Serum lactate dehydrogenase in diagnosis of megaloblastic anaemia

The present study was carried out in 75 patients of macrocytic anaemia categorised on bone marrow examination (into megaloblastic and non-megaloblastic anaemia) to evaluate the efficacy of total serum LDH levels and LDH isoenzyme pattern in the diagnosis of megaloblastic anaemia. 25 healthy adults were taken as controls. From this study it can be concluded that total serum LDH levels more than 3000 IU/L are diagnostic of megaloblastic anaemia. Reversed LDH isoenzyme pattern (LDH1 > LDH2) by chloroform inhibition test is an adjuvant in the diagnosis where total serum LDH levels are between 451-3000 IU/L and it will also differentiate megaloblastic anaemia from haemolytic anaemia.     

The efficiency of lactate dehydrogenase isoenzyme determination for the diagnosis of acute myocardial infarction

Values for total lactate dehydrogenase (LDH; EC 1.1.1.27) activity and LDH isoenzymes 1 and 2 were determined in 80 patients with acute myocardial infarction (AMI) and in 40 without AMI every 24 hours up to 15 days after admission, when total serum LDH level returned to normal. The sensitivity, specificity, and efficiency of three LDH isoenzyme factors (LDH-1, greater than 90 U/L; LDH-1 greater than LDH-2; LDH-1/LDH ratio, greater than 0.4) for diagnosing AMI were assessed in three groups of patients according to total serum LDH values--group A, LDH level over 600 U/L; group B, 400 to 599 U/L; group C, 225 to 399 U/L--and in five groups of patients according to the time after admission--(1) first 48 hours; (2) three to five days; (3) six to eight days; (4) nine to 11 days; (5) 12 to 15 days. All three factors were found to be highly efficient for diagnosing AMI (91.5% to 97.5%) in groups A and B, but the most efficient factor in each group was LDH-1 value above 90 U/L. In group C, the only efficient factor was the LDH-1 value over 90 U/L (96%). The most efficient factor for diagnosing AMI in relation to time after admission up to 15 days after AMI was the LDH-1 value over 90 U/L (96% to 97.5%). The factors LDH-1 greater than LDH-2 and LDH-1/LDH above 0.4 were more efficient in patients up to five days after AMI (91.5% to 97.5%) than in patients six to 15 days after admission. We conclude that the most efficient LDH value for diagnosing AMI is the absolute value of LDH-1 above 90 U/L. Its superiority over other LDH isoenzyme values is best documented in a group of patients six to 15 days after admission and with only slight to moderate elevation of total serum LDH values (225 to 399 U/L).     

Relationship between IgE and specific aeroallergen sensitivity in Alaskan native children.

BACKGROUND: The relationship between atopic disease and serum IgE levels varies among populations and geographic regions. The close association of atopy with IgE may not occur in subarctic populations as it does in developed countries in temperate climates. OBJECTIVE: To evaluate the relationship between total and specific IgE concentrations and clinical atopy in 5- to 8-year-old Alaskan native children. METHODS: Medical record reviews, interviews, physical examinations, serum IgE measurements, and radioallergosorbent testing (RAST) were performed. RESULTS: The IgE geometric mean was 122.1 IU/mL. Fifty-eight percent of patients had IgE levels greater than 70 IU/mL, and 17% had levels greater than 1,000 IU/mL; 14% had RAST values greater than 0.35 kU/L. Both IgE levels greater than 70 IU/mL and greater than 1,000 IU/mL were associated with RAST values greater than 0.35 IU/L (P = .004) and early wheezing (P = .005) but not with current wheezing, asthma, eczema, or a history of allergies. A RAST value greater than 3.51 kU/L was associated with eczema (P = .04) but not with allergies or wheezing. Children with current wheezing were more likely to have allergies (P = .03) but not eczema, an IgE level greater than 70 IU/mL, or a positive RAST value. Children hospitalized with respiratory syncytial virus (RSV) were not more likely than controls to have current wheezing. CONCLUSIONS: Elevated serum IgE concentrations, including levels greater than 1,000 IU/mL, are common among Alaskan native children; positive RAST reactions to aeroallergens are not. The IgE levels do not relate to wheezing, eczema, a history of allergies, or past hospitalization for RSV infection but likely reflect infections other than RSV and environmental factors in subarctic indigenous populations.     

Upper lobe relapse ofPneumocystis carinii Pneumonia during aerosolized pentamidine prophylaxis

Summary A patient with a history ofPneumocystis carinii pneumonia (PCP) inhaled aerosolized pentamidine (AP) for secondary prophylaxis of PCP. Nine months after the first PCP episode he presented with pulmonary upper-lobe infiltrations demonstrated by chest x-ray, and bronchoalveolar lavage confirmed the diagnosis of PCP. The clinical course and possible explanations for this unusual form of PCP are presented. The case emphasizes the importance of clinical controls for early diagnosis of relapse of PCP in patients inhaling aerosolized pentamidine. Monitoring of serum lactate dehydrogenase levels appeared to be important in the follow-up of the patient described.Abbreviations PCP Pneumocystis carinii pneumonia - AP aerosolized pentamidine - LDH lactate dehydrogenase - AIDS acquired immunodeficiency syndrome - HIV human immunodeficiency virus - BGA blood gas analysis - WBC white blood cell count - BAL bronchoalveolar lavage     

Compliance and laboratory data predict relapse rate of pneumocystis carinii pneumonia during prophylaxis with aerosol pentamidine

Summary We evaluated 43 AIDS patients on prophylaxis with aerosol pentamidine (60 mg biweekly) after Pneumocystis carinii pneumonia (PCP). The effects of patients' inhalation compliance and of laboratory data during the initial PCP on subsequent PCP relapses were assessed. After a median of 8 months (range, 2–21.5 months) on pentamidine prophylaxis, 13 patients suffered a PCP relapse. Six of them had missed at least one inhalation within the last month before the relapse. Two of these six relapses were fatal. The relapse occurrence was significantly associated with the percentage of missed inhalations. Additional significant associations were found between relapses, low levels of T4 lymphocytes, and elevated serum lactate dehydrogenase during the initial PCP episode (29 patients). Mean levels of T4 lymphocytes were 27/mm³ and 47/mm³ in patients with and without subsequent relapses, mean levels of lactate dehydrogenase were 692 U/L and 605 U/L, respectively. Multivariate Cox regression did not reveal further differences between patients with and without relapses. The increased relapse risk associated with poor inhalation compliance stresses the need for appropriate guidance and motivation of the patients.Abbreviations AIDS acquired immune deficiency syndrome - HIV human immunodeficiency virus - LDH serum lactate dehydrogenase - PCP Pneumocystis carinii pneumonia     

A complementary tool for management of disseminated Histoplasma capsulatum var. capsulatum infections in AIDS patients

In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66–0.92], Sp: 1.00 [95% CI: 0.86–1.00], LR+: >10, LR−: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available.     

Quantitative real-time PCR and the (1→3)-β-D-glucan assay for differentiation between Pneumocystis jirovecii pneumonia and colonization

We evaluated whether quantitative PCR (qPCR) and (1 → 3)-β-d-glucan assays could be used to differentiate Pneumocystis pneumonia (PCP) from Pneumocystis jirovecii colonization in immunocompromised patients with pulmonary infiltrates. A total of 40 bronchoalveolar lavage samples and 107 induced sputum samples from 147 patients who were suspected of having PCP were obtained for PCR detection of P. jirovecii. Diagnoses of definite PCP, probable PCP, pneumonia with P. jirovecii colonization (colonization) and pneumonia without colonization (non-colonization) were made in 11, 42, 15 and 60 patients, respectively. A PCP diagnosis was undetermined in 19 patients. The copy numbers, determined using qPCR, were significantly higher in definite PCP and probable PCP patients than in colonized patients. The area under the receiver-operating characteristic curve (AUC), sensitivity and specificity for discriminating definite PCP from colonization were 0.96, 100.0% and 80.0%, respectively, at a cut-off value of 1300 copies/mL. The values for discriminating probable PCP from colonization were 0.71, 66.7% and 73.3%, respectively, at a cut-off value of 340 copies/mL. β-d-glucan levels were significantly higher in patients with both definite PCP and probable PCP than in colonized patients. The AUC, sensitivity and specificity for discriminating definite PCP were 0.91, 100.0% and 80.0%, respectively, at a cut-off value of 15.6 pg/mL. The values for discriminating probable PCP were 0.78, 76.2% and 73.3%, respectively, at a cut-off value of 6.0 pg/mL. Both qPCR and the β-d-glucan assay displayed high accuracy for discriminating colonization from definite PCP and displayed moderate accuracy for discriminating colonization from probable PCP.     

Palynziq clinic: One year and 43 patients later

Pegvaliase-pqpz (Palynziq) is an enzyme substitution therapy FDA approved May 2018 to treat phenylketonuria in adults with blood phenylalanine levels greater than 600 μmol/L (10 mg/dL). Pegvaliase is administered via subcutaneous injection and carries a high risk of side effects including anaphylaxis. A consensus statement on its use recommends careful education and monitoring of patients. We established a dedicated Palynziq Clinic in October 2018 with detailed protocols to minimize these risks. In the first year, we evaluated 43 patients, initiated Palynziq in 37 and transitioned two trial patients to commercial drug. 13/37 patients (35.1%) have sustained blood phenylalanine levels <360 μmol/L (6 mg/dL) without adjunct sapropterin dihydrochloride treatment or medical food. The timing and dosage needed to achieve a response did not correlate with patient weight, starting phenylalanine level, starting diet, or co-treatment with sapropterin dihydrochloride. Some patients had consistently low phenylalanine levels <30 μmol/L (0.5 mg/dL) and required doses as low as 20 mg weekly. Anaphylactic episodes were reported by 21.6% (8/37 patients) versus 10% seen in the clinical trial. Rates of other side effects were similar to or less than those in the trial. Adverse reactions commonly occurred shortly after dosage increases. We provide a model for safely introducing and managing pegvaliase in adult patients with PKU.     

Prognostic Factors of AL-PCMM and AL-MM: A Single-Center Retrospective Study

Background: Patients with amyloid light-chain (AL) amyloidosis with a bone marrow plasma cell ratio > 10% (AL-PCMM) have a poorer prognosis than patients with AL amyloidosis with a bone marrow plasma cell ratio of <10% (AL-only), similar to that of patients with AL amyloidosis and multiple myeloma (AL-MM). However, the prognostic factors for AL-PCMM and AL-MM have not been studied.Methods: A total of 49 patients with AL-PCMM or AL-MM in the Peking University First Hospital registry in 2010-2018 were enrolled. Clinical and follow-up data were collected. The relationship between clinical parameters and survival time was also assessed.Results: Compared with patients with AL-PCMM, patients with AL-MM only had a higher incidence of bone marrow plasma cell ratio ≥ 20%. In AL-PCMM and AL-MM, the survival time was significantly shorter in patients with alkaline phosphatase (ALP) ≥ 187.5 IU/L, γ-glutamyl transpeptidase (GGT) ≥ 85 IU/L, total bilirubin (TBIL) ≥ 20 µmol/L, cardiac troponin I (CTNI) ≥ 0.1 ng/mL, ejection fraction (EF) < 50%, initial therapeutic effect (ITE) < very good partial response (VGPR), and Boston University (BU) staging system stage ≥ III. ALP at diagnosis was correlated with brain natriuretic peptide (BNP) level, CTNI level, and EF rather than TBIL level. Cox regression analyses revealed that BU staging system stage ≥ III (P=0.001, hazard ratio [HR]=5.579), ALP ≥ 187.5 IU/L (P=0.011, HR=3.563), and ITE < VGPR (P=0.002, HR=7.462) were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM.Conclusion: ALP level, which is related to cardiac amyloidosis rather than liver involvement, can be a prognostic factor for this group of patients. A BU staging system stage ≥ III, ALP ≥ 187.5 IU/L, and ITE < VGPR were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM.     

Predictors of success of repeated injections of single-dose methotrexate regimen for tubal ectopic pregnancy

The purpose of this study is to evaluate predictors of success of repeated injections of methotrexate in the single-dose regimen for the treatment of tubal ectopic pregnancy. All patients who had ectopic tubal pregnancy and were treated with a single dose regimen were retrospectively identified. 126 patients were treated with methotrexate. Among them, 39 patients were adequate for this study. 33 were treated with the 2nd dose and 27 were successfully cured. Additionally, 6 who were injected with the 3rd dose were all cured as well. Therefore, in our study, the success rate for the repeated injections of methotrexate was found to be 84.6% (33/39). The mean initial beta-hCG level was significantly lower in patients who were successfully treated than in patients who failed (3915.3+/-3281.3 vs. 8379.7+/-2604.4 IU/mL, p<0.05). The success rate is 96% when the beta-hCG level is less than 6,000 IU/mL and is 58% when beta-hCG is greater than 6,000 IU/mL (OR=18.57, 95% CI 1.86-185.89). The initial beta-hCG level is the only factor that has significant meaning as predictor of success of repeated injections of methotrexate in the single-dose regimen. Repeated injections of methotrexate may be particularly effective when the initial beta-hCG level is below 6,000 IU/mL.     

Evaluation of CSF-adenosine deaminase activity in tubercular meningitis

Sixty patients of inflammatory brain disease were diagnosed and classified according to clinico-investigational criteria by Ahuja et al into tuberculous meningitis group (36 patients) and non-tuberculous meningitis group (24 patients). Tuberculous meningitis (TBM) patients were classified as probable (9 patients) and possible (27 patients) TBM. Non-TBM group comprised of pyogenic meningitis (8.3%), viral encephalitis (23.3%), cerebral malaria (5%) and enteric encephalopathy (3.3%). Cerebrospinal fluid-adenosine deaminase (CSF-ADA) activities were measured in both TBM and non-TBM groups. Mean CSF-ADA levels in TBM patients was 9.61 +/- 4.10 IU/L and was significantly elevated as compared to viral encephalitis and enteric encephalopathy cases; but difference was insignificant in comparison to pyogenic meningitis (7.92 +/- 0.95 IU/L) and cerebral malaria. Using 8 IU/L as cut off value for diagnosis of TBM a sensitivity of 44% and specificity of 75% was observed.     

Clinical prediction model for differentiation of disseminated Histoplasma capsulatum and Mycobacterium avium complex infections in febrile patients with AIDS

BACKGROUND: Disseminated infection with Histoplasma capsulatum and Mycobacterium avium complex (MAC) in patients with AIDS are frequently difficult to distinguish clinically. METHODS: We retrospectively compared demographic information, other opportunistic infections, medications, symptoms, physical examination findings and laboratory parameters at the time of hospital presentation for 32 patients with culture documented disseminated histoplasmosis and 58 patients with disseminated MAC infection. RESULTS: Positive predictors of histoplasma infection by univariate analysis included lactate dehydrogenase level, white blood cell (WBC) count, platelet count, alkaline phosphatase level, and CD4 cell count. By multivariate logistic regression analysis, those characteristics that remained significant included a lactate dehydrogenase value > or =500 U/L (risk ratio [RR], 42; 95% confidence interval [CI], 18.53-97.5; p < .001), alkaline phosphatase < or =300 U/L (RR, 9.35; 95% CI, 2.61-33.48; p = .008), WBC < or =4.5 x 10(6)/L (RR, 21.29; 95% CI, 6.79-66.75; p = .008), and CD4 cell count (RR, 0.958; 95% CI, 0.946-0.971; p = .001). CONCLUSIONS: A predictive model for distinguishing disseminated histoplasmosis from MAC infection was developed using lactate dehydrogenase and alkaline phosphatase levels as well as WBC count. This model had a sensitivity of 83%, a specificity of 91%, and a misclassification rate of 13%.     

Epstein-Barr virus-associated infectious mononucleosis and risk factor analysis for complications in hospitalized children.

The characteristics of Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM) in Chinese children are rarely reported. To evaluate the clinical presentations and risk factors for complications of EBV-associated IM in previously healthy children in Taiwan, hospitalized children with the diagnosis of IM due to EBV infection from January 1998 to December 2002 were enrolled. Patients had to fulfill the serologic criteria for the diagnosis of primary EBV infection [viral capsid antigen immunoglobulin M (IgM)-(+), viral capsid antigen IgG-(+), and anti-Epstein-Barr nuclear antigen (EBNA) antibody-(-) with exclusion of other concurrent infections or underlying diseases]. Ninety eight children were eligible, with 79% younger than 5 years old (mean, 4.0 +/- 2.3 years). The male-to-female ratio was 2:1. Nearly all patients suffered from fever (mean duration 10.3 +/- 6.0 days). Cough/rhinorrhea, tonsillopharyngitis, cervical lymphadenopathy and hepatosplenomegaly were found over half of the patients. Atypical lymphocytosis (mean, 12 +/- 13%) and elevated serum aspartate aminotransferase (AST; mean, 167 +/- 183 IU/L) and alanine aminotransferase (mean, 221 +/- 222 IU/L) were the most striking laboratory findings. Various complications, including hematologic, hepatobiliary, central nervous system, and obstructive airway problems occurred in about 20% of patients with significantly prolonged course of hospitalization. All patients recovered uneventfully under supportive and immunomodulating management. Female gender, no signs of tonsillopharyngitis, white blood cell count < or =10,000/mm3 and AST > or =150 IU/L were significant risk factors for the occurrence of complications. Clinicians should monitor such patients closely and give proper treatment to decrease possible morbidity or even mortality should complications occur.     

Pneumocystis carinii pneumonia recurrence in HIV patients on highly active antiretroviral therapy: secondary prophylaxis

The incidence and risk factors for Pneumocystis carinii pneumonia (PCP) recurrence were evaluated in 451 HIV-infected patients enrolled in the French Hospital Database on HIV who started highly active antiretroviral therapy (HAART) while receiving secondary PCP prophylaxis after a first episode occurring between January 1995 and December 1998. There were 18 episodes of recurrent PCP. On HAART, the CD4+ cell count increased to above 200 x 106/L in 274 patients, 51 of whom stopped PCP prophylaxis. None of these patients had PCP recurrences during 363 person-years (PY) of follow-up after the CD4+ cell count had reached 200 x 106/L (incidence rate [IR], 0.00 cases/100 PY; 95% confidence interval [CI], 0.00-0.82), and 37 PY of follow-up after the CD4+ cell count had reached 200 x 106/L and PCP prophylaxis had been discontinued (IR, 0.00 cases/100 PY; 95% CI, 0.00-7.84). The CD4+ cell count remained < 200 x 106/L in 177 patients; 9 patients stopped PCP prophylaxis, and 6 of these had a disease recurrence. Multivariate Cox analysis (time censored when CD4+ cell count > 200 x 106/L) showed that discontinuation of secondary prophylaxis (relative hazard [RH], 25.95; p <.0001) was associated with recurrence, whereas higher CD4+ cell counts during follow-up (RH, 0.39/50 x 106/L increment; p <.002) were protective.     

Ein Fall von AIDS-assoziierter Histoplasmose in Deutschland

Summary In a thirty-year-old patient with AIDS the diagnosis of disseminated histoplasmosis was established via biopsy and culture. The patient had grown up in Argentina, where histoplasmosis is endemic. He had not been in an endemic region during the last two years anteceding the manifestation of systemic histoplasmosis. Accordingly, in patients with a progressive immunodeficiency syndrome, reactivation of a former (possibly inapparent) infection withHistoplasma capsulatum must be considered. Therapy with Amphotericin B lead to a remarkable improvement of clinical, laboratory and sonographic findings. Due to the fact that total eradication ofH. capsulatum from the infected host cannot be achieved with any known drug regimen, a life-long follow-up therapy was begun. The patient showed no signs of relapse after a follow-up of 7 months.

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Abkürzungsverzeichnis HIV human immunodeficiency virus - AIDS acquired immunodeficiency syndrome - BSG Blutkörperchensenkungsgeschwindigkeit - n.W. nach Westergren - LDH Laktatdehydrogenase - ASAT Aspartat-Aminotransferase - ALAT Alanin-Aminotransferase - AP alkalische Phosphatase - -GT Glutamyl-Transpeptidase     

Production and evaluation of reagents for detection of Histoplasma capsulatum antigenuria by enzyme immunoassay

The detection of urinary Histoplasma capsulatum polysaccharide antigen (HPA) by enzyme immunoassay (EIA) has proven useful for the presumptive diagnosis of histoplasmosis in AIDS patients. Assay limitations include (i) detection of a largely uncharacterized antigen and (ii) difficulty in reproducibly generating antibodies for use in the EIA. To improve antibody production for use in this test and to better understand the antigen being detected, we compared rabbit antibodies elicited using various immunization schedules, routes, and H. capsulatum-derived antigens. Antibodies were evaluated by EIA for their ability to detect purified H. capsulatum C antigen (C-Ag) and antigenuria. Reported as enzyme immunoassay (EI) units (the A(450) with antigen divided by the A(450) without antigen), results demonstrated that intravenous immunization of rabbits with whole, killed yeast-phase cells (yeast-i.v. regimen) produced antibodies giving the highest EI values in the C-Ag EIA (mean EI units +/- standard deviation, 14.9 +/- 0.6 versus 6.4 +/- 0.4 for rabbits immunized with C-Ag versus 2.4 +/- 0.3 for all other regimens combined). Yeast-i.v. antibodies were highly sensitive for the detection of antigenuria in patients with histoplasmosis, as shown by the following results: 12/12 patients compared to 10/12, 6/12, 3/12, and 3/12, respectively, for antibodies from rabbits immunized with (i) C-Ag; (ii) whole, killed yeast-phase cells administered subcutaneously and intramuscularly; (iii) yeast-phase culture filtrates; and (iv) HPA-positive urine. Rabbits immunized using the yeast-i.v. regimen also gave higher peak antibody titers than rabbits immunized by any other regimen (P < 0.03), and their antibodies were most comparable in reactivity to antibodies produced for use in the standard HPA-EIA test (P < 0.001). Therefore, rabbits immunized using the yeast-i.v. regimen produced the most sensitive antibodies with the highest titers for detection of C-Ag and antigenuria in histoplasmosis patients.     

The effect of iodine restriction on thyroid function in patients with hypothyroidism due to Hashimoto's thyroiditis

Lifelong thyroid hormone replacement is indicated in patients with hypothyroidism as a result of Hashimoto's thyroiditis. However, previous reports have shown that excess iodine induces hypothyroidism in Hashimoto's thyroiditis. This study investigated the effects of iodine restriction on the thyroid function and the predictable factors for recovery in patients with hypothyroidism due to Hashimoto's thyroiditis. The subject group consisted of 45 patients who had initially been diagnosed with hypothyroidism due to Hashimoto's thyroiditis. The subjects were divided randomly into two groups. One group was an iodine intake restriction group (group 1) (iodine intake: less than 100 micro g/day) and the other group was an iodine intake non-restriction group (group 2). The thyroid-related hormones and the urinary excretion of iodine were measured at the baseline state and after 3 months. After 3 months, a recovery to the euthyroid state was found in 78.3 % of group 1 (18 out of 23 patients), which is higher than the 45.5% from group 2 (10 out of 22 patients). In group 1, mean serum fT4 level (0.80 +/- 0.27 ng/dL at the baseline, 0.98 +/- 0.21 ng/dL after 3 months) and the TSH level (37.95 +/- 81.76 micro IU/mL at the baseline, 25.66 +/- 70.79 micro IU/mL after 3 months) changed significantly during this period (p < 0.05). In group 2, the mean serum fT4 level decreased (0.98 +/- 0.17 ng/dL at baseline, 0.92 +/- 0.28 ng/dL after 3 months, p < 0.05). In the iodine restriction group, the urinary iodine excretion values were higher in the recovered patients than in non-recovered patients (3.51 +/- 1.62 mg/L vs. 1.21 +/- 0.39 mg/ L, p=0.006) and the initial serum TSH values were lower in the recovered patients than in the non-recovered patients (14.28 +/- 12.63 micro IU/mL vs. 123.14 +/- 156.51 micro IU/mL, p=0.005). In conclusion, 78.3% of patients with hypothyroidism due to Hashimoto's thyroiditis regained an euthyroid state iodine restriction alone. Both a low initial serum TSH and a high initial urinary iodine concentration can be predictable factors for a recovery from hypothyroidism due to Hashimoto's thyroiditis after restricting their iodine intake.     

Diagnostic accuracy of ascitic fluid IFN-gamma and adenosine deaminase assays in the diagnosis of tuberculous ascites.

In this study, we evaluated the diagnostic accuracy and cost-effectiveness of ascitic fluid interferon-gamma (IFN-gamma) and adenosine deaminase (ADA) assays in the diagnosis of tuberculous ascites. Ascitic fluid from patients with proven tuberculosis (TB) (n = 31) and non-TB ascites (n = 88) was analyzed for IFN-gamma and ADA levels. Areas under the receiver operative characteristic (ROC) curves (AUCs) for the two biologic markers were compared. Levels of ascitic fluid IFN-gamma, median (range): 560 (104-1600) pg/mL vs. 4.85 (0-320) pg/mL (p < 0.001), and ADA, median (range): 58 (16-331) IU/L vs. 10 (0-59) IU/L (p = 0.001), were significantly different between TB and non-TB groups. IFN-gamma and ADA assays showed equal sensitivity (0.97) and differed marginally in specificity (0.97 vs. 0.94). Difference in AUCs was not significant (0.99 vs. 0.98, p < 0.62). For differentiating TB from non-TB ascites, optimal cutoff points were 112 pg/mL for IFN-gamma and 37 IU/L for ADA. The accuracy of the ADA assay was similar to that of the IFN-gamma assay in differentiating of TB from non-TB ascites. Because both material and human costs of the ADA assay are far less than those of the IFN-gamma assay, the former is probably the most appropriate diagnostic test for analysis of peritoneal fluid in resource- limited settings.     

Atazanavir Plasma Concentrations Vary Significantly Between Patients and Correlate with Increased Serum Bilirubin Concentrations

Abstract

Background: Atazanavir (ATV) is recommended to be dosed at 400 mg once daily or 300 mg daily coadministered with 100 mg ritonavir (RTV). Method: 31 male patients receiving ATV either alone or boosted with RTV for more than 2 weeks had ATV concentration measured by high performance liquid chromatography (HPLC). ATV concentrations were adjusted to obtain a 24-hour trough level using a standard pharmacokinetic formula. Results: 25 samples were taken from patients who received 300 mg ATV, 6 with 200 mg, 3 with 400 mg, and 2 with 150 mg, all boosted with 100 mg RTV. In the unboosted group, patients received 400 mg (7) or 600 mg (2). The median adjusted 24-hour trough ATV concentration was 630 ng/mL (interquartile range [IQR] 355-1034) in the boosted and 113 ng/mL (IQR 50-225) in the unboosted group (p = .001). Median serum bilirubin concentration was 34 IU/L (IQR 27.5-49) and 41 IU/L (IQR 31-45) in the boosted and unboosted groups, respectively. In the boosted group, high ATV concentrations were significantly correlated with increased serum bilirubin concentrations (p = .003). Conclusion: ATV concentrations showed considerable interpatient variability. Bilirubin concentrations are an indicator of high ATV concentrations and may prove to be useful in selecting patients for therapeutic drug monitoring (TDM).     

Serum (1-3)-β-d-Glucan as a Tool for Diagnosis of Pneumocystis jirovecii Pneumonia in Patients with Human Immunodeficiency Virus Infection or Hematological Malignancy

(1-3)-β-d-Glucan (BG) reactivity was tested in serum samples from 28 patients with human immunodeficiency virus infection or a hematological malignancy and Pneumocystis jirovecii pneumonia (PCP) and 28 control patients. The sensitivity and specificity of BG detection with the Fungitell assay for PCP were 100 and 96.4%, respectively, using a cutoff value of 100 pg/ml. Serum BG testing looks promising for the noninvasive diagnosis of PCP. Our data suggest that a higher cutoff value for the diagnosis of PCP than for the diagnosis of invasive aspergillosis or candidiasis could be used safely and will improve the specificity of the test.Pneumocystis jirovecii pneumonia (PCP) remains a serious cause of morbidity and mortality in immunocompromised patients. PCP may be difficult to diagnose owing to nonspecific signs and symptoms and possible coinfection with microorganisms other than P. jirovecii. Moreover, Pneumocystis cannot be propagated in culture. Diagnosis relies on the visualization of the fungus upon microscopic examination of induced sputum samples, bronchoalveolar lavage (BAL) fluids, or biopsy specimens. The sensitivity of microscopy varies according to the staining technique (it is highest with monoclonal antibodies) and the sample type (10). PCR detection of Pneumocystis nucleic acids has been shown to have higher sensitivity for the diagnosis of PCP than conventional staining techniques (1). However, PCR may also give positive results for patients with P. jirovecii colonization, and the clinical management of the disease in patients with positive PCR results but negative microscopy findings remains challenging. Furthermore, the diagnosis of PCP generally relies on invasive diagnostic tests, such as bronchoscopy, which is not always feasible for patients with severe respiratory distress.The measurement of serum (1-3)-β-d-glucan (BG), a cell wall component of most pathogenic fungi, including P. jirovecii, may be a useful aid for establishing the diagnosis of PCP. There are a number of diagnostic kits commercially available for detecting BG. The Fungitell BG assay (Associates of Cape Cod, East Falmouth, MA) is approved by the U.S. Food and Drug Administration as an adjunct for the diagnosis of invasive fungal disease, and the assay kit also carries the European CE mark. Up to now, data about the performance characteristics of the Fungitell BG test for the diagnosis of PCP have been scarce (2, 5, 8, 9). Few patients were included in the studies reported, and generally no relevant control patients were included. It is not known whether the cutoff value proposed by the manufacturer (80 pg/ml) can be used for the diagnosis of PCP. Elevated BG levels in PCP patients have been detected, but since many factors were reported to cause false-positive results, data for control groups are needed before the test can be used in routine practice.We retrospectively measured BG concentrations in sera from PCP patients and controls in two major risk groups, namely, patients with advanced human immunodeficiency virus (HIV) infection and patients with a hematological malignancy, with the aim of determining the diagnostic potential of BG testing for both groups.