Search PubMed⌕ Search

Biomedical subjects

D J Winston

Publications and source records attributed to D J Winston.

At least 91 records · Page 5Linked to original sources
PubMed1980

Trimethoprim-sulfamethoxazole for the treatment of Pneumocystis carinii pneumonia.

Intravenous trimethoprim-sulfamethoxazole therapy was evaluated in 11 consecutive patients with documented Pneumocystis carinii pneumonia and the results compared to those from previously published studies of trimethoprim-sulfamethoxazole therapy for P. carinii pneumonia. Although six patients needed mechanical ventilation, intravenous therapy was successful in seven of 11 patients (64%), and seven of nine patients (78%) receiving 4 or more days of intravenous trimethoprim-sulfamethoxazole therapy were cured. Side effects occurred in two patients (skin rash in one, nausea and vomiting in one). A review of 80 reported cases of confirmed P. carinii pneumonia initially treated with trimethoprim-sulfamethoxazole alone revealed response rates of 67.5% in all treated patients and 85.5% in patients treated for 9 or more days. The clinical response was similar in adults (63.2%) and children (68.9%). Side effects were noted in only 11 of 80 patients (13.8%). Compared to pentamidine, trimethoprim-sulfamethoxazole has a narrower toxic-therapeutic ratio and should be preferred treatment for P. carinii pneumonia in adults as well as children.

Adolescent↗
PubMed1980

Cytomegalovirus infections associated with leukocyte transfusions.

Patients randomized to receive or not to receive prophylactic leukocyte transfusions were evaluated prospectively for serologic, histologic, and cultural evidence of cytomegalovirus infection. Recipients of prophylactic leukocyte transfusions and control subjects were similar with regard to age, sex, underlying disease, immunosuppressive therapy, and number of other transfusions. The recipients of prophylactic leukocyte transfusions (mean, 23.1) had significantly more cytomegalovirus infections (19 of 31 versus seven of 27, p = 0.01) than did control patients receiving no leukocytes or only therapeutic leukocyte transfusions (mean, 3.8). Twenty-seven of 66 donors of leukocytes were seropositive for cytomegalovirus complement-fixation antibody, but cytomegalovirus was not isolated from any of 62 leukocyte transfusions cultured for virus. These results are consistent with the hypothesis that latent cytomegalovirus may be present in leukocytes of blood donors with previous cytomegalovirus infection and after transfusion may be activated to produce active cytomegalovirus infection.

Adolescent↗
PubMed1979

Antimicrobial therapy of septicemia due to Klebsiella pneumoniae in neutropenic rats.

Three different isolates of Klebsiella pneumoniae, highly sensitive to amikacin but varying in susceptibility to cefazolin, were injected intraperitoneally into neutropenic rats. Animals were treated every 8 hr for 72 hr with saline (controls), cefzolin (full dose, 40 mg/kg; one-fourth dose, 10 mg/kg), amikacin (full dose, 8 mg/kg; one-fourth dose, 2 mg/kg), or a combination of both drugs at either full dose or one-fourth dose. All drugs were given intramuscularly. Combination therapy with full doses produced higher mean bactericidal titers in serum and more rapid clearance of bacteria from blood and peritoneal washings. However, cumulative mortality at 72 hr in rats treated with amikacin plus cefazolin in full doses (24%, 23%, and 44%) was not significantly different from mortality in rats treated with amikacin alone (34%, 17%, and 62%). Results with cefazolin alone were not significantly different from the mortality in control animals for two of the three challenge organisms. When the minimal inhibitory concentration of cefazolin was less than or equal to 8 micrograms/ml, in vivo synergy was suggested by the similar survival rate obtained with a combination of a one-fourth dose of each agent and with amikacin alone in a full dose. These results demonstrate the relative ineffectiveness of cefazolin for therapy of klebsiella septicemia and suggest that in vivo antimicrobial synergy occurs in combination therapy against strains of bacteria relatively sensitive to cephalosporins.

Agranulocytosis↗
PubMed1979

Infectious complications of human bone marrow transplantation.

Infections are an almost inevitable complication of human bone marrow transplantation and account for the majority of deaths in transplant recipients. Even prior to the initiation of the transplantation procedure, patients may present with infections complicating previously unsuccessful chemotherapy for hematological malignancy or aplastic anemia. Nevertheless, these pre-transplantation infections should not exclude the possibility of bone marrow transplantation if they can be successfully controlled with specific antimicrobial therapy and necessary adjunctive measures. The immediate post-transplantation period prior to engraftment is characterized by severe marrow aplasia that results from high-dose chemotherapy and total-body irradiation. Infections are primarily septicemias and localized processes caused by bacteria and fungi and their incidence increases as the intensity of immunosuppression is escalated. The high mortality associated with bacterial septicemia makes early, empirical antibacterial therapy mandatory. However, the reduction in mortality from bacterial infection resulting from such an aggressive approach may be offset by a higher mortality from invasive fungal infection, especially in patients with prior fungal colonization and undergoing prolonged conditioning therapy. Thus, until more specific and sensitive tests for the diagnosis of invasive fungal infection become available, empirical intravenous amphotericin should be considered in patients who are persistently febrile and deteriorate clinically in the face of appropriate antibacterial therapy. Interstitial pneumonia associated with severe GVHD is the major infectious complication after successful marrow engraftment and is the most significant barrier to long-term survival. Trimethoprim-sulfamethoxazole is effective prophylaxis against interstitial pneumonia due to Pneumocystis carinii, but one half of the patients still develop a pneumonitis either associated with CMV or of unknown etiology. Mortality from interstitial pneumonia is related to prior radiation therapy while survival is associated with a four-fold rise in CMV CF antibody titer. The latter observation supports the need to investigate passive immunization with CMV antibody as a means of preventing some interstitial pneumonias. Despite the progress made in many areas of human bone marrow transplantation, the majority of graft recipients still die of infectious complications. Thus, new approaches to the management of infections in transplant recipients are urgently needed. Better-tolerated oral nonabsorbable antibiotics, laminar-air-flow rooms, granulocyte transfusions, and chemotherapy and immunotherapy for CMV are among the prophylactic and therapeutic measures that must be critically evaluated in well-controlled, prospective studies. Continued assessment of the infectious complications of bone marrow transplantation is a critical aspect of any ongoing transplant program, not just a research goal...

Acute Disease↗
PubMed1979

Pneumococcal infections after human bone-marrow transplantation.

Seven of 26 long-term survivors (greater than 7 months post-transplant) of bone-marrow transplantation developed penicillin-sensitive pneumococcal infections more than 7 months after transplantation. One patient had two infections. Six of eight infections were associated with pneumococcal bacteremia, and Streptococcus pneumoniae type 6A was isolated in three cases. Two infections were fatal. All patients had normal nematopoietic function, and none was receiving immunosuppressive therapy. The development of pneumococcal infection was significantly associated with males and with abnormally low or high serum IGG and IgM levels but not with graft-versus-host disease. Serum opsonic activity for S. pneumoniae type 6A was decreased in six of the seven patients when compared to normal pooled serum in an in-vitro bactericidal assay. Four of the six patients with impaired opsonic activity had low serum antibody levels for S. pneumoniae type 6A capsular polysaccharide, while the other two patients had low serum CH100 complement activity. Bone-marrow transplant recipients have an increased susceptibility to pneumococcal infections and should be evaluated for prophylactic penicillin or pneumococcal vaccination.

Adolescent↗
PubMed1978

Infectious osteitis pubis.

Osteitis pubis is a well-recognized painful inflammation involving the structures of the anterior half of the pelvic girdle, but its cause remains controversial. Biopsy and culture of the pubic bone in 3 patients with osteitis pubis after implantation of a urinary anti-incontinence device were consistent with pubic osteomyelitis which responded to antibiotic therapy. Infection was also found in almost all previously reported cases of osteitis pubis subjected to similar biopsy and culture. Bone biopsy and culture should be strongly considered before initiating frequently unsuccessful empirical therapy in patients with osteitis pubis.

Aged↗
PubMed1978

In vitro studies of piperacilin, a new semisynthetic penicillin.

Piperacillin, a new semisynthetic penicillin, was compared with other semisynthetic penicillins, cephalosporins, and aminoglycosides by the agar dilution method against 3,600 isolates of facultative gram-negative bacilli, Bacteroides fragilis, and enterococci. At 64 mug/ml, piperacillin inhibited 90% of the isolates in each group of organisms tested except for Escherichia coli (83% inhibited by 64 mug/ml). Compared with carbenicillin, piperacillin had a 16-fold increase in activity by weight against Pseudomonas aeruginosa and the enterococcus, an 8-fold increase against Serratia marcescens, and a 4-fold increase against B. fragilis and Enterobacter species. Piperacillin was highly active against carbenicillin-resistant Klebsiella pneumoniae and inhibited many aminoglycoside-resistant organisms. Except for P. aeruginosa, the minimum bactericidal concentration of piperacillin was usually within one tube dilution of the minimum inhibitory concentration. Approximately one-third of the gram-negative bacilli were inhibited synergistically by piperacillin plus amikacin, but no synergy could be demonstrated against enterococci. Piperacillin's in vitro activity against gram-negative bacilli was similar to gentamicin's except that it also included B. fragilis, and piperacillin was decidedly superior to presently available penicillins against K. pneumoniae.

Amikacin↗
PubMed1978

In vitro evaluation of opsonic and cellular granulocyte function by luminol-dependent chemiluminescence: utility in patients with severe neutropenia and cellular deficiency states.

Actively phagocytizing polymorphonuclear leukocytes (PMN) emit light or chemiluminescence (CL) which has been shown to be linked to the oxidative activity of the PMN. The measurement of CL has been demonstrated to be a useful tool for the in vitro assessment of intracellular and opsonophagocytic function of PMN. We have increased the sensitivity of the CL measurement by the addition of luminol to the in vitro reaction of PMN, bacteria, and serum. The presence of luminol, which can be oxidized to emit light, amplifies the detection of CL and PMN cellular activity. This amplification effectively reduces the number of PMN that are necessary for assessment of PMN function from 1 x 10(7) to as low as 2 x 10(4) PMN/assay and permits the evaluation of PMN function in severely neutropenic patients (100 PMN/mm3) in whom cellular PMN function has been heretofore extremely difficult to assess by other methodology. When this luminol-dependent CL method was used, three of eight neutropenic leukemic patients with gram-negative septicemia were found to have deficient opsonic activity and/or increased or depressed cellular oxidative activity. Because the initial slope of CL is dependent on the amount of serum and heat-labile factors, this method can also be used effectively as a simple technique for the analysis of specific rates of opsonophagocytosis of various microorganisms. Additionally, this method can detect the cellular PMN abnormalities of chronic granulomatous disease and myeloperoxidase deficiency. The luminol-dependent CL method is a simple, sensitive, reproducible technique that provides useful information about PMN metabolic activity, particularly in studies in which the number of PMN is limited.

Agranulocytosis↗
PubMed1977

Allescheria boydii infections in the immunosuppressed host.

Allescheria boydii, a true fungus frequently isolated from soil, is best known as a causative agent of maduromycosis of the foot. In our report we describe two patients under treatment for acute leukemia who died from rapidly progressive A. boydii infections. One patient had signs of central nervous system infection and was found at autopsy to have had a large brain abscess. The second patient had a cavitary necrotizing pneumonia with thoracic inlet obstruction (Pancoast's syndrome) and failed to show improvement despite treatment with amphotericin B. The clinical spectrum of allescheriasis is reviewed with particular emphasis on its role as a pathogen in the compromised host. Since A. boydii may resemble other fungi morphologically in tissue sections and may produce infections clinically similar to other mycoses, culture of the organism is required for definitive diagnosis. Based on recently reported in vitro susceptibility studies, miconazole may have a future role in the therapy of A. boydii infections which are resistant to presently available antifungal agents.

Adult↗
PubMed1977

Paracoccidioidomycosis (South American Blastomycosis) in the United States.

The findings in a patient with paracoccidiodomycosis (South American blastomycosis) diagnosed by open-lung biopsy and treated successfully with a combination of trimethoprim and sulfamethoxazole are reported, and the clinical spectrum of the disease is reviewed. Although paracoccidioidomycosis is rarely encountered in the United States and is clinicially similar to other deep mycoses, it should be considered in patients who are suspected of having a fungal infection and have had previous exposure in an area endemic for paracoccidiodomycosis.

Granuloma↗
PubMed1977

Disseminated Trichosporon capitatum infection in an immunosuppressed host.

Trichosporon is a frequent cause of superficial mycotic infections but has rarely been associated with invasive disease. A patient undergoing bone marrow transplantation who died from disseminated Trichosporon capitatum infection with endocarditis is reported, and the clinical spectrum of human infection caused by fungi of this genus is reviewed. To our knowledge, this is the first reported case of clearly invasive disease caused by this specific organism and emphasizes the expanding spectrum of unusual infections in the severely immunosuppressed patient.

Adult↗
PubMedDate not supplied

Ganciclovir therapy for cytomegalovirus infections in recipients of bone marrow transplants and other immunosuppressed patients.

The efficacy and safety of ganciclovir were evaluated for the treatment of 39 life-threatening or sight-threatening cytomegalovirus (CMV) infections in recipients of bone marrow transplants (15 patients), recipients of liver or renal transplants (8 patients), patients with AIDS (11 patients), and one patient each with lymphoma or systemic lupus erythematosus. Twenty-eight (72%) of 39 CMV infections improved during ganciclovir therapy, which was associated with elimination of CMV from cultures. Improvement occurred more frequently in patients with viremia, fever, and wasting (8 of 8), hepatitis (3 of 4), retinitis (5 of 5), or colitis (1 of 1), than in patients with pneumonia (11 of 21). Only two of nine marrow transplant recipients with CMV pneumonia survived, as compared with nine of 12 other immunosuppressed patients with pneumonia. However, all six marrow transplant recipients who were treated for CMV viremia, fever, and wasting without pneumonia survived. Neutropenia was the only adverse reaction associated with ganciclovir therapy and was more frequent in patients with AIDS (6 [55%] of 11) than in transplant recipients (5 [20%] of 25). These results suggest that ganciclovir is of clinical benefit for immunosuppressed patients with serious CMV infections. For bone marrow transplant recipients, ganciclovir may be more effective when used prophylactically or earlier in the course of CMV infection before the development of pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Cytomegalovirus infections after allogeneic bone marrow transplantation.

Cytomegalovirus (CMV) infection occurs in approximately 50% of all recipients of allogeneic bone marrow transplants and is seen more frequently in CMV-seropositive patients than in CMV-seronegative patients. Sources of infection include reactivation of latent endogenous virus, blood products from CMV-seropositive blood donors, and the use of marrow from a CMV-seropositive donor for a CMV-seronegative recipient. The most common and severe clinical syndrome associated with CMV infection in allogeneic transplant recipients is interstitial pneumonia, which occurs in approximately 15% of patients. Risk factors for CMV pneumonia include old age, conditioning with total-body irradiation, and severe graft-vs.-host disease. The rapid diagnosis of CMV pneumonia has been facilitated by immunochemical staining of bronchoalveolar lavage fluid or by centrifugation of cell cultures with CMV monoclonal antibodies. The treatment of CMV pneumonia remains problematic, but therapy with a combination of intravenous immune globulin (IVIG) plus ganciclovir has resulted in survival rates substantially better than those achieved in previous trials of antiviral therapy. In CMV-seronegative patients, CMV infection and pneumonia can be prevented or modified by the use of CMV-seronegative blood products and IVIG. IVIG may also have the additional benefits of preventing other infectious complications and graft-vs.-host disease in patients receiving CMV-seronegative blood products. For CMV-seropositive patients, effective prophylaxis for CMV reactivation and pneumonia has not yet been established, but a clinical trial of prophylactic ganciclovir is now under way.

Bone Marrow Transplantation↗