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Biomedical subjects

A P Griffiths

Publications and source records attributed to A P Griffiths.

At least 37 records · Page 2Linked to original sources
PubMed1999

Maximizing the utilization of donor organs offered for lung transplantation.

The number of patients awaiting lung transplantation (LT) and waiting time for surgery is increasing. In Australia, LT rates are 4. 6/million population/yr, which despite low organ donation rates, are the highest published in the world. The Australian organ allocation system allows identification of marginal donors and therapeutic manipulation where appropriate. This study aims to assess the impact of utilization of marginal donors and aggressive donor management. A comparison between published donor criteria and local practice is made, allowing assessment of the effect of using marginal donors on outcome. Donor management included antibiotic therapy, strict fluid management, physiotherapy, bronchoscopy and bronchial toilet, and alteration of ventilatory settings including initiation of pressure support. Blood gases were repeated to assess the results of interventions. Between January 1, 1995 and May 31, 1998, we performed 140 transplants from 112 of 219 (51%) lung donor offers. Of these donors, 48 (43%) satisfied all published criteria for suitable donor organs (Group 1 = ideal donors) and 64 (57%) did not (Group 2 = marginal donors). Criteria breached by the marginal donors were: an initial ratio of arterial oxygen pressure to fraction of inspired oxygen (PaO2/FIO2) < 300 mm Hg (n = 20), abnormal radiology (n = 39), pulmonary infection (n = 24), 20 pack-years smoking (n = 5) and age > 55 yr (n = 4). Therapeutic manipulation resulted in improvement in the PaO2/FIO2 ratio in 20 donors (Group 3) who would not otherwise have been used. Immediate and 24 h postoperative gas exchange and length of intensive care unit (ICU) stay was not different for recipients from donors from all three groups. Overall survival was 94% at 30 d, 83% at 1 yr, 70% at 2 yr, and 62% at 3 yr and was not significantly different from the three groups. We conclude that organ utilization can be maximized by therapeutic manipulation and utilization of marginal donors without compromising results from transplantation.

Adult↗
PubMed1999

Coronary artery disease in potential lung transplant recipients > 50 years old: the role of coronary intervention.

STUDY OBJECTIVES: To review the experience of the Alfred Hospital in the systematic assessment of coronary artery disease (CAD) using coronary angiography (CA), and the subsequent management of CAD, in potential lung transplant recipients. DESIGN: Retrospective study. SETTING: The Alfred Hospital Lung and Heart Transplant Service. PATIENTS: CAD risk factors were sought in potential recipients of lung transplantation (LTx) who were > 50 years old, including a history of smoking, male gender, hypertension, diabetes, hypercholesterolemia, angina, and a family history of CAD. When feasible, and in the presence of more than one cardiac risk factor, CA was performed. RESULTS: From 243 referral patients who were > 50 years old, 97 were listed for LTx, and 77 underwent LTx. Four patients were refused LTx on the basis of CAD. Of 101 patients undergoing a detailed cardiac assessment for LTx, 83 had smoked, 56 were male, 48 had hypercholesterolemia, 22 had hypertension, 4 had diabetes, and 3 had a history consistent with angina. Eighty-five patients underwent CA. In 32 cases, CA revealed CAD, and half of these cases were significant stenoses. Eight patients who were assessed required intervention. Five patients of this group have been transplanted; of these, three patients underwent coronary artery grafting at the time of LTx, and two patients underwent preoperative angioplasty or stenting. Only one of these five patients died < 90 days postoperatively. CONCLUSION: Significant CAD is a common finding in older patients who are presenting for LTx. Coronary revascularization for severe large vessel stenoses can allow safe LTx. CAD risk factors may predict who should undergo CA, but further studies of clinical and noninvasive assessments of CAD are needed if CA is to be safely avoided in patients at low risk of CAD.

Combined Modality Therapy↗
PubMed1997

Dimerization of Fab fragments enables ready screening of phage antibodies that affect hepatocyte growth factor/scatter factor activity on target cells.

A number of applications of antibodies in diagnosis and therapy require multivalent reagents either because of the polymeric nature of the antigens or because biological activity depends on an effect on the formation of homodimeric species. Here, we report a procedure for mass screening of phage-derived monomeric antibody fragments that depend on valency for activity. As a model system, a set of 13 phage-derived human Fab fragments were first selected against mouse and human recombinant hepatocyte growth factor/scatter factor (HGF/SF), a high molecular weight polypeptide growth factor related to the blood protease plasminogen and involved in development and cancer. These Fab fragments were subsequently screened for an effect on HGF/SF activity either as monomeric fragments or after dimerization with a monoclonal antibody (9E10) directed against a peptide tag on the fragments. Fab were identified that either inhibited or enhanced HGF/SF activity on target cell lines, but dimerization was required for this effect. The approach proposed should facilitate mass screening of phage-derived antibody fragments that depend on multiple valency for activity.

Amino Acid Sequence↗
PubMed1997

Massive osteolytic bone metastases from a primary aortic sarcoma: a case report.

We present an unusual case of an aortic intimal sarcoma, which originally manifested itself by the presence of extensive radiologically osteolytic lesions in the long bones of the lower limbs. The histology of these was puzzling and was first considered to represent a low grade sarcoma of vasoformative tissue and subsequently skeletal angiomatosis. Despite a good initial clinical response to disodium etidronate, the patient ultimately developed small bowel infarction and the true diagnosis only came to light at autopsy. This revealed a tumour in the lower thoracic aorta which, unusually for aortic sarcoma, consisted of loosely packed bland spindle cells with no necrosis and infrequent mitoses. Immunocytochemistry was unhelpful but electron microscopy suggested myofibroblastic differentiation. The majority of previous reports of the tumour in the literature lack information on electron microscopy and immunocytochemistry and have suggested that these tumours are generally pleomorphic in appearance. Embolic phenomena and post mortem diagnosis are usual although occasional antemortem diagnosis has been made using computed tomography (CT) and magnetic resonance imaging (MRI) scanning with the latter being the investigation of choice.

Aorta, Thoracic↗
PubMed1997

Gastrointestinal tumour masses due to multiple myeloma: a pathological mimic of malignant lymphoma.

AIMS: To describe and evaluate two cases of gastrointestinal involvement by multiple myeloma. METHODS AND RESULTS: Clinical details were obtained from patients records and routine histopathological sections were correlated with haematological and immunohistochemical investigations. As shown in the accompanying illustrations, myeloma manifests as large, atypical, non-cohesive cells which may mimic high-grade lymphoma. CONCLUSIONS: Extraskeletal spread of multiple myeloma occurs more frequently than is currently recognized, but clinical involvement of gut is rarely reported. Gut involvement may occur soon after initial diagnosis of myeloma and may be of serious clinical consequence. Histologically, it may mimic high-grade lymphoma. Failure to recognize myelomatous involvement of gut may result in inappropriate surgery or oncological therapy.

Aged↗
PubMed1994

Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma.

A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma.

Adenocarcinoma↗
PubMed1993

Flow cytometry and AgNORs in benign, borderline, and malignant mucinous and serous tumours of the ovary.

We performed flow cytometry and AgNOR counts on 117 serous and mucinous ovarian tumours, comprising 56 cystadenomas, 21 borderline tumours, and 40 cystadenocarcinomas. DNA aneuploidy was present in one cystadenoma and in 11% of mucinous and 46% of serous cystadenocarcinomas. All borderline tumours were DNA diploid. Major and minor FIGO stages and flow cytometrically determined DNA ploidy and DNA index were prognostically significant. Age, histological type (serous versus mucinous), flow cytometric proliferative index, and AgNOR counts were not predictive of survival. Cystadenomas and borderline tumours had lower rates of proliferation than cystadenocarcinomas. AgNORs correlated with DNA ploidy and proliferative index. Borderline tumours showed elevated AgNOR numbers despite low proliferative indices and universal DNA diploidy, suggesting that AgNOR numbers may be related to nuclear events other than proliferation and DNA ploidy.

Adult↗
PubMed1991

Oncocytic metaplasia of the nasopharynx or extra-parotid Warthin's tumour?

A case of oncocytic metaplasia obstructing the Eustachian tube in an elderly patient is described. Histologically, it was similar to Warthin's tumour of the parotid gland. The lymphocytes were predominantly T cell, unlike those of Warthin's tumour which are predominantly B cell. It is proposed that oncocytic metaplasia represents an early stage in the evolution of Warthin's tumour.

Adenolymphoma↗
PubMed1989

Silver-stained structures (AgNORs), their dependence on tissue fixation and absence of prognostic relevance in rectal adenocarcinoma.

The value of a one-stage silver staining technique for nucleolar organizer region (NOR)-associated protein was investigated as a predictor of clinical outcome in 100 rectal adenocarcinomas. In formalin-fixed tissues, a variety of silver-stained structures ranging from 0.5 to 7 microns are seen, the abundance of which bears no relation to prognosis, cell proliferation, or ploidy. Evidence is presented that the silver-stained structures are the result of coalescence of smaller particles caused by formalin fixation, and that assessment of NOR activity is not reliable in routinely formalin-fixed archival tissues.

Adenocarcinoma↗
PubMed1989

Effect of phototherapy on serum 25-hydroxyvitamin D in the Antarctic.

The hypothesis that sunlight may induce the enzymes involved in the vitamin D pathway has been tested by comparing the ability to synthesize vitamin D3 and its 25 hydroxy metabolite (25-OHD) in 2 groups of male volunteers resident at the British Antarctic base at Rothera Point (67 degrees 34'S.). One group endured the UV depleted winter and the other group received regular phototherapy throughout the winter. Both groups then received a course of 14 days phototherapy in October (Southern Hemisphere spring). The group receiving regular phototherapy had a trend towards a higher level of serum 25-OHD, and the October phototherapy course produced a further small increase in serum 25-OHD values. In the previously non irradiated group the October phototherapy produced a much larger increase in serum 25-OHD so that they attained the previously higher values of the pre-iradiated group. There was a negative correlation between the pre October phototherapy serum concentration of 25-OHD and the subsequent increment (r-0.78, p less than 0.01) but no relationship between the serum 25-OHD and D3 after phototherapy. These results provide evidence against the existence of enzyme induction of vitamin D 25 hydroxylase by light.

Adult↗