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Biomedical subjects

D Maher

Publications and source records attributed to D Maher.

At least 91 records · Page 5Linked to original sources
PubMed1994

Cryptococcal meningitis in Lilongwe and Blantyre, Malawi.

Infection with Human Immunodeficiency Virus is widespread in Malawi and cryptococcal meningitis is a common problem in those with AIDS. A review of microbiology laboratory records in Lilongwe and Blantyre between July 1991 and January 1993 identified 31 patients with cryptococcal meningitis. Diagnosis was based on a positive India ink stain of CSF and/or culture of Cryptococcus neoformans. There were 16 men (median age 38 years) and 15 women (median age 28 years) in the investigation. The median duration of symptoms was 2 weeks. The clinical presentation was varied, the most frequent features being headache (97%), neck stiffness (74%), fever (61%) and altered consciousness (58%). CSF WBC count, glucose and protein concentrations were non-specific. Most patients could not afford anti-cryptococcal chemotherapy and their median survival time after diagnosis was 4 days. Patients who could afford such treatment survived for up to several months. Diagnosis is useful for prognostic reasons and may save patients unnecessary treatment if tuberculous meningitis is the alternative diagnosis. Cryptococcal antigen detection tests may improve diagnostic accuracy. The problem of cryptococcal meningitis is likely to become increasingly common as HIV infection becomes more widespread.

AIDS-Related Opportunistic Infections↗
PubMed1994

Endogenous haemopoietic growth factors in neutropenia and infection.

Haemopoietic growth factors (HGFs) are being administered to patients with neutropenic fever; however, little is known about the endogenous HGF response in these patients. Specific assays were used to study four HGFs, granulocyte (G-) CSF, granulocyte-macrophage (GM-) CSF, macrophage (M-) CSF and interleukin (IL-) 6 levels in the blood of patients with neutropenic fever (46 episodes). For comparison, levels were also measured in three control populations: normals (20), afebrile neutropenic (14), and bacteraemic but not neutropenic patients (20). In febrile patients, levels of G-CSF (median, range) (0.46, < 0.10-142 ng/ml). IL-6 (0.054, 0.005-24.3 ng/ml) and M-CSF (18.5, 9.9-79.1 ng/ml) were elevated compared with afebrile subjects (< 0.10, < 0.10-1.62 ng/ml). (0.008, 0.002-0.024 ng/ml) and (6.45, < 5.0-31.3 ng/ml) respectively. GM-CSF was not elevated (< 0.02, < 0.02-8.0 ng/ml) compared with afebrile subjects (0.021, < 0.02-0.20 ng/ml). Variables significantly associated (P < 0.05) with elevated cytokine levels were determined by multiple regression analyses. Factors associated with G-CSF elevation were fever, neutropenia, pathogen type and raised bilirubin and creatinine. In contrast, neutropenia was not associated with IL-6 elevation although there was an association between IL-6 elevation and fever, Gram-negative and fungal infections and raised creatinine and bilirubin. M-CSF elevation was associated with fever, renal impairment and known pathogen. Elevated G-CSF and IL-6 levels normalized rapidly (hours-days) with the resolution of infection, whereas M-CSF concentrations remained elevated for up to 10 d. Cytokine levels remained elevated in septic neutropenic patients who did not recover. In summary, G-CSF, IL-6 and M-CSF levels were significantly elevated in sepsis. In contrast, GM-CSF levels were not elevated. These studies should assist the development of therapeutic strategies using HGFs in the treatment of sepsis.

Adolescent↗
PubMed1994

Genetic and nucleotide sequence analysis of the gene htdA, which regulates conjugal transfer of IncHI plasmids.

IncHI plasmids are naturally repressed for conjugative transfer and do not allow efficient propagation of the IncH pilus-specific phage Hgal. Transposons Tn7, Tn5, and TnlacZ were inserted into IncHI plasmids R478, R477-1, and R27, respectively, leading to the isolation of several plasmid mutants which exhibited increased levels of transfer and also permitted good lysis with phage Hgal. A 4.3-kb HindIII fragment from R478 reversed both phenotypic effects of derepression for the R477-1::Tn5 and the R478::Tn7 derivatives, pKFW99 and pKFW100, respectively. Exonuclease III deletions of this fragment and nucleotide sequence analysis indicated that the gene responsible for transfer repression, named here htdA, encoded a polypeptide of 150 amino acids. Cloning and sequence analysis of pDT2454 (R27::TnlacZ) revealed that the transposon had inserted into an open reading frame (ORF) which had an 83% amino acid identity with the R478 htdA gene. Maxicell analysis showed both the R27 and R478 HtdA products had molecular masses of 19.9 kDa. Conjugation experiments showed that the cloned htdA determinants caused a significant reduction of the transfer frequencies of wild-type R478 and R27 plasmids. Examination of both R478 derepressed mutants, pKFW100 and pKFW101, indicated that both transposon insertions occurred upstream of the htdA ORF. The results suggest that HtdA is a regulatory component of IncH plasmid transfer and also show that the region upstream of the htdA ORF is involved in transfer repression. The locations of the htdA determinants were identified on the plasmid maps of R27 and R478.

Amino Acid Sequence↗
PubMed1994

Retinal findings in Malawian patients with AIDS.

The purpose of this study was to determine the prevalence of retinal disease in a group of patients with AIDS in Malawi. Indirect ophthalmoscopy was performed on 99 patients with AIDS who were admitted consecutively to a medical ward at a central hospital. Necrotising retinitis was present in one eye of one patient examined. Non-infectious retinopathy was present in 13%. Retinitis is less common in AIDS patients from Africa compared with those from developed countries; it is believed that most patients die before acquiring it. Non-infectious retinopathy may also be less common.

AIDS-Related Opportunistic Infections↗
PubMed1994

Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood progenitor cells to restore hemopoiesis after high-dose chemotherapy for lymphoid malignancies.

The hemopoietic growth factor filgrastim (r-metHu G-CSF) stimulates granulopoiesis after autologous BMT and can also be used as a peripheral blood progenitor cell (PBPC)-mobilizing agent. Rapid platelet recovery follows the addition of filgrastim-mobilized PBPC to autologous BMT. We have now studied 29 adults with malignant lymphoma, Hodgkin's disease or ALL to assess the ability of filgrastim-mobilized PBPC to rapidly and durably restore hemopoiesis without bone marrow (BM) infusion. Patients with a high yield of PBPC from three leukaphereses, defined as > 30 x 10(4)/kg GM-CFC, were eligible for PBPC transplant without BM. Patients with a low yield of GM-CFC received both PBPC and BM infusion. After filgrastim therapy 12 or 24 micrograms/kg/day by continuous sc infusion for 6 or 7 days, a high yield was obtained in 11 of 29 patients. Kinetics of recovery of both the platelet and neutrophil counts were more rapid in the high yield group than in the low yield group. The platelet count recovered to > 20 x 10(9)/l at a median of 9 days, to > 50 x 10(9)/l at 11 days and the neutrophil count to > 0.5 x 10(9)/l at 9 days in the high yield group compared with 12 days, 37 days and 10 days, respectively, in the low yield group (p = 0.028, p < 0.001 and p = 0.027). Fewer platelet transfusions were required in the high yield group (median 11 vs 29.5 units, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

H-pilus assembly kinetics determined by electron microscopy.

The kinetics of pilus outgrowth were examined for Escherichia coli containing pDT1942, a TnlacZ insertion derivative of the IncHI1 plasmid R27, which was derepressed for transfer. IncHI1 plasmids are thermosensitive for transfer. The pili specified by pDT1942 were examined by transmission electron microscopy after the pilus had been labeled with the H-pilus-specific bacteriophage Hgal, which had been inactivated with RNase A. H pili were extended by extrusion from the cell surface and not by the addition of pilin subunits to the pilus tip. After pili were removed by vortexing, the outgrowth of full-length pili (2 microns long) required 20 min. H pili expressed at the transfer optimal temperature (27 degrees C) remained stable after incubation at the transfer inhibitory temperature (37 degrees C), but the formation of mating aggregates was inhibited at 37 degrees C. Within 1 min of exposure of the host cell to a heat stimulus of 50 degrees C, pili vanished. Pili were observed in straight and flexible forms with a field emission scanning electron microscope, which may indicate a dynamic role for the pilus in conjugation.

Escherichia coli↗
PubMed1993

Host range and transfer efficiency of incompatibility group HI plasmids.

HI plasmids are distinguished by their thermosensitive mode of conjugation (transfer efficiency is optimal at 22-30 degrees C) and their capacity to encode multiple antibiotic resistance. These traits have implicated HI plasmids as potential vectors in the dissemination of antibiotic resistance among pathogenic and indigenous bacterial species in water and soil environments. We compared the transfer efficiency of HI plasmids with that of plasmids from 13 other incompatibility groups at 37, 24, and 14 degrees C in intragenic conjugations between laboratory strains of Escherichia coli K-12 under in vitro conditions. Only the HI plasmids and a representative plasmid from incompatibility groups M, N, P alpha, T, and W were observed to be transmissible at 14 degrees C. These plasmids, along with HI plasmids and the related HII representative, were tested for their host range and transfer proficiency to Enterobacteria species and some other Gram-negative organisms of environmental significance at 24 and 14 degrees C. Notable differences in the host range of HI plasmids compared with plasmid representatives from the other enterobacterial groups were not evident at 24 degrees C. At 14 degrees C, R478 (HI2) displayed the broadest host range and transfer proficiency among the test plasmids. The ability of several plasmid groups, including HI, to transfer at 14-24 degrees C to Vibrio cholerae non 01, Salmonella typhi, and the fish pathogens Aeromonas salmonicida, Vibrio anguillarum, and Yersinia ruckeri needs to be corroborated by in situ studies.

Conjugation, Genetic↗
PubMed1993

Effect of peripheral blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy.

The haematopoietic growth factor (HGF), granulocyte colony stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral blood progenitor cells (PBPC) and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. Seventeen patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for six days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leukapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral blood progenitors; the platelet count reached 50 x 10(9)/L a median of 15 days after infusion of haematopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. Subsequently, 10 patients received filgrastim-mobilised PBPC without marrow after high-dose chemotherapy. The rate of platelet and neutrophil recovery in these patients was at least equal to that observed in the patients receiving PBPC and bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Support of human cord blood progenitor cells on human stromal cell lines transformed by SV40 large T antigen under the influence of an inducible (metallothionein) promoter.

We describe the development of a human bone marrow (BM) culture system which allows study of the interaction of stromal cell lines (SCL) and highly purified hematopoietic progenitor cells. Normal BM stromal cells were electroporated with a plasmid containing the simian virus 40 (SV40) large T antigen (SV40 T Ag) under the control of a synthetic metallothionein promoter (MT4); this construct is designated MT4 SV40 T Ag. SCL in which the rate of proliferation could be controlled by altering the zinc (Zn) concentration were characterized, demonstrating that the SCL were heterogeneous with respect to G-CSF and GM-CSF production. Suppression of SCL proliferation on removal of Zn made it possible to use these lines in coculture with purified CD34+ progenitor cells from umbilical cord blood. The ability to control proliferation of SCL has allowed us to maintain the survival and expansion of colony-forming cells in culture for up to 2 months. These lines have enabled us to test for stromal cell characteristics at a clonal level and provided us with a tool to analyze the events leading to lineage commitment and hematopoietic differentiation, as demonstrated by suppression of hematopoiesis by an antibody directed against the c-kit molecule.

Antigens, CD↗
PubMed1992

Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy.

The haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone-marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral-blood progenitor cells and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. 17 patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for 6 days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leucapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone-marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral-blood progenitors; the platelet count reached 50 x 10(9)/l a median of 15 days after infusion of haemopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. This method may be widely applicable to aid both neutrophil and platelet recovery after high-dose chemotherapy; it will allow investigation of peripheral-blood progenitor-cell allotransplantation.

Adolescent↗
PubMed1992

Guarantees come to professional service firms.

Can lawyers, doctors, investment bankers, accountants, and consultants guarantee their work? Your money back if not absolutely delighted? Some professional service firms are doing exactly that, and they believe they are gaining not only satisfied customers but higher market share and improved service quality. The authors discuss the benefits and risks of unconditional and more limited guarantees. Firms that address this issue proactively now, they argue, will be less likely to rush into poorly considered guarantees later.

Commerce↗
PubMed1991

Bacteriophages for incompatibility group H plasmids: morphological and growth characteristics.

Two independently isolated temperature-sensitive bacteriophage that are specific for enterobacterial hosts harboring HI and HII plasmids were characterized to determine if any identifiable differences existed between them. The traits examined included adsorption pattern of phage to H pili, bacteriophage size, sensitivity to chloroform, RNA strandedness, reaction with F-specific antiphage serum, virion protein pattern, temperature range of lytic ability, and plaque morphology. No differences between the phages were observed for any of the features analyzed. Ecological questions on the origin and maintenance of temperature-sensitive phages are discussed.

Bacteriophages↗