Effect of sputum induction on arterial oxygen saturation and spirometry in HIV-infected patients

We wanted to study the effect of sputum induction on forced expiratory volume in one second (FEV1) and on oxygen saturation in normal controls, asymptomatic human immunodeficiency virus (HIV)-seropositive individuals, and HIV-seropositive patients under investigation for suspected Pneumocystis carinii pneumonia (PCP). Over a five month period, sputum induction with ultrasonically nebulized 3% saline was performed on 110 HIV-seropositive patients with suspected PCP, 10 asymptomatic HIV-seropositive patients, and 15 normal controls. Oxygen saturation (peak, trough and change in oxygen saturation (delta O2)) was measured throughout the procedure using pulse oximetry, and these results compared with the chest radiograph and the final pulmonary diagnosis. In addition, the effect of sputum induction on FEV1 was measured in the 15 control subjects and 10 asymptomatic HIV-seropositive patients. Compared with bronchoalveolar lavage, sputum induction had a diagnostic sensitivity for PCP of 76%. Chest radiography was 79% sensitive, and had specificity of 83%. Patients with PCP had lower peak and trough oxygen saturation values compared with the non-PCP group (mean peak 95 vs 97%; mean trough 88 vs 91%), and greater falls in O2 saturation during the procedure (mean delta O2 7.6 vs 5.5%). One subject desaturated to 76%, requiring supplemental oxygen. Sputum induction caused significant but temporary falls in FEV1 both in control and HIV-seropositive groups (mean maximum fall in FEV1 10.4 vs 12.5%). We conclude that although sputum induction causes significant falls in oxygen saturation and FEV1, it remains sensitive and safe, and provides a useful alternative to bronchoscopy for the diagnosis of PCP.     

Use of dapsone in the prevention and treatment of Pneumocystis carinii pneumonia: a review

Dapsone, with or without trimethoprim or pyrimethamine, has strong anti-Pneumocystis carinii activity, as demonstrated by in vitro methods, animal studies, and clinical trials. The drug blocks folic acid synthesis of P. carinii by inhibition of dihydropteroate synthetase activity. Dapsone is efficiently absorbed (70%-80%) from the gastrointestinal tract, reaches peak serum concentration in 2-6 hours, and is adequately distributed to the fluid of the alveolar spaces. Synergistic effects against P. carinii are noted when trimethoprim is combined with dapsone. This combination is recommended for therapeutic use for P. carinii pneumonia (PCP) as an alternative for patients who cannot take trimethoprim-sulfamethoxazole (TMP-SMZ). Evidence from more than 40 studies of dapsone as prophylaxis for PCP in AIDS patients shows that dapsone, either alone or in combination with pyrimethamine, is as effective as aerosolized pentamidine or atovaquone but slightly less effective than TMP-SMZ. Adverse effects include rash, anemia, methemoglobinemia, agranulocytosis, and hepatic dysfunction. Desensitization can be accomplished with many cases. Dapsone is the most cost-effective prophylaxis currently available for PCP.     

Advances in the treatment and prophylaxis of Pneumocystis carinii pneumonia

Pneumocystis carinii pneumonia (PCP) is the most common illness associated with the acquired immunodeficiency syndrome (AIDS) in the United States and also occurs in immunocompromised persons not infected with the human immunodeficiency virus.. Several advances have taken place in the treatment and prophylaxis of PCP, with most clinical trials conducted in patients with AIDS. Treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMX). Desensitization regimens are available for those who have a fever or rash associated with the agent. Patients with severe PCP who cannot tolerate TMP-SMX may be treated successfully with pentamidine or trimetrexate. Those with mild to moderate disease may receive dapsone-trimethoprim, clindamycin-primaquine, or atovaquone if they cannot take TMP-SMX. Adjunctive therapy with corticosteroids improves the outcome in patients with AIDS and severe PCP.     

Pneumocystis carinii meningoradiculitis in a patient with AIDS

Pneumocystis carinii is a common opportunistic pathogen in patients infected with the human immunodeficiency virus (HIV). Pneumocystis carinii pneumonia is common, while extrapulmonary infections with Pneumocystis carinii have been reported sparingly. The clinical features are frequently nonspecific. The detection of Pneumocystis carinii in cerebrospinal fluid (CSF) has not been reported thus far. In this report, an unusual case of Pneumocystis carinii meningoradiculitis in an HIV-infected patient who had previously received primary prophylaxis with trimethoprim-sulfamethoxazole is presented.     

Analysis of life-long strategies to prevent Pneumocystis carinii pneumonia in patients with variable HIV progression rates

OBJECTIVE: To compare strategies for life-long prophylaxis of Pneumocystis carinii pneumonia (PCP) in a group of AIDS patients with a wide range of disease progression rates. DESIGN: Markov decision models. METHODS: Prophylaxis strategies using high and low doses of trimethoprim-sulfamethoxazole (TS), dapsone, and/or aerosolized pentamidine in sequence, were compared. Efficacy and toxicity rates for prophylaxis regimens were taken from a meta-analysis of pertinent randomized controlled trials. Outcomes measured included lifetime episodes of PCP and drug toxicity per 100 patients treated, average life expectancy, and cost. RESULTS: For patients with an expected survival of 3 years after commencement of prophylaxis, the use of standard or low dose TS as the first choice agent was comparable, and both were superior to the other strategies for preventing PCP (between nine and 26 fewer episodes of PCP per 100 patients treated) though they were more toxic (11-44 more episodes of toxicity per 100 patients treated). Life expectancy was similar for all of the treatment strategies. With slower rates of disease progression (expected survival > 3.8 years), as seen with current antiretroviral regimens, the use of low dose TS as the first choice agent dominated the use of standard dose TS; when the expected survival time was 7 years, initial use of low dose TS led to 2.8 fewer episodes of PCP per 100 patients treated, 32 fewer episodes of toxicity per 100 patients treated, and US$1381 per patient lower cost, compared with prophylaxis with standard dose TS. CONCLUSION: For patients with AIDS and expected survival > 3.8 years, low dose TS is better than standard dose TS as the first choice agent for preventing PCP. As patients with AIDS live longer, the routine use of low dose TS will be more than adequate for patients at risk for PCP.     

Discontinuation of prophylaxis for Pneumocystis carinii pneumonia in HIV-1-infected patients treated with highly active antiretroviral therapy

BACKGROUND: Prophylactic drugs for Pneumocystis carinii pneumonia (PCP) are strongly recommended for HIV-1-infected patients with CD4 cell counts of less than 200 cells/microL. Because of the highly active antiretroviral therapy (HAART) currently available, we speculated that prophylaxis can be discontinued in patients with CD4 cell counts of more than 200 cells/microL. METHODS: In this prospective observational study, PCP prophylaxis (primary or secondary) was discontinued in HIV-1-infected patients whose CD4 cell count had increased above 200 cells/microL (documented twice with an interval of at least 1 month) as a result of HAART. Patients and their CD4 cell counts were monitored every 3 months. The primary endpoint of the study was the occurrence or reoccurrence of PCP. FINDINGS: 78 patients were enrolled: 62 patients were receiving prophylaxis for primary prevention of PCP and 16 patients for secondary prevention of PCP. At the time of discontinuation of prophylaxis, the mean CD4 cell count was 347 cells/microL, and HIV-1-RNA was not detectable in 61 patients. The lowest mean CD4 cell count during prophylaxis was 79 cells/microL. Patients stopped prophylaxis 9.8 (SD 6.4) months after they started HAART. The mean follow-up after discontinuation of prophylaxis was 12.7 (SD 7.6) months, and none of the patients developed PCP (97.5% one-sided CI 0-4.4%). INTERPRETATION: The preliminary results of this study indicate that PCP prophylaxis can be stopped safely in HIV-1-infected patients whose CD4 cell counts have increased above 200 cells/microL after treatment with HAART.     

Clindamycin/primaquine as prophylaxis for Pneumocystis carinii pneumonia

The records of 206 patients with advanced infection due to human immunodeficiency virus type 1 who were receiving prophylaxis with clindamycin/primaquine (C/P), trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone to prevent Pneumocystis carinii pneumonia (PCP) were retrospectively examined. Two hundred sixty-two patient-years of prophylaxis were accrued (176.2 of TMP-SMZ, 63.4 of dapsone, and 22.8 of C/P). The rates of PCP in the TMP-SMZ, dapsone, and C/P groups were 3.4, 11.0, and 30.7 per 100 patient-years, respectively. Pairwise comparisons showed C/P to be less effective than TMP-SMZ (relative risk [RR], 9.02; 95% confidence interval [CI], 3.03-26.83). A similar trend was apparent for C/P vs. dapsone (RR, 2.78; 95% CI, 0.98-7.93). When only those receiving primary prophylaxis were analyzed, C/P recipients remained at greater risk than TMP-SMZ recipients (RR, 13.19; 95% CI, 3.54-49.12) and dapsone recipients (RR, 3.85; 95% CI, 1.12-13.31). Failure of C/P prophylaxis could be due, at least in part, to underdosing (clindamycin, 300 mg/d; primaquine, 15 mg/d). C/P recipients had more nonspecific diarrhea than did TMP-SMZ recipients (RR, 2.99; 95% CI, 1.61-5.55).     

Successful desensitization to dapsone for Pneumocystis carinii prophylaxis in an HIV-positive patient

OBJECTIVE: To report a case of successful desensitization to dapsone for Pneumocystis carinii pneumonia (PCP) prophylaxis in a patient unable to tolerate trimethoprim/sulfamethoxazole (TMP/SMX) desensitization or dapsone at standard doses. CASE SUMMARY: A 37-year-old HIV-positive African-American man was treated for pneumonia with TMP/SMX and then continued on the drug for PCP prophylaxis. After experiencing a pruritic maculopapular rash with TMP/SMX, both at standard doses and after attempting a desensitization regimen to the drug, he was started on dapsone for PCP prophylaxis. He experienced a rash and fever after taking dapsone at standard PCP prophylactic doses. At this time, an 18-day oral dapsone rechallenge by dose escalation was attempted, and it was well tolerated. CONCLUSIONS: This case suggests that utilization of a dapsone desensitization regimen may permit a viable treatment option in patients previously thought to be intolerant to the agent. More regimens of this type should be attempted and the results published, using both dapsone and TMP/SMX, so that standard desensitization treatment guidelines may eventually be adopted.     

Pneumocystis carinii pneumonia in HIV-negative immunocompromised adults

OBJECTIVES: To identify patient populations at risk of Pneumocystis carinii pneumonia (PCP) and assess the potential role of chemoprophylaxis. METHODS: Review of cases of PCP among patients admitted to a tertiary referral hospital in Sydney between January 1990 and April 1993. Cases were identified by indirect immunofluorescent antibody microscopy performed on respiratory tract specimens. RESULTS: Ninety-two episodes of PCP were diagnosed in 64 HIV-positive patients and 28 others. All HIV-negative patients had received corticosteroids combined with other immunosuppressive agents before the onset of PCP symptoms, which occurred within six months of immunosuppression. The group included nine of 150 kidney transplant recipients (6%) six of 138 liver transplant recipients (4.3%) and three of 25 patients with Wegener's granulomatosis (12%). Mortality associated with PCP in HIV-negative patients was significantly higher than in those who were HIV-positive (32% v. 8%, P < 0.005). CONCLUSION: Solid organ transplant recipients and individuals receiving treatment for Wegener's granulomatosis have a significant risk of developing PCP. Given the high mortality associated with this disease in HIV-negative patients, primary PCP chemoprophylaxis should be considered during the first six months of immunosuppression.     

Pneumocystis carinii alters surfactant protein A concentrations in bronchoalveolar lavage fluid

To understand better the interaction between surfactant protein A (SP-A), human immunodeficiency virus (HIV) and Pneumocystis carinii pneumonia (PCP), we measured SP-A from bronchoalveolar lavage (BAL) fluid in immunosuppressed patients (HIV-positive [HIV+] and HIV noninfected [HIV-]) who were examined for possible pneumonia. Forty-five HIV+ patients, 16 with PCP and no other pathogen (HIV+/Pc) and 29 with no evidence of pulmonary pathogen (HIV+ controls), were compared with 6 HIV- patients with PCP (HIV-/Pc) and 11 control patients with no underlying disease (controls). Despite a similar inflammatory response in the HIV-infected patients whether they had PCP or not, we found increased BAL SP-A concentrations in HIV+/Pc patients as compared with HIV+ control patients (HIV+/Pc: median, 10.3 micrograms/ml; range, 2.8 to 24.3 micrograms/ml; HIV+ control: median, 1.9; range, 0.06 to 3.83 micrograms/ml; p < 0.05). The amount of SP-A in the HIV+ control group was significantly lower than healthy, uninfected volunteers, suggesting that HIV itself may lower SP-A levels. Six HIV+/Pc patients underwent BAL after 21 days of therapy and showed complete resolution of the P. carinii organism. There was a significant drop in the amount of SP-A at follow-up lavage (initial mean, 14.1 micrograms/ml; follow-up mean, 7.4 micrograms/ml; p < 0.02). We also found a significant correlation between the amount of P. carinii and the amount of SP-A in the BAL fluid (Spearman rank, 0.74; p < 0.01). We conclude that SP-A content is increased in HIV+ patients with PCP. The relationship between SP-A concentration and the abundance of P. carinii present in the BAL fluid may be related to SP-A binding to P. carinii or to alterations in surfactant protein homeostasis.     

Sex differences in disease course: analysis of the Swiss HIV cohort study

The Swiss HIV Cohort Study (SHCS) is a prospective multicentre study of HIV-infected adults. Participants have been followed up at six-monthly intervals since 1988. The purpose of the present study was to examine sex differences in developing AIDS-defining events and in survival among participants of the SHCS (1042 women, 1507 men). A statistically significant higher risk of Pneumocystis carinii pneumonia (PCP) was evident among women. This difference was particularly pronounced in 1989 (hazard ratio 2.11, p = 0.01). Other opportunistic events and survival showed no statistically significant sex differences. The results are compatible with slower introduction of PCP prophylaxis among women. A reason for this may be that women were less likely to be enrolled in clinical trials than men. This hypothesis will be examined in a further study.     

Clinical study on mechanism of Pneumocystis carinii pneumonia by polymerase chain reaction

Pneumocystis carinii is a human respiratory pathogen which causes fatal pneumonia in patients under immunosuppressed or immune deficient conditions. Recent work have documented the usefulness of the polymerase chain reaction (PCR) method in the detection of P. carinii from clinical samples. Therefore, we described our experience in using PCR method in the detection of P. carinii from respiratory samples. In our study, bronchial washing or BALF were good for diagnosis of P. carinii pneumonia (PCP) by PCR. However, PCR method in the detection of P. carinii from swab or sputum was too sensitive because small numbers of P. carinii organisms might be insignificant in causing the disease. It might reveal colonization or asymptomatic carrier state in the upper respiratory tract. Therefore, our result suggested that colonization or asymptomatic carrier state in the upper respiratory tract could eventually evolve into PCP. This would also facilitate basic progress in the pathology or epidemiology of P. carinii infection. In addition, an usefulness of prophylactic therapy for PCP was documented by PCR.     

Fulminant Pneumocystis carinii pneumonia in 4 patients with dermatomyositis

Between 1989 and 1996, 4 cases of Pneumocystis carinii pneumonia (PCP) were observed in patients seronegative for the human immunodeficiency virus who were receiving corticosteroid therapy for dermatomyositis in our institution. These cases were considered unusual in light of the short delay of their onset after initiation of immunosuppressive therapy and their fulminant course: 3 of these patients died of PCP occurring during the first month of treatment with prednisone. In all 4 patients lymphopenia was observed before the initiation of corticosteroid treatment and low CD4 and CD8 cell counts were evident at the time of PCP. These observations support the view of an increase in both the severity and incidence of PCP in patients without human immunodeficiency virus infection and question the need for a primary prophylaxis in patients with connective tissue diseases receiving high-dose corticosteroid therapy.     

Identification of Pneumocystis carinii f. sp. hominis gene sequences in filtered air in hospital environments

To evaluate the risk of a nosocomial spread of Pneumocystis carinii f. sp. hominis (P. carinii hominis), air filter samples from rooms of P. carinii pneumonia (PCP) patients, adjacent corridors, and other hospital environments have been investigated for the presence of P. carinii hominis. Amplified DNA from air filters and sputum or bronchoalveolar lavage samples from the PCP patients have been genotyped with the P. carinii hominis genes of the mitochondrial large-subunit (mtLSU) rRNA and the internal transcribed spacers (ITS1 and ITS2) of the rRNA. Genotypes of the two loci were identified by direct sequencing, and for site 85 of the mtLSU locus, three allele-specific PCR assays were used. P. carinii hominis DNA was identified in the air of five of seven PCP patient rooms and in the air of two of four air filtrations from the ward corridors. The P. carinii hominis genotypes were the same in four of the five room air samples as those in the corresponding patients, suggesting a risk of person-to-person transmission of P. carinii hominis from PCP patients. Three of 16 air samples collected in infectious disease wards without the presence of PCP patients and one sample from a cardiology unit in a separate hospital building were also positive, which further strengthens the possibility of acquisition of P. carinii hominis from the environment.     

Community-acquired bacteremia in HIV-positive patients: protective benefit of co-trimoxazole

OBJECTIVE: To evaluate the effect of the type of Pneumocystis carinii pneumonia (PCP) prophylaxis on the development of community-acquired bacteremia. DESIGN: Case-control study using all cases of community-acquired bacteremia identified prospectively during a longitudinal study of all infections in a cohort of HIV-infected persons. SETTING: University-affiliated Department of Veterans Affairs Medical Center HIV program. PATIENTS: All patients with community-acquired bacteremia seen at the facility between January 1990 and December 1995 were included. Controls, seen at the same facility and matched by date and CD4 count, were used to assess risk factors. A total of 57 cases and 114 controls were analysed. MAIN OUTCOME MEASURES: Risk of development of bacteremia, distribution of organisms, and effect of specific prophylactic regimens for PCP. RESULTS: Bacteremia was caused by Staphylococcus aureus (23%), Pseudomonas aeruginosa (18%), Escherichia coli (16%), Streptococcus pneumoniae (14%) and others (31%). Groups were similar by age, race, HIV risk factors and CD4 count. The presence of an intravenous catheter was mildly predictive of the development of bacteremia [odds ratio (OR), 2.67; P = 0.024]. Type of PCP prophylaxis in cases and controls with CD4 < 200 x 10(6)/l included co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX; 31 and 60%, respectively), dapsone (33 and 24%, respectively) and aerosolized pentamidine (27 and 13%, respectively). Use of TMP-SMX (but not dapsone or aerosolized pentamidine) was associated with the absence of bacteremia (OR, 0.28; P = 0.001). A similar protective effect was found when controlling for the presence of an intravenous catheter. CONCLUSION: PCP prophylaxis with TMP-SMX apparently protects against community-acquired bacteremia in HIV-infected persons.     

Serial pulmonary function tests in the diagnosis of P. carinii pneumonia

The predictive value of serial versus isolated measurements of transfer factor for carbon monoxide (TLCO) in the diagnosis of pneumocystis carinii pneumonia (PCP) in a cohort of 474 HIV-1 seropositive patients, with all stages of HIV disease, was evaluated. Two groups of patients were studied, one group with serial lung function measurements (Group 1) and another with only a single set of measurements (Group 2). During the study period 118 patients performing serial tests developed a respiratory illness of which 58 were performing monthly and 60 three monthly measurements of lung function (Group 1). In 36 patients from Group 1, where PCP was diagnosed, monthly lung function tests showed a decrease in TLCO from 68% (+/- 3.2) (SEM), (8 weeks prior to illness), to 44% (+/- 2.5) predicted normal at presentation, whereas in 22 patients who did not have PCP, TLCO fell from 71% (+/- 4.5) to 57% (+/- 3.1). TLCO was thus reduced to lower values in these with PCP than in those without PCP (p < 0.05). A fall of TLCO of 5% from initial values when used as predictive for presence of PCP had a sensitivity of 75% and a specificty of 28% (positive predictive value 56%; negative predictive value 48%). TLCO was < 70% predicted in 72/78 patients with PCP who performed only single lung function tests (Group 2), which gave a sensitivity of 92% and a specificity of 71% as a diagnostic test for PCP when compared with the cohort as a whole. The positive predictive value was 34%, negative predictive value was 98%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis of pneumocystis carinii pneumonia in AIDS patients

BACKGROUND: Based on the changing disease pattern of human immunodeficiency virus (HIV) associated pulmonary complications we conducted a prospective study in order to compare the value of laboratory tests in patients with Pneumocystis (P.) carinii pneumonia (PCP) and other pulmonary complications and of different identification methods of P. carinii in bronchoalveolar lavage fluid (BALF) in PCP patients. PATIENTS AND METHODS: In 217 HIV-1-infected patients we evaluated the following parameters: platelets, serum lactat dehydrogenase (LDH), total serum protein (TP), hemoglobin (Hb), and CD4+ and CD8+ T-lymphocyte count. P. carinii was identified in BALF by May Grünwald Giemsa stain (MGG), direct immunofluorescence test (DIFT), and polymerase chain reaction (PCR). We correlated these parameters in patients with a presumptive diagnosis of PCP and compared them with those of patients suffering from other pulmonary complications. RESULTS: All patients underwent bronchoscopy. 55 patients (25.3%) had a presumptive diagnosis of PCP. The sensitivity values of MGG stain, DIFT, and PCR differed considerably (79.1%, 56.1%, and 65.9%, respectively), but specificity values did not (99.2%, 97.3%, and 98.2%, respectively) as well as accuracy values (93.8%, 86.2%, and 89.7%, respectively). The mean values of platelets, of LDH, and of total serum protein of PCP patients and those of patients with other pulmonary diseases differed statistically significant as well as the mean values of these parameters of PCP patients and those of patients with bacterial pneumonia. Logistic-regression analysis revealed the number of platelets and the amount of total serum protein as independent, significant prognostic factors. Moreover, each PCP patient had a CD4+ T-lymphocyte count of less than 200 cells/mm3 blood. The CD4/CD8 ratio of PCP patients was statistically significant lower than that of patients with bacterial pneumonia. CONCLUSIONS: A detection of P. carinii in BALF is inevitable for a definitive diagnosis of a PCP. The most efficient identification method in this case is the MGG stain. Platelets, total serum protein, and CD4+ T-lymphocyte count should be included into the criteria for the presumptive diagnosis of PCP.     

Serial prognostic capabilities of electrocardiographic indices of infarcted and hibernating myocardium in predicting short- and long-term outcome following coronary artery bypass surgery

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.     

Toxoplasma gondii infection in marrow transplant recipients: a 20 year experience

Twelve of 3803 consecutive marrow allograft patients treated at this center over the past 20 years have had a post-transplant tissue diagnosis of toxoplasmosis: 10 at autopsy and 2 by brain biopsy. This infection was identified in none of 509 autologous marrow recipients. Occurrence of toxoplasmosis was 0.31 cases per 100 allogeneic transplants and 1.0 per 100 autopsies. An estimated 15% of allogeneic transplant recipients were seropositive for Toxoplasma gondii and 2% of seropositive patients developed toxoplasmosis. Pre-transplant serology was positive by both dye and agglutination tests in 11 infected patients tested. Sequential IgG, IgM, IgA, IgE antibody titers to T. gondii and the differential agglutination ratio were not helpful in diagnosing toxoplasmosis. Median day of clinical presentation was day 59 post-transplant (35-97 days) and of diagnosis, day 62 after transplant (37-143 days). Eleven patients had graft-versus-host disease (GVHD) of grades II-IV. All 12 patients died. Infection was diagnosed prior to death in only 16% of patients and contributed to death in at least 40%. Histopathology revealed tachyzoites of T. gondii most prevalent in brain (100%), heart (67%) and lungs (33%), and toxoplasma cysts alone in heart (33%) and lungs (22%). Toxoplasma infection was diagnosed in two patients receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis suggesting this was insufficient prophylaxis for toxoplasmosis. Toxoplasmosis appeared to occur by reactivation within the first 6 months after marrow transplant. Infection developed in patients who were seropositive for T. gondii pre-transplant, had received allogeneic marrow and had severe GVHD.     

Shear bond strength of amalgam adhesives to dentin

Recent studies have suggested that failure of pentamidine prophylaxis against Pneumocystis carinii pneumonia (PCP) may be due to reduced deposition of pentamidine in the upper lobes. In this study, we performed bronchoalveolar lavage from the apical segment of the upper lobe and the middle lobe in 51 HIV-positive patients, all of whom were receiving prophylaxis with aerosolized pentamidine, who had presented with acute respiratory symptoms. Lavage fluid from each lobe was assayed for pentamidine using high-performance liquid chromatography (HPLC). The number of clusters of P carinii were counted after staining with a Wright-Giemsa stain. The patients were subclassified as PCP-positive (32 patients) and PCP-negative (19 patients) on the basis of the presence/absence of P carinii clusters in their BAL fluid. The concentration of pentamidine in the upper lobe compared with the middle lobe was no different (using paired Student's t tests) for either PCP-positive patients or PCP-negative patients. In comparing the positive with the negative subjects, using unpaired Student's t test, there was no difference in the concentration of pentamidine in the upper lobe or the middle lobe. For PCP-positive patients, the numbers of P carinii clusters were on average higher in the upper lobes (mean +/- SD: upper = 14.9 +/- 16.6, middle 7.5 +/- 10.8, p = 0.013, paired Student's t test), but there was no correlation between lobar P carinii cluster counts and pentamidine levels. We conclude that the absence of a relationship between cluster count and pentamidine level, the similarity in regional pentamidine levels between upper and middle lobes, as well as the similarity in pentamidine levels between the PCP-positive and PCP-negative groups indicate that the regional dose of pentamidine is not the determining factor as to whether aerosolized pentamidine prophylaxis will succeed or fail.