The carbonic anhydrase inhibitors methazolamide and acetazolamide have different effects on the hypoxic ventilatory response in the anaesthetized cat

We compared the effects of the carbonic anhydrase inhibitors methazolamide and acetazolamide (3 mg kg⁻¹, i.v .) on the steady-state hypoxic ventilatory response in 10 anaesthetized cats. In five additional animals, we studied the effect of 3 and 33 mg kg⁻¹ methazolamide. The steady-state hypoxic ventilatory response was described by the exponential function: where     is the inspired ventilation_, G is hypoxic sensitivity, D is the shape factor and A is hyperoxic ventilation. In the first group of 10 animals, methazolamide did not change parameters G and D , while A increased from 0.86 ± 0.33 to 1.30 ± 0.40 l min⁻¹ (mean ± s.d. , P = 0.003). However, the subsequent administration of acetazolamide reduced G by 44% (control, 1.93 ± 1.32; acetazolamide, 1.09 ± 0.92 l min⁻¹, P = 0.003), while A did not show a further change. Acetazolamide tended to reduce D (control, 0.20 ± 0.07; acetazolamide, 0.14 ± 0.06 kPa⁻¹, P = 0.023). In the second group of five animals, neither low- nor high-dose methazolamide changed parameters G , D and A . The observation that even high-dose methazolamide, causing full inhibition of carbonic anhydrase in all body tissues, did not reduce the hypoxic ventilatory response is reminiscent of previous findings by others showing no change in magnitude of the hypoxic response of the in vitro carotid body by this agent. This suggests that normal carbonic anhydrase activity is not necessary for a normal hypoxic ventilatory response to occur. The mechanism by which acetazolamide reduces the hypoxic ventilatory response needs further study.     

Characterization of the gene for the membrane and secretory form of the IgM heavy-chain constant region gene (C mu) of the cow (Bos taurus).

Our present understanding of the evolution of immunoglobulins is derived from a few vertebrate species. In order to obtain additional information on the development of the humoral immune system, we cloned and determined the nucleotide sequence of the bovine cDNA and genomic IgM heavy-chain constant region gene (C mu). The gene contains four constant region domain-encoding exons (CH1 to CH4) and two exons encoding the transmembrane domain (TM1, TM2), expressed in the membrane-bound receptor form of the IgM. The sequence of a cDNA clone encoding the 3' portion of the membrane form of the mu-chain revealed that the TM1 exon is spliced to the CH4 exon, as occurs in other mammals. Comparison of deduced amino acid sequence data from different vertebrates revealed a high similarity to sheep C mu (88%) and a lower degree of similarity to pig (62%), rat (62%), rabbit (58%) human (56%), hamster (55%), mouse (54%), chicken (28%) and horned shark (22%) C mu.     

Open treatment of ankle fracture as inpatient increases risk of complication

Background

Ankle fracture is one of the most common injuries treated by orthopaedic surgeons, and its incidence is only expected to rise with an aging population. It is also associated with often costly complications, yet there is little literature on risk factors, especially modifiable ones, driving these complications. The aim of this study is to reveal whether inpatient treatment after ankle fracture is associated with higher incidence of postoperative complications. As the USA moves towards a bundled payment healthcare system, it is imperative that orthopaedists maximize patient outcome and quality of care while also reducing overall costs.

Materials and methods

We used the American College of Surgeons National Surgical Quality Improvement Program database to compare complication rates between inpatient and outpatient treatment of ankle fracture. We collected patient demographics, comorbidities, and postoperative complications from both groups, then compared treatments using a multinomial logistic regression model.

Results

We identified 7383 patients, with 2630 (36%) in the outpatient and 2630 (36%) in the inpatient group. Of these, 104 (4.0%) inpatients compared with 52 (2.0%) outpatients developed a complication (p < 0.001).

Conclusions

Inpatients developed major complications including deep wound infection and pulmonary embolism, as well as minor complications such as pneumonia and urinary tract infection, at significantly greater rates. As reimbursement models begin to incorporate value-based care, orthopaedic surgeons need to be aware of factors associated with increased incidence of postoperative complications.

Level of evidence

Level III retrospective comparative study.

     

Neuropatía óptica compresiva secundaria a reacción alérgica a hialuronidasa

A 58 year-old woman presented with severe chemosis and ophthalmoparesis on her left eye 8 hours after uncomplicated cataract surgery under sub-tenon anaesthesia. Recovery of extrinsic motility was observed after corticosteroid and antihistamine treatment, but a non-haemorrhagic papillary oedema and a concentric defect of visual field were found. It progressed to papillary atrophy with preserved central vision, but with a significant visual field constriction. The aetiological study revealed an allergy to hyaluronidase that was used as adjuvant to the anaesthesia. This complication needs to be promptly diagnosed and treated, as the swelling of the orbital tissues can cause damage to the optic nerve.     

The effect of maternal and infant factors on cord blood yield

Umbilical cord blood (CB) can be used as an alternative hematopoietic stem cell source for transplantation in hematological malignancy and blood disorders. The success of transplantation is highly related to the levels of total nucleated cell and CD34⁺ cell counts. The evaluation of optimal conditions can decrease the rate of graft rejection due to low cell count and increases the quality of CB units (CBUs) in the blood bank and the success rate of engraftment. To this end, we review the maternal and infant parameters affecting the quality and quantity of CBUs.     

Fish Mouth and Parachute Surgical Technique for Hirschsprung’s Disease

Purpose  This study examined the long-term therapeutic effect of fish mouth and parachute technique anastomosis for Hirschsprung’s disease. Methods  From March 1992 to October 2002, we performed one-stage fish mouth and parachute technique anastomosis for 293 patients with Hirschsprung’s disease. Two hundred and fifty-four patients (79 percent) were followed up for three to five years. The operative outcome and postoperative complications were retrospectively analyzed. Results  Two hundred ninety-three patients were included in the study, the majority of patients were male (n = 205, 70 percent) and ages ranged between 8 months and five years. Early complications were low (n = 7, 2.3 percent) and included urine retention (n = 2), enteritis (n = 2), and intestinal obstruction (n = 3). No infection of the abdominal cavity or wound, anastomotic leakage, or death occurred in any patients. Late complications were present in 10 cases (3.4 percent). Conclusions  The fish mouth and parachute surgical technique procedure showed some practical benefits and fewer complications than traditional surgical techniques for the treatment of Hirschsprung’ s disease. Presented at the 12th Council Meeting of the World Federation of Association of Pediatric Surgeons (WOFAPS). Zagreb, Croatia, June 22 to 27, 2004.     

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma

Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.Oral squamous cell carcinoma (OSCC) is the most malignant tumor of the oral cavity. OSCC is more aggressive than cutaneous squamous cell carcinoma (CSCC). Although the incidence of OSCC is 20 times lower than CSCC with 30,000 (0.01%) and 700,000 (0.2%) new cases each year in the United States, respectively^{1, 2}; two-thirds of OSCC patients have evidence of disseminated disease at diagnosis,¹ yet CSCC is rarely malignant with only 4% of cases developing nodal metastases.² All tumor growth beyond the volume of 1 to 2 mm³ is angiogenesis dependent.³ The extent of tumor angiogenesis and lymphangiogenesis are two of the most important prognostic factors in OSCC.⁴ Understanding the mechanisms that control tumor neovascularization may lead to new therapeutic options for cancer patients.Neuropilin 1 (NRP1) has been studied extensively in the vascular system where it acts as a coreceptor for angiogenic proteins such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) and in the neuronal system where it serves as a receptor for guidance molecules called class 3 semaphorins (SEMA3s).^{5, 6} Our laboratory previously demonstrated that epithelial cells in the skin and CSCC tumor cells express high levels of NRP1.^{7, 8, 9} However, the function of NRP1 in epithelial cells and carcinoma cells is not as well understood as its role in endothelial cells.^{10, 11}Several studies have reported that overexpressing the NRP1 receptor via transfection into tumor cells results in enhanced tumor size in vivo, although NRP1 does not directly increase proliferation of tumor cells in vitro.^{12, 13} In addition, tumors overexpressing NRP1 formed hypervascular xenografts, suggesting that NRP1 expression in the tumor compartment influences neovascularization from the stromal compartment.^{14, 15} This effect is apparently caused by the binding (and release) of angiogenic factors [VEGF, placenta growth factor (PlGF), HGF] to the NRP1 receptor on tumor cells, resulting in an increased chemogradient of these ligands within the local tumor microenvironment that attracts and induces sprouting of neighboring endothelial cells.To test our hypothesis that NRP1 may increase the vascularity and invasiveness of OSCC, we investigated the expression and function of NRP1 in oral (tongue) epithelial cells and OSCC cells. Our results found an up-regulation in NRP1 receptor expression in oral dysplastic epithelium that persists throughout the stages of oral carcinogenesis and progression. In addition, the expression of NRP1 protein within the OSCC tumor compartment correlates with the pattern of blood vessel infiltration within the tumor microenvironment.     

Malignant melanoma of parotid glands from a neglected lesion: A case report

Observing a metastatic malignant melanoma and its primary lesion at the same time is rare. The histopathological detection of any unusual pigmented lesion is critical.