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Biomedical subjects

M J Leyland

Publications and source records attributed to M J Leyland.

At least 19 recordsLinked to original sources

Demonstration of polymorphism among Brucella ovis field isolates by pulsed-field gel electrophoresis.

Brucella ovis is recognized worldwide as an important pathogen of sheep, and has also been identified in farmed deer in New Zealand. Previously, only one strain type of B. ovis has been identified. The objective of this paper was to perform pulsed-field gel electrophoresis (PFGE) on field isolates of B. ovis to determine whether strain variations exist, whether sheep and deer are affected by the same strains, and to compare the performance of the rare-cutting restriction enzymes XbaI and SwaI. Ten B. ovis isolates from sheep and two from deer in New Zealand, as well as the type strain, were subjected to PFGE analysis using both XbaI and SwaI. PFGE of XbaI restriction fragments produced two banding patterns consisting of 27-28 bands, which were found to be 98% similar by cluster analysis, and were named X1 and X1a. PFGE of SwaI restriction fragments resulted in three banding patterns consisting of 13-15 bands each. Ten of the isolates had identical banding patterns and were named S1. One isolate differed by one band, representing a subtype named S1a. Two isolates differed by six bands, representing a different strain type of B. ovis and this was named S2. Cluster analysis showed S2 to be 78% similar to the S1/S1a cluster. Both strain types were isolated from both sheep and deer. Thus, two distinct strain types of B. ovis were identified in New Zealand, which is the first report of more than one strain type being identified worldwide. Neither strain was species-specific for sheep or deer. The restriction endonuclease SwaI was found to be more discriminatory than the enzyme XbaI, which has been used in previous studies.

Animals↗

A comparison of Salmonella serotypes isolated from New Zealand sea lions and feral pigs on the Auckland Islands by pulsed-field gel electrophoresis.

The Salmonella serotypes S. Cerro and S. Newport were isolated from New Zealand sea lions (Phocarctos hookeri) and feral pigs on the Auckland Islands in the New Zealand subantarctic region. The isolates were typed by pulsed-field gel electrophoresis using Xba1 as the restriction enzyme. The isolates were indistinguishable, which suggests that Salmonella infection cycles between sea lions and pigs in this environment. Apart from a previous isolation from a single New Zealand fur seal (Arctocephalus forsteri), S. Newport has not been recorded in any animals from New Zealand, but it is associated with gastroenteritis in humans. Contamination of the marine environment by human waste is a possible source of infection for marine mammals and warrants further investigation.

Animals↗

An epidemic of salmonellosis caused by Salmonella Typhimurium DT160 in wild birds and humans in New Zealand.

AIM: This study reports an outbreak of salmonellosis due to S. Typhimurium DT160 which caused extensive mortality in wild birds and enteric disease in humans in New Zealand during the winter and spring months of the year 2000. METHODS: Necropsies were performed and microbiological examinations undertaken on wild birds from populations in which mass mortality was reported, and on captive indigenous birds which died suddenly during the winter and spring of 2000. Affected tissues were examined histologically and isolates of S. Typhimurium were phage typed and examined using pulsedfield gel electrophoresis (PFGE). Isolates of S. Typhimurium obtained from cases of human enteric disease which occurred during these months were phage typed, examined using PFGE and compared with the bird isolates. RESULTS: Central and northern areas of the South Island and the southern North Island were worst affected with die-offs of several hundreds of sparrows and other birds reported in rural areas. Mortalities reached a peak in winter (July-August) 2000 and decreased to small numbers during the spring and early summer. The birds usually died of an acute septicaemia with multifocal necrotising lesions in the liver and spleen. Human cases throughout the country increased gradually over the same period. Isolates from birds, livestock and humans examined using PFGE were indistinguishable from one another. CONCLUSION: This strain of Salmonellahas emerged as a major cause of septicaemia in wild birds in New Zealand. Because of the close association between house sparrows (Passer domesticus) and humans, the organism also poses a serious zoonotic risk. The possibility that the infection may spread to involve indigenous species needs investigation.

Journal Article↗

Leukaemic mantle cell lymphoma with t(11;14) and trisomy 12 showing clinical features of state A0 B cell chronic lymphocytic leukaemia.

The precise diagnosis of lymphoma usually requires the histological examination of lymph nodes or involved tissues. Mantle cell lymphoma is a form of intermediate grade non-Hodgkin's lymphoma in which typical morphological immunophenotypic and cytogenetic features have been recognised. A case of leukaemic mantle cell lymphoma with the characteristic reciprocal translocation t(11;14) together with trisomy 12, a chromosomal abnormality usually associated with B cell chronic lymphocytic leukaemia (CLL), is presented. This combination of cytogenetic abnormalities has not been reported previously. The lack of lymphadenopathy and hepatosplenomegaly in this patient is more in keeping with stage A0 CLL. This case demonstrates the close clinical and biological relationship between mantle cell lymphoma and CLL.

Journal Article↗

Implementing a policy for pneumococcal prophylaxis in a haematology unit after splenectomy.

People who have had a splenectomy for any reason are 40 times more likely to have an overwhelming infection, especially pneumococcal infection, and 17 times more likely to suffer fatal sepsis. The incidence of such life threatening infections is reduced by prophylactic immunisation with polyvalent pneumococcal vaccine and long term antibiotic prophylaxis or instituting prompt antibiotic treatment in the event of fever. This haematology unit agreed a policy of immunisation and antibiotic prophylaxis in June 1988 for all patients undergoing elective splenectomy. The success of this policy was audited in July 1993 by a retrospective analysis of patients' case notes. Seventy four patients were identified as having had a splenectomy, 54 (73%) before June 1988, of whom only 13 (24%) had received both pneumococcal immunisation and antibiotic prophylaxis before implementation of the agreed policy. At the time of audit, 46/74 (62%) patients were recorded as having received immunisation and 64/74 (86%) as receiving antibiotic prophylaxis or a supply of antibiotics to take in the event of a fever. All but one of the 20 patients who had a splenectomy after June 1988, since implementation of the agreed policy, received immunisation and antibiotic prophylaxis. The authors conclude that establishment of a formal agreed policy for pneumococcal prophylaxis for patients undergoing splenectomy has improved the quality of care.

Antibiotic Prophylaxis↗

Primary gastrointestinal non-Hodgkin's lymphoma: a review of 175 British National Lymphoma Investigation cases.

A retrospective analysis was performed upon 175 patients with Non-Hodgkin's Lymphoma involving the gastrointestinal tract and entered into BNLI trials and studies between 1974-1988. Malignant histiocytosis of the intestine (MHI), which was present in 16 patients, was associated with a survival of less than 25% at 18 months, and probably accounted for the poor survival of patients with jejunal involvement. Histopathological evidence of tumour origin from mucosa-associated lymphoid tissue (MALT) was found in 50% of patients with gastric involvement and in 27% of those with intestinal involvement. The overall survival of the series as a whole was 44% at 10 years. Multivariate analysis identified evidence of tumour origin from MALT as the only factor to attain prognostic significance in patients with gastric involvement, and clinical stage and the presence of MHI as the only factors to attain prognostic significance in patients with intestinal involvement. It is suggested that there is a need for a large multicentre prospective study of GIT lymphoma.

Adolescent↗

Trisomy 12 in B-cell chronic lymphocytic leukaemia: an evaluation of 33 patients by direct fluorescence in situ hybridization (FISH).

An adaptation of the standard fluorescence in situ hybridization (FISH) technique allowing rapid analysis (4 h) has been used to study the prevalence of trisomy 12 in 33 patients with B-CLL, of whom 54% have been shown to have this abnormality. The presence of trisomy 12 has been compared with clinical parameters, and there may be a relationship between the prevalence of trisomy 12 in B-CLL and duration of disease.

Adult↗

Listeria meningitis after bone marrow transplantation.

Over the past decade infections from food-borne Listeria monocytogenes have become an important cause of septicaemia and meningitis and immunocompromised patients are at particular risk. We report three cases of Listeria meningitis occurring post-BMT. The patients were aged 53, 51 and 56 years and presented 4, 7 and 90 months post-transplant, respectively. The first patient had undergone allogeneic BMT for myelodysplasia and the other two patients had ABMT for AML in second and first CR, respectively. All the patients presented with classical features of meningitis and L. monocytogenes was cultured from cerebrospinal fluid. All made a full recovery with appropriate antibiotic therapy. We have not seen cases of meningitis due to other organisms in our transplant programme and the cases represent a risk of one episode per 59 surviving patient years. None of the patients was receiving prophylactic post-BMT antibiotics and the episodes may strengthen the case for using prophylactic penicillin. Recent epidemics of septicaemia and meningitis caused by L. monocytogenes-contaminated milk and cheese suggest that these patients should be informed about potential sources of infection.

Acute Disease↗

A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies.

Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.

Adolescent↗

Recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma: a British National Lymphoma Investigation double-blind, placebo-controlled trial.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is active in enhancing the production of mature myeloid cells in vitro and several phase I/II clinical trials have suggested that its administration may accelerate neutrophil recovery after autologous bone marrow transplantation (ABMT). We have conducted a multicentre randomized double-blind placebo controlled trial in patients with poor prognosis malignant lymphoma receiving an identical high-dose combination chemotherapy regimen with ABMT. 61 patients were entered and 29 in each arm of the trial were evaluated. Treatment with GM-CSF did not affect the period of severe neutropenia (absolute neutrophil count (ANC) of < 0.1 x 10(9)/l) but accelerated recovery to an ANC of 0.5 x 10(9)/l (median 14 d v 20 d in controls, P = 0.001). There was no significant difference in platelet recovery between the groups (GM-CSF group platelet dependent for 25 d v control 19 d, P = NS). The number of positive blood cultures was similar in both groups (GM-CSF 14 v placebo 13) and there were no differences in days of fever > 37.5 degrees C (median 8 v 6) or days on parenteral antibiotics (11 v 10). Patients receiving GM-CSF had a median period of hospitalization following BMT of 24 d (control 25). No significant major toxicity attributable to GM-CSF administration was detected. We have confirmed in a randomized trial that GM-CSF accelerates neutrophil but not platelet recovery following ABMT. We were unable to demonstrate any accompanying changes in clinical outcome and believe that further trials are necessary to assess the clinical value of GM-CSF in BMT.

Adolescent↗

BEAM autografting in lymphoma--experience at one centre.

Since December 1987, we have examined the use of high-dose chemotherapy and unpurged bone marrow rescue in 31 patients with advanced or refractory lymphoma. Twenty-one patients had Hodgkin's disease (HD) and 10 had Non-Hodgkin's lymphoma (NHL). At ABMT, 22 patients had relapsed or resistant disease. All patients, excluding 3 early deaths, engrafted. There was no relationship between cell numbers harvested, CFU-GM and bone marrow recovery. The mean times to 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets were 20 d and 43 d respectively. However, 5 patients with HD had a significantly slower platelet recovery time of up to 203 days (p = 0.05). Disease-free survival was 72% for HD and 40% for NHL at 40 months. Relapsed or refractory disease at ABMT, bulky disease, extensive salvage therapy and Karnofsky scores below 80% were all associated with a poorer outcome. The most striking observation has been the dramatic radiological response of some patients with advanced/refractory disease.

Adolescent↗

Pharmacokinetics of imipenem/cilastatin in neutropenic patients with haematological malignancies.

The pharmacokinetics of imipenem/cilastatin were studied in febrile neutropenic patients with haematological malignancies. The peak plasma concentrations (36.4 +/- 4.96 mg/l), plasma half-life (60 min), volume of distribution (0.28 +/- 0.02 l/kg) and plasma clearance (3.23 +/- 0.38 ml/min/kg) were comparable with those in normal healthy volunteers suggesting that the drug handling is not appreciably altered in this group of patients. The administration of 12.5 mg/kg (max 1 g), 6-hourly achieved levels that were up to 3.5 times MICs of most relevant bacteria. The drug therefore has a potential use as empirical monotherapy in febrile neutropenic patients.

Acute Disease↗

Sequential demonstration of nucleolar organizer regions and Ki67 immunolabelling in non-Hodgkin's lymphomas.

In order to investigate the relationship between the numbers of interphase silver-stained nucleolar organizer regions (AgNORs) and cell proliferation, we have studied prospectively a small series of non-Hodgkin's lymphomas (NHL). We applied the recently described double staining technique for sequential immunostaining and the AgNOR reaction to the same sections of tumour from each case. The immunostaining was performed with the antibody Ki67, known to demonstrate the nuclei of proliferating cells. A significant difference was found between the AgNOR scores in Ki67+ and Ki67- cells, the counts being much higher in the former than the latter. This was the case for both high- and low-grade NHL and is further evidence that interphase AgNOR counts reflect cell proliferation level, at least in lymphomas.

Antibodies, Monoclonal↗

Small intestinal bacterial overgrowth in patients with chronic lymphocytic leukaemia.

As part of a study to assess the possible contribution of lymphoid infiltration of the gastrointestinal mucosa to occult blood loss or malabsorption 20 patients with chronic lymphocytic leukaemia (CLL) had a lactulose hydrogen breath test. In 10 cases (50%) a small intestinal peak was detected, suggesting small bowel bacterial overgrowth, and this was confirmed in seven patients by the positive culture of jejunal aspirate. Of the patients with a positive hydrogen breath test, radiological examination showed a duodenal diverticulum in two but no anatomical abnormalities in the other cases. There was no evidence of achlorhydria and transit times were normal. There was no difference in the incidence of hypogammaglobulinaemia among those patients with evidence of small intestinal bacterial overgrowth and those without. Seven patients with a positive hydrogen breath test, however, had undetectable secretory piece in their jejunal aspirates whereas this was present in all patients with a normal breath test who had local immunoglobulin concentrations measured (p less than 0.05), indicating that the small intestinal bacterial overgrowth may be due to impaired local immunity.

Agammaglobulinemia↗