the identified prognostic factors, is a risk factor for DSS. The exact mechanism by which LR has an influence on survival cannot be clarified from these data.

Adult↗
PubMed1995

dra-related X adhesins of gestational pyelonephritis-associated Escherichia coli recognize SCR-3 and SCR-4 domains of recombinant decay-accelerating factor.

Bacterial adhesins are important virulence factors that allow colonization of the human urogenital tract by Escherichia coli. Adhesins of the Dr family have been found to be more frequently expressed in strains associated with symptomatic urinary tract infections. Because of the high frequency of symptomatic urinary tract infections during pregnancy, we screened E. coli isolates from 64 gestational pyelonephritis patients for the expression of Dr and X adhesins to address their potential virulence roles in this population. Using PCR and primers for the afaB gene, we detected dra-related operons in 17 isolates (27%). On the basis of the lack of hemagglutination of Dr(a-) erythrocytes containing a point mutation in the decay-accelerating factor (DAF) short consensus repeat-3 (SCR-3) domain, 12 of these strains were categorized as classical Dr adhesins. The hemagglutination of O erythrocytes by Dr+ strains was blocked or reduced by a monoclonal antibody to the DAF SCR-3 domain. The remaining five dra-positive strains agglutinated Dr(a-) erythrocytes. Monoclonal antibody to the DAF SCR-3 domain failed to block O-erythrocyte hemagglutination. Adhesins in these strains did not fulfill criteria for Dr hemagglutinins because of the undefined receptor specificities and were categorized as X. E. coli strains bearing dra-related X adhesins bound to DAF cDNA-transfected Chinese hamster ovary cells. Three of these dra-related X-adhesin-bearing E. coli strains failed to attach to the SCR-3 delta deletion transfectant, which suggested that binding sites were located in the SCR-3 domain but outside the region blocked by the monoclonal anti-SCR-3 immunoglobulin G. The binding sites of the remaining two dra-related X adhesin strains were localized to the SCR-4 domain, as the attachment was shown to be abolished on an SCR-4 delta mutant but unaffected by an SCR-3 delta deletion. The heterogeneity in the binding sites of E. coli DAF (Dr) family adhesins from gestational pyelonephritis isolates may reflect the ability of the adhesins to evolve to recognize alternate peptide epitopes for efficient colonization.

Adhesins, Escherichia coli↗
PubMed1995

N of 1 study: amantadine for the amotivational syndrome in a patient with traumatic brain injury.

Severe amotivation, apathy, and abulia, significantly retard rehabilitation following traumatic brain injury. Preliminary, uncontrolled research has suggested possible benefit with amantadine for this behavioural syndrome. This N of 1, double-blind, placebo-controlled study employed amantadine 100 mg three times daily in one such patient. Therapists and nurses completed inventories scoring efforts towards initiation of therapeutic activities during each session, progress in therapy, and participation in therapy. Four treatment periods (two active medication, two placebo), of 2 weeks duration, were completed. Across four therapists, and for both treatment pairs, the average effect score increased from 0.86 on placebo to 1.74 on amantadine (possible range 0-6, 3 = 'average'). There were no side-effects. The study suggests possible benefit with amantadine for patients with amotivational syndrome after traumatic brain injury; a randomized clinical trial appears warranted and required.

Adult↗
PubMed1994

Dose and volume effects on fibrosis after breast conservation therapy.

PURPOSE: To analyze factors involved in the development of fibrosis in the boost area after breast conservation therapy (BCT) in patients treated with continuous low dose rate iridium implants following 50 Gy whole breast irradiation. METHODS AND MATERIALS: Fibrosis was estimated by palpation in 404 patients by four physicians. The median follow-up (FUP) duration was 70 months (range 30-133 months). Original implant data were used for reconstruction and dose-volume calculations. The total dose of the external whole breast irradiation and iridium implants was expressed in Normalized Total Dose (NTD): the total dose given in fractions of 2 Gy, which is biologically equivalent to the actual dose given according to the linear-quadratic model, using an alpha/beta value of 2 Gy, and 1.5 h for the recovery half-life of sublethal damage repair. To identify predictors of fibrosis we used a proportional odds model in a polychotomous logistic regression analysis. RESULTS: Seven independent factors were identified that were related to the severity of fibrosis: age, duration of FUP, clinical T-size, photon beam energy, NTD level, implant volume, and adjuvant chemotherapy. From the proportional odds model, a volume exponent could be estimated (0.16 +/- 0.04) that enabled us to determine dose-effect relations for different volumes. A 10-fold higher risk of fibrosis was seen when the total dose was above 79 Gy as compared with doses lower than 70 Gy. A fourfold increase in risk of fibrosis was seen for each 100 cm3 increase in irradiated boost volume. The use of adjuvant chemotherapy resulted in a twofold increase in the risk of fibrosis (dose modifying factor approximately 1.08). The application of Co-60 beams had a similar effect. The relative odds for the other factors were smaller (1.4 for each 10 years of older age, and 1.2 for clinical T-size over 20 mm). The FUP-period had a nonlinear effect: relative odds 2.2 at 6 years, 3.6 at 7-8 years, and 2.8 at 9-11 years. The dose rate (mean 0.57, range 0.26-0.89 Gy/h) had no influence on the development of fibrosis and there was no correlation between dose rate and irradiated volume. CONCLUSIONS: To optimize cosmetic results after BCT, both the total dose and the irradiated volume should be kept as low as possible. Minimum effective dose levels still have to be established. The boost volume can be minimized by more conformal brachytherapy techniques and optimal localization. It may be worthwhile to take adjuvant chemotherapy into account in decisions on boost dose levels.

Adult↗
PubMed1994

Thyrotoxic periodic paralysis terminated with intravenous propranolol.

Thyrotoxic periodic paralysis (TPP) is an uncommon syndrome that can be fatal. We report the case of a patient with acute, severe muscle weakness and hypokalemia who was diagnosed in the emergency department to have thyrotoxicosis with acute TPP. The hypokalemia was treated aggressively with potassium without effect. After administration of i.v. propranolol, the patient had complete resolution of symptoms, with mild rebound hyperkalemia. The literature on the use of propranolol in TPP is reviewed, and the known pathophysiology of TPP is discussed.

Adult↗
PubMed1994

The synthesis of novel HIV-protease inhibitors.

The syntheses, enzyme inhibition and antiviral activity of potent HIV-protease inhibitors containing novel beta-hydroxy ether and thioethers based on the transition state mimetic concept are discussed.

Amino Acid Sequence↗
PubMed1994

Decay-accelerating factor is expressed in the human endometrium and may serve as the attachment ligand for Dr pili of Escherichia coli.

PROBLEM: We evaluated the hypothesis that different tissue substructures in uteri may express decay accelerating factor (DAF), a complement regulatory protein that also may serve as ligand for bacterial attachment. METHOD: Purified Dr pili, anti-Dr pili IgG, anti-DAF (SCR-3) IgG, and fluorescein-isothiocyanate-conjugated secondary IgG were used for binding and inhibition experiments. RESULT: We observed staining of endometrial glands, spiral arterioles, and myometrial arteries with Dr adhesin (pili) and anti-DAF (SCR-3) IgG, and found variation in distribution and amount of Dr ligands in different individuals. Anti-DAF (SCR-3) IgG blocked the binding of Dr pili to the endometrium. CONCLUSION: Presence of DAF in endometrium may protect tissues from complement-induced damage. Differences between individuals in DAF density in the endometrium may affect sensitivity to attachment of Dr-bearing E. coli and/or complement activation.

Adhesins, Bacterial↗
PubMed1994

Risk factors in breast-conservation therapy.

PURPOSE: To identify clinical and pathologic factors associated with an increased risk of local recurrence following breast-conservation therapy (BCT) to assess the safety of this procedure for all subgroups of patients. PATIENTS AND METHODS: The study population consisted of 1,026 patients with clinical stage I and II breast cancer treated between 1979 and 1988 at the Netherlands Cancer Institute. The BCT regimen consisted of local excision and axillary lymph node dissection (ALND) followed by whole-breast irradiation to a total dose of 50 Gy in 2-Gy fractions and boost irradiation (mostly by iridium implant) of 15 to 25 Gy. RESULTS: With a median follow-up duration of 66 months, the actuarial breast recurrence rate was 4% at 5 years, counting all breast recurrences. Univariate analysis showed seven factors to be associated with an increased risk of local recurrence; age, residual tumor at reexcision, histologic tumor type, presence of any carcinoma-in-situ component, vascular invasion, microscopic margin involvement, and whole-breast radiation dose. Three factors remained independently significant after proportional hazard regression analysis: age, margin involvement, and the presence of vascular invasion. When the analysis was repeated, but counting only those breast recurrences that occurred before regional or distant failures, only young age and vascular invasion were independent predictive factors. In the third analysis, factors predicting the necessity of local salvage treatment were analyzed. In this analysis, the possible bias in the former analysis caused by censoring actuarial methods was avoided. The results were the same as in the second analysis, showing young age and vascular invasion as the only independent predictive factors. Breast recurrence rates were 6% for patients less than 40 years of age and 8% for patients with tumors showing vascular invasion. In the absence of risk factors, the breast recurrence rate is only 1% at 5 years. CONCLUSION: Slightly higher recurrence rates were found in patients less than 40 years of age and in patients with tumors showing vascular invasion. The role of margin involvement is uncertain.

Actuarial Analysis↗
PubMed1993

Short consensus repeat-3 domain of recombinant decay-accelerating factor is recognized by Escherichia coli recombinant Dr adhesin in a model of a cell-cell interaction.

A bacterial pathogen that is important in both urinary tract and intestinal infections is Escherichia coli which expresses Dr or related adhesins. In this report, we present a model for testing cell-cell interaction, using both molecularly characterized laboratory cells that express recombinant molecules of human decay-accelerating factor (DAF), and recombinant bacterial Dr colonization factors. Dr adhesin ligand was identified as DAF (CD55), a membrane protein that protects autologous tissues from damage due to the complement system. Structure-function studies mapped the adhesin-binding site on the DAF molecule. A single-point substitution in the third short consensus repeat domain, Ser165 to Leu, corresponding to the Dra to Drb allelic polymorphism, caused complete abolition of adhesin binding to DAF.

Adhesins, Escherichia coli↗
PubMed1993

Children who are seen but not referred: hearing assessment after bacterial meningitis.

Bacterial meningitis is an important cause of hearing loss in children. Previous studies have shown that a proportion of survivors of childhood bacterial meningitis do not have a formal hearing assessment. To confirm this finding amongst children treated for bacterial meningitis in our hospital, a retrospective audit was performed. The hospital case notes and community audiological records were examined to see how many children were referred for hearing assessment after their illness, and how many actually attended. Between 1984 and 1991, 194 children were directly admitted to our hospital with bacterial meningitis. Thirteen children died, and hearing assessment was carried out on 135 of the 181 survivors (75%), 15 of whom had evidence of sensorineural hearing loss. The major reason for hearing not being assessed was non-referral (31 out of 46 cases), 12 children did not attend for assessment despite referral, and three moved shortly after discharge. Thirty of the children remaining in the area who had no assessment (69.7%) were however seen in hospital out-patients. Routine referral for hearing testing at discharge, with re-referral at out-patient attendance, could help increase the number of children assessed after bacterial meningitis.

Aftercare↗
PubMed1992

The effectiveness of differential moments in establishing and maintaining anchorage.

The purpose of the present study is to both clinically and cephalometrically investigate maximum and minimum anchorage control in four first premolar extraction cases, using the "differential moments (torque)" concept. Data were obtained from the pretreatment and posttreatment lateral cephalometric radiographs of 30 patients, 13 boys and 17 girls, who were treated exclusively with "differential torque" mechanics. Of the 30 patients selected, 18 were classified as having Angle Class I malocclusion (crowded and/or bimaxillary alveolar protrusion) and 12 as having Angle Class II, Division 1 malocclusion (crowded and/or severe overjet). The sample was divided into two groups, according to the severity of crowding. Subjects with 6.0 mm or more of crowding, in at least one quadrant per arch, were placed in the maximum anchorage group, suggesting the desirability of maintaining a relatively stable position of the anchor unit. Subjects with less than 6.0 mm of crowding per quadrant were categorized as moderate or minimum anchorage cases, indicating desirability of some intermediate degree of controlled movement of the anchor teeth. Comparison of the two groups in each malocclusion category revealed their comparability with respect to molar relationship and incisor overjet. The major finding of this study is the clinical effectiveness of differential moments as a means of controlling intraoral anchorage. It proves to be optimal and controllable for clinical purposes, regardless of the type of malocclusion or the severity of crowding.

Adolescent↗