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C Duff

Publications and source records attributed to C Duff.

11 recordsLinked to original sources
PubMed1992

Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia.

Twenty-one polymorphic sequence variants of the RYR1 gene, including 13 restriction fragment length polymorphisms (RFLPs), were identified by sequence analysis of human ryanodine receptor (RYR1) cDNAs from three individuals predisposed to malignant hyperthermia (MH). All RFLPs were detectable in PCR-amplified products, and their segregation was consistent with our initial finding of linkage to MH in the nine families previously informative for one or more intragenic markers (MacLennan et al., 1990, Nature 343:559-561). Four amino acid substitutions were identified in the study: Arg for Gly248, Cys for Arg470, Leu for Pro1785, and Cys for Gly2059. Of 45 families tested, a single family presented the Arg for Gly248 substitution where it segregated with malignant hyperthermia, making it a candidate mutation for predisposition to MH in man. The other three polymorphic substitutions failed to segregate with malignant hyperthermia in those families in which they occurred, implying that they represent polymorphisms with little or no effect on the function of the RYR1 gene.

Amino Acids↗
PubMed1992

[Severe necrotizing fasciitis].

The pathophysiology of necrotizing fasciitis remains unclear in patients with no apparent immunologic disorders. Between 1987 and 1990 we treated six patients with necrotizing fascitis and septic-toxic multiple organ failure, three patients survived. The mean age was 38 years (25-62). In all patients the primary bacteriological examination revealed streptococcus. Between the first symptoms and an adequate therapy were 4 days in surviving patients and 7 days in patients who died. Four patients showed spread of the gangrene into the adjacent tissue: muscles (n = 3), bowel (n = 2), mediastinum (n = 1). Adequate débridement was not possible or not performed in patients with spread into the abdominal cavity or the mediastinum. These patients did not survive. The duration of intensive care treatment in surviving patients were 14 to 78 days. We conclude that survival of patients with severe necrotizing fasciitis is influenced by the delay before adequate treatment, the localisation of the gangrene and intensive care facilities.

Adult↗
PubMed1991

[False aneurysm in a vascular surgery patient population].

40 false aneurysms have been diagnosed at the University Hospital in Zürich during the last three years. These aneurysms are mainly (24) anastomotic aneurysms with synthetic arterial substitutes. 6 false aneurysms were found after arterial catheterization. The majority of these 40 aneurysms (60%) were localized in vicinity of joints. The time interval between the original procedure (anastomosis, arterial catheterization, trauma) and the diagnosis of false aneurysm varies from a few days to 21 years. In seven cases a endarterectomy preceded the development of a false aneurysm. Three therapeutic groups are presented.

Adult↗
PubMed1991

[Emergency hospitalization for acute, non-accidental abdominal pain. Prospective data of a surgical university clinic].

During a 19-month period 549 patients (278 women, 271 men) suffering from abdominal pain unrelated to trauma (mean age 48.2 years) entered the emergency room of the Department of Surgery of the University Hospital Zürich. 43% presented during business hours, whereas 57% were admitted during nighttime and/or weekends. Clinical examination, abdominal roentgenograms (upright and supine) as well as sonography were the most commonly used diagnostic tools. 40% suffered from abdominal pain of unknown cause. The most common diagnosis on admission was appendicitis. Only half of these cases really proved to be an appendicitis. In 36% the diagnosis on admission corresponds both to the initial diagnosis made by a member of staff during his first visit, as well as to the final diagnosis. The initial diagnosis agrees in 57% with the final diagnosis. In 10% of the patients the cause of pain was not elucidated despite extensive diagnostic procedures. High technology and sophisticated diagnostics are less important than the clinical evaluation. The decision between operative or nonoperative treatment was mainly based on clinical findings.

Abdomen, Acute↗
PubMed1991

Emergency room patients with abdominal pain unrelated to trauma: prospective analysis in a surgical university hospital.

During an 8-month-period, 241 patients suffering from abdominal pain unrelated to trauma (mean age 48 years) attended the emergency room of the Department of Surgery of the University Hospital, Zürich. Forty-three percent presented during working hours, while 57% were admitted during the night or at the weekend. Clinical examination, abdominal roentgenograms (upright and supine) and sonography were the most commonly used diagnostic tools. Forty percent suffered from abdominal pain of unknown origin. The most common diagnosis on admission was appendicitis, but only half of these cases proved to be appendicitis. In 36% the diagnosis on admission corresponded both to the initial diagnosis made by a member of staff during his first visit, and to the final diagnosis. The initial diagnosis agreed with the final diagnosis in 57%. In 10% of the patients the cause of pain was not elucidated despite extensive diagnostic procedures. High technology and sophisticated diagnostic evaluation are less important than the clinical evaluation. The decision between operative and nonoperative treatment was based mainly on clinical findings.

Abdominal Pain↗
PubMed1990

Ryanodine receptor gene is a candidate for predisposition to malignant hyperthermia.

Malignant hyperthermia (MH) is a potentially lethal condition in which sustained muscle contracture, with attendant hypercatabolic reactions and elevation in body temperature, are triggered by commonly used inhalational anaesthetics and skeletal muscle relaxants. In humans, the trait is usually inherited in an autosomal dominant fashion, but in halothane-sensitive pigs with a similar phenotype, inheritance of the disease is autosomal recessive or co-dominant. A simple and accurate non-invasive test for the gene is not available and predisposition to the disease is currently determined through a halothane- and/or caffeine-induced contracture test on a skeletal muscle biopsy. Because Ca2+ is the chief regulator of muscle contraction and metabolism, the primary defect in MH is believed to lie in Ca2+ regulation. Indeed, several studies indicate a defect in the Ca2+ release channel of the sarcoplasmic reticulum, making it a prime candidate for the altered gene product in predisposed individuals. We have recently cloned complementary DNA and genomic DNA encoding the human ryanodine receptor (the Ca2(+)-release channel of the sarcoplasmic reticulum) and mapped the ryanodine receptor gene (RYR) to region q13.1 of human chromosome 19 (ref. 14), in close proximity to genetic markers that have been shown to map near the MH susceptibility locus in humans and the halothane-sensitive gene in pigs. As a more definitive test of whether the RYR gene is a candidate gene for the human MH phenotype, we have carried out a linkage study with MH families to determine whether the MH phenotype segregates with chromosome 19q markers, including markers in the RYR gene. Co-segregation of MH with RYR markers, resulting in a lod score of 4.20 at a linkage distance of zero centimorgans, indicates that MH is likely to be caused by mutations in the RYR gene.

Animals↗
PubMed1990

Gluteal necrosis after acute ischemia of the internal iliac arteries.

Ligation of the internal iliac artery mostly remains without consequences because of the well established collateral network. In patients with compromised collateral circulation however, acute interruption of both hypogastric arteries during aorto-iliac surgery or transluminal embolisation can lead to necrosis of the gluteal muscles and other adjacent organs (rectum, bladder, lumbosacral plexus). Experience with 3 similar cases after aorto-iliac surgery demonstrates two main intraoperative mechanisms: 1. Embolisation, 2. Ligature of both internal iliac arteries in patients with compromised arteriosclerotic collaterals. Despite of adequate therapy, mortality is over 70%. The most important feature during aorto-iliac operations is to preserve at least one internal iliac artery by either reimplantation of the main stem or by an additional bypass to this artery.

Aged↗
PubMed1989

Gene inactivation as a mechanism for the expression of recessive phenotypes.

A series of Chinese hamster ovary cell hybrids were constructed which were heterozygous at the emtB and chr loci. These loci encode two recessive drug-resistance genes (emetine resistance and chromate resistance, respectively) located on a structurally hemizygous region on the long arm of chromosome 2. These heterozygous hybrids therefore exhibit wild-type sensitivity to both emetine and chromate. Drug-resistant variants were then selected in medium containing either emetine or chromate, and the mechanism of reexpression of the recessive drug-resistant allele was determined by karyotypic analysis of the resultant colonies. In previous studies at these loci we have determined that segregation of the recessive phenotype occurs primarily by (1) the loss of the chromosome 2 carrying the wild-type, drug-sensitive, allele, (2) deletion of the long arm of chromosome 2, or (3) loss of one chromosome 2 followed by duplication of the remaining homologue. However, a small proportion of segregants have also been detected which may have arisen by the mechanisms of de novo gene inactivation or mutation. In this report, hybrids are described which were constructed to allow selection for the retention of the chromosome carrying the wild-type allele and which therefore optimize isolation of these rare segregants. We demonstrate by karyotypic analysis, mutation frequency analysis, and microcell-mediated chromosome transfer that these rare segregants occur primarily by gene inactivation. We also demonstrate a dramatic increase in the proportion of segregants occurring by gene inactivation in two of these hybrids as compared with those previously reported, indicating that this mechanism may be an important mode of phenotype segregation in diploid cells and, therefore, in the development of cancers--such as the childhood tumors retinoblastoma and Wilms tumor--resulting from recessive alleles

Animals↗
PubMed1979

Karyotyping.

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Animals↗
PubMed1977

Chromosome stability in CHO cells.

The established cell line derived many years ago from Chinese hamster ovary (CHO cells) has been studied for the extent of chromosomal variation. Because this cell line is used extensively for genetic studies, the contribution of chromosome variability to genetic variability has also been examined. The quasidiploid CHO cells were found to have a banded karyotype somewhat altered from that of the Chinese hamster from which the line was derived. However, most of the genome could be accounted for among the rearranged marker chromosomes. In addition, the CHO line was found to have a relatively stable karyotype, the same basic karyotype being found in a majority of the uncloned cells, as well as in most cells of several but not all independent clones. Many, but not all, mutant cell lines derived from CHO also showed the same basic karyotype. Quasitetraploid cells, derived either spontaneously or by Sendai-virus-induced fusion, showed considerably more variation resulting in loss or gain of whole chromosomes, rearrangement of chromosomes, and appearance of new "marker" chromosomes.

Cell Line↗