MDR1 (P-glycoprotein) is an important factor in the disposition of many drugs, and the involved processes often exhibit considerable interindividual variability that may be genetically determined. Single-strand conformational polymorphism analysis and direct sequencing of exonic MDR1 deoxyribonucleic acid from 37 healthy European American and 23 healthy African American subjects identified 10 single nucleotide polymorphisms (SNPs), including 6 nonsynonymous variants, occurring in various allelic combinations. Population frequencies of the 15 identified alleles varied according to racial background. Two synonymous SNPs (C1236T in exon 12 and C3435T in exon 26) and a nonsynonymous SNP (G2677T, Ala893Ser) in exon 21 were found to be linked (MDR1*2 ) and occurred in 62% of European Americans and 13% of African Americans. In vitro expression of MDR1 encoding Ala893 (MDR1*1 ) or a site-directed Ser893 mutation (MDR1*2 ) indicated enhanced efflux of digoxin by cells expressing the MDR1-Ser893 variant. In vivo functional relevance of this SNP was assessed with the known P-glycoprotein drug substrate fexofenadine as a probe of the transporter's activity. In humans, MDR1*1 and MDR1*2 variants were associated with differences in fexofenadine levels, consistent with the in vitro data, with the area under the plasma level-time curve being almost 40% greater in the *1/*1 genotype compared with the *2/*2 and the *1/*2 heterozygotes having an intermediate value, suggesting enhanced in vivo P-glycoprotein activity among subjects with the MDR1*2 allele. Thus allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P-glycoprotein function.

Psoriasis is an immune-mediated chronic inflammatory disorder of the skin. Association with kidney disease has been debated for a long time. Secondary renal amyloidosis in psoriatic arthropathy and drug-induced renal lesions secondary to methotrexate or cyclosporine are accepted accompaniments of psoriasis. IgA nephropathy is also known to occur in psoriatics. We report three interesting cases of renal involvement in long-standing established psoriasis on topical therapy alone. The patients presented with hypertension, significant proteinuria, hypoalbuminemia, and dyslipidemia. Kidney biopsies revealed "mesangioproliferative glomerulonephritis with IgA nephropathy," "focal proliferative glomerulonephritis," and "membranous glomerulonephropathy." The former two had marked active urinary sediment. Patients improved on prednisolone and angiotensin-converting enzyme inhibitors. Contrary to the belief that renal involvement in psoriasis is coincidental, we propose that kidney disease may be a common accompaniment of psoriasis, which may be labeled as "psoriatic nephropathy" or "psoriatic kidney disease." The exact mechanism of this entity is yet to be elucidated.

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Nephrotic syndrome can be associated with various neoplasms, especially solid tumors and lymphomas. This patient presented with painless hematuria of transitional cell carcinoma of urinary bladder, underwent transurethral resection, but developed recurrence 16 months later. Repeat resection was done and intravesical Bacillus Calmette-Guerin (BCG) injections were started. After six months, the patient developed hypertension and nephrotic syndrome with a biopsy revealing membranous glomerulonephritis, though there was no radiological evidence of tumor. This is the first case of nephrotic syndrome with intravesical BCG instillation in a bladder carcinoma patient.

Anemia is common with connective tissue disorders, but pancytopenia is rare. We report a 22-year-old female who presented with menorrhagia, seizures, anemia, leukocytosis, thrombocytopenia, pericardial effusion, positive ANA, and evidence of vasculitis on CT head scan and was diagnosed with systemic lupus erythematosus (SLE). After 7 months of remission, she was readmitted with menorrhagia and pancytopenia. Investigations revealed aplastic anemia. She survived on transfusion support for 6 weeks, during which period she received methylprednisolone and cyclophosphamide pulses, and phenytoin was omitted but to no avail. Cyclosporine (300 mg/day) was started and the aplastic anemia responded. After 4 months of therapy, the cyclosporine was gradually tapered over the next 2 months. The patient has been on 10 mg/day of prednisolone for the last 6 months. Aplastic anemia is rare in SLE and the response to immunosuppressants is variable, but here is a success story.

Pigmentation of skin, nails and mucosae has frequently been described in HIV positive patients. Various causes for this phenomenon have been ascribed, which include intake of various drugs like zidovudine, opportunistic infections like toxoplasmosis and adrenocortical suppression. However, there has been no uniform explanation. We describe three AIDS patients with different personal and disease profiles but essentially the same pattern of pigmentation. This pattern of pigmentation is thereby discussed. We also propose that this pigmentation could be a result of late stage HIV disease per se and thus could serve as a useful cutaneous marker for the same.

The human immunodeficiency virus (HIV) pandemic is nearly 20 years old. HIV infection is characterized by profound immunodeficiency resulting in an increased incidence of opportunistic infections and neoplasms. However, the greatest paradox is the occurrence of certain autoimmune disorders in the setting of HIV. These include diffuse interstitial lymphocytosis syndrome (DILS), reactive arthritis, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). It has also been seen that even in the absence of these well-defined diseases, various rheumatological manifestations such as arthralgias, arthritis, myopathy, vasculitis, and sicca syndrome are commonly associated with HIV. To the best of our knowledge, the association of HIV with scleroderma has not previously been reported.

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