Management of the side-effects of intravenous bisphosphonates: targeting the serum parathyroid hormone elevation.

In their recent review article, Tanvetyanon and Stiff [1] pointedout that hypocalcemia is a frequent side-effect of intravenousbisphosphonates. This adverse event is usually mild and exceptionallysymptomatic, with the principle risk factors being pre-existinghypovitaminosis D, previous parathyroid surgery and intestinalresections. A direct consequence of hypocalcemia     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

Limited role of aortic size in the genesis of acute type A aortic dissection

Objective: Increased dimension of the aortic root and proximal aorta is considered a significant risk factor for catastrophic events that involve the ascending aorta. The objective of this study was to determine the possible correlation between pre-dissection aortic diameter and the occurrence of Stanford type A aortic dissection. Methods: Samples of dissected ascending aortas were obtained from 220 patients at the time of their operation. Two groups were identified: patients with connective tissue disorders (Group 1, n = 94) and those without (Group 2, n = 126). Measurements of the true (intimal) lumen were conducted and extrapolated as reliable approximation of pre-dissection aortic diameter. The possible association of intimal diameter with anthropometric and demographic data was analyzed. Results: Median aortic diameter was, respectively, 41.8 and 41.3 mm for patients with and without connective tissue disorders (41.4 mm for the entire cohort). Data analysis indicated that 57% of patients had aortic diameter above 40 mm, while patients with frank aneurysm accounted only for 10%; this proportion was higher in Group 1 compared to Group 2 (17.2% vs 4.7%). Poor or no correlation was demonstrated between aortic size and any of the anthropometric or demographic variables essayed. Significant subgroup differences were found among patients with a history of cigarette smoking, hypertension, diabetes, chronic renal insufficiency, and bicuspid aortic valve. Conclusion: Although aortic diameter remains a strong indication for preventive surgery in patients with inherited connective tissue disorders, acute aortic dissection occurs rarely in the setting of true ascending aortic aneurysms, and despite normal or near-normal aortic size in more than one-third of subjects. Dissection superimposing on small aortic diameters can be regarded as an expression of substantial functional tissue susceptibility to aortic catastrophic events.     

Primary lymphoma of the temporal bone.

Involvement of the temporal bone by lymphoreticular neoplasm is rare; all reported cases have been of secondary involvement. This article presents what we believe to be the first two reported cases of primary temporal bone lymphoma. The patients, an elderly man and a boy, both presented with infection of the ear, hearing loss, and facial nerve paresis. In both cases, facial paresis resolved after appropriate chemotherapeutic treatment. Patient presentation and clinical course are discussed in light of published work on temporal bone malignancy. Further investigation, including computed tomography and biopsy, should be considered for patients who present with an apparent middle ear infection unresponsive to medical therapy. The development of facial paralysis in such a patient warrants heightened suspicion of malignancy.     

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Identification of a gene essential for piliation in Haemophilus influenzae type b with homology to the pilus assembly platform genes of gram-negative bacteria.

Haemophilus influenzae type b (Hib) pili are complex filamentous surface structures consisting predominantly of pilin protein subunits. The gene encoding the major pilin protein subunit of Hib adherence pili has been cloned and its nucleotide sequence has been determined. In order to identify specific accessory genes involved in pilus expression and assembly, we constructed isogenic Hib mutants containing insertional chromosomal mutations in the DNA flanking the pilin structural gene. These mutants were screened for pilin production, pilus expression, and hemagglutination. Pili and pilin production were assessed by immunoassays with polyclonal antisera specific for pilin and pili of Hib strain Eagan. Hemagglutination was semiquantitatively evaluated in a microtiter plate assay. Six Hib mutants produced proteins immunoreactive with antipilin antiserum but no longer produced structures reactive with antipilus antiserum. In addition, the mutants were unable to agglutinate human erythrocytes. Nucleotide sequence analysis localized the insertion sites in the six mutants to 2.5-kb open reading frame upstream of the pilin structural gene and immediately downstream of an Hib pilin chaperone gene. The amino acid sequence encoded by this open reading frame has significant homology to members of the pilus assembly platform protein family, including FhaA of Bordetella pertussis, MrkC of Klebsiella pneumoniae, and the Escherichia coli assembly platform proteins FimD and PapC. This open reading frame, designated hifC, appears to represent a gene essential to Hib pilus biogenesis that has genetic and functional similarity to the pilus platform assembly genes of other gram-negative rods.