25. Ischemic Pain in the Extremities and Raynaud’s Phenomenon

Two important groups of disorders result from an insufficient blood supply to the extremities: critical vascular disease and the Raynaud’s phenomenon. The latter can be subdivided into a primary and a secondary type. Critical ischemic disease is often caused by arteriosclerosis due to hypertension or diabetes. Primary Raynaud’s is idiopathic and will be diagnosed as such if underlying systemic pathology has been excluded. Secondary Raynaud’s is often a manifestation of a systemic disease. It is essential to try to establish a diagnosis as soon as possible in order to influence the evolution of the disease. A sympathetic nerve block can be considered in patients with critical ischemic vascular disease after extensive conservative treatment, preferably in the context of a study (2B±). If this has insufficient effect, spinal cord stimulation can be considered in a selected patient group (2B±). In view of the degree of invasiveness and the costs involved, this treatment should preferably be applied in the context of a study and with the use of transcutaneous pO₂ measurements. In case of primary Raynaud’s, life style changes are the first step. Sympathectomy can be considered as a treatment of Raynaud’s phenomenon (2C+), but only after multidisciplinary evaluation of the patient and in close consultation with the patient’s rheumatologist, vascular surgeon or internist.     

Role of fine‐needle aspiration cytology in tuberculosis of bone

This study was designed to evaluate the role of fine‐needle aspiration cytology (FNAC) in diagnosis of skeletal tuberculosis (TB). In this retrospective study, 20 cases were retrieved over a 10‐year period in which a cytologic diagnosis of osseous TB was rendered. The aspirations were performed with a 22‐gauge needle attached on a 20‐ml syringe after taking into consideration the radiological findings. The cytologic findings were subdivided into the following categories—epithelioid cell granulomas with necrosis, epithelioid cell granulomas without necrosis, and necrosis only. These cases were either with or without AFB positivity. The smears showed epithelioid cell granulomas in 23 cases (85.2%), multinucleate and Langhans' giant cells in 15 cases (55.6%), and inflammatory cells were noted in the background in 15 cases (55.6%). AFB was positive in six cases (22.7%). FNA provides a simple and safe outpatient procedure for the diagnosis of osseous TB and obviates the need of an open biopsy. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

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.     

Impaired acetylcholine-induced release of nitric oxide in the aorta of male aromatase-knockout mice: regulation of nitric oxide production by endogenous sex hormones in males

The consequences of estrogen deficiency on the cardiovascular system have been widely examined in females. The effects of endogenous estrogen deficiency in males are less clear. The aromatase-knockout (ArKO) mouse lacks a functional Cyp19 gene, which encodes aromatase, and is thus incapable of synthesizing endogenous estrogen. In the present study, we examined the effect of lack of endogenous estrogens on vascular function in aortic rings isolated from male ArKO mice and compared these effects to rings from wild-type (WT) littermates. Full concentration-response curves to norepinephrine, acetylcholine, isoprenaline, and sodium nitroprusside were obtained in the absence and presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine in aortic segments set up in isometric myographs. Responses to noradrenaline were not different in aorta from ArKO compared with WT mice. Both Nomega-nitro-L-arginine and endothelium denudation significantly shifted the noradrenaline concentration-response curve to the left; however, this shift was not different in ArKO compared with WT. Responses to the endothelium-dependent vasodilator acetylcholine were significantly blunted in aortic rings from ArKO mice (Emax, 58.2+/-0.9% and 34.0+/-0.5% in wild-type and ArKO, respectively; P<0.05), whereas responses to the endothelium-independent agonist sodium nitroprusside and to the partial endothelium-dependent agonist isoprenaline were not affected. These findings suggest that endogenous estrogen facilitate vasorelaxation in males. This may be via modulating endothelial function rather than vascular smooth muscle cell responsiveness.     

McKeown esophagogastrectomy for esophageal carcinoma after free jejunal graft

Several well-described options exist for reconstruction after total esophagectomy for esophageal carcinoma. We present the case of a patient who was treated for squamous cell carcinoma of the esophagus; the patient had undergone treatment with neoadjuvant chemoradiation and free jejunal transfer for a cervical esophageal tumor 13 years earlier. Through a three-field approach, esophagectomy and reconstruction with a cervical gastrojejunal anastomosis were performed.