Diagnosis of kidney transplant obstruction using Mag3 diuretic renography.

Kidney transplant obstruction (KTO) following renal transplantation remains an important reversible cause of allograft dysfunction, requiring prompt diagnosis to prevent long-term graft damage. Although ultrasound can accurately diagnose renal transplant hydronephrosis, it cannot be used to assess its functional significance. We prospectively assessed the utility of technetium-99m mercaptoacetyltriglycine (Tc99m MAG3) diuretic renography for the diagnosis of allograft KTO, using standard visual and quantitative parameters, as well as calculated renal output efficiency (OE), which has been postulated to improve diagnostic yield. From a cohort of 45 renal transplant patients, two subgroups were formed. The first group of transplant recipients (n = 21) with stable function and no obstruction was used to derive normal values for Tc99m MAG3 scans. A second group of transplant recipients with acute renal dysfunction in whom KTO was clinically suspected was used to test the diagnostic utility of these derived values (n = 43 scans). KTO was diagnosed independently of the MAG3 scans by a fall in the serum creatinine in response to renal pelvis urinary drainage. OE in 12 renal allografts with KTO was significantly reduced compared with 31 Tc99m MAG3 scans without KTO (59.6 +/- 18.9 vs. 81.6 +/- 5.4%, p < 0.001). In KTO, the mean time of isotope appearance in the bladder (time to bladder [TTB]) was extended compared with unobstructed allografts (7.9 +/- 4.1 vs. 3.6 +/- 1.5 min, p < 0.001). Measurement of OE significantly improved the accuracy of diuretic MAG3 renography in the diagnosis of renal allograft KTO, especially when supplemented by the TTB, parenchymal transit time and shape of the renogram curve. Ureteric obstruction of the kidney transplant can be diagnosed with an OE reduced to < 75% (sensitivity 92%, specificity 87%) and confirmed by isotope hold-up in the pelvicalyceal system. A normal or slowly declining renogram curve effectively excluded KTO (sensitivity of 96%, negative predictive value of 84%). A parenchymal transit time of > 5 min and a TTB of > 7 min both yielded a sensitvity of 92% and a specificity of 81%. In conclusion, MAG3 renography is a clinically useful investigation for the diagnosis of KTO.

Early mycological treatment failure in AIDS-associated cryptococcal meningitis.

Cryptococcal meningitis causes significant morbidity and mortality in persons with AIDS. Of 236 AIDS patients treated with amphotericin B plus flucytosine, 29 (12%) died within 2 weeks and 62 (26%) died before 10 weeks. Just 129 (55%) of 236 patients were alive with negative cerebrospinal fluid (CSF) cultures at 10 weeks. Multivariate analyses identified that titer of cryptococcal antigen in CSF, serum albumin level, and CD4 cell count, together with dose of amphotericin B, had the strongest joint association with failure to achieve negative CSF cultures by day 14. Among patients with similar CSF cryptococcal antigen titers, CD4 cell counts, and serum albumin levels, the odds of failure at week 10 for those without negative CSF cultures by day 14 was five times that for those with negative CSF cultures by day 14 (odds ratio, 5.0; 95% confidence interval, 2.2-10.9). Prognosis is dismal for patients with AIDS-related cryptococcal meningitis. Multivariate analyses identified three components that, along with initial treatment, have the strongest joint association with early outcome. Clearly, more effective initial therapy and patient management strategies that address immune function and nutritional status are needed to improve outcomes of this disease.

The effect of curdlan sulphate on development in vitro of Plasmodium falciparum.

Sulphated glycoconjugates have been reported to inhibit malarial merozoite invasion and interfere with rosetting and adhesion. Curdlan sulphate, a sulphated glycoconjugate with a favourable toxicity profile, exhibits antimalarial activity in vitro. The aim of this study was to characterize the antimalarial activity of curdlan and investigate its effect on adhesion. The antimalarial activity of curdlan at different points in the intraerythrocytic developmental cycle was investigated using morphological observation and radiolabelled hypoxanthine uptake as indices of parasite growth. Effects on adhesion were investigated using a platelet model. Curdlan suphate had no effect on the ability of the parasite to develop through the intraerythrocytic cycle. Inhibition of invasion was dependent on the drug being present at the time of invasion. Curdlan did not interfere with the ability of the parasite to adhere to the C36 receptor in the platelet model. In conclusion, the low toxicity of curdlan and its marked anti-invasion activity on merozoites make curdlan a potential auxiliary treatment for severe malaria.

Citalopram enhances the activity of chloroquine in resistant plasmodium in vitro and in vivo.

Citalopram, is an extremely potent inhibitor of neuronal serotonin reuptake. It is structurally unrelated to other antidepressants, but it contains the chemical features associated with reversal of drug resistance and exhibits minimal cardiotoxic side effects and fewer of the anticholinergic and adrenolytic side effects associated with other psychotropic agents. Sensitivity tests to citalopram alone and in combination with chloroquine were performed against chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum and Plasmodium chabaudi. Citalopram alone showed intrinsic activity against the chloroquine-resistant strains of P. falciparum (IC50 = 1.51 +/- .6 microM) but only limited activity against the chloroquine-sensitive strain (IC50 = 33.27 +/- 5.87 microM) and no activity in vivo. The interaction of chloroquine and citalopram in vitro resulted in a synergistic response in the chloroquine-resistant strain but there was no interaction between the drugs in the chloroquine-sensitive strain--a pattern found with other reversal agents. Citalopram enhanced chloroquine susceptibility in both strains of P. chabaudi, however, the potentiating effect was seen at lower doses in the chloroquine-resistant strain. The results of this study suggest that citalopram may have potential as a chemosensitizer in Plasmodium infections on the basis of the low toxicity of citalopram at concentrations potentiating chloroquine activity both in vitro and in vivo.

Effect of pH on in vitro potency of amantadine against Plasmodium falciparum.

Amantadine is a monoprotic weak base that inhibits intraerythrocytic growth in in vitro cultures of Plasmodium falciparum, specifically chloroquine-resistant strains. Changes in the external PH of the medium are expected to result in a shift in the relative proportion of ionized and unionized species of amantadine by virtue of the weak base characteristic of the drug, influencing passage of the drug through the membrane. The ability of amantadine to alkalinize the food vacuole was determined using the accumulation of acridine orange as a vacuolar probe. Drug sensitivity following alteration of the pH gradient was assessed using the hypoxanthine method. Amantadine was able to alkalinize the food vacuole in the millimolar range; however, since its antimalarial activity is in the micromolar range, alkalinization of the food vacuole is not the primary action of the drug. The pH of the medium profoundly influenced susceptibility to chloroquine; the log of the 50% inhibitory concentration (IC50) values were linearly dependent on the external pH in both chloroquine-resistant and chloroquine-sensitive strains. Log IC50 values of amantadine exhibited a linear dependence on external pH in the chloroquine-sensitive strain, but in the chloroquine-resistant strain, a nonlinear parabolic function was found with the minimum IC50 at pH 7.03. Ammonium chloride did not interfere with the antimalarial activity of amantadine. The presence of the amine group on the hydrocarbon cage is essential for the activity of amantadine in Plasmodium falciparum. These results suggest factors in addition to pH gradient are involved in the effect of amantadine, possibly interactions with membrane phospholipids.

In vitro drug interaction between amantadine and classical antimalarial drugs in Plasmodium falciparum infections.

The interactions of amantadine with classical antimalarial drugs were evaluated against a chloriquine-resistant and a chloroquine-sensitive strain of Plasmodium falciparum in vitro. Amantadine potentiated the effect of chloroquine and quinine in both strains; it also potentiated the effect of mefloquine, halofantrine and primaquine in the chloroquine-resistant strain but had no effect in the chloroquine-sensitive strain. Amantadine had no effect on the response to pyrimethamine of either strain. Amantadine does not interfere with the activity of these compounds and may possibly enhance it.

Plasmodium falciparum: effects of amantadine, an antiviral, on chloroquine-resistant and -sensitive parasites in vitro and its influence on chloroquine activity.

The lysosomotropic nature of amantadine suggested potential as an antimalarial. Sensitivity tests to amantadine hydrochloride alone and in combination with chloroquine were carried out in 96-well microtitre plates using the tritiated hypoxanthine uptake method to measure parasite growth. Amantadine alone has antimalarial activity. Amantadine is more potent against chloroquine-resistant strains. Combinations of amantadine and chloroquine result in slight synergy in both resistant and sensitive strains.

Pseudallescheria boydii infection in the acquired immunodeficiency syndrome.

Pulmonary and renal infection developed in a 44-year-old Hispanic man due to the fungus Pseudallescheria boydii. Pseudallescheria boydii has been associated with cutaneous infection known as mycetoma but occurs very infrequently in extracutaneous sites. To our knowledge, this is the second reported case of P boydii in a patient with the acquired immunodeficiency syndrome and the first case with pulmonary and/or renal involvement.

Determination of minimum weaning scrotal circumference in Santa Gertrudis bulls fed a low energy ration.

The scrotal circumference (SC) of 374 Santa Gertrudis bulls was measured prior to and following a period of low energy feed intake. A step by step regression was performed to formulate prediction equations in which the future SC of young bulls could be determined. These equations accounted for only 30 to 50% of the variation. Analysis of variance was used to determine the minimum SC at 7, 8 and 10 mo of age needed to obtain a 30-cm SC by 1 yr of age. At 7 mo, the bulls with the largest final SC, were those with an SC larger than 18 cm (P < 0.01). As the 8-mo SC increased so did the 13-mo SC (P < 0.01). As the 10-mo SC increased, the 15-mo SC also increased but bulls with less than a 21-cm SC were smaller (P < 0.01). Differences were also found between the 7 and 8-mo old weights of bulls and the initial SC (P < 0.01). As the initial testicle size increased, the 7, 8 and 10-mo ages and the 10-mo weight tended to increase. Few differences were found in initial SC measurements between the bulls that reached a 30-cm SC and those that did not at the end of one year regarding weight and age within each SC. These findings indicate that the SC at the beginning of a low energy feed period can be useful in determining the minimum SC outcome by the end of the test period.

Genitourinary coccidioidomycosis.

Symptomatic involvement of the genitourinary tract as a manifestation of disseminated Coccidioides immitis infection is uncommon. We report a case of a colovesical fistula secondary to Coccidioides immitis infection and review the pertinent medical literature.