A Novel Obturator Device for Management of Dilated Trachea-esophageal Puncture Tract Fistulas

Voice rehabilitation in laryngectomized patients by tracheoesophageal puncture is a time tested technique. In some patients the tracheoesophageal puncture gets inordinately dilated leading to leakage around the prosthesis. Most of these fistulas are managed by a variety of conservative treatments like temporary removal of prosthesis, placement of silastic ring over the prosthesis, placement of nasogastric tube and airway protection by a cuffed tracheostomy tube. Intractable fistulas are tackled by surgical closure but are fraught with failures. We hereby suggest a novel temporary obturator that can be can be easily made at a very low cost in any hospital having prosthetic rehabilitation services and obviates the need for a tracheostomy tube, nasogastric tube and repeated hospital visits.     

Unusual mid‐shaft fractures during long‐term bisphosphonate therapy

Background Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Although existing evidence supports a good safety profile, there is concern that chronic administration of these agents could result in severe suppression of bone turnover with increased risk of nonvertebral fractures. Objective The objective of this study was to report the clinical presentation, selected bone histomorphometry and X‐ray images of patients who developed mid‐shaft long bone fractures during bisphosphonate therapy, six of whom had bone biopsy for histomorphometery. Results Of the 13 patients who sustained atraumatic mid‐shaft fractures, 10 were on alendronate and three were on risedronate therapy before the fractures. In addition to bisphosphonates, three patients were on oestrogen and two on tamoxifen concomitantly. Four patients with glucocorticoid‐induced osteoporosis were on alendronate for 3–11 years along with glucocorticoid therapy. Bone histomorphometry showed severe suppression of bone turnover in five patients and low bone turnover in one patient. Conclusion Long‐term bisphosphonate therapy may increase the risk of unusual long bone mid‐shaft fractures. This is probably due to prolonged suppression of bone turnover, which could lead to accumulation of microdamage and development of hypermineralized bone. At present, the scope of this complication in the larger context of patients receiving bisphosphonate therapy remains unknown, but appears to be small.     

Management protocols of Allergic Fungal Sinusitis

Controversy surrounds the appropriate surgical approach and the appropriate medical therapy for Allergic Fungal Sinusitis. The present prospective study aims to assess the impact of these factors on the treatment outcome of Allergic Fungal Sinusitis. In the present study 34 cases with AFS were randomized into one of 3 methods of post operative therapy i.e. systemic itraconazole (group A, n=11), topical steroids (group B, n=12) and nasal alkaline douches only (group C, n=11). Outcome was assessed at 6 months post-operative by the Kupferberg grading system for assessment of nasal and sinus mucosa. Grade ‘3’ mucosal disease was defined as recurrence. Complete pre-operative opacification of sphenoid and frontal sinus was a predictor of poorer outcome. Postoperative systemic itraconazole therapy demonstrated a trend towards a better outcome but was not statistically significant. Larger trials are required to conclusively evaluate the merit of various post-operative treatment regimens for AFS.     

Receptor tyrosine kinases expressed in metastatic colon cancer

Using a PCR-based cloning technique, we have isolated a series of DNA fragments coding for tyrosine kinases that are expressed in a metastatic human colon tumor, and have subsequently analyzed their expression pattern at the protein level in human tumors. We identified both the α and the β forms of the platelet-derived growth factor receptor (PDGFR), axl and 8 other genes, including 3 cytoplasmic tyrosine kinases. To study their expression in human colon cancer, we performed Western blots of matched sets of normal tissues and of carcinomas from the same patient. These revealed that the α-PDGFR migrates predominantly as a 200-kDa band in 8/8 normal tissues, and as a 170-kDa band in 17/17 malignant tissues, as well as in colonic polyps, suggesting that expression of an isoform of this receptor may be a marker for the progression of colon cancer. Additional studies showed that the Axl receptor tyrosine kinase was expressed at 10-fold higher levels in a peritoneal metastatic nodule than in other normal and malignant tissues. Immunohistochemistry revealed Axl over-expression specifically in the malignant cells of the tumor. This indicates that over-expression and possibly a differential processing event of tyrosine kinase receptors may be involved in colon cancer, and that they are potential markers for the progression of this disease. © 1995 Wiley-Liss. Inc.     

Bilateral macular hemorrhage caused by azathioprine-induced aplastic anemia in a corneal graft recipient

PURPOSE: To report the occurrence of bilateral macular hemorrhage following the use of azathioprine for immunosuppression in a corneal transplant recipient. METHODS: The patient underwent therapeutic penetrating keratoplasty for progressive fungal keratitis in his left eye. Although the infection did not recur, the graft failed with vascularization of the cornea in three quadrants. He underwent repeat penetrating keratoplasty 2 years later and was treated with azathioprine (100 mg daily) to enhance graft survival. Four months after instituting azathioprine therapy, he developed aplastic anemia and macular hemorrhage in both eyes. RESULTS: Fluorescein angiography revealed a preretinal location of the macular hemorrhage. After cessation of azathioprine therapy and treatment with blood component replacement, hematological parameters improved and the macular hemorrhage cleared with good visual recovery during the next 2 months. CONCLUSION: This report highlights the serious ocular and systemic complications that can occur following the use of systemic immunosuppressants after ophthalmic surgery.     

Design,synthesis, and immunostimulatory properties of CpG DNAs containing alkyl-linker substitutions: role of nucleosides in the flanking sequences

Bacterial and synthetic DNA containing unmethylated CpG dinucleotides activate the innate immune system and promote Th1-like immune responses. Recently, a receptor, TLR9, has been shown to recognize CpG DNA and activate immune cascade. But there have been no reports on the molecular mechanisms of recognition between CpG DNA and the receptor(s). Our earlier studies described a number of the chemical and structural characteristics of CpG dinucleotide and the sequences flanking the CpG dinucleotide that are critical for immunostimulatory activity. In the present study, we examined the effect of the presence and absence of a nucleoside in the flanking sequences by replacing one or two natural deoxyribonucleosides at various positions with one or more alkyl- (C2-C12), branched alkyl- (glyceryl or aminobutyryl-propanediol), or ethyleneglycol- (tri or hexa) linkers. The results suggest that a linker substitution at the first two nucleoside positions adjacent to the CpG dinucleotide on the 5'- or the 3'-side neutralizes the immunostimulatory activity, as determined by in vitro mouse spleen cell proliferation, cytokine secretion, and in vivo mouse spleen enlargement. The same substitutions placed about three to six nucleotides away from the CpG dinucleotide either did not affect or potentiated immunostimulatory activity compared with parent CpG-DNA without modifications. Substitution of deoxyribonucleosides with a C3 or C4 alkyl-linker was found to be optimal for potentiating immunostimulatory activity.