[Therapy-resistant pneumonia in a middle-aged man].
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Adult↗
Biomedical subjects
J Nikoskelainen
Publications and source records attributed to J Nikoskelainen.
A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group.
Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.
Adolescent↗
Salivary defense factors and oral health in patients with common variable immunodeficiency.
Studies of oral health in patients with common variable immunodeficiency have given controversial results. Obviously, one major factor modifying the oral health of these patients is saliva, in which the antibody-mediated defense is remarkably impaired compared to that of healthy subjects. However, the occurrence of nonimmunoglobulin (innate) antimicrobial agents in saliva of these patients is virtually unknown. Therefore, we analyzed both immune (total IgA, IgG, IgM, anti-Streptococcus mutans IgA, IgG, and IgM antibodies) and nonimmune (lysozyme, lactoferrin, salivary peroxidase, myeloperoxidase, hypothiocyanite, thiocyanate, and agglutinins) factors in whole saliva of 15 patients with common variable immunodeficiency. All patients were on Ig-replacement therapy (median duration, 10 years; range, 2-25 years), which had normalized their IgG but not their IgA or IgM levels both in serum and in saliva. Also, comprehensive clinical and microbiological analyses were made. The control group comprised 15 age- and sex-matched immunologically healthy subjects. The results showed no notable differences in dental caries, periodontal diseases, or salivary microorganisms but the patients had a history of more frequent oral mucosal lesions and respiratory infections. All innate, nonimmune salivary defense factors were equally abundant in the patients as in the controls, in many cases even at somewhat higher concentrations. These findings suggest that in spite of immunodeficiency, patients with common variable immunodeficiency display normal, perhaps even slightly elevated, levels of nonimmunoglobulin defense factors in whole saliva.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A randomized trial comparing busulfan vs total body irradiation in allogeneic marrow transplant recipients with hematological malignancies.
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Bone Marrow Transplantation↗
Fatal encephalitis caused by concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi.
We describe a 38-year-old farmer from the southwestern archipelago of Finland where both tick-borne encephalitis (TBE) virus and Borrelia burgdorferi are endemic. He presented with fever and headache, developed severe meningoencephalitis in 3 days, and, after 1 month, died without regaining consciousness. High titers of IgG and IgM antibodies to TBE virus were present in both serum and CSF. Serology for Borrelia was negative. Autopsy revealed necrotizing encephalitis and myelitis with involvement of the dorsal root ganglion. With use of polymerase chain reaction tests, segments of two separate genes of B. burgdorferi were amplified from the patient's CSF. This case demonstrates that the possibility of dual infection should be considered for patients residing in geographic areas where Ixodes ticks may carry both the TBE virus and B. burgdorferi. We believe that the most severe damage in this case was caused by TBE virus rather than by B. burgdorferi. Nevertheless, the coinfection might have contributed to the fatal outcome that has not been previously observed in Finnish patients with TBE.
Adult↗
Bone marrow transplantation for acute myeloblastic leukaemia: an EBMT Leukaemia Working Party prospective analysis from HLA-typing.
The optimal post-remission therapy for patients with acute myeloblastic leukaemia remains controversial. Allogeneic bone marrow transplantation, autologous bone marrow transplantation, and consolidation chemotherapy are the major options. In order to evaluate their respective value the European Group for Bone Marrow Transplantation conducted a prospective registration study. Patients with newly diagnosed acute myeloblastic leukaemia were registered at the time of HLA-typing and intention to treat in case of presence or absence of an HLA-identical donor was recorded. 27/79 (34%) patients HLA-typed at diagnosis had an identical donor identified. The estimated survivals at 3 years from HLA-typing were 44% and 21% among patients with or without HLA-identical donor, respectively (P = 0.02). 22/26 (85%) patients for whom allogeneic bone marrow transplantation was intended were transplanted but only 15/47 (32%) patients for whom autologous bone marrow transplantation was intended were indeed transplanted (P < 0.001). The survival was 50%, 29% and 17% (P = 0.004) for patients treated with allogeneic bone marrow transplantation, autologous bone marrow transplantation, or chemotherapy, respectively. 40/68 patients HLA-typed in first complete remission had an HLA-identical donor. The estimated 3-year survival among patients typed in first remission with and without HLA-identical donors was 42% and 35% (n.s.), respectively. This technique of early patient registration illustrates the problems of patient selection during the course of the disease and might be used as a complement to randomized trials when comparing bone marrow transplantation and other treatment options.
Adolescent↗
Lethal infections in patients with hematological malignancies.
The hospital files of 410 patients with hematological malignancy treated at our clinic between 1977 and 1990 were reviewed to determine the importance of infections as a cause of death. The total number of infections was 203 (49.5%). A microbiologically documented infection was detected in 27.3%, a clinically documented infection in 9.5% and a possible infection in 12.7% of the patients. Gram-positive bacteria were responsible for 25.9%, gram-negative bacteria for 31.3%, anaerobic bacteria for 2.7%, viruses for 4.5% and fungi for 25.9% of the microbiologically documented infections. Of 29 systemic fungal infections only 2 were diagnosed before the patients died. The remaining diagnoses rested on autopsy findings. Empiric antifungal therapy was introduced in 1983; still, 74.2% of systemic fungal infections in 1977-1990 were detected after 1982. Patients with a verified infection had statistically significantly higher CRP concentrations than patients who died of other causes (152 mg/l vs. 117.5 mg/l, p = 0.018). We conclude that infection is a significant cause of death in patients with these diseases. The number of systemic fungal infections is increasing, despite the widespread use of antifungal medication and thus better diagnostic methods and more effective treatment are needed.
Aspergillosis↗
Value of measurement of C-reactive protein in febrile patients with hematological malignancies.
The maximum serum levels of C-reactive protein (CRP) in 126 patients with hematological malignancies who had 554 febrile episodes were analyzed retrospectively with regard to documented infections and fever of unknown origin. The CRP levels were significantly higher when the blood culture was positive than when it was negative (p = 0.002). The CRP levels were significantly higher when the infection focus was identified than when it was not (p = 0.010). In patients with fever of unknown origin the CRP was significantly lower than in patients with microbiologically documented infections (p < 0.001). Cytotoxic treatment neither reduced nor enhanced the CRP reaction. The serial measurement of CRP is a reliable and readily available means for differentiating between bacterial infections and other causes of fever in patients with hematological malignancies, also during neutropenia and after cytotoxic treatment.
Adult↗
Infections and serum IgG levels in patients with chronic lymphocytic leukemia.
To review our policy of prophylactic treatment with intravenous immunoglobulin (i.v.IG) in chronic lymphocytic leukemia (CLL), we analyzed the infection history, serum IgG levels (S-IgG) and disease stage of 146 patients who were treated and followed at our institution in 1980-1989. S-IgG was available for 98 patients: 55% were hypogammaglobulinemic and 56% had had at least one severe infection. There were significant associations between S-IgG and the occurrence of infections (p less than 0.01) and disease stage (p less than 0.02). There was also a significant association between disease stage and occurrence of infections (p less than 0.001). Severe infections tended to accumulate in patients with subnormal S-IgG and advanced disease stage. Totally, 292 infections were recorded, and the incidence of moderate to severe infections was 0.47 per patient year. Infection mortality was high: 42 patients died of a severe infection (46% of all causes of death). Patients with a low S-IgG and advanced disease stage are the most susceptible to death from infection and would be most likely to benefit most from i.v.IG prophylaxis; however, the cost of this therapy is so high that strict individual consideration still remains crucial for treatment decisions.
Adult↗
[Fundus oculi findings in a surgical patient with systemic candidiasis].
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Adult↗
[Carnitine deficiency and severe nausea-induced thiamine deficiency causing a metabolic crisis].
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Adult↗
Bone marrow transplantation for acute myeloid leukemia: the EBMT experience. A prospective analysis from HLA-typing. The EMBT Leukemia Working Party.
In 1990, 4,234 BMT were performed in Europe; 2,097 autologous BMT (388 AML) and 2,137 allogeneic BMT (494 AML). Although an established therapy with leukemia free survival (LFS) at five years of 41% +/- 5% (EBMT results) its value compared to alternative therapies remains controversial. During the year 1985, the EBMT conducted a prospective evaluation study. In 12 centres 168 patients with AML were registered at the time of HLA-typing. Basic patient data and treatment intention were recorded. 79 patients were HLA-typed at diagnosis. 68 patients in 1st CR and 21 at other stages. Follow-up of these patients was obtained as of January 1, 1991. Three-year LFS is 44% for patients with an HLA-identical donor and 21% for those without (p = 0.02). Of the 68 patients HLA-typed in first CR, 40 had an HLA-identical donor and 28 no donor. Three-year LFS is 42% and 35%. resp. (n.s.). The difference in results between patients typed at diagnosis and first CR patients illustrates the problem of selection. We conclude that patient registration early in the disease can give insight into the process of selection. Allogeneic BMT incorporated prospectively at diagnosis into therapy offers a survival advantage for patients in this age category compared to alternative therapies.
Acute Disease↗
Antibiotic susceptibility of coagulase-negative staphylococcal blood isolates with special reference to adherent, slime-producing Staphylococcus epidermidis strains.
The epidemiologic relationship between slime-producing coagulase-negative staphylococci and antibiotic resistance was evaluated by analyzing the in vitro susceptibility of 278 blood isolates to 10 different antimicrobial agents. The strain collection consisted of 60 coagulase-negative staphylococcal septicemia isolates, recovered from at least 2 successive blood cultures from 59 septicemia patients and 218 single blood isolates defined as insignificant. When the slime-producing Staphylococcus epidermidis isolates were compared with all non-slime-producing S. epidermidis isolates, the slime-producing isolates exhibited higher MIC50 and/or MIC90 values than the non-slime-producing isolates, and were also more commonly resistant against many of the antimicrobials tested. The association between slime production and resistance against tobramycin, gentamicin and rifampicin was statistically significant (p less than 0.05). A similar finding was observed among the S. epidermidis septicemia isolates when they were analyzed separately from the single (suspected blood contaminant) S. epidermidis isolates. Further characterization of the septicemia isolates revealed that the positive correlation between slime production and antibiotic resistance reflected, to some extent, multiresistance of 1 epidemic slime-producing S. epidermidis strain. No difference in resistance was observed between the slime-producing and non-slime-producing single S. epidermidis blood isolates.
Anti-Bacterial Agents↗
Antimicrobial therapy of septicemic patients in intensive care units before and after blood culture reporting.
68 cases of positive blood cultures from 54 intensive care unit (ICU) patients were analyzed retrospectively. The empiric antimicrobial therapy was correct in 65% of the cases as judged by the species and sensitivity of the blood culture isolate. After initial Gram-staining results were known, coverage increased to 77%. After the final blood culture results the coverage was still only 81%. The bacteremia-related mortality was 13%. Although there was no significant difference between the occurrence of bacteremia-related and non-bacteremia-related deaths either in patients with correct or non-optimal empiric treatment, this study emphasizes the need for better utilization of culture reporting. A considerable part of the final blood culture results went unnoticed by the ICU physicians which stresses the importance of good communication between the laboratory and wards.
Adolescent↗
Prosthetic valve endocarditis.
Prosthetic valve endocarditis is an infrequent but serious complication of valve surgery. It occurred in 25 (3.2%) of 772 patients who received aortic, mitral or double valve replacement in 1971-1987. The total follow-up time was 3,976 patient years, giving an incidence of 0.63/100 patient years. Staphylococci were the most common of the cultured organisms in early and late infections-60% and 64%, respectively. The endocarditis was disclosed at autopsy in two cases. Treatment was antibiotics alone in 11 cases, and surgery was required in 12, the indication always being congestive heart failure. C-reactive protein level fell more rapidly than erythrocyte sedimentation rate in response to antibiotic or surgical management. The mortality rate was 73% in the antibiotic group and 33% in the surgical group. The findings demonstrated that an infected valve prosthesis should be replaced without delay if complications develop.
Anti-Bacterial Agents↗
[New cephalosporins and imipenem].
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Bacterial Infections↗
The reappearance of 10 differentiation antigens on peripheral blood lymphocytes after allogeneic bone marrow transplantation.
Ten monoclonal antibodies and flow cytometry were applied to characterize the recovery of lymphocyte subsets in peripheral blood after allogeneic bone marrow transplantation (BMT). Ten patients were first followed for 150 days (short-term survey) and then analysed 2 years after BMT on average (long-term analysis). Eight of the 10 recipients showed increased relative and absolute numbers of CD8+ cells and reduced numbers of CD4+ cells resulting in an inverse helper/suppressor ratio. In these eight patients the CD8+ cell predominance was long-lasting and still detectable in the long-term analysis. Two patients had a normal helper/suppressor ratio throughout the study but otherwise a similar reconstitution. Despite the slow recovery of CD4+ cells, CD4+ Leu8- and CD4+ CD45RA- helper subsets were in a normal range already on day 30 and their proportions stayed higher than those of CD4+ Leu8+ and CD4+ CD45RA+ helper cells for the whole short-term survey. The number of activated suppressor cells (CD8+ HLA-DR+) increased markedly after BMT. Similarly, in eight patients high numbers of cytotoxic CD8+ CD57+ cells were found from day 50 onwards. An early and sharp rise of NK cells (CD16+, CD56+) was observed in all recipients, and seven recipients also showed an early increase in CD20+ B cells. Later on, normal or slightly elevated numbers of these cells occurred.
Adult↗
Analysis of the relationship between bacterial adherence and extracellular production of mannose, galactose, glucose and ribose in Staphylococcus epidermidis and Staphylococcus hominis.
Gas-liquid chromatography-mass spectrometry was used to analyze the extracellular extracts of 108 coagulase-negative staphylococcal strains for the presence of mannose, galactose, glucose and ribose, in order to determine whether production of these four monosaccharides, regarded as potential staphylococcal slime components, was associated with the adherence capacity of the individuals strains. A total of 90 Staphylococcus epidermidis and 18 Staphylococcus hominis strains were studied. Using the quantitative spectrophotometric assay, 21 Staphylococcus epidermidis strains were classified as strongly adherent, 12 as moderately adherent, 11 as weakly adherent, and 46 as nonadherent. All 18 Staphylococcus hominis strains were nonadherent. Mannose, galactose, glucose and ribose were detected as the main monosaccharide components in the extracellular extracts of all strains examined. Moreover, the mean relative concentrations of these monosaccharides were essentially the same for the different adherence phenotypes within the species Staphylococcus epidermidis. These results showed that there was no causal connection between the adherence of coagulase-negative staphylococci and the extracellular production of any of the four monosaccharides analyzed.
Bacterial Adhesion↗