Biomedical subjects

W Peters

Publications and source records attributed to W Peters.

At least 127 records · Page 7Linked to original sources

PubMed1993

Heterogeneity of cutaneous leishmaniasis with emphasis on the Old World.

Leishmaniasis of the integument which may result from infection with a number of different species of Leishmania can be primary, or can arise as a late manifestation of systemic infection of the reticuloendothelial organs (kala-azar). Infection of the skin and/or mucosae assumes many different clinical forms which are reviewed here. The immune response is essentially a cell-mediated one. Even left untreated, the majority of tegumentary lesions will eventually self-heal but the process may be very prolonged and severe scarring can result. The main features of diagnosis, prevention and treatment are discussed. No vaccines are generally available at present. Organic pentavalent antimonials remain the drugs of choice.

Africa↗

PubMed1993

Hematopoietic recovery following high-dose combined alkylating-agent chemotherapy and autologous bone marrow support in patients in phase-I clinical trials of colony-stimulating factors: G-CSF, GM-CSF, IL-1, IL-2, M-CSF.

Hematopoietic recovery in 115 patients with metastatic breast cancer or metastatic melanoma, enrolled in phase-I studies of recombinant growth factors while undergoing treatment with high-dose chemotherapy with autologous bone marrow support, was examined with assays of bone marrow progenitor cells and peripheral blood progenitor cells, and by evaluation of peripheral blood counts. Groups of patients receiving hematopoietic cytokine support [with interleukin-1 (IL-1), interleukin-2 (IL-2), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or monocyte CSF (M-CSF)] post marrow infusion were compared with contemporaneous control patients not receiving growth factor support. Patients receiving GM-CSF demonstrated statistically significant increases in the growth of granulocyte/macrophage colony-forming units (CFU-GM) in the bone marrow and peripheral blood compared with control patients. The effect of GM-CSF was dose dependent in the early period post marrow infusion (day +6) with bone marrow CFU-GM colonies at doses 8-16 micrograms/kg/day 34 times those measured in controls. Significant increases in bone marrow multipotential progenitor cells (CFU-GEMM) were seen in patients receiving GM-CSF day +21 post marrow infusion. Patients receiving IL-1 demonstrated significant increases in bone marrow CFU-GM at day +21, maximal at dosages of 24-32 ng/kg/day. There were no significant increases in burst forming unit-erythroid (BFU-E) among any study group. Patients receiving G-CSF had significantly increased absolute neutrophil counts (ANC) and total white blood cell counts (WBC) by day +11 post transplant compared with control patients. Patients receiving GM-CSF demonstrated significantly increased WBC (greater than 2000/mm3) at day +11 and ANC greater than 500/mm3 at day +16. Optimal dose of G-CSF and GM-CSF to stimulate neutrophil recovery post transplant was 4-8 micrograms/kg/day and 8-16 micrograms/kg/day, respectively. Platelet recovery did not differ among the six study groups. These data demonstrate accelerated myeloid recovery after high-dose chemotherapy and autologous bone marrow support in patients receiving either G-CSF or GM-CSF. Moreover, GM-CSF and IL-1 stimulate myelopoiesis at the level of bone marrow CFU-GM, while G-CSF causes earlier neutrophil recovery peripherally.

Alkylating Agents↗

PubMed1993

Pathology of the pancreas in bone marrow transplant patients.

Review of 51 autopsy cases of patients receiving high-dose chemotherapy followed by bone marrow transplantation revealed a high prevalence of pancreatic ductal and acinar changes compared with control groups. Forty-five percent (23 of 51) of bone marrow transplant cases had squamous metaplasia of the pancreatic ducts compared with 10% of randomly selected control cases. Although squamous metaplasia was more common in bone marrow transplant patients receiving chemotherapy, it was not associated with whole body radiation, allogeneic transplantation, or specific drugs. Squamous metaplasia was more common in patients dying 30 days or more after transplantation. Dilatation of the pancreatic acini was present in 78.4% of transplant cases, 35.0% of control cases, and 50.0% of a group of 12 breast cancer patients treated with conventional doses of chemotherapy without bone marrow transplantation. This lesion was associated with uremia. Oncocytic change of the acinar epithelium was present in 52.9% of transplant cases, no control cases, and 41.7% of breast cancer cases. Squamous metaplasia of the pancreas is common in bone marrow transplant patients receiving high-dose chemotherapy and may be a late manifestation of toxic injury to the ducts. A high prevalence of acinar dilatation was associated with terminal uremia. Oncocytic change of acinar epithelium was associated with chemotherapy.

Adult↗

PubMed1993

Burns in the disabled.

A retrospective analysis of 812 patients admitted to the Ross Tilley Burn Centre between 1984 and 1992 resulted in 37 cases of burn injuries which were directly related to premorbid disabilities. The majority of these burns (83.8 per cent) occurred in the patient's home, most commonly as scald injuries in the bath tub, the shower, or following hot water spills. Nineteen patients were male, 17 were female. The median age was 58 years. Six patients had spinal cord disorders: four had traumatic cord damage, two had spina bifida. Six patients had seizure disorders. Five of these patients had been taking anti-seizure medications, but all had subtherapeutic blood levels on admission to hospital. Two patients had diabetes mellitus with peripheral neuropathies. Thirteen patients had four miscellaneous neurological disorders, including: tardive dyskinesia (two), CVA (four), Parkinson's disease (two), Alzheimer's disease (two), cerebral palsy (one), multiple sclerosis (one) and blindness (one). Three patients had a diagnosis of syncope. Two patients had emphysema, and four were morbidly obese. The average length of stay (LOS) for the disabled patients was 27.6 days for a median burn size of 10 per cent body surface area (BSA), compared to an average LOS for the general population of 25.7 days for a larger median burn size of 21 per cent BSA. The mortality rate was also much higher in the disabled population (22.2 per cent vs. 6.0 per cent). Most of these burn injuries were preventable. A series of burn prevention guidelines is presented, in an attempt to reduce the incidence of these burn injuries in disabled patients.

Adult↗

PubMed1993

The chemotherapy of rodent malaria. XLVIII. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 1: Studies leading to the development of novel cis-fused cyclopenteno derivatives.

The new Chinese antimalarial blood schizontocide, artemisinin, derived from the plant Artemisia annua, displays a high level of activity against polyresistant Plasmodium falciparum. Several synthetic 1,2,4-trioxanes were examined in a search for compounds that exhibit a similar type of action against drug-resistant parasites. This paper, the first of a series, describes the examination of these trioxanes against drug-sensitive and drug-resistant malaria parasites in a rodent model, using artemisinin and arteether as comparison standards. Cis-fused cyclohexeno-1,2,4-trioxanes (10-17) substituted with various side-chains revealed for the most part variable but weak antimalarial activity. On the other hand, cis-fused cyclopenteno-1,2,4-trioxanes (18-19) showed greater activity, 19 showing about 1/30th of the activity of arteether against drug-sensitive Plasmodium berghei in vivo, thereby providing a clue to the structure-activity relationship.

Animals↗

PubMed1993

The chemotherapy of rodent malaria. XLIX. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 2: Structure-activity studies on cis-fused cyclopenteno-1,2,4-trioxanes (fenozans) against drug-sensitive and drug-resistant lines of Plasmodium berghei and P. yoelii ssp. NS in vivo.

The activity of 51 synthetic cis-fused cyclopenteno-1,2,4-trioxanes has been examined against drug-sensitive and chloroquine-resistant malaria parasites in vivo. Some of them display high levels of blood schizontocidal activity when administered orally or subcutaneously. They retain their activity against lines of parasites that are resistant to widely differing antimalarials such as 4-aminoquinolines, aminoalcohols, dihydrofolate reductase inhibitors and artemisinin. The most potent compound of the present series is cis-(+/-)-4a,7a-dihydro-6,7a-di(p-fluorophenyl)spiro [cyclopentane-3,3'-7H-cyclopenta-1,2,4-trioxin], otherwise known as Fenozan-50F.

Animals↗

PubMed1993

The chemotherapy of rodent malaria. L. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 3: Observations on 'Fenozan-50F', a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane.

A novel difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane ('Fenozan-50F') is a potent blood schizontocide against drug-sensitive and drug-resistant rodent malaria parasites. It also exerts some action against pre-erythrocytic schizogony, is a potent gametocytocide, and exerts a direct sporontocidal effect in infected mosquitoes. In the '4-day test' the ED90s are 6.8 and 6.0 mg/kg/day for four consecutive days by the subcutaneous and oral routes respectively against drug-sensitive Plasmodium berghei N, and 6.3 and 25 mg/kg against chloroquine-resistant P. yoelii NS in vivo. By the oral route against P. berghei N infection in mice, Fenozan-50F is about half as active as arteether but nearly three times as active as sodium artesunate. The activity of Fenozan-50F is retained against a wide spectrum of drug-resistant parasite lines, although those highly resistant to quinine or to artemisinin are less responsive at the ED90 level. At the ultrastructural level the compound, when administered to infected mice, causes marked changes in the membranes and ribosomes of trophozoites and young schizonts and of immature gametocytes, although few changes are apparent in mature gametocytes. Its toxicity appears to be very low when it is administered to mice by either the oral or subcutaneous route. Fenozan-50F is considered to be a good candidate for eventual use as a therapeutic agent for infection with polyresistant malaria in man.

Animals↗

PubMed1993

The chemotherapy of rodent malaria. LI. Studies on a new 8-aminoquinoline, WR 238,605.

WR 238,605, a novel 3-phenoxy-substituted 8-aminoquinoline, possesses causal prophylactic, blood schizontocidal and gametocytocidal activity against rodent malaria parasites. Against the asexual, intra-erythrocytic stages of drug-sensitive Plasmodium berghei N strain, it is about nine times as active as primaquine (PQ). It is from four to 100 times as active as PQ against lines of P. berghei or P. yoelii that are resistant to currently used antimalarials. WR 238,605 is three times as active as PQ against the pre-erythrocytic stages of P. y. nigeriensis but it has very poor gametocytocidal action and no sporontocidal activity against this parasite. In combination with chloroquine (CQ), WR 238,605 and PQ display a synergistic or 'resistance-reversing' action against CQ-resistant P. yoelii NS parasites. No such effects are seen when WR 238,605 is deployed with mefloquine against a mefloquine-resistant line or with artemisinin against an artemisinin-resistant line and it appears to be antagonistic to halofantrine against a halofantrine-resistant parasite. It is suggested that WR 238,605 is a good candidate compound for clinical trials against polyresistant P. falciparum, possibly in combination with CQ.

Aminoquinolines↗

PubMed1993

Capsular contracture simulating myocardial infarction on ECG.

A patient is presented with severe bilateral class IV capsular contractures who presented 16 years after prepectoral breast augmentation with a "septal infarct" pattern on ECG. This abnormal ECG proved to be an artifact caused by unavoidable misplacement of the V2 and V3 leads because of the severe capsular contracture. Following open capsulotomy, normal anatomic lead placement was possible, and a normal ECG was produced.

Artifacts↗

PubMed1993

Haploidentical bone marrow stem cell transplantation in human severe combined immunodeficiency.

From May 1992 to March 1993, 50 infants with severe combined immunodeficiency (SCID) were given bone marrow transplants at Duke University Medical Center. None received chemotherapy for conditioning or for graft-versus-host disease (GVHD) prophylaxis. Forty-one received haploidentical parental marrow depleted of T cells by soybean lectin and sheep red blood cell resetting, and nine received HLA-identical marrow. Forty (80%) survived from 1 week to almost 11 years posttransplantation, including nine of nine (100%) HLA-identical marrow recipients and 31 of 41 haploidentical recipients. T-cell function was present within 2 weeks after transplantation of unfractionated HLA-identical marrow, but not until 3 to 4 months after T-cell-depleted haploidentical marrow stem cells. All 37 patients who are more than 4 months posttransplantation have good T-cell function, and all but one have 100% donor T cells. B-cell function developed slowly or not at all in some recipients of haploidentical marrow. Fourteen (four HLA-identical and 10 haploidentical recipients) have some donor B cells; 19 patients are receiving intravenous immune globulin (IVIG) therapy.

B-Lymphocytes↗

PubMed1993

ELISA for detection of anti-Giardia specific IgM: response in serum.

Infection with Giardia lamblia (G. duodenalis, G. intestinalis) is common all over the world, especially in children. Traditional diagnosis by faecal microscopy has only moderate sensitivity; serological tests, although not always positive, are acceptable to patients and useful in epidemiological studies. We show here that serum IgM separated by column chromatography and assayed by an indirect ELISA test can be a useful tool for the diagnosis of giardiasis. One hundred and thirty-nine positive sera (based on a single faecal examination), and 97 negative serum samples from Riyadh, Saudi Arabia, were examined. Taking positive results as being 2 s.d. above the mean of the controls, there were 117 positive results among the microscopically negative controls (3% false positives). The sensitivity of the test was 84% and the specificity 97%; the predictive value of a positive result is 97.5% and of a negative one 81%.

Acute Disease↗

PubMed1993

Ultrasound analysis of 150 patients with silicone gel breast implants.

One-hundred fifty patients with silicone gel breast implants were investigated using ultrasound (US) studies, to assess the integrity of their implants. US testing demonstrated 8 patients (5.33%) with implant rupture, which was subsequently confirmed at surgery. A further 4 patients were "false negatives," wherein they presented with normal US tests, but at subsequent surgery, demonstrated secondary alterations in their implant envelopes. Two of these patients demonstrated profound local silicone gel "bleed," whereas the 2 others had frank implant rupture. There was also one "false positive" patient. The total known prevalence of patient implant alteration was therefore 12, i.e., 10 with ruptures and 2 with profound local gel "bleed," in 150 patients (8.0%). Five of the 10 patients with ruptured implants had undergone multiple closed capsulotomies in the past. The mean time of diagnosis after implant insertion was 8.5 years (range, 2.0-18 yr). US analysis may provide a safe, simple, inexpensive, noninvasive tool to assist in the identification of ruptured silicone gel breast implants. There were significant limitations with technique, however, in that there were 4 false negatives, and 1 false positive result, and US analysis was not helpful in diagnosing profound silicone gel bleeds.

Breast Neoplasms↗

PubMed1992

Comparative investigations of the morphology and chemical composition of the eggshells of Acanthocephala. II. Palaeacanthocephala.

Eggshells of the palaeacanthocephalans Acanthocephalus anguillae, Pomphorhynchus laevis and Polymorphus minutus were investigated for their fine structure as well as their chemical composition. The acanthor larvae are surrounded by four eggshells (E1-E4) separated by interstices (G1-G4). Immature eggs do not exhibit the complete set of eggshells. The chemical composition of the outermost, thin eggshell (E1) remains unknown. E2 is supplied by outer filaments of different strength; it contains keratin, which was localized electron microscopically using anti-keratin. In P. laevis and P. minutus, E3 seems to contain glycoproteins, which could not be visualized in this eggshell of A. anguillae. The innermost eggshell (E4) uniformly contains chitin. The electron-lucent interstices of the eggs of P. laevis and P. minutus are rich in polysaccharides and/or proteoglycans, whereas those of A. anguillae contain low amounts of such substances. The differences observed in the abundance of carbohydrates are discussed with respect to the life cycles of the three acanthocephalans.

Acanthocephala↗

PubMed1992

Comparative investigations of the morphology and chemical composition of the eggshells of Acanthocephala. III. Eoacanthocephala.

Eggshells of the eoacanthocephalans Neoechinorhynchus rutili (Neoechinorhynchidae) and Paratenuisentis ambiguus (Tenuisentidae) were investigated for their fine structure and their chemical composition. The acanthor larvae of P. ambiguus are surrounded by four eggshells (E1-E4) separated by electron-lucent interstices (G1-G4). This resembles the stratification of the eggshells of archiacanthocephalans and palaeacanthocephalans. However, an additional outer envelope (E0) exists in N. rutili. In mature eggs of this species, the broad interstice between E0 and E1 is densely packed with polysaccharides, but the other interstices also showed an intense Thiéry label. In both species, E2 along with its outer protuberances contains keratin, as does E2 in archiacanthocephalans and palaecanthocephalans, whereas E4 does not contain chitin, which contrasts with findings in the eggs of the two other classes of acanthocephalans. The results are discussed with respect to the classification of the Acanthocephala and to their transmission to the intermediate hosts.

Acanthocephala↗

PubMed1992

Combination alkali/thermal burns caused by 'black liquor' in the pulp and paper industry.

Three patients are presented, who sustained a unique type of burn injury while working in the pulp and paper industry in Canada. These patients suffered combination chemical (pH 11-13) and thermal (85-95 degrees C) injuries, when they were exposed to 'black liquor'--a solution which is used in the pulp and paper industry to convert wood chips to pulp. Black liquor can rapidly cause devastating thermal-corrosive burns to the skin, eyes, lungs, and upper gastrointestinal tract. One patient sustained a relatively minor, full skin thickness 3 per cent body surface area (BSA) injury to both feet and lower legs. The second patient, who was sprayed with the heated black liquor solution, sustained a full skin thickness injury to 40 per cent BSA and also suffered virtual loss of vision in one eye. The third patient, who was also sprayed with the solution, sustained a 98 per cent full skin thickness burn and severe inhalation injury, and died during day 1 postburn. Photographic documentation of all three patients is presented. The principles of treatment of this type of burn injury are reviewed. All of these burns were preventable.

Accidents, Occupational↗

PubMed1992

Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B.

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).

Adenocarcinoma↗

PubMed1992

Genetic variability of the murine creatine kinase B gene locus and related pseudogenes in different inbred strains of mice.

The role of genetic variation in isoenzyme gene families is often poorly appreciated. We report here on the determination of DNA sequences and typing of genetic variability in four creatine kinase B (CKB) gene loci in different inbred strains of mice. The unique functional murine CKB gene was found to be nearly identical to the previously characterised rat and human sequences in both size and exon-intron structure. In this gene, approximately 0.5% allelic nucleotide positions as well as the lengths of simple A-rich and [TG]n repetitive elements located at the 5' and 3' sides of the transcribed segment, differed between inbred strains of mice. Preliminary experiments suggest that this sequence divergence is of importance for design of gene targeting strategies involving homologous DNA recombination. The three additional CKB-like gene loci in mice all had the characteristics of processed pseudogenes. By Southern blot analysis we could demonstrate that both the type and number of pseudogenes differed between inbred strains. Analysis of the CKB gene sequences enabled us to speculate about the evolutionary history of this highly polymorphic subfamily of genes.

Amino Acid Sequence↗

PubMed1992

The chemotherapy of rodent malaria. XLVII. Studies on pyronaridine and other Mannich base antimalarials.

The activities of Mannich base antimalarials, including pyronaridine, have been explored against drug-sensitive (Plasmodium berghei N) and chloroquine-resistant (Plasmodium yoelii NS) rodent malaria parasites in vivo. Lines of these parasites have been developed with resistance to pyronaridine, amodiaquine, or WR 228,258. The responses and patterns of cross-resistance of these lines to Mannich bases and other blood schizontocides are inconsistent. It is concluded that some Mannich bases may prove still to be of value inthe treatment of chloroquine-resistant Plasmodium falciparum infection.

Aminoquinolines↗