Nifedipine attenuates the intraocular pressure response to intubation following succinylcholine

Forty patients without eye disease, undergoing elective nonophthalmic surgery, were studied to evaluate the efficacy of sublingual nifedipine in attenuating the intraocular pressure response to succinylcholine administration, laryngoscopy and intubation. The patients were randomly given either nifedipine 10 mg or placebo sublingually 20 minutes before induction of anaesthesia. Intraocular pressure (IOP) and systolic blood pressure (SBP) were recorded before and after induction of anaesthesia. The IOP response to succinylcholine administration, laryngoscopy and intubation was significantly less in patients receiving nifedipine (P > 0.01). The mean maximum rise in IOP above basal level at one minute postintubation was 7.82 mmHg in the control group compared with 0.15 mmHg in the nifedipine pretreated group. These results suggest that sublingual nifedipine is effective in attenuating the IOP response after succinylcholine administration, laryngoscopy and intubation.     

Low-dose mitomycin C as a prophylaxis for corneal haze in myopic surface ablation

PURPOSE: To evaluate the efficacy of low-dose (0.002%) mitomycin C (MMC) vs no prophylactic MMC (control) in reducing corneal haze after surface laser ablation. DESIGN: Two-year retrospective follow-up study performed in Jaipur, India. METHODS: Ninety-two eyes with no MMC application and 83 eyes with 0.002% MMC application during laser epithelial keratomileusis (LASEK) were analyzed in a retrospective chart review with one month, two months, three months, six months, one year, and two years of postoperative follow-up. Postoperative haze, visual acuity, and efficacy ratio (EFFR) then were analyzed statistically. RESULTS: The no-dose MMC and low-dose MMC groups were statistically similar except for a thinner corneal pachymetry (P < .001), higher spherical equivalent error (P = .006), and smaller ablation zone (P = .009) in eyes not treated with MMC when subjected to univariate analysis. Multivariate analysis was used to overcome the preoperative statistical differences among the two groups. Eyes treated with low-dose MMC (0.002%) demonstrated statistically less haze at all postoperative time points and in each myopic subgroup (P < .001). The postoperative uncorrected visual acuity (UCVA) and EFFR, however, showed no difference between the groups, except for better EFFR with MMC at one month (P < .001) and two months (P = .034). CONCLUSIONS: Low-dose MMC (0.002%) in eyes after LASEK results in less corneal haze than in eyes not receiving this agent. Concerns regarding the potential toxicity of MMC make a 10-fold less concentration more desirable in refractive surgery. Further comparative study of low- vs higher-dose MMC is recommended to characterize its clinical benefit fully.     

Pattern of relapses in sporozoite induced Plasmodium cynomolgi B infection in rhesus monkeys

The pattern of sequential relapses in 10 rhesus monkeys following inoculation of sporozoites of Plasmodium cynomolgi B has been studied after administering curative dose of chloroquine (5 mg/kg base X 7 days) to eliminate blood parasitaemia after each relapse. Observation for periods ranging from 109 to 245 days showed that the interval between first six relapses was 19.3 +/- 6.77 days (1st relapse), 20.9 +/- 8.43 days (2nd relapse), 22.8 +/- 8.55 days (3rd relapse), 27.8 +/- 10.0 days (4th relapse), 31.67 +/- 11.50 days (5th relapse) and 32.5 +/- 16.26 days (6th relapse). The results of this study indicate a gradual extension of the relapse interval in successive relapses.     

Intravenous streptokinase in the management of a subset of patients with unstable angina: a randomized controlled trial

We report the results of a randomized controlled trial of intravenous streptokinase in a subset of patients with unstable angina. Seventy-six patients were admitted with prolonged (more than 20 minutes) angina at rest of less than 3 weeks onset. Fifty-two patients continued to have more than 3 episodes of prolonged angina in 48 hours on medical therapy with metoprolol, isosorbide dinitrate, nifedipine and intravenous nitroglycerin. Forty-eight patients consented to enter the study and were randomized into two groups. The first group, of 24 patients, received 1.5 million units of streptokinase infusion and the second group, also of 24 patients, received a placebo. Pain relief within 48 hours was achieved in 19/24 (79.1%) patients after streptokinase infusion as compared to 9/24 (37.5%) of the controls (P less than 0.05). Approximately 90% (17/19) of patients responding to streptokinase therapy were relieved of chest pain within the first six hours as against none in the controls. The incidence of acute myocardial infarction within six months was 12.5% (3/24) in those receiving streptokinase and 25% (6/24) in the controls. Mortality at six months stood at 8.33% (2/24) in the treated patients and 16.6% (4/24) in the controls. Intravenous streptokinase thus appears to be of benefit in patients with angina at rest of recent onset which does not respond to conventional medical therapy.     

Rare causes of hereditary iron overload

Iron is a vitally important element in mammalian metabolism because of its unsurpassed versatility as a biologic catalyst. However, when not appropriately shielded or when present in excess, iron plays a key role in the formation of extremely toxic oxygen radicals, which ultimately cause peroxidative damage to vital cell structures. Organisms are equipped with specific proteins designed for iron acquisition, export, transport, and storage as well as with sophisticated mechanisms that maintain the intracellular labile iron pool at an appropriate level. These systems normally tightly control iron homeostasis but their failure can lead to iron deficiency or iron overload and their clinical consequences. This review describes several rare iron loading conditions caused by genetic defects in some of the proteins involved in iron metabolism. A dramatic decrease in the synthesis of the plasma iron transport protein, transferrin, leads to a massive accumulation of iron in nonhematopoietic tissues but virtually no iron is available for erythropoiesis. Humans and mice with hypotransferrinemia have a remarkably similar phenotype. Homozygous defects in a recently identified gene encoding transferrin receptor 2 lead to iron overload (hemochromatosis type 3) with symptoms similar to those seen in patients with HFE-associated hereditary hemochromatosis (hemochromatosis type 1). Transferrin receptor 2 is primarily expressed in the liver but it is unclear how mutant forms cause iron overload. Mutations in the gene encoding the iron exporter, ferroportin 1, cause iron overload characterized by iron accumulation in macrophages yet normal plasma iron levels. Plasma iron, together with dominant inheritance, discriminates iron overload due to ferroportin mutations (hemochromatosis type 4) from hemochromatosis type 1. Heme oxygenase 1 is essential for the catabolism of heme and in the recycling of hemoglobin iron in macrophages. Homozygous heme oxygenase 1 deletion in mice leads to a paradoxical accumulation of nonheme iron in macrophages, hepatocytes, and many other cells and is associated with low plasma iron levels, anemia, endothelial cell damage, and decreased resistance to oxidative stress. A similar phenotype occurred in a child with severe heme oxygenase 1 deficiency. Recently, a mutation in the L-subunit of ferritin has been described that causes the formation of aberrant L-ferritin with an altered C-terminus. Individuals with this mutation in one allele of L-ferritin have abnormal aggregates of ferritin and iron in the brain, primarily in the globus pallidus. Patients with this dominantly inherited late-onset disease present with symptoms of extrapyramidal dysfunction. Mice with a targeted disruption of a gene for iron regulatory protein 2 (IRP2), a translational repressor of ferritin, misregulate iron metabolism in the intestinal mucosa and the central nervous system. Significant amounts of ferritin and iron accumulate in white matter tracts and nuclei, and adult IRP2-deficient mice develop a movement disorder consisting of ataxia, bradykinesia, and tremor. Mutations in the frataxin gene are responsible for Friedreich ataxia, the most common of the inherited ataxias. Frataxin appears to regulate mitochondrial iron (or iron-sulfur cluster) export and the neurologic and cardiac manifestations of Friedreich ataxia are due to iron-mediated mitochondrial toxicity. Finally, patients with Hallervorden-Spatz syndrome, an autosomal recessive, progressive neurodegenerative disorder, have mutations in a novel pantothenate kinase gene (PANK2). The cardinal feature of this extrapyramidal disease is pathologic iron accumulation in the globus pallidus. The defect in PANK2 is predicted to cause the accumulation of cysteine, which binds iron and causes oxidative stress in the iron-rich globus pallidus.     

Transesophageal echocardiographic identification of a descending aortic aneurysm rupture into the left lung

This case report describes a patient in whom a descending aortic aneurysm ruptured into the left lung, producing hemoptysis. With transesophageal echocardiography, we were able to define the site and extent of the aneurysm, as well as the two sites of rupture into lung tissue.     

Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients

It has been suggested that the retinoid X receptor beta (RXRB) gene is a risk factor for Wegener's granulomatosis. We addressed if there is a functional difference in the response to retinoic acid (RA) and vitamin D in Antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis (AASV) patients and if this was associated with RXRB genotypes. TNFα and IL-10 production were measured in whole blood assay from AASV patients (n = 51) and healthy controls (HC, n = 67). One micromolar of 1,25-(OH)₂ D3, 9-cis RA (9c-RA) or all-trans RA (ATRA) was added to the assay. Genotyping was performed for exons 7 and 2 of the RXRB gene and for a microsatellite in vicinity of the RXRB gene. Lipopolysaccharide (LPS) mediated TNFα production and IL-10 were significantly lower in patients. Addition of 1,25-(OH)₂ D3, ATRA or 9c-RA, blunted TNFα production, more pronounced in patients. Although all three compounds inhibited IL-10 production significantly in HC, only 1,25-(OH)₂ D3 was found to be effective in patients. Allele distribution of the RXRB microsatellite differed significantly between patients and HC. This was not found for the SNP in exons 2 and 7. Genotype of the latter correlated with the ability of 1,25-(OH)₂ D3 and ATRA to inhibit IL-10 production. We provide immunological evidence for a functional difference in vitamins D and A responsiveness in AASV patients. Since the inhibition of TNFα was more effective in patients, vitamin D supplementation might be an additional therapeutical approach.