High prevalence of adrenal insufficiency in patients with sickle cell disease: results from a community hospital in the U.S.

OBJECTIVE: Despite the low prevalence (0.008%) of adrenal insufficiency (AI) in the general population, this disorder was recently diagnosed in a substantial number of sickle cell disease (SCD) patients at our hospital. The main objective of this study was to assess the prevalence of AI in SCD patients. METHODS: All adult patients admitted to the Department of Medicine at Interfaith Medical Center from October 2010 to November 2011 were eligible for this retrospective study. Medical records of adult SCD patients hospitalized for painful crisis and who had undergone cosyntropin testing were reviewed. Adult non-SCD patients hospitalized for painful crisis and who had undergone cosyntropin testing served as controls. The result of the cosyntropin test was the primary outcome. The prevalence of positive cosyntropin tests was compared between the 2 groups by using Student's t-test, and odds ratios. RESULTS: 62 adult SCD patients were enrolled in the study. 15 underwent cosyntropin testing and 12 (19.4%) of these patients were found to have AI. AI was also diagnosed in 1 of 1,340 non-SCD patients. The odds ratio for AI in SCD to non-SCD patients [(12/62)/(1,340)] was 259. The odds ratio for the prevalence of AI in SCD patients in our study (19.4%) vs. the general population (approximately 0.008%) was 2,375. CONCLUSION: AI occurred in 19.4% of SCD patients included in this study. These patients thus have a 2,375-fold higher risk of developing AI than the general population, and a 259-fold greater risk of developing AI than do hospitalized non-SCD patients.

Gastric marginal zone B cell lymphoma of the duodenum.

Small bowel lymphomas of the extranodal type occur in the young and are characteristically associated with malabsorption syndrome. We present the case of an elderly in whom there was no malabsorption and the duodenal tumor was a gastric type marginal zone B cell lymphoma also known as gastric mucosa-associated lymphoid tissue (MALT) lymphoma. A 73-year-old woman presented to the emergency room with 2 weeks of general weakness, recurrent vomiting containing food particles and abdominal distension. She had been diagnosed with diabetic gastroparesis 4 years prior. CT of the abdomen and pelvis was suggestive of gastric outlet obstruction but no evidence of pancreatic or duodenal mass. Endoscopy and biopsy of the tumor obstructing the distal first part of the duodenum confirmed a gastric marginal MALT lymphoma. The patient's symptoms improved with radiotherapy. Gastric MALT lymphoma, an extranodal lymphoma primarily described in the stomach, can also present in the small bowel and is not associated with malabsorption.

Serum leptin concentration in patients infected with human immunodeficiency virus.

OBJECTIVE: To assess the potential effect of serum leptin levels in human immunodeficiency virus (HIV)-related wasting. METHODS: Morning serum leptin levels of 94 randomly chosen HIV-infected patients were measured and correlated with age, sex, weight, height, body mass index (BMI), routine blood chemistries (SMA 18), complete blood cell count, HIV viral load, and CD4/CD8 ratio. RESULTS: The mean serum leptin level was 7.0 +/- 6.9 ng/mL. Leptin levels were significantly higher in the 38 female patients than in the 56 male patients (10.0 +/- 8.4 ng/mL versus 5.0 +/- 4.9 ng/mL; P<0.001). Leptin levels were positively correlated with BMI (r = 0.71; P<0.05). The correlation of leptin levels with BMI was improved when the results were analyzed stratified by the sex of the patients (r = 0.74 for female patients; r = 0.81 for male patients). CONCLUSION: This study showed that the serum leptin levels in HIV-infected patients with BMI between 18 and 25 kg/m 2 were comparable to leptin levels in lean, healthy subjects. Leptin distribution was positively correlated with BMI, as expected. These data do not support the hypothesis for a major role of serum leptin in HIV-related wasting.

Studies on the in vitro and in vivo expression of a dysfunctional alpha-globin gene.

In a black family with members having alpha-thalassemia and hemoglobin H (HbH) disease, a deletion of an AG dinucleotide at the 3' end of exon 1 near the junction with intron 1 was shown previously to produce a dysfunctional alpha-thalassemia gene with a reading frame-shift and a nonsense codon (Safaya S, Rieder RF: J Biol Chem 263:4328-4332, 1988). We have found that the same mutation is responsible for alpha-thalassemia and HbH disease in a second unrelated black family (Bellevue R, Dosik H, Rieder RF: Br J Haematol 41:193-202, 1979). Despite the loss of two nucleotides from the consensus sequence at the 5' splice donor site of intron 1, studies employing an in vitro plasmid-based expression system indicated that the mutant alpha-globin mRNA was spliced normally and expressed in amounts equal to normal alpha-globin mRNA in COS-7 cells. The correct processing of the mRNA in these studies is probably due to the presence of a tandem repeat of the affected AG dinucleotide. However, in reticulocytes from subjects bearing the mutant gene, we were unable to detect any of the abnormal mRNA. These findings suggest that there is accelerated post-transcriptional loss of mRNA bearing a premature terminator codon.

Highly attenuated vaccinia virus mutants for the generation of safe recombinant viruses.

An attenuated vaccinia virus mutant with specific genetic lesions has been used to develop a vehicle for safer live recombinant virus vaccines. The mutant virus 48-7 has an 8-MDa deletion starting 2.2 MDa from the left end of the viral genome and point mutations in the gene encoding the 14-kDa fusion protein that determines the plaque-size phenotype of the virus. Using the highly sensitive reporter gene luciferase, we have shown that this mutant can generate recombinant viruses that infect cultured cells and animals with normal vaccinia virus tropism. Insertion of the envelope and gag genes of human immunodeficiency virus type 1 into the attenuated vaccinia mutant resulted in their efficient expression and precursor processing in infected cultured cells. Infection of mice with human immunodeficiency virus-vaccinia recombinant viruses elicited human immunodeficiency virus-specific antibodies. Using mice pretreated with cyclophosphamide as a model for immunosuppression, the reduced virulence of the mutant recombinant virus was clearly evident. These findings demonstrate that the highly attenuated vaccinia virus mutant 48-7 can be used to generate effective and safer vaccines.

A 66-base pair insert bridges the deletion responsible for a mouse model of beta-thalassemia.

The breakpoints of the deletion responsible for the Hbb(th-1) mouse model of beta-thalassemia have been isolated. A 3709 (+/- 2)-base pair (bp) region, including the entire beta major globin gene and 2 kilobases of 5' flanking region, is deleted. A novel 66 (+/- 2)-bp sequence, ending in a stretch of 25 dA:dT base pairs, was found to bridge the deletion. A region of the normal murine genome, containing the first 43 bp of the deletion-associated insert (DAI), but lacking the 25-bp dA:dT sequence, was isolated. All normal mice tested contain this DAI-like element and several inbred strains contain an additional DAI-like element. The sequence spanning the Hbb(th-1) deletion may be a reverse transcript of this region.

Factors involved in production of helper virus-free retrovirus vectors.

Retrovirus vectors allow efficient transfer of genetic material into cells. We describe an improved method for making cell lines which secrete broad host range retrovirus vectors in the absence of helper virus. This method was used to make virus-producing cell lines from several retrovirus vector constructions that encode dominant selectable markers. Virus titers from such lines exceeded 10(6) colony-forming units per milliliter of medium exposed to the cells. Cell lines that secreted certain vectors remained free of helper virus, while cell lines made using other vectors always secreted helper virus. Secretion of helper virus apparently depended on recombination between vector and the retrovirus packaging system, and factors involved in this event were investigated.

Humoral factor that specifically regulates factor X levels in rabbits (coagulopoietin-X).

A heat-stable humoral substance (coagulopoietin-X) is present in rabbits partially depleted of Factor X, which is capable of raising Factor X levels when injected into recipient rabbits. Rabbits were partially depleted of Factor X by slow infusion of a globulin fraction of goat anti-rabbit Factor X antibody. This resulted in the reduction of Factor X to 40--50% of normal at 1 h and 60--70% of normal at 6 h. No effect was noted on levels of Factors II, V, or VII. Plasma from these animals, when injected into 10 recipients, specifically raised Factor X levels when measured by four different assay: one-stage assay with bovine VII- and X-deficient plasma and Russell's viper venom; one-stage assay with human X-deficient plasma and thromboplastin; chromogenic substrate assay with Russell's viper venom; and an immunologic assay (Laurell technique). No rise was noted in two control experiments in which normal plasma was injected into recipient rabbits from 2 rabbits injected with a globulin fraction of normal goat serum, nor in 12 rabbits injected with plasma from normal rabbits, nor in 5 rabbits injected with boiled plasma from normal rabbits. The rise in biologic activity of 120--150% of base line was significantly greater than the rise in immunologic activity of 114--117% of base line (P less than 0.05) on 3 different days, suggesting the production of a molecule with greater specific activity rather than increased protein synthesis.