Mid-aortic syndrome in two preterm infants.

We report mid-aortic syndrome (MAC) in two preterm infants. Both infants developed malignant hypertension refractory to medical therapy and died early in infancy. Thus far, this account is of the two youngest patients with MAC.

Congenital focal segmental glomerulosclerosis associated with beta4 integrin mutation and epidermolysis bullosa.

We report the occurrence of congenital nephrotic-range proteinuria secondary to focal segmental glomerulosclerosis in an infant with epidermolysis bullosa and pyloric atresia. A homozygous missense mutation, R1281W, in exon 31 of the beta4 integrin gene, ITGB4, was identified. By immunofluorescence, beta4 integrin expression was reduced in both dermal keratinocytes and glomerular podocytes. This is the first demonstration of beta4 integrin expression in human glomeruli. We postulate a role for altered beta4 integrin function in the mediation of the glomerular permeability defect.

Renal manifestations of concurrent systemic lupus erythematosus and HIV infection.

Autoimmune phenomena are common in human immunodeficiency virus (HIV) infection, yet systemic lupus erythematosus (SLE) and HIV infection rarely are seen concurrently in the same patient. Many of the cases of combined HIV infection and SLE reported in the literature are patients with SLE before HIV infection and who did not undergo renal biopsy at a time when both processes were present. We report the clinical manifestations and renal biopsy findings in four subjects with concurrent HIV infection and SLE and compare them with the seven previously reported cases in the literature. Taken together, most patients were black (91%) and male (73%), and approximately half (55%) were children with perinatal HIV infection. These demographics differ markedly from those of idiopathic SLE, a disease that predominantly affects female adults. Renal presentations included proteinuria and hypocomplementemia, frequently with hematuria and renal insufficiency. Renal biopsy findings in 10 cases included all classes of lupus nephritis (class IIb in two cases, class III in one case, class IV in three cases, class V in three cases, class III and V in one case), two of which also displayed overlapping features of HIV-associated nephropathy (HIVAN). One case had isolated findings of HIVAN. This cohort provides a unique population in which to study interacting pathomechanisms between HIV infection and SLE.

Idiopathic collapsing focal segmental glomerulosclerosis: a clinicopathologic study.

A review of all native kidney biopsies at our center from 1974 to 1993 identified 43 cases of idiopathic focal segmental glomerulosclerosis (FSGS) with predominantly collapsing features and lacking evidence of HIV-1 infection or intravenous drug use. No case was identified before 1979 and the incidence of this entity has progressively increased over the past two decades. Compared to 50 age-matched controls of idiopathic FSGS with typical perihilar scars, the group of idiopathic collapsing FSGS displayed black racial predominance, a higher serum creatinine and more severe features of nephrotic syndrome at biopsy. Morphologic features of visceral epithelial cell hypertrophy and hyperplasia, tubular microcysts, tubular epithelial degenerative and regenerative features and interstitial edema were more prevalent and severe in collapsing FSGS. Median time to ESRD was rapid in collapsing FSGS versus controls (13.0 months vs. 62.5 months, P < 0.05). Correlates of progression to ESRD included a higher initial serum creatinine and failure to undergo remission of proteinuria. Both glomerulosclerosis and certain features of tubular damage were independent predictors of the level of renal function at time of biopsy, but not of the rate of progression of renal insufficiency. Although three patients had partial or complete spontaneous remissions, none of 26 patients treated with steroids alone responded. Idiopathic collapsing FSGS is a variant of FSGS with increasing incidence, distinct clinicopathologic features, black racial predominance, a rapidly progressive course and relative steroid resistance.

Mitochondrial DNA deletion: a cause of chronic tubulointerstitial nephropathy.

We report the first case of a mitochondrial DNA (mtDNA) deletion diagnosed by renal biopsy. An eight-year-old girl with megaloblastic anemia and severe growth retardation developed progressive renal insufficiency accompanied by partial Fanconi syndrome. Histologic examination of the renal biopsy disclosed nonspecific chronic tubulointerstitial disease characterized by tubular atrophy and interstitial fibrosis. On ultrastructural examination, tubular cell mitochondria were extremely dysmorphic with prominent size variation, abnormal arborization, disorientation of the cristae and osmiophilic electron-dense inclusions. Functional histochemical stains for mitochondrial enzymes performed on cryostat renal sections revealed focal tubular absence of cytochrome C oxidase (COX), a respiratory chain enzyme partially encoded by mtDNA, with preservation of succinate dehydrogenase (SDH), a respiratory chain enzyme entirely encoded by nuclear DNA (nDNA). Immunoreactivity for COX subunit 2 (encoded by mtDNA) was weak to undetectable in most tubular cells, whereas reactivity for subunit 4 (encoded by nDNA) was intense in all cells. Molecular analysis of the mtDNA of kidney and peripheral blood leukocytes was performed using Southern blot and PCR. Both techniques disclosed a 2.7 kb mtDNA deletion located between nucleotide (nt) 9700 and nt 13700, a common site for mtDNA deletions associated with encephalomyopathies. Mitochondrial DNA deletions may be an under-recognized cause of idiopathic tubulointerstitial nephropathy in children lacking neurologic or myopathic manifestations.

Population and family studies of HLA-DR4 by use of oligonucleotide typing.

Using PCR and DR4 group-specific primers and SSO's we have examined DRB1*04 nucleotide polymorphisms in a population of 123 DR4-positive individuals (86 NAC, 27 Hispanics and 10 African Americans) from New York carrying a total of 134 DR4 haplotypes. We found that the distribution of DRB1*04 alleles on DR4 haplotypes differs in these three ethnic groups. In this relatively small population, certain alleles such as DRB1*0406 and 0411 were encountered only in Hispanics, while others such as DRB1*0403, 0408 and 0409 were found only in NAC (North American Caucasians). Such differences may be important in studies of HLA-DR4 and disease associations. Evidence from MLC and PLT studies of an HLA-B/DR crossover family, which was informative for the segregation of HLA-DRB1*0406 and DRB1*0407, supports the concept that subtypes of HLA-DR4 and/or associated HLA-DP alleles elicit T-cell alloreactivity, and may thus play a role in transplantation.

Coexistence of AIDS and lupus nephritis: a case report.

We report the first case of membranous lupus nephritis occurring in a child with congenital AIDS. Hypocomplementemia, elevated titers of anti-nuclear antibody and antibody to double-stranded DNA supported the diagnosis of associated systemic lupus erythematosus (SLE). The pathogenetic implications of this coexistence of AIDS and SLE are discussed.

Availability of personal counseling in medical schools.

The deans of student affairs at 114 medical schools were surveyed about the availability of counseling services for medical students. There were 85 respondents (75 percent), all of whom indicated that some counseling services were available at their schools. One-third felt the services were not adequate. In addition, student representatives at these 114 schools were surveyed on the same topic, 53 responded (46 percent), and most said there was underutilization due to poor communication, problems resulting from initial contacts through the administration, and concern about confidentiality. Recommendations are made to help increase the utilization of counseling resources.