Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 127 records · Page 7Linked to original sources

PubMed1999

Periocular atypical mycobacterial infections.

OBJECTIVE: To examine the clinical characteristics and management of periocular infections caused by atypical mycobacteria. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Six patients were identified with periocular atypical mycobacterial infections: four with Mycobacterium chelonae and two with Mycobacterium fortuitum. INTERVENTION: The treatment of these infections included removal of the foreign bodies with debridement of the lesions. Specimens were sent for histopathologic examination, routine cultures, and fresh tissue for culture after homogenization. MAIN OUTCOME MEASURES: A retrospective review of culture-proven atypical mycobacterial infections involving the periocular tissues was performed. Charts were reviewed for age, gender, infectious organism, medical history, surgical history, presenting symptoms, clinical features, and treatment. RESULTS: Four associations with infection were identified in these patients: immunosuppression, nasolacrimal duct obstruction, the presence of a foreign body, and a history of recent surgery. All six of the patients had at least one of these associations and five of the patients had at least two. Clinical characteristics that may distinguish atypical mycobacterial infections from acute bacterial infections include subacute presentation, firm nodular lesions, mild erythema, mild tenderness, and minimal purulent discharge. All patients had resolution of their infections after debridement and several weeks of systemic antibiotic therapy guided by susceptibility testing. CONCLUSIONS: Periocular atypical mycobacterial infections are uncommon. The clinical history and examination can raise the suspicion of this infection by revealing the clinical characteristics of these infections. Treatment includes removal of foreign bodies, debridement, and long-term systemic antibiotic therapy.

Adult↗

PubMed1999

Treatment strategies and visual acuity outcomes in chronic postoperative Propionibacterium acnes endophthalmitis.

PURPOSE: To report the treatment strategies and visual acuity outcomes of chronic postoperative endophthalmitis caused by Propionibacterium acnes. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: All patients presenting 8 or more weeks after cataract surgery with intraocular inflammation caused by culture-proven P. acnes infection and treated at two institutions from 1974 through 1996 were included. METHODS: Patients underwent three different initial treatment strategies. The study did not have a defined treatment protocol, but all patients received intraocular antibiotics. Patients were not randomly assigned to the various treatment strategies. MAIN OUTCOME MEASURES: Final visual acuity and effectiveness of various treatment procedures either as initial or follow-up therapy were assessed. RESULTS: Using the 3 initial strategies, 36 patients were treated: (1) intraocular antibiotic injection alone (IOAB; n = 12); (2) pars plana vitrectomy and IOAB injection (PPV; n = 10); and (3) PPV with subtotal capsulectomy and IOAB injection (PPV-PC; n = 14). The number of patients with recurrent or persistent inflammation after one of the three initial treatment strategies were as follows: (1) IOAB alone, 12 (100%); (2) PPV, 5 (50%); and (3) PPV-PC, 2 (14%). None of the patients that underwent subsequent PPV, total capsular bag removal, IOAB injection, and either intraocular lens (IOL) exchange or removal had persistent or recurrent intraocular inflammation. Overall, final visual acuity was 20/40 or better in 18 patients (50%), and a total of 28 patients (78%) retained 20/400 or better vision. The mean follow-up after the last treatment was 2.9 years. CONCLUSIONS: In this series of chronic P. acnes endophthalmitis, initial treatment with IOAB injection alone or vitrectomy without capsulectomy was associated with high rates of recurrent or persistent intraocular inflammation. Pars plana vitrectomy, partial capsulectomy, and IOAB injection without IOL exchange was usually successful on long-term follow-up. In patients with recurrent intraocular inflammation, pars plana vitrectomy, total capsular bag removal, IOAB injection, and IOL exchange or removal was a uniformly successful strategy. In contrast to other types of postoperative endophthalmitis, IOL exchange can be considered in these patients after total capsular bag removal.

Anti-Bacterial Agents↗

PubMed1999

Proton dosimetry intercomparison based on the ICRU report 59 protocol.

BACKGROUND AND PURPOSE: A new protocol for calibration of proton beams was established by the ICRU in report 59 on proton dosimetry. In this paper we report the results of an international proton dosimetry intercomparison, which was held at Loma Linda University Medical Center. The goals of the intercomparison were, first, to estimate the level of consistency in absorbed dose delivered to patients if proton beams at various clinics were calibrated with the new ICRU protocol, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration factors. MATERIALS AND METHODS: Eleven institutions participated in the intercomparison. Measurements were performed in a polystyrene phantom at a depth of 10.27 cm water equivalent thickness in a 6-cm modulated proton beam with an accelerator energy of 155 MeV and an incident energy of approximately 135 MeV. Most participants used ionization chambers calibrated in terms of exposure or air kerma. Four ionization chambers had 60Co-based calibration in terms of absorbed dose-to-water. Two chambers were calibrated in a 60Co beam at the NIST both in terms of air kerma and absorbed dose-to-water to provide a comparison of ionization chambers with different calibrations. RESULTS: The intercomparison showed that use of the ICRU report 59 protocol would result in absorbed doses being delivered to patients at their participating institutions to within +/-0.9% (one standard deviation). The maximum difference between doses determined by the participants was found to be 2.9%. Differences between proton doses derived from the measurements with ionization chambers with N(K)-, or N(W) - calibration type depended on chamber type. CONCLUSIONS: Using ionization chambers with 60Co calibration factors traceable to standard laboratories and the ICRU report 59 protocol, a distribution of stated proton absorbed dose is achieved with a difference less than 3%. The ICRU protocol should be adopted for clinical proton beam calibration. A comparison of proton doses derived from measurements with different chambers indicates that the difference in results cannot be explained only by differences in 60Co calibration factors.

Algorithms↗

PubMed1999

Risk, science and policy: definitional struggles, information management, the media and BSE.

This article examines the role of definitional struggles in the science policy interface using the example of the cattle disease bovine spongiform encephalopathy (BSE) or mad cow disease in the UK. A central contention is that an explicit focus on definition illuminates the processes by which scientific judgements are made, promoted, communicated, assessed and judged and gives an improved picture of policy making. Neglected areas such as the role of secrecy, public relations and the mass media in the science-policy interface are brought into sharper focus as an intrinsic part of the wider operation of definitional struggles. The focus on definitional struggles also sheds light on some current work on risk in social theory. It is argued that the neglect of questions of agency which are central to definitional struggles has led to some theorists presenting risks as inevitable concomitants of technological and cultural developments leaving them in the grip of political quietism.

Animals↗

PubMed1999

The effect of butylated hydroxytoluene on selected immune surveillance parameters in rats bearing enzyme-altered hepatic preneoplastic lesions.

Selected immune function parameters were examined in male Fischer 344 rats following (a) induction of enzyme-altered preneoplastic liver foci (EAF), and (b) growth modulation of EAF by 30-day feeding with the food antioxidant butylated hydroxytoluene (BHT). Glutathione S-transferase-P (GSTP)-positive EAF were observed in livers of rats receiving diethylnitrosamine (DEN), 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH) (Solt-Farber procedure), with or without BHT treatment. The induction of EAF and/or 0.5% BHT treatment resulted in a significant reduction in the natural killer (NK) cell activity of splenocytes. PH did not affect NK activity significantly compared with control (no PH) rats. The concanavalin A-induced lymphoproliferative activity of splenocytes was increased in rats with PH compared with those without. A lag in time needed to attain maximum calcium release was observed only in the rats with PH compared with those without PH. None of the treatments affected the phagocytic activity of resident peritoneal macrophages. Only EAF-bearing rats without BHT treatment had increased granulocyte and monocyte levels, while the leucocyte and lymphocyte levels were reduced by the initiator DEN. but not by BHT treatment. Further investigations are necessary to determine whether the observed suppression of NK cell activity during EAF induction and growth modulation by BHT is a contributing factor in enhancement of rodent liver neoplasia by this non-genotoxic food antioxidant.

Animals↗

PubMed1999

Comparing physician-specific two-year patient outcomes after coronary angiography: methodologic issues and results.

OBJECTIVES: We sought to evaluate methodologies to compare physician-related long-term patient outcomes appropriately. BACKGROUND: Evaluation of physicians on the basis of short-term patient outcome is becoming widely practiced. These analyses fail to consider the importance of long-term outcome, and methods appropriate to such an analysis are poorly defined. METHODS: All patients undergoing coronary angiography between 1992 and 1994 who received all of their cardiac care at our institution were followed for 27+/-13 months (mean+/-SD). Patients (n = 754) were cared for by one or more of 17 staff physicians. Risk-adjusted models were developed for four candidate clinical end points and cost. Physicians were then evaluated for each outcome measure. RESULTS: Of the clinical end points, death could be modeled most accurately (c-statistic = 0.83). The c-statistics for other end points ranged from 0.63 to 0.70. Physicians with outcomes statistically different (p < 0.05) from other physicians were identified more commonly than would be expected from the play of chance (p = 0.005). However, improvement in the c-statistics by the addition of physician identifiers was very modest. Physician's evaluations by the four measures of clinical outcome were variably correlated (r = .00 to .85). Graphic display of clinical and cost results for each physician did identify certain physicians who might be judged to provide more cost-effective care than others. CONCLUSIONS: Although comparisons of groups of physicians on the basis of long-term patient outcomes may have merit, individual physician-to-physician comparisons will be more difficult, owing to 1) multiple physicians contributing care to individual patients; 2) the poor predictive capacity of models other than that for survival; and 3) the modest apparent impact of differences in physician providers on long-term patient outcome. With these caveats in mind, modeling to compare patient outcomes of individual physicians with homogeneous patient populations or to identify gross outliers (good or bad) may be practicable in some patient-care systems, but may be inappropriate in others.

Aged↗

PubMed1999

Viscocanalostomy for open-angle glaucoma in black African patients.

PURPOSE: To study the clinical effectiveness of viscocanalostomy in a population of black African patients with open-angle glaucoma that was uncontrolled on medical treatment. SETTING: Department of Ophthalmology, Medical University of Southern Africa, Medunsa, South Africa. METHODS: In this prospective study viscocanalostomy was performed in 214 eyes of 157 black African patients with open-angle glaucoma that was poorly controlled by medical therapy. The procedure involves the production of superficial and deep scleral flaps. The deep flap is disserted to the plane of Schlemm's canal. From this plane, an intact window in Descemet's membrane is created by gentle pressure at the level of Schwalbe's line using a cellulose sponge. Aqueous humor diffuses through this window into a subscleral space (lake). Reflection of the inner flap unroofs Schlemm's canal, creating a trough leading to 2 entrances into Schlemm's canal (surgical ostia). A delicate cannula is introduced into the entrance of Schlemm's canal left and right and high-viscosity sodium hyaluronate is gently injected into the canal for 4 to 6 mm. The deeper scleral flap is excised (deep sclerectomy) and the superficial flap is sutured securely using 5, 11-0 polyester fiber (Mersilene) sutures. High-viscosity sodium hyaluronate is then injected into the subscleral lake to act as a physical barrier to fibrinogen migration postoperatively. RESULTS: Postoperative intraocular pressure (IOP) of 22 mm Hg or less was achieved without medical therapy in 82.7% of eyes. If a beta blocker was added to the cases not achieving 22 mm Hg or less postoperatively, the success rate increased to 89.0%. The average follow-up was 35 months (range 6 to 64 months). CONCLUSION: Viscocanalostomy produced an encouraging long-term reduction in the IOP of black African patients with glaucoma who would otherwise have had a poor prognosis.

Adolescent↗

PubMed1999

Testing the association between residential fungus and health using ergosterol measures and cough recordings.

Questionnaire surveys in several countries have consistently detected an association between symptoms and residential mould growth. Confirmation by objective measures would strengthen the argument for causality. To address this issue, quantitative and qualitative fungal measures (airborne ergosterol and viable fungi in dust) were compared to respiratory symptoms (n = 403) and nocturnal cough recordings (n = 145) in Canadian elementary schoolchildren during the winter of 1993-1994. There was a 25 percent to 50 percent relative increase in symptom prevalence when mould was reported to be present (p < 0.05). However, neither symptoms nor recorded cough was related to objective measures of mould. In conclusion, the inability to find an association between objective measures of fungus and health suggest that either these objective measures, or the traditionally used questionnaire data are inaccurate. This discrepancy limits the acceptance of a causal relation between indoor fungal growth and illness.

Air Microbiology↗

PubMed1999

Effect of an o-raffinose cross-linked haemoglobin product on oesophageal and lower oesophageal sphincter motor function.

The present experiments evaluate the effects on oesophageal motility of an o-raffinose cross-linked haemoglobin-based oxygen carrier (HBOC) purified from outdated donated human blood cells (HemolinkTM), with attention to dose-response (0.6-2.4 g kg-1), oxygenation status and low molecular weight components (4.4-36.4% 64 kDa or less). In ketamine-anaesthetized cats, lower oesophageal sphincter (LES) function and oesophageal peristalsis were monitored 0.5 h before, during and up to 3.5 h after HBOC infusion, and in some cats at 24 h. (1) All products significantly inhibited LES relaxation and increased peristaltic velocity in the distal smooth muscle oesophagus, without consistently altering resting LES pressure. (2) Effects on peristaltic velocity reached a maximum at the smallest dose, whereas the effects on LES relaxation had a maximum effect at 1.2 g kg-1. (3) Effects were not significantly altered by the haemoglobin oxygenation status or presence of low molecular weight components. (4) Repetitive oesophageal contractions occurred. In the cat, an o-raffinose cross-linked human haemoglobin product produces changes in oesophageal body and LES function, which are independent of the HBOC oxygenation status and composition of the low molecular weight components tested. Changes may persist for at least 24 h. These motility changes are likely due to scavenging of nitric oxide by the haemoglobin.

Animals↗

PubMed1999

The future role of international agencies in control of acute respiratory tract infections.

Achievements in the control of acute respiratory infection (ARI) owe much to international collaboration in research, education, and delivery of services. This article highlights some of the current activities of the many international agencies involved and summarizes thoughts on their future roles. Key recent scientific advances include better surveillance, new and improved vaccines, refinement of standard clinical management plans and behavioral change techniques, and demonstration of the effectiveness of their application. Agencies involved include the World Health Organization, the International Union Against Tuberculosis and Lung Disease, national government agencies for overseas aid, many academic departments, and professional lung health associations. However, much remains to be done, especially in collaborative research, in the devising, implementing, and evaluating of health care delivery systems in low-income countries, and in mobilizing political will and resources. These are tasks beyond the capacity of any lone agency. Success will depend on how effectively we collaborate.

Acute Disease↗

PubMed1999

Current activities at the Centers for Disease Control and Prevention's National Diabetes Laboratory.

In 1997, the Centers for Disease Control and Prevention established the National Diabetes Laboratory in order to help prevent and treat type 1 diabetes. This state-of-the-art laboratory collaborates with research scientists and key national and international organizations throughout the world to identify and study risk factors for type 1 diabetes by developing measurements for glycosylated proteins, developing and evaluating technology for measuring genetic risk factors for the disease, and working to standardize autoantibody measurements. Developing improved technologies for diagnosing and managing diabetes and developing reference materials for properly calibrating and standardizing blood glucose meters are also critical aspects of the laboratory's work. In addition, the laboratory provides quality storage for valuable collections of biologics and other materials and facilitates sharing of specimens, associated epidemiologic data, and test results. Working with our partners in diabetes research, we are improving the diagnosis, treatment, and prevention of type 1 diabetes.

Autoantibodies↗

PubMed1999

Transcervical recovery of fetal cells from the lower uterine pole: reliability of recovery and histological/immunocytochemical analysis of recovered cell populations.

The aim of this work was to isolate, enumerate and attempt the identification of fetal cells recovered from the lower uterine pole. Immediately before elective termination of pregnancy at 7-17 weeks gestation, samples were recovered by transcervical flushing of the lower uterine pole (n = 108) or transcervical aspiration of mucus from just above the internal os (n = 187), and their contents examined using histological, immunohistochemical and molecular techniques. Syncytiotrophoblasts were identified morphologically in 28 out of 89 (31%) and 50 out of 180 (28%) flushings and aspirates respectively (mean 29%). Immunocytochemistry with monoclonal antibodies (mAbs) recognizing trophoblast or epithelial cell antigens on a smaller number of samples (n = 69) identified putative placental cells in 13 out of 19 (68%) and 25 out of 50 (50%) flushings and aspirates respectively (mean 55%). These included groups of distinctive cells with a small, round, hyperchromatic nucleus, strongly reactive with mAbs PLAP, NDOG1 and FT1.41.1. Smaller groups of larger, amorphous cells, usually containing multiple large, pale staining nuclei, reactive with mAb 340 and to a lesser degree with mAb NDOG5 were also observed. Taking cellular morphology and immunophenotype into consideration, the smaller uninucleate cells were likely to be villous mesenchymal cells, while the larger cells were possibly degrading villous syncytiotrophoblast. There was no significant difference in the frequency of fetal cells obtained by the two recovery methods. Squamous or columnar epithelial cells, labelled strongly with antibodies to cytokeratins or human milk fat globule protein, were observed in 97% (29 out of 30) of aspirates. The use of cervagem in a small number of patients prior to termination of pregnancy did not appear to influence the subsequent recovery of placental cells. Y-specific DNA was detected by polymerase chain reaction (PCR) in 13 out of 26 (50%) flushings and (99 out of 154) 64% aspirates analysed (mean 62%). In-situ hybridization (ISH) revealed Y-specific targets in 40 out of 69 (60%) of aspirates analysed. A comparison of PCR data obtained from transcervical recovered samples and placental tissues showed a concordance of 80% (76 out of 95), with 10 false positives. Comparing the PCR data from tissues with data derived by ISH from 41 aspirates gave a concordance of 90% with two false positives. Although syncytiotrophoblasts were much more likely to be present in samples containing immunoreactive placental cells, the detection rates of fetal-derived DNA were similar regardless of the morphological and/or immunological presence of placental cells. We conclude that the transcervical recovery of fetal cells, while promising, requires considerable additional effort being expended in further research and development, particular in the sampling procedure.

Antibodies, Monoclonal↗

PubMed1999

Transferrin in the developing ovarian follicle: evidence for de-novo expression by granulosa cells.

Transferrin is produced primarily by the liver and is best known as a carrier of iron in the circulation. Transferrin is also produced extra-hepatically where it may serve to suppress the generation of reactive oxygen species and act as a growth factor, in addition to its role in the endocytosis of iron. There is evidence that transferrin and its cognate receptor are important for successful development of follicles but little is known about their precise roles in this context. To learn more about their modus operandi, we undertook immunocytochemical studies which revealed that transferrin and its receptor are distributed heterogeneously in human granulosa cells, with more pronounced expression in more mature follicles. Expression within the oocyte itself was not prominent until the antral stage of development. Using nested reverse trancription-polymerase chain reaction (RT-PCR), transferrin mRNA expression was demonstrated in granulosa cells of the human and mouse ovary but not in the oocyte. Hence it appears that local production of transferrin is possible in addition to the likely uptake of circulating protein into the follicle by endocytosis. Values of transferrin in the follicular fluid were found to be highly correlated with those in serum, suggesting that the small contribution made by its localized synthesis in the granulosa cell may be important for some as yet unknown mechanism in follicle maturation.

Adult↗

PubMed1999

Effects of methylprednisolone and cyclosporine A on fungal growth in vitro.

PURPOSE: The management of corneal transplants after mycotic keratitis often poses a therapeutic dilemma. Clinicians are hesitant to use topical steroids because of their potential enhancement of fungal growth. This study seeks to evaluate the in vitro effects of methylprednisolone and cyclosporine A on the growth of various molds that often are responsible for keratomycoses. METHODS: Fusarium oxysporum, Fusarium solani, and Aspergillus fumigatus were grown in the presence of varying concentrations of methylprednisolone, cyclosporine A, and vehicle controls. Fungal growth was evaluated in a masked fashion based on the number of colonies and their morphologies. RESULTS: All tested concentrations of cyclosporine A (1%, 2%, 4%) had a statistically significant suppressive effect on the growth of F. oxysporum (p<0.001) and F. solani (p<0.001) compared with methylprednisolone and vehicle control solutions. A dose-dependent decrease in the number of colonies grown also was noted for F. oxysporum (p<0.001) and F. solani (p<0.001). In the case of A. fumigatus, cyclosporine A significantly decreased the colony size (p<0.015) in a dose-dependent fashion. CONCLUSIONS: Cyclosporine A appears to have an inhibitory effect on fungal growth in vitro. Cyclosporine A may be an important alternative to topical steroids for management of corneal transplants after mycotic keratitis.

Antifungal Agents↗

PubMed1999

Prognostic factors in Paget's disease of the vulva: a study of 21 cases.

Twenty-one cases of vulvar Paget's disease were studied to assess possible prognostic indicators, including presence and depth of invasion, status of resection margins, tumor DNA cell content, and immunoreactivity for p53 and estrogen receptor proteins. Immunostaining for cytokeratin 7 (CK7), cytokeratin 20 (CK20), and gross cystic disease fluid protein-15 (GCDFP) were also performed. Patients were 45 to 82 years of age (mean, 66.9 years). Ten of 21 patients (47.6%) had invasive Paget's disease. Dermal invasion was < or = 1 mm in 7 of 10 cases and 2 mm, 3 mm, and 8 mm in the remaining three invasive tumors. Of the seven patients with minimally invasive Paget's disease (< or = 1 mm depth of invasion), five are alive with no evidence of disease, one died of an unrelated illness, and one is alive with biopsy-proven in situ Paget's disease, having refused operative treatment. Of the three patients with more than minimally invasive Paget's disease (> 1 mm), all had nodal metastases; one patient is alive with no evidence of disease, one died of undertermined causes, and one died of metastatic Paget's disease. The remaining 11 patients had Paget's disease confined to the epidermis and its adnexal structures. Seven of these patients were alive at last follow-up with no evidence of disease. Of the remaining four patients, one died of metastatic cervical cancer, one died of metastatic bladder cancer, one died of an unrelated illness, and one patient is alive with biopsy-proven in situ Paget's disease and awaiting operative treatment. Twenty of the 21 cases represented primary vulvar Paget's disease while one represented possible local spread from a cervical adenocarcinoma. The immunoprofiles were GCDFP+/CK7+/CK20- in 14 cases, GCDFP+/CK7+/CK20+ in 4 cases, and GCDFP-/CK7+/CK20- in 2 cases. All tumors were estrogen receptor-negative. Immunostaining for p53 was positive in 16 tumors and negative in four tumors. Seven of 12 (58%) patients with positive margins experienced local recurrence of Paget's disease, while the disease recurred in 1 of 4 patients with negative margins. Recurrence was observed in 3 of 5 patients with diploid tumors and in 4 of 10 patients with aneuploid tumors. Neither of these differences is statistically significant. This study supports the recognition of a category of minimally invasive vulvar Paget's disease that has a low risk of distant metastasis and death caused by disease. Status of surgical resection margins, tumor cell DNA ploidy, estrogen receptor expression, and p53 immunoreactivity are not predictive of local recurrence.

Aged↗

PubMed1999

Treatment of patients with metastatic melanoma with bryostatin-1--a phase II study.

Bryostatin-1 is a protein kinase C regulator which has shown antitumour activity against B16 melanoma in animal models. Safety trials revealed this agent to be minimally toxic, thus a phase II trial of bryostatin-1 was conducted to determine its efficacy In patients with melanoma. Eighteen patients with metastatic melanoma, seven of whom had been previously treated, were enrolled in the study. Patients received bryostatin-1 25 microg/m2 intravenously weekly over 1 h for 3 out of 4 weeks. No objective responses were observed. One patient who had not previously received chemotherapy had stable disease for 4 months, and two patients (one previously treated) had a marked decrease in the skin component of their disease. The major toxicity was myalgia (one patient with grade III, two patients with grade II and five patients with grade I), with no grade IV toxicities reported. To Indirectly evaluate the stimulation of protein kinase C, a sensitive assay that measures the upregulation of the activated form of CD62 (glycoprotein IIb/IIIa) on platelets was performed. There was a statistically significant upregulation of this antigen 1 h after bryostatin-1 therapy. A bioassay based on the ability of bryostatin-1 to bind protein kinase C was used to measure bryostatin-1 levels in serum. This assay showed that bryostatin-1 has a volume of distribution of 2.1 l/m2, an elimination clearance of 32.9 ml/min per m2 and a half-life of 43.9 min. In conclusion, this phase II trial demonstrates that, although it is relatively non-toxic, bryostatin-1 therapy had minimal activity in metastatic melanoma.

Adult↗

PubMed1999

Non-invasive RNA-based determination of fetal Rhesus D type: a prospective study based on 96 pregnancies.

OBJECTIVES: To develop a non-invasive method for determining fetal RhD status in order to provide improved care for women most at risk. DESIGN: A prospective study. METHODS: Fetal erythroblasts were enriched from the peripheral circulation of 96 RhD negative women with pregnancies at various stages in gestation using discontinuous density gradients. Amplification of RhD-specific mRNAs was carried out by reverse transcription-polymerase chain reaction assay. RNA, rather than DNA, was selected for amplification because it rarely contaminates samples, thus resulting in fewer false positives; moreover, its presence in multiple copies per cell should enhance the sensitivity of the assay, resulting in fewer false negatives. The study was prospective, relying on postnatal serological confirmation of RhD phenotype. RESULTS: The assay was 75% accurate at predicting fetal RhD status, comparing favourably with standard genomic DNA-based assays. However, we found that accuracy dropped from 85% (29/34) in the third trimester of pregnancy, to 82% (32/39) in the second and 48% (11/23) in the first trimester. Discordant data were due to false negatives in the majority (78%) of cases. CONCLUSIONS: We suggest that reverse transcription may be a useful and perhaps more sensitive alternative to standard genomic polymerase chain reaction in the majority of cases. However, under certain circumstances the absence or reduction of fetal erythroblasts or possibly RhD mRNA in some preparations may compromise the accuracy of the assay.

Biomarkers↗

PubMed1999

Residential fungal contamination and health: microbial cohabitants as covariates.

An association between symptoms and residential mold growth has been consistently observed in several countries, but the contribution of dust mites and bacterial endotoxins to this relation has not been established. To address this issue, we studied a sample of 403 Canadian elementary school children during the winter months. Reported mold growth was compared to respiratory and nonspecific symptoms before and after adjusting for dust mite antigens and bacterial endotoxin. A 12-50% relative increase in symptom prevalence was associated with reported mold growth both before and after adjusting for subject characteristics, dust mite antigens, and endotoxins. In conclusion, the association between residential fungal contamination and symptoms is not confounded by dust mites or bacterial endotoxins or other known disease-causing agents.

Child↗