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Biomedical subjects

A M Griffin

Publications and source records attributed to A M Griffin.

At least 19 recordsLinked to original sources

Giant cell tumor of the proximal fibula: surgical management.

Five patients with giant cell tumor of the proximal fibula were treated with intralesional excision of the lesion, preservation of the peroneal nerve, and reconstruction of the lateral collateral ligament. At minimum 24-month follow-up there have been no local recurrences. Four patients exhibit normal function of the peroneal nerve and one has grade 4 strength of the muscles innervated by this nerve. No patient demonstrated varus instability. Marginal excision with nerve preservation and reconstruction of the ligament is a worthwhile procedure for treatment of this relatively uncommon lesion.

Adult

The effect of intramedullary cement on intercalary allograft reconstruction of bone defects after tumour resection: a pilot study.

OBJECTIVE: A pilot study to evaluate the surgical and functional results of resection and reconstruction of diaphyseal bone tumours with cemented and uncemented intercalary allografts. DESIGN: A retrospective case series. SETTING: A quaternary care unit within a teaching hospital. PATIENTS: Twenty-two patients with diaphyseal bone tumours treated between 1988 and 1992, with mean follow-up of 38 months (range from 20 to 70 months). INTERVENTIONS: Diagnostic biopsy in all patients. Preoperative and postoperative chemotherapy in patients with high-grade sarcoma. En-bloc excision of all tumours. Reconstruction of the defect with cemented (15 patients) or uncemented (7 patients) intercalary allografts. MAIN OUTCOME MEASURES: Nonunion at one or both osteosynthesis sites, death from systemic disease, amputation. RESULTS: Six of the 22 patients died of systemic disease with the graft intact, and 3 subsequently had amputation for either local recurrence (2 patients) or failure of free tissue transfer (1 patient), leaving 13 patients alive with the allograft in situ at an average of 36 months (range from 24 to 64 months). There were no revision procedures to remove or replace the original allograft. Five patients had nonunion at one or more osteosynthesis sites on plain radiographs 9 months after resection. Four patients with nonunion were in the cemented group of 13 patients available for assessment at 9 months, and 1 was in the uncemented group of 5 patients available for assessment at 9 months. There were two graft fractures, both in the uncemented group. CONCLUSION: The results of this pilot study offer guarded support for the use of pressurized cement in allografts prior to reconstruction of intercalary defects.

Adolescent

Genetic analysis of the acetan biosynthetic pathway in Acetobacter xylinum.

We have identified, cloned and sequenced an 8422 base pair fragment of Acetobacter xylinum genomic DNA containing part of the acetan biosynthetic gene cluster. Computer analysis of the nucleotide sequence data generated revealed the presence of six open reading frames. Comparison of the translated sequences of putative genes to the amino acid sequences of genes from other organisms was used to assign functions to the aceA, aceC and manB genes. These genes were predicted to encode a UDP-glycosyl transferase, a GDP-mannosyl transferase and a phosphomannose isomerase/GDP-mannose pyrophosphorylase, respectively.

Bacterial Proteins

The take-home message: patients prefer consultation audiotapes to summary letters.

PURPOSE: Despite reports of poor patient understanding and recall after cancer consultations, few doctors provide communication aids. We conducted a randomized trial comparing an audiotape of the consultation versus individualized summary letters to patients after their first consultation with a medical oncologist. METHODS: One hundred eighty-two cancer patients were randomized to receive either (1) the audiotape followed 7 to 10 days later by the letter or (2) the letter followed by the audiotape. Outcome measures included patient recall, anxiety and depression, satisfaction with and use of the communication aids, and patient preferences for six communication options. Demographic and disease variables and information and involvement preferences were documented. RESULTS: Eighty percent of patients wanted all information and 72% wanted to participate in treatment decisions. Patients listened to the tape on average 2.3 times and read the letter 2.8 times over 4 weeks, and 90% showed the tape or letter to a friend, relative, or doctor. Satisfaction with the tape and letter were uniformly high and they did not differentially affect recall, anxiety, or depression. When asked to rank six communication options, 46% of patients gave the highest rank to the tape and 21% to the letter. CONCLUSION: Patients use audiotapes of their cancer consultation and individualized letters to review the information given and communicate information to relatives and friends. They prefer audiotapes to letters. Clinicians should consider installing audiotape-recording facilities that could be used to tape new-patient consultations.

Adult

Diagnosis and management of sacral bone tumours.

OBJECTIVE: To evaluate the efficacy of current treatment in patients with sacral bone tumours. DESIGN: Retrospective case series. SETTING: A quaternary care unit within a teaching hospital. PATIENTS: Twenty-nine patients with sacral tumours referred to the unit between 1983 and 1991. Follow-up was a minimum of 18 months. INTERVENTIONS: Diagnostic biopsy in all patients. Plain radiography, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and bone scanning. Sacral resection in patients with malignant or aggressive primary bone tumours. MAIN OUTCOME MEASURES: The accuracy of biopsy and local and systemic recurrence of the disease. RESULTS: Symptoms were present for a mean of 12 months to the time of presentation. Low-back pain was present in 28 of 29 patients. Radicular pain and sacral nerve dysfunction were found more often in patients with malignant tumours. Only three patients had altered bowel habits. On rectal examination a mass was palpable in 61% of patients. The sacral abnormality was demonstrated by plain radiography in 6 of 9 cases, by ultrasonography in 2 of 7 cases, by bone scanning in all of 17 cases, by CT in 24 of 25 cases and by MRI in 17 of 18 cases. Fine-needle aspiration biopsy provided the correct diagnosis in only one of four patients. Transrectal biopsy resulted in tethering of the rectum to the tumour in two patients. Core needle biopsy gave an accurate diagnosis in eight of nine patients. Open biopsy was repeated to obtain adequate tissue in 3 of 19 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms

DNA sequencing.

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Automation

Plasmid sequencing.

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Bacteriophage M13

Retrospective review of chemotherapy for small cell lung cancer in the elderly: does the end justify the means?

Between 1978 and 1983, 72 patients aged 70 years or older (median 72, range 70-80) were treated for biopsy-proven, small cell lung cancer (SCLC). Intercurrent disorders were common, including ischaemic heart disease, peripheral vascular disease, chronic airflow limitation and second malignancies. 26 patients (36%) had limited extent of disease, and 46 (64%) had extensive disease. "Intensive" chemotherapy incorporating vincristine, cyclophosphamide and doxorubicin (OCA regimen) was administered to 32 patients [complete response (CR) + partial response (PR) = 84%]; less rigorous regimens (e.g. single agent chemotherapy, planned dose reductions, radiotherapy only) were used in 34 cases (CR + PR = 52%); and 6 received no active treatment. In the intensively treated group, there were 3 treatment-related deaths and 26 episodes of WHO grade 3-4 toxicity. In the less intensively treated group, there were no treatment-induced deaths and only 1 episode of severe toxicity. The overall median survival was 25 weeks (36 weeks for intensive treatment, 16 weeks with less intense treatment). For patients with limited disease only, the median survival in each group was 43 and 26 weeks, respectively. Intensive treatment for elderly patients with small cell lung cancer is associated with substantially increased toxicity and higher response rates than for gentle treatment, but without a major survival benefit.

Age Factors

The nucleotide sequence of the glycoprotein gB gene of infectious laryngotracheitis virus: analysis and evolutionary relationship to the homologous gene from other herpesviruses.

A 3698 bp region of the genome of infectious laryngotracheitis virus (ILTV) was sequenced and found to contain the entire glycoprotein gB gene and the C-terminal region of a gene homologous to the ICP 18.5 protein gene of herpes simplex virus type 1. The ILTV gB gene encoded a protein with an Mr of 100K possessing all the characteristics of a transmembrane glycoprotein. Alignment of the ILTV gB sequence with homologous sequences from six other herpesviruses revealed that 10 cysteine residues on the surface of the molecule were completely conserved and that the positions of several N-linked glycosylation sites were largely conserved. Evolutionary trees based on the gB amino acid sequences from a total of 13 herpesviruses were constructed and the relationships among these herpesviruses were examined.

Amino Acid Sequence

Cloning and DNA sequence analysis of the serC-aroA operon from Salmonella gallinarum; evolutionary relationships between the prokaryotic and eukaryotic aroA-encoded enzymes.

The serC-aroA operon of Salmonella gallinarum was isolated from a gene library using a labelled oligonucleotide probe and by complementation of an aroA Escherichia coli strain. The nucleotide sequence of a 2.6 kbp fragment was determined. The predicted amino acid sequence of the aroA gene product was compared to the equivalent sequence from ten other organisms. Computer-generated evolutionary trees clearly divide the eleven sequences into four different groups: Gram-negative bacteria, Gram-positive bacteria, fungi and plants. These trees depict a close evolutionary relationship between the sequences from Gram-negative bacteria and higher plants.

3-Phosphoshikimate 1-Carboxyvinyltransferase

Kinetic evidence that arachidonate-induced calcium efflux from platelet microsomes involves a carrier-type ionophoric mechanism.

Arachidonate, at concentrations up to 50 microM, induced dose-dependent calcium efflux from preloaded microsomes prepared from human platelets, but not from unilamellar egg phosphatidylcholine vesicles. Arachidonate-induced efflux from microsomes was not inhibited by indomethacin, 13-azaprostanoic acid, or catalase and superoxide dismutase, indicating that the release was due to arachidonate and not a metabolite. Linolenate (18:3, cis) and linoleate (18:2, cis) induced calcium efflux in a manner similar to arachidonate (20:4, cis), while arachidate (20:0), linolelaidate (18:2, trans), elaidate (18:1, trans), oleate (18:1, cis), stearate (18:0) and palmitate (16:0) had no effect. An experimental method was developed for distinguishing between carrier ionophore, small aqueous pore (i.e., calcium channel), or large aqueous pore (i.e., detergent effect) mechanisms in vesicular efflux systems in which calcium efflux occurs over a period of minutes. This development predicted that with a carrier ionophore mechanism, an increase in either internal or external calcium should competitively inhibit 45Ca efflux. In contrast, 45Ca efflux by diffusion through a small aqueous pore or a large aqueous pore should be measurably insensitive to variations in internal or external calcium. These predictions were experimentally verified in the platelet microsomal system using efflux agents with known mechanisms. Efflux of 45Ca by A23187, a calcium ion carrier ionophore, was sensitive to internal or external calcium competition, while alamethicin, a small aqueous pore channel model, and Triton X-100, a detergent which forms large aqueous pores, mediated 45Ca efflux which was measurably insensitive to variations in internal or external calcium concentration. Arachidonate-induced 45Ca efflux was inhibited by increasing either internal and external calcium concentration, suggesting that the fatty acid functions as a carrier ionophore. Arachidonate-induced 45Ca efflux was also inhibited with extravesicular Sr2+, but not Mn2+ or Ba2+. The dependence of the initial arachidonate efflux rate on arachidonate concentration showed that at least two arachidonates were contained in the calcium-carrier complex. These results are consistent with a model in which arachidonate (A) and an endogenous microsomal component (B) translocate calcium across the membrane through a carrier ionophore mechanism as part of a complex with a stoichiometry of A2B.Ca.

Adenosine Triphosphate

Analysis of the nucleotide sequence of DNA from the region of the thymidine kinase gene of infectious laryngotracheitis virus; potential evolutionary relationships between the herpesvirus subfamilies.

We have sequenced a 5.4 kb region of the genome from the avian herpesvirus infectious laryngotracheitis virus (ILTV) and identified genes homologous to the thymidine kinase (TK) gene, the capsid p40 gene of herpes simplex virus type 1 (HSV-1), a gene encoding a protein antigenic in Epstein-Barr virus infections plus one other highly conserved gene encoding a protein implicated in cell fusion in HSV-1. Computer analysis of the TK gene and the upstream overlapping gene sequence is used to produce trees showing potential evolutionary relationships between the herpesvirus subfamilies.

Amino Acid Sequence

Use of recombinant activated factor VII for treatment of a retropharyngeal hemorrhage in a hemophilic patient with a high titer inhibitor.

Treatment options during an acute hemorrhage for a hemophilic patient who has an inhibitor (antibody) to factor VIII (FVIII) are limited. If the inhibitor titer is high, even massive doses of FVIII are not sufficient to neutralize the antibody. Likewise, immunoadsorption techniques or plasmapheresis cannot remove enough antibody to permit treatment with FVIII. Allergic reactions and cross-reacting inhibitors complicate therapy with porcine FVIII. Prothrombin complex concentrates (PCC) may be effective but the mechanism is unclear. The theory that activated factor VII (FVIIa) is the active principle in PCC prompted our treatment of a patient with a recombinant FVIIa (rFVIIa) product (NOVO Industries). The patient presented with a large retropharyngeal hemorrhage and an initial inhibitor titer of 129 Bethesda units (BU). Despite Autoplex therapy (100U/kg), tracheal compression by the hematoma increased and asphyxiation was imminent. RFVIIa therapy (60 micrograms/kg) was substituted for Autoplex and nine doses were given without complication. The hemorrhage was controlled. By 18 hr breathing was normal and swallowing and speech were greatly improved. Clinically, the patient dramatically responded to rFVIIa. In addition, the purity, the lack of known infectious agents, and the ease of administration make rFVIIa a potentially attractive new therapy. Use of this product also promises to further our understanding of in vivo hemostasis.

Adult

Identification of 21 genes of infectious laryngotracheitis virus using random sequencing of genomic DNA.

DNA from infectious laryngotracheitis virus (ILTV) was randomly sheared and cloned into the M13 bacteriophage. Clones containing ILTV DNA were sequenced and the predicted amino acid sequences were compared to the known sequences of other herpesviruses using computer analysis. Twenty-one ILTV genes were identified, 20 by comparison to varicella-zoster virus and 19 by comparison to herpes simplex virus type 1; only 12 genes, giving consistently lower homology scores, were found by comparison with the gammaherpesvirus Epstein-Barr virus, indicating that ILTV sequences bear greater similarity to other alpha- than to gammaherpesvirus sequences.

Amino Acid Sequence