Cyclophosphamide in the treatment of focal segmental glomerulosclerosis

Prednisone is the initial treatment of primary focal segmental glomerulosclerosis. However, when immunosuppressive agents in combination with steroids are used in the treatment of prednisone-dependent and prednisone-resistant patients the remission rate is variable. We report a long-term trial using cyclophosphamide (2.0 to 3.0 mg/kg body weight for 12 weeks) in combination with prednisone (1.0 to 2.0 mg/kg body weight), as compared with prednisone alone for the treatment of prednisone-resistant and frequently relapsing nephrotic syndrome and focal segmental glomerulosclerosis. Fifty-four patients (34 males and 20 females) with a diagnosis of idiopathic nephrotic syndrome and focal segmental glomerulosclerosis, followed-up for an average of 86.1 ± 82.4 months, were evaluated. Complete remission occurred in 20.4 percent and partial remission in 14.8 percent of the patients treated with steroids and in 26.7 and 20.0 percent of the patients treated with cyclophosphamide + prednisone, respectively. Of the 24 prednisone-resistant patients treated with steroids in combination with cyclophosphamide, 33.3 percent obtained a complete/partial response. At the time of final evaluation, 25 percent of the patients treated with prednisone and 10.0 percent of those treated with prednisone in combination with cyclophosphamide had reached end-stage renal disease. Persistent nephrotic syndrome and progressive renal insufficiency were more frequently observed among the patients treated with prednisone alone (50.0 vs 33.3 percent and 33.3 vs 16.7 percent, respectively). The treatments were well tolerated and no patient experienced adverse reactions requiring discontinuation of medications. Although open-label and non-randomized, the present trial showed that cyclophosphamide is a reasonable choice for the treatment of primary focal segmental glomerulosclerosis and prednisone-resistant nephrotic syndrome.

Cyclophosphamide in the treatment of focal segmental glomerulosclerosis.

Prednisone is the initial treatment of primary focal segmental glomerulosclerosis. However, when immunosuppressive agents in combination with steroids are used in the treatment of prednisone-dependent and prednisone-resistant patients the remission rate is variable. We report a long-term trial using cyclophosphamide (2.0 to 3.0 mg/kg body weight for 12 weeks) in combination with prednisone (1.0 to 2.0 mg/kg body weight), as compared with prednisone alone for the treatment of prednisone-resistant and frequently relapsing nephrotic syndrome and focal segmental glomerulosclerosis. Fifty-four patients (34 males and 20 females) with a diagnosis of idiopathic nephrotic syndrome and focal segmental glomerulosclerosis, followed-up for an average of 86.1 +/- 82.4 months, were evaluated. Complete remission occurred in 20.4% and partial remission in 14.8% of the patients treated with steroids and in 26.7 and 20.0% of the patients treated with cyclophosphamide + prednisone, respectively. Of the 24 prednisone-resistant patients treated with steroids in combination with cyclophosphamide, 33.3% obtained a complete/partial response. At the time of final evaluation, 25% of the patients treated with prednisone and 10.0% of those treated with prednisone in combination with cyclophosphamide had reached end-stage renal disease. Persistent nephrotic syndrome and progressive renal insufficiency were more frequently observed among the patients treated with prednisone alone (50.0 vs 33.3% and 33.3 vs 16.7%, respectively). The treatments were well tolerated and no patient experienced adverse reactions requiring discontinuation of medications. Although open-label and non-randomized, the present trial showed that cyclophosphamide is a reasonable choice for the treatment of primary focal segmental glomerulosclerosis and prednisone-resistant nephrotic syndrome.

Allozyme diversity in endemic flowering plant species of the Juan Fernandez Archipelago, Chile: ecological and historical factors with implications for conservation.

The level and apportionment of allozyme diversity were determined for 29 endemic (and 1 native) species from the Juan Fernández Islands, Chile. Mean diversities at the species level (H(es) = 0.065) are low but comparable to those measured for other insular endemics in the Pacific. A high mean proportion (0.338) of species-level diversity resides among populations. Diversity statistics were compared for species in different ecological-life history trait categories and abundance classes. Species occurring in large populations and those present in scattered small populations have higher diversities than species occurring in one or two populations. Although not significant with the conservative statistical test employed, lower diversity was found in highly selfing species as compared to animal- or wind-pollinated species. The apportionment of genetic diversity within and among populations (G(ST) values) is not significantly different for any of the species categories. Of particular interest is the lack of difference between animal- and wind-pollinated species because previous analyses of large data sets showed higher differentiation between populations of animal- than wind-pollinated species. Historical factors, both ecological and phylogenetic in nature, can influence the level and apportionment of diversity within insular endemics, and thus ecological correlates of diversity seen in many continental species may not apply to endemics. The results have several conservation implications. The preservation of large populations or several small populations is important for conserving diversity within species because when species are reduced to one or two populations, allozyme diversity is sharply reduced. High mean G(ST) values for the species examined illustrate the need for conserving as many populations as possible, either in the wild or in the garden, to preserve maximal diversity within species. Effective conservation strategies require empirical knowledge of each species.

RAPD marker diversity within and divergence among species of Dendroseris (Asteraceae: Lactuceae).

Random Amplified Polymorphic DNA (RAPD) markers were used to measure genetic diversity within and divergence among species of Dendroseris (Asteraceae: Lactuceae), a genus endemic to the Juan Fernandez Islands, Chile. Results were compared to previous studies employing allozymes. For five of the species, RAPD banding patterns distinguished all individuals examined, and different mutilocus genotypes were found even in species exhibiting no allozyme diversity. RAPD band diversities ranged from 0.003 to 0.022 within species; >90% of total diversity was among species and <10% within them. Relative levels of allozyme and RAPD diversity were similar for some species, particularly those with highest and lowest diversities, but overall there was no significant correlation. Relationships inferred from a neighbor-joining tree generated from RAPD bands were similar to results obtained from morphology, chloroplast DNA (cpDNA) restriction site mutations, and sequences from the internal transcribed spacer regions of nuclear ribosomal DNA (ITS), but somewhat better resolution was achieved. Relationships shown by allozymes differed from trees based on other data; this ostensibly is a result of the sharing of ancestral alleles and the absence of alleles generated subsequent to speciation. Dendroseris represents an example where RAPD markers, because of their greater variability, provide a useful alternative to allozymes for assessing diversity in rare species endemic to oceanic islands and for resolving relationships among the species.

Effect of thymectomy on zoxazolamine paralysis and metabolism in untreated and (PCN) pregnenolone-16alpha-carbonitril- or ACTH-pretreated rats.

The effect of thymectomy on zoxazolamine paralysis and metabolism was investigated in young female untreated and PCN- or ACTH-pretreated rats. Thymectomy performed at least 24 hr before injection of zoxazolamine significantly prolonges paralysis time. Pretreatment with PCN (an inducer of hepatic microsomal enzymes) or ACTH (known to alter protein binding and excretion of zoxazolamine) shortened paralysis in thymectomized animals; but only in comparison to thymus ablated controls. The surgical intervention seemed to decrease the metabolism of zoxazolamine in the 9,000g supernatant fraction of the liver.