Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

Effect of FK-506 on xenografted human Graves' thyroid tissue in severe combined immunodeficient mice

OBJECTIVE We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenograft-ing, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-7). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS After 4–6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-7 were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.     

The vascular supply of splenic autotransplants.

The close opposition of blood to phagocytic cells lining the pulp cords and marginal sinus has been proposed as a contributing factor in the clearance mechanism of the spleen. The vasculature of splenic autotransplants was investigated in rats using microcorrosion casts. Six-month-old splenic autotransplants and unoperated control spleens were selectively perfused and a methyl methacrylate cast was made. Scanning electron microscopy of these corroded casts was performed. In autotransplants, the marginal zone capillary network was abnormal with the fine network of capillaries replaced by dilated blood vessels. The red pulp cords were also found to be abnormal with increased diameter and loss of the fine saccular dilations found in normal spleens. The abnormally dilated capillaries and cords in the autotransplants may decrease antigen contact with these cells and hence explain previous reports of reduced phagocytic function.     

Successful treatment of periungual warts using photodynamic therapy: a pilot study

AIM: The aim of this pilot study was an investigation on photodynamic therapy (PDT) whether it is a good alternative for treating periungual and subungual warts of the hands. STUDY DESIGN: Twenty patients (mean age: 30.5 years) with a total of 40 periungual and subungual warts were treated with PDT. A photosensitizer, 20%delta-aminolevulinic acid was applied on the warts. After a mean incubation time of 4.6 h (SD: 1.2), the warts were irradiated with the VersaLight for 5-30 min (15.2 +/- 4.3 min). RESULTS: After a mean of 4.5 treatments a mean clearance of 100% was achieved in 90% of the patients. One patient (5%) showed a clearance of 50% and another showed no improvement. The subungual or periungual location of the wart had no influence on the number of treatments or end result (P > 0.05). There were two recurrences during the mean follow-up period of 5.9 months (SD: 7.6). Besides mainly pain and hyperpigmentation, most treatments had no side-effects. CONCLUSION: PDT can offer a good alternative for treating periungual warts of the hands. Larger studies are indicated.     

Mortality risk associated with ejection fraction differs across resting nuclear perfusion findings.

BACKGROUND: Left ventricular ejection fraction (LVEF) is a significant predictor of morbidity and death. The nuclear summed rest score (SRS) measures myocardial perfusion defects and provides prognostic information, but its effects on long-term outcomes are not fully established. Moreover, information regarding the potential interaction between these 2 covariates is limited. The purpose of this study was to determine whether the mortality risk associated with LVEF is the same across all values of SRS in a population undergoing evaluation for ischemic heart disease. METHODS AND RESULTS: We examined 3,187 patients who underwent cardiac catheterization and perfusion single photon emission computed tomography imaging with a maximum follow-up of 8.1 years and median follow-up of 3.1 years. Cox proportional hazards modeling showed that increasing nuclear SRS and decreasing LVEF were independently associated with a higher long-term mortality rate, with a clinically significant interaction between them (P = .032). Patients with a normal LVEF and a high SRS (greater perfusion abnormality) have a prognosis similar to those with a reduced LVEF. CONCLUSIONS: Resting perfusion studies provide prognostic information for long-term survival and significantly impact the interpretation of mortality risk associated with changes in LVEF. Patient prognostication, risk stratification, and future research using these variables should take this interaction into account.     

Mortality risk associated with ejection fraction differs across resting nuclear perfusion findings

Background  Left ventricular ejection fraction (LVEF) is a significant predictor of morbidity and death. The nuclear summed rest score (SRS) measures myocardial perfusion defects and provides prognostic information, but its effects on long-term outcomes are not fully established. Moreover, information regarding the potential interaction between these 2 covariates is limited. The purpose of this study was to determine whether the mortality risk associated with LVEF is the same across all values of SRS in a population undergoing evaluation for ischemic heart disease. Methods and Results  We examined 3,187 patients who underwent cardiac catheterization and perfusion single photon emission computed tomography imaging with a maximum follow-up of 8.1 years and median follow-up of 3.1 years. Cox proportional hazards modeling showed that increasing nuclear SRS and decreasing LVEF were independently associated with a higher long-term mortality rate, with a clinically significant interaction between them (P=.032). Patients with a normal LVEF and a high SRS (greater perfusion abnormality) have a prognosis similar to those with a reduced LVEF. Conclusions  Resting perfusion studies provide prognostic information for long-term survival and significantly impact the interpretition of mortality risk associated with changes in LVEF. Patient prognostication, risk stratification, and future research using these variables should take this interaction into account. Supported by a grant from the Tom & Lynn Royster Foundation. Durham, NC, and a National Institutes of Health Research Fellowship Grant (T5 GM08679-04), Bethesda, Md.     

An analysis of the components in UW solution using the isolated perfused rabbit liver

The isolated perfused rabbit liver model has been used to determine the essential components of the UW solution for hepatic preservation by simple cold storage. Livers were stored on ice for 48 hr after initial flushing with the solution being tested, and then reperfused at 38 degrees C in an isolated perfusion circuit; bile flow and enzyme (SGOT, SGPT, and LDH) release during a 2-hr period were recorded. All solutions tested contained phosphate (25 mM) as a buffer and magnesium sulfate (5 mM). Sodium can be substituted for potassium without adverse effects. Lactobionate, raffinose and glutathione cannot be omitted; all other components can be eliminated without altering the effectiveness of the solution in this model.