Development of pulmonary alveolar microlithiasis in a renal transplant recipient.
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Biomedical subjects
Publications and source records attributed to G Miller.
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OBJECTIVE: To ascertain the relation between postoperative neurologic complications and variables occurring before, during, and after hypothermic cardiopulmonary bypass surgery to correct congenital heart disease in young infants. DESIGN: Prospective analysis of mortality and neurologic morbidity before hospital discharge; systematic comparison with patient characteristics, metabolic status, surgery variables; and preoperative neurologic findings of the patients. SETTING: Intensive care unit in tertiary care center. PATIENTS: Consecutive sample of 91 full-term infants who underwent 100 operations between January 1989 through December 1992. Nine infants had more than one operation during the study period. MAIN OUTCOME MEASURES: Levels of alertness, tone, focal signs, dyskinesia, pyramidal signs, seizures, and death. RESULTS: Reduced level of alertness at discharge from the hospital in 19% of patients; seizures in 15% (70% focal); severe hypotonia in 11% before surgery, and in 7% at discharge from hospital; generalized pyramidal findings in six (7%); asymmetry of tone in 5%; and chorea that did not persist in 11%. Results of cranial ultrasound tests were abnormal in 20% of patients. Of these those with abnormal cranial ultrasound examinations 55% were abnormal before surgery. Overall mortality was 18%. Of the patients who died, 59% had interrupted aortic arch or hypoplastic left heart syndrome. Mortality for patients with these lesions was 40%. Alertness (P = .005), chorea (P = .03), and hypotonia (P = .02) were associated with duration of deep hypothermia longer than 60 minutes. No association was found among other outcomes and study variables, except the relation between severe left-sided heart lesions and mortality. CONCLUSIONS: Mortality and neurologic morbidity after open heart surgery on young infants may be due to several factors, including type of lesion, preexisting brain abnormalities, duration of deep hypothermia, and strokes.
To determine the efficacy of cisapride, 10 mg three times daily, in improving gastric emptying, reducing distress during meals, and facilitating weight gain in anorexia nervosa, we conducted an 8-week, randomized, double-blind, placebo-controlled trial on 29 inpatients. Measures included scintigraphic gastric emptying studies at 0, 2, 4, and 8 weeks; subjective distress during meals measured by visual analogue scales; self-rating of degree of global improvement in symptoms associated with eating at end of study; and weight measured weekly. Gastric emptying improved significantly but equally in both groups over the study period. Yet subjective measures were better in the cisapride group; they rated themselves as more hungry (p = .02) and more improved on the global measure of change in symptoms (p = .02). Even so, the cisapride group did not gain more weight. The correlation between gastric emptying and weight gain was modest (r = .30; p = .11), and between gastric emptying and the subjective measures, virtually absent.
The complete genomic sequence of the gene responsible for the predominant form of polycystic kidney disease, PKD1, was determined to provide a framework for understanding the biology and evolution of the gene, and to aid in the development of molecular diagnostics. The DNA sequence of a 54 kb interval immediately upstream of the poly(A) addition signal sequence of the PKD1 transcript was determined, and then analyzed using computer methods. A leucine-rich repeat (LRR) motif was identified within the resulting predicted protein sequence of the PKD1 gene. By analogy with other LRR-containing proteins, this may explain some of the disease-related renal alterations such as mislocalization of membrane protein constituents and changes in the extracellular matrix organization. Finally, comparison of the genomic sequence and the published partial cDNA sequence showed several differences between the two sequences. The most significant difference detected predicts a novel carboxy-terminus for the PKD1 gene product.
A novel assay for antibodies to an immunodominant component of the Epstein-Barr virus (EBV) capsid antigen (VCA) complex was developed by creation of a chimeric protein containing the DNA-binding domain of the yeast GAL4 protein fused to the capsid antigen encoded by the BFRF3 gene of EBV. GAL4-BFRF3 antigen fusion protein bound specifically to a duplex DNA oligonucleotide containing GAL4-binding sites. Antibodies to the antigen were revealed by retardation of the electrophoretic mobility of the DNA-protein complex. Antibodies to the BFRF3 component of VCA became detectable approximately 2 months after onset of infectious mononucleosis. Kinetics of the antibody response to BFRF3 were identical using supershift or immunoblotting assays. Concordance between the DNA-binding assay and the classical indirect immunofluorescence assay for antibody to VCA was 97%. The GAL4 epitope assay is applicable for detection of antibodies to many cloned gene products.
Clinically, the measurement of grip strength is a static measure. It is performed in a standardized posture with the arm at the side, elbow flexed to 90 degrees, and the wrist-forearm positioned in neutral. Many functional activities require dynamic grip strength when an individual moves the wrist-forearm while simultaneously gripping an object. This preliminary study investigated dynamic forearm rotation with isometric grip strength over real time. Thirty wrists from 15 normal subjects were measured with a tilt sensor attached to a strain gauge dynamometer. Each subject underwent randomized trials of maximally gripping the dynamometer while rotating the forearm over a 10-second period. A multiple-regression model was fit for the parameters of extremity, forearm rotation order, fatigue, and loss of strength with supination and pronation. For each parameter, the mean and standard error of its estimate were computed and compared with zero. The significant effects (p = 0.05) of interest were for fatigue and the loss of grip strength from 70 degrees of supination to the end range of supination. Comparisons to existing static grip strength literature were made. We concluded that there is a decrease in grip strength over time as a result of fatigue, there is a decrease in grip strength at supination angles greater than 70 degrees. There is no decrease in grip strength resulting from supination angles less than 70 degrees, nor is there a decrease in grip strength with pronation when measured dynamically. It is suggested that there may be a difference in static and dynamic GS measurements related to forearm rotation.
OBJECTIVE: To compare the extravasation rates and insertion complications under gravity and 300 mm Hg (40 kPa) pressure infusion of threaded (SurFast and Sussmane-Raszynski intraosseous needles, Cook Critical Care, Bloomington, IN); and nonthreaded needles (16-gauge disposable intraosseous needle with 45 degrees trocar Cook Critical Care, Bloomington, IN; Jamshidi bone marrow needle; Baxter Health Care Corp, Valencia, CA). DESIGN: A prospective, randomized study. SETTING: An animal laboratory at a university center. SUBJECTS: Five healthy mix breed piglets, weighing 15 to 15.5 kg. INTERVENTIONS: Piglets were anesthetized and ventilated. Tibial, femoral, and humeral osseous sites were exposed by dissection of overlying tissue. All bleeding points were cauterized and oozing was prevented by sealing with cyanoacrylate. Intraosseous access devices then were inserted one at a time in random order and rated for difficulty of insertion. Normal saline solution was infused under gravity or 300 mm Hg (40 kPa) pressure. Extravasation rates then were calculated from the increase in weight of a gauze sponge wrapped tightly at the base of the needle during infusion. MEASUREMENTS AND MAIN RESULTS: No significant (p > .05) differences in extravasation rates were noted among the different types of needles, either under gravity or pressure infusions. The Sussmane-Raszynski needle was significantly more difficult to insert than the others (rated difficult to insert and control in 16 of 34 attempts). Inadvertent penetration of both cortices occurred with nonthreaded needles only (three of 66 attempts). The SurFast needle provided greatest penetration control and was most resistant to accidental dislodgement. CONCLUSIONS: Under ideal conditions, needle type does not influence extravasation rates. However, difficulty with insertion and penetration of both cortices occur commonly and may lead to extravasation during stressful emergency situations or when performed by unskilled personnel.
Choledochal cyst mimicking a pancreatic pseudocyst radiographically has not yet been reported. We report such a patient with a choledochal cyst whose initial presentation was acute pancreatitis. Ultrasound and computed tomography scan showed images that resembled a pancreatic pseudocyst.
A 25-year-old woman with hyperemesis gravidarum developed acute Wernicke's encephalopathy during prolonged intravenous fluid therapy without vitamin supplements. Delay in diagnosis led to a persistent severe neurological deficit, including coma. Gadolinium-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging revealed symmetrical lesions around the aqueduct and fourth ventricle, which resolved after treatment with thiamine. She did not regain consciousness. This report demonstrates the diagnostic value of enhanced magnetic resonance imaging in acute Wernicke's encephalopathy.
Business Process Reengineering (BPR) principles have been around for a long time, piecemeal and under other labels. In recent years they started coming together as a discipline, incorporating world class business principles and focusing on quantum improvements--not merely continuous gradual improvement. BPR is the complete or partial "reinventing" of how business processes are done to attain major performance improvement. It questions the underlying assumptions and principles, including what, why, by whom, and even if things should be done. This article will contribute by stating and helping to clarify a number of important principles, plus some useful insights, techniques, and hints--40 in all!
Since clear cell meningioma has only recently been recognized as a morphologic entity, its pathobiology has not been studied. Fourteen examples occurring in seven females and six males, ages 9 to 82 years (mean 29 years), were examined; one was associated with type 2 neurofibromatosis. Of these cases, seven (50%) were spinal-intradural (six lumbar, one thoracic), three (21%) arose in the posterior fossa (cerebellopontine angle), three (21%) were supratentorial, and one (7%) was centered upon the foramen magnum. In one case (8%), two tumors were considered to be independent primaries. One tumor (8%) appeared to show no dural attachment. Thirteen tumors were subject to complete study. All were composed of sheets of clear, glycogen-rich, polygonal cells forming only a few vague whorls. Hyalinization, both stromal and perivascular, was often extensive. Mitoses were rare in primary tumors. Immunohistochemistry showed vimentin and epithelial membrane antigen staining to be reactive in 100%. Stains for S-100 protein and CAM 5.2 were negative. Progesterone and estrogen receptor staining was observed in 77% and 0%, respectively. Ultrastructural study showed abundant cytoplasmic glycogen, a few cytoplasmic lumina, intermediate filaments, interdigitation of cell membranes, and desmosomal junctions. The means, medians, and ranges of proliferating cell nuclear antigen (PCNA) and MIB-1 antigen labeling indices for nonrecurring and recurring tumors were 10.4%, 8.8%, 0.8-23.4% and 11%, 1.4%, 0.1-50.3%, as compared with 7.4%, 6.7%, 2.9-17.2% and 13.3%, 13.4%, 3.3-25.7%, respectively. Twelve successful DNA ploidy studies showed that 11 tumors (85%) were diploid and one was tetraploid; percentage S-phase determinations varied from 4 to 9% (mean 6.0%). Recurrence was noted in eight patients (61%) (five of whom had multiple recurrences); there was local discontinuous spread in two cases (15%) and widespread cranial to spinal metastasis in one case (8%). Three patients (23%) are dead of disease. In summary, clear cell meningiomas are morphologically unique, show no sex predilection, affect primarily the lumbar region and cerebellopontine angle, and despite their benign appearance, may be inordinately aggressive, particularly intracranial examples. No close association was noted between recurrence or clinical outcome and such factors as mitotic activity, PCNA proliferation indices, percent S-phase determination, or DNA ploidy status. In contrast, MIB-1 proliferation indices were appreciably higher among recurring tumors.
Recently, the Information Management Steering Group (IMSG) [a RACGP-AMA-Commonwealth Government committee responsible for the planning of information management in general practice], held a Coding Workshop at which available coding systems and their application in general practice computerised medical records were reviewed. As there has been in the past some discussion as to the value of coding, the workshop participants agreed that a paper outlining the reasons for coding and classifying clinical data should be prepared and disseminated to all general practitioners.
A mutation in the lipoprotein lipase (LPL) gene, resulting in the substitution of asparagine by serine at residue 291 (LPL-S291), was found to occur in young survivors of a myocardial infarction from Sweden, combined hyperlipidemic subjects from the United Kingdom, and type III hyperlipidemic subjects from Germany at allelic carrier frequencies no different from those found in companion healthy control subjects (3.63 vs. 3.37; 1.85 vs. 1.60; and 2.00 vs. 1.56%, respectively). In a group of 620 healthy middle-aged men from the United Kingdom with baseline and three subsequent annual lipid measurements, mean plasma triacylglycerol (TG), (but not plasma cholesterol) concentrations in carriers of the mutation were significantly elevated over non-carriers (1.95 vs. 1.61 mmol/l, P = 0.05, and 5.83 vs. 5.65 mmol/l, P = 0.29, respectively). When these healthy control subjects were divided according to tertiles of body mass index (BMI), as expected, non-carriers whose BMI was in the upper two tertiles (BMI > or = 25.0 kg/m2) had higher plasma TG concentrations than those in the lowest tertile (1.90 vs. 1.54 mmol/l), but this difference was much greater in LPL-S291 carriers (2.33 vs. 1.36 mmol/l, P = 0.01, BMI x genotype interaction, P = 0.02). To confirm this effect, a second group of 319 healthy subjects from the United Kingdom was screened for LPL-S291. The allelic frequency of the mutation was found to be 1.88% and the effect on plasma lipid concentrations was very similar to that observed in the first control group (plasma TG, 2.31 vs. 1.27 mmol/l, P < 0.001 for LPL-S291 carriers vs. non-carriers, respectively). As before, those carriers whose BMI was in the top two tertiles for this sample (BMI > or = 23.3 kg/m2) had higher plasma TG concentrations than non-carriers (2.31 vs. 1.42 mmol/l). Thus, the LPL-S291 variant may predispose individuals to elevated plasma TG concentrations under conditions such as increased BMI.
Direct injection of plasmid DNA into skeletal muscle has been proposed as a method of effecting somatic gene therapy. This article describes the construction and testing of a plasmid derived expression cassette believed to confer skeletal muscle specific expression. Expression constructs were designed containing the full-length cDNAs for both coagulation factor VIII and factor VII. The engineered genes were flanked by two muscle specific regulatory elements from different myosin isoforms and by an artificial polyadenylation signal sequence. In vitro transfection of C2-myoblasts led to expression of the factor VIII gene, shown by reverse transcription and polymerase chain reaction, upon differentiation of the myoblasts. The expression of the FVII construct was tested in a C2 cell culture system and also when injected directly into mouse muscle. It was found that in cell culture the level of factor VII antigen outside the cell, ie in the cell culture medium was two- to three-fold higher than inside the cell, ie in the cell lysate. This level of expression was found to continue for the duration of cell culture maintenance and a fully functional protein was produced. In vivo transfection experiments in mice showed a substantial increase in factor VII antigen compared with the background level 4-5 days after injection. An anti-human factor VII antibody was detected 7-10 days after injection. We conclude that muscle cells in vitro secrete and efficiently carry out post-translational modifications of the engineered gene product and in vivo secrete the gene product resulting in elevation of systemic levels. The data provide the basis for the use of muscle cells as an in vivo expression system for coagulation proteins in the treatment of inherited haemostatic and thrombotic disorders.
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The established practice of doctors using medical records for research purposes is threatened by the recent proposed guidelines from the Department of Health, the BMA, and the European Commission. The European Commission has proposed that explicit consent should be obtained from each patient before his or her medical records can be used; the proposals from the Department of Health and the BMA would require all research that needs access to personal medical records to be submitted to an ethics committee. We believe that these proposals would seriously impair an entire category of research and suggest therefore that another set of guidelines, proposed by a Royal College of Physicians' working group, should be used to modify the proposals. The guidelines of the working group encourage the use of medical records for research and ensure that such use can be made in a confidential manner without causing harm.
We have identified conserved autoantigenic cellular proteins that bind to G-rich sequence motifs in recombinogenic regions of Epstein-Barr virus (EBV) DNA. This binding activity, called TRBP, recognizes the EBV terminal repeats, a locus responsible for interconversion of linear and circular EBV DNA. We found that TRBP also binds to EBV DNA sequences involved in deletion of EBNA2, a gene product required for immortalization. We show that TRBP binds sequences present in repetitive cellular DNA, such as variable-number tandem repeats (VNTR) and immunoglobulin heavy-chain class switch regions. We propose that EBV utilizes cellular DNA recombination systems to mediate several types of viral genome alterations. These findings may lead to an understanding of the mechanism of rearrangements of EBV DNA that are a central feature of the biology of the virus.