Myelodysplastic syndromes, from French-American-British to World Health Organization: comparison of classifications on 431 unselected patients from a single institution.

In 1999 a working group of the World Health Organization (WHO) published a revised classification for myelodysplastic syndromes (MDS): RA, RARS, refractory cytopenia with multilineage dysplasia (RC+Dys), RAEB I and II, del (5q) syndrome, and MDS unclassifiable. Chronic myelomonocytic leukemia (CMML) and RAEB-t were excluded. Standard French-American-British (FAB) and new WHO classifications have been compared in a series of patients (n = 431) from a single center, analyzing morphologic, clinical, and cytogenetic data. According to the WHO findings, dysgranulocytopoiesis or dysmegakaryocytopoiesis only were found in 26% of patients with less than 5% medullary blasts. These patients are thus unclassified and should remain in the subgroups RA and RARS. Splitting of heterogeneous RAEB into 2 subgroups according to blast count was supported by a trend to a statistically significant difference in the single-center study population. Patients with CMML whose white blood cell counts are above 13 000/microL may be excluded from the MDS classification, as warranted by WHO, but a redistribution of patients with dysplastic CMML according to medullary blast count leads to more heterogeneity in other WHO subgroups. Although the natural courses of RAEB-T and acute myeloid leukemia (AML) with dysplasia are different, comparable median survival durations after treatment in patients with RAEB-T and AML were in favor of the proposed 20% medullary blast threshold for AML. The homogeneity of subgroups was studied by evaluating prognostic scores. A significant shift into lower IPSS risk groups was evident in the new classification. These data cannot provide evidence for the new WHO proposal, which should not be adopted for routine clinical use at present. Some of its aspects can provide a starting point for further studies involving refined cytogenetics and clinical results.

Dysplastic versus proliferative CMML--a retrospective analysis of 91 patients from a single institution.

In chronic myelomonocytic leukemia (CMML) segregation of two subtypes has been suggested depending on WBC count-myelodysplastic (MD-CMML) and myeloproliferative (MP-CMML). In a retrospective analysis of 91 (60/31) previously untreated CMML patients, we compared the presenting clinical, haematological, laboratory and bone marrow features and examined the clinical impact of this reclassification. LDH values and bone marrow cellularity were significantly increased in MP-CMML. Median survival was significantly longer for patients with MD-CMML, progression rate was higher for MP-CMML. Patients with MD-CMML had longer median preleukemic duration; after transition to AML, MP-CMML patients had longer median survival. In MDS phase anemia was more common in MP-CMML and thrombocytopenia more common in MD-CMML whereas transfusion rates showed no difference. Evaluation of prognostic scoring systems for both groups confirmed that patients' characteristics and outcome could be well compared. Our data suggest that segregation into MD-CMML and MP-CMML is justified.

Cross-validation of prognostic scores in myelodysplastic syndromes on 386 patients from a single institution confirms importance of cytogenetics.

In myelodysplastic syndromes (MDS) different prognostic risk analysis systems based on clinical and morphological data are used for predicting survival. Data on diagnostic and prognostic relevance of karyotype aberrations have prompted the development of scores including cytogenetics. The aim of this study was to assess and compare the explanatory power of different scoring systems and to assess the additional explanatory power of cytogenetics by evaluating the clinical and laboratory data of MDS patients from a single institution. Data of 386 MDS patients was available, with cytogenetic analysis at time of diagnosis in 256. Clinical/morphological scores: Bournemouth, modified Bournemouth and Düsseldorf; and scores including cytogenetics: Lausanne-Bournemouth, Lille and the International Prognostic Scoring System (IPSS), were calculated and their predictive power was compared for both overall survival and preleukaemic duration. Each of the scores had significant correlation on both endpoints. Calculating the prognostic value of different cytogenetic aberrations we found that differentiating between evidence for no aberration, single aberrations excluding chromosomes 7 and 8, aberrations on chromosomes 5, 7 or 8 and complex aberrations was important. These data were incorporated in a 'prognostic index cytogenetics' (pi score). Cytogenetic scores significantly improved the prognostic value of the best clinical/morphological score in regard to both overall survival and preleukaemic duration. In conclusion, our data further stress the importance of cytogenetics for predicting prognosis in MDS.

Effectiveness of multiple-level sectioning in detecting axillary nodal micrometastasis in breast cancer: a retrospective study with immunohistochemical analysis.

OBJECTIVE: To evaluate the effectiveness of original multiple-level sectioning in detecting axillary nodal micrometastasis in breast carcinoma. DESIGN: Retrospective analysis of 707 axillary nodes from 34 consecutive node-negative invasive breast cancers from the years 1989 and 1990. All but 2 cases were originally examined by multiple-level sectioning. The original histologic sections were reviewed. Additional sections were cut for hematoxylin-eosin staining and cytokeratin immunohistochemistry. RESULTS: A micrometastasis was found in only 1 case (1 node) on the original histologic section, which was 1 of the 2 cases not originally processed by multiple-level sectioning. Additional sections and cytokeratin immunostains were negative on all cases, including the false-negative case identified on original section. CONCLUSIONS: The finding of a micrometastasis in 1 case on the original, but not on any additional recuts or cytokeratin immunostains, indicates that the original multiple-level sectioning was very effective (0% false negatives). Immunohistochemistry provided no additional benefit in detecting micrometastases in cases already examined by multiple-level sectioning. Thorough histologic examination on properly prepared sections is probably the most efficient and cost-effective way to detect the vast majority of axillary nodal micrometastases.

Comparison of the polyethylene glycol antiglobulin test and the use of enzymes in antibody detection and identification.

BACKGROUND: The polyethylene glycol indirect antiglobulin test for detection of red cell antibodies was compared with a proven, highly sensitive test system using papain. STUDY DESIGN AND METHODS: Parallel, prospective testing of 1508 samples with polyethylene glycol and with albumin and papain evaluated the sensitivity and specificity of polyethylene glycol. Retrospective analysis of antibody specificities was performed for the 2 years before and the 2 years after the institution of polyethylene glycol testing. RESULTS: Of 1508 prospective screens, 53 (3.5%) had discordant results: 5 were positive only in polyethylene glycol and 48 were positive only in albumin and papain. Upon antibody identification, the 5 samples that were positive only in polyethylene glycol showed 1 anti-D, 2 warm autoantibodies, and 2 false-positive results. The 48 samples that were positive only in albumin and papain showed 1 each of the following: anti-Le(b); anti-P1; anti-S; high-titer, low-avidity antibody; and cold autoantibody; there were 43 false-positive results. False-positive results totaled 12 (0.8%) with polyethylene glycol and 53 (3.5%) with albumin and papain. The retrospective analysis of antibody specificity with polyethylene glycol showed a significant increase in the detection of Fy(a) and/or Fy(b) (p < 0.0002) and Jk(b) (p < 0.0002) antibodies and a decrease in the detection of Le(a) and/or Le(b) antibodies (p < 0.0002). CONCLUSION: Polyethylene glycol retained the high sensitivity of the albumin and papain, while significantly lowering the number of false-positive results and decreasing the detection of antibodies of doubtful clinical significance.

Large Brunner's gland hamartoma simulating a pancreatic mass with obstruction and bleeding.

Brunner's gland hamartomas can present as a mass lesion causing obstruction but are also an uncommon cause of upper gastrointestinal bleeding. These tumors may not be accurately identified on radiographic study. Endoscopic examination may be used for diagnostic purposes and may also have therapeutic benefits. Endoscopy can complement surgical intervention, when necessary, for the proper treatment of these lesions.

[Experiences with anti-Rhesus-D therapy in pretreated patients with idiopathic thrombocytopenia]. / Erfahrungen mit Anti-Rhesus-D-Therapie bei vorbehandelten Patienten mit idiopathischer Thrombozytopenie.

OBJECTIVE: We tested the effect of anti Rhesus D [anti Rh(D)]-specific IgG in heavily pretreated patients with idiopathic thrombocytopenic purpura (ITP). DESIGN: Retrospective single case studies. SETTING: Clinical department of hematology. PATIENTS: 6 consecutive patients with heavily pretreated therapy-refractory ITP. INTERVENTIONS: 5 patients received one cycle of Anti Rh(D) in doses between 1,200 and 6,000 micrograms in 1 patient 2 consecutive cycles were applied. Treatment effect, durability, and side effects were monitored. RESULTS: Patients after splenectomy and/or immunosuppressive therapy did not respond. Response was short-lived in 2 other patients, one long-term remission could be achieved. Responders showed slight decreases in hemoglobin indicating mild hemolysis. Other major side effects were not observed and the therapy was well tolerated. CONCLUSIONS: Our results suggest that therapy with Anti Rh(D) is safe and comparably inexpensive. No clear dose/effect correlation was found in our investigation. Only patients with platelet sequestration into the spleen might respond to Anti Rh(D) therapy.

The differentiation of delayed hemolytic and delayed serologic transfusion reactions: incidence and predictors of hemolysis.

BACKGROUND: After differentiation of the entities of clinically detectable delayed hemolytic (DHTR) and delayed serologic transfusion reactions (DSTR), previous investigators calculated a DHTR:DSTR incidence ratio of 18:72 from a retrospective review of patients with serologic evidence of DHTR or DSTR. There are no published data on factors that may influence the occurrence of DHTR versus DSTR in a given patient. STUDY DESIGN AND METHODS: Retrospective review was conducted of 292 patients at the Mayo Clinic who, between 1980 and 1992, received a clinical diagnosis of DHTR or DSTR concurrently with a serologic diagnosis. Red cell alloantibody specificity, the activity of the patient's reticuloendothelial system, and concurrent immunosuppression were evaluated as potential predictors of the occurrence of DHTR versus DSTR in different patients. RESULTS: The incidence of DHTR or DSTR was 1 in 1899 allogeneic red cell units transfused, with a DHTR:DSTR ratio of 36:64. Alloantibody specificity was the only variable that affected the occurrence of DHTR versus DSTR at the clinical level, with the anti-Jka and anti-Fya specificities, as well as multiple coexisting specificities, significantly associated with detectable hemolysis (p < 0.05). CONCLUSION: Clinically detectable DHTRs are found to occur more commonly than previously believed when the clinical and serologic diagnoses are made concurrently and appropriate work-ups for hemolysis are ordered. The association of certain alloantibody specificities with detectable DHTRs may have implications for clinical transfusion practice.

Gallstone ileus: a review of 1001 reported cases.

Although rare in the general population, gallstone ileus accounts for 25 per cent of nonstrangulated small bowel obstructions in those over the age of 65. While mortality has declined over the years, it remains high at 15-18 per cent. This is largely due to the patient population, with comorbid medical conditions contributing to mortality. The proper extent of surgery continues to be actively debated. Proponents of minimal surgery feel that relief of the obstruction is all that is required. Others argue that the gallbladder and biliary-enteric fistula must be removed to prevent future recurrence (a one-stage procedure). The one-stage procedure carries an associated mortality of 16.9 per cent, compared to 11.7 per cent for simple enterolithotomy. Morbidity after enterolithotomy is low. The recurrence rate of gallstone ileus was less than 5 per cent, and only 10 per cent of patients required reoperation for continued symptoms related to the biliary tract. Simple enterolithotomy is both safe and effective in dealing with a patient with gallstone ileus.

Effect of TCDD on the density of Langerhans cells in murine skin.

Tetrachlorodibenzo-p-dioxin (TCDD) is a prototype for a group of toxic polyhalogenated aromatic hydrocarbons. We have studied the effect of TCDD on skin, specifically the difference in cutaneous response of congenic haired (hr/+) and hairless (hr/hr) mice. Topical application of 0.6 microgram of TCDD induces epidermal hyperplasia/hyperkeratinization in the skin of hr/hr mice, but does not affect the epidermis of congenic hr/+ littermates. Suppression of various parameters of the immune response has been found to be another effect of TCDD exposure in experimental animals. In the present study, we investigated the effect of topical treatment with TCDD on the density of epidermal immune cells, the Langerhans cells (LC), in the skin of hr/hr and hr/+ mice. Results showed that TCDD-induced epidermal hyperplasia/hyperkeratinization in skin of hr/hr mice is accompanied by an increase in the density of LC. In the skin of hr/+ mice, in which TCDD exposure does not induce hyperplastic changes, LC densities are not affected. The increase in LC densities in TCDD-treated hr/hr mouse skin did not result in increased sensitivity of the skin to contact hypersensitization with dinitrofluorobenzene, as measured by changes in ear thickness. When hr/hr murine skin was grafted into skin of hr/+ mice and the entire dorsal skin (including the graft) treated with TCDD, LC were increased in the grafted skin, but not in the surrounding hr/+ skin. Conversly, when hr/+ murine skin was grafted into hr/hr mice and both treated with TCDD, there was no increase in the density of LC in the grafted hr/+ skin. Concomitant treatment of hairless mice with TCDD and with indomethacin did not affect the increase in the density of LC induced by TCDD treatment alone. These findings suggest that TCDD-induced epidermal changes in hr/hr murine skin involve production of factors which mediate the increase in epidermal LC.

Morning admission for a same-day surgical procedure: resolution of a blood bank problem.

To minimize the risks associated with an elective surgical procedure on the day of admission without adequate time for blood bank serologic analysis, we implemented two administrative changes: (1) collection of blood samples from patients on the evening before operation and (2) a system for recommending a 3-hour delay of the operation in those cases without such a sample. During a 4-month period before implementation of these changes, 70 patients had serologic problems; morning blood samples had been obtained from 36 of these patients. For a comparable time after implementation of these changes, a serologic problem was encountered in 41 surgical cases, in 7 of which morning blood samples had been obtained. Similarly, the number of cases in which the operation was begun before resolution of a serologic problem decreased from 19 to 3. These decreases occurred despite a 13.4% increase in total morning-admission cases between the first and second study periods. Although no patient experienced adverse transfusion-related events during either study period, simple administrative changes that necessitated no increases in costs were instrumental in substantially decreasing the risks to patients.

Delayed hemolysis resulting from anti-A1 after liver transplantation.

The authors report a case of a delayed hemolytic transfusion reaction in a type A2 recipient of a type O liver allograft. An anti-A1 antibody reactive at 37 degrees C in the indirect antiglobulin test was identified both in the patient's serum and in an eluate. Hemolysis secondary to the production of anti-A1 has been reported to be extremely rare. The English-language literature has six cases before 1979. During the 1980s, an additional seven cases were reported; six involved transplantation of a solid organ, and in each such case the donor was type O and the recipient was type A1 or A2. Recommendations regarding transfusion practice in such cases are made. An association among the transplantation of a type O organ to a type A recipient, the use of cyclosporine, and an apparent increase in the occurrence of clinically significant anti-A1 is suggested.

Delayed immune hemolysis in a patient receiving cyclosporine after orthotopic liver transplantation.

Immune hemolytic anemia in patients after organ transplantation has been reported generally to be graft-cell-derived due to elaboration by the donor's "passenger" lymphocytes of the antibodies directed against the recipient's red cell antigens. In contrast, this report presents a case that illustrates postoperative red cell alloantibody production by the recipient of an orthotopic liver transplant. Anti-Jka, -c, and -S, detected in the recipient's serum 9 days after transplantation, resulted in significant hemolysis. These alloantibodies had not been present in the recipient's serum before transplantation or in the sera of the liver or blood donors. In addition, anti-Jka and -c were eluted from posttransfusion red cells. The patient was transfused during surgery with crossmatch-compatible blood, that carried the alloantigens Jka, c, and S. The liver donor's red cells also carried the Jka, c, and S antigens. The recipient's pretransplantation red cell phenotyping was Jk(a-), c-, S-. The recipient had received only one transfusion 10 years prior to this operation, after which time he was noted to have anti-K. Immunosuppression initially consisted of cyclosporine, azathioprine, and prednisolone. This is believed to be the first report of delayed immune hemolysis due to non-ABO antibodies in a liver transplant patient treated with cyclosporine.

Morning admission to the hospital for surgery the same day. A practical problem for the blood bank.

Morning admissions for surgery the same day are increasing because of economic incentives. These admissions permit less time for red cell serologic preparation before surgery than do the more conventional methods of patient admission. During a 4-month period, serologic problems arose in 70 of 2859 cases. In 36 of the 70 cases, the sample arrived at the blood bank about the time of the beginning of the operation; in 19 of these 36 cases, the operation had begun before serologic resolution, and in 7 of these 19, the antibody was found to be of hemolytic potential. It was concluded that administrative and logistic changes need to be made to ensure sufficient time for the serologic testing necessary for safe transfusion support for same-day surgical admissions.

Comparison of three methods for detecting antibody to cytomegalovirus.

To determine the availability of cytomegalic inclusion virus (CMV) antibody-negative blood among our local donor population, 1384 consecutive group O donors were tested for CMV antibody by the indirect hemagglutination assay (IHA); 51 percent (711) were seronegative (titer less than 8). The highest percentage of seronegative findings (60%) was among donors 18 to 35 years old. This age group represented 57 percent of the donors. IHA, enzyme immunoassay (EIA), and passive latex agglutination (PLA) methods were compared on 491 donor samples. The reference method was the anticomplement immunofluorescence test. Sensitivities were: IHA, 89 percent; EIA, 93 percent; and PLA, 90 percent. Specificities were: IHA, 90 percent; EIA, 95 percent; and PLA, 100 percent. All but two of the false-negative samples contained antibody at low titer (less than or equal to 10), which is of doubtful significance relative to transfusion-transmitted CMV infections. All three methods were suitable for screening blood donors. The PLA was easy to perform and had a short processing time that would allow rapid assay of fresh (less than 7 days old) untested blood at the time of selection for transfusion. Thus, both the amount of pretested blood kept in stock and the cost of obtaining each CMV-seronegative unit could be reduced.

Evaluation of topical erythromycin and oral tetracycline in acne vulgaris.

A double-blind study was conducted to compare topical erythromycin 1.5 percent solution (Staticin solution) with oral tetracycline (250 mg) twice a day in fifty-four patients with Grades II and III acne vulgaris. Although both therapies produced a statistically significant reduction in the number and severity of the acne lesions, the topical preparation usually showed an effect earlier and to a greater degree than the oral medication. By the end of the study, some of these differences were statistically significant. After twelve weeks of treatment, topical erythromycin therapy produced a 58 percent reduction in the overall lesion count, as opposed to the 38 percent reduction produced by oral tetracycline therapy. In addition, the Propionibacterium acnes counts were reduced with erythromycin by over 90 percent and with tetracycline treatment by over 80 percent. Two patients treated with tetracycline developed vaginal candidiasis and therapy had to be discontinued. During topical treatment with erythromycin only mild adverse experiences were reported and none resulted in withdrawal from the study.

Differences in the lipid constituents of sebum from pre-pubertal and pubertal subjects.

Significant differences have been reported in the composition of skin surface lipid in pre-pubertal subjects when compared to pubertal subjects. Analytical studies were performed to determine whether group mean changes in the fatty acid composition of the triglyceride and wax ester fractions of sebum could be detected in pre-pubertal versus pubertal subjects. Twenty males (ages 6-9), twenty females (ages 6-9) and twelve teenagers (ages 11-16) were studied. Skin surface lipid was examined by densitometry and gas chromatography. There were significant changes in the fatty acid composition of the wax fraction of sebum in the 11-16-year-old children when compared to the 6-9-year-old group. As wax is of sebaceous gland origin, this may represent a change in sebum composition probably in response to the hormonal stimulus. Changes in the fatty acid fraction of triglycerides were also noted with age, but this may be due to the change in source of triglyceride from predominantly epidermal origin to sebaceous gland origin.