Massive subcutaneous emphysema developing before surgery for mandibular fracture: a case report

Abstract – Preoperative massive subcutaneous emphysema before intubation is extremely rare. However, this complication may be potentially lethal, depend on the condition of air spreading. Subcutaneous emphysema which occurs intra‐ or postoperative period is sometimes iatrogenic because the air is introduced into the tissue space through the hole injured by the operation. But the emphysema in this case occurred preoperatively by the pressure of the bag valve mask, because the patient had an intra‐oral wound, which reaches the submental space. In this report, we describe an extremely rare case of preoperative massive emphysema of the patient with the mandibular fracture.     

Aberrant Regulation of Planar Cell Polarity in Polycystic Kidney Disease

Mutations in PKD1, which encodes polycystin-1 (PC1), contribute to >85% of cases of autosomal dominant polycystic kidney disease (ADPKD). The planar cell polarity (PCP) pathway is necessary for the oriented cell division and convergent extension that establishes and maintains the structure of kidney tubules, but the role of this pathway in the pathophysiology of ADPKD is incompletely understood. Here, we show that inactivation of Pkd1 in postnatal developing mouse kidneys leads to a defect in oriented cell division in precystic kidney tubules. We also observed this defect in precystic Pkd1-inactivated mature kidneys subjected to ischemia-reperfusion injury as a “third hit.” Cystic kidneys exhibited striking upregulation and activation of Frizzled 3 (Fz3), a regulator of PCP, and its downstream effector, CDC42. Precystic kidneys demonstrated upregulation of CDC42, but the localization of the polarity proteins Par3 and Par6 was similar to control. Fz3 was expressed on the cilia of cystic kidneys but barely detected on the cilia of normal kidneys. In vitro, PC1 and Fz3 antagonized each other to control CDC42 expression and the rate of cell migration in HEK293T cells. Taken together, our data suggest that PC1 controls oriented cell division and that aberrant PCP signaling contributes to cystogenesis.Polycystic kidney disease (PKD) is a common genetic disorder, affecting one in 500 individuals in the United States. This disease is identified by the growth of numerous cysts in the kidneys, which eventually lead to ESRD necessitating dialysis and kidney transplantation.¹ Autosomal dominant PKD (ADPKD) is the most common inherited form, caused by mutations in PKD1 and PKD2 in 85 and 15% of the cases, respectively. ADPKD also affects other tissues, resulting in hepatic and pancreatic cysts, intracranial aneurysms, and heart valve defects.¹ Overexpression or downregulation of polycystin-1 (PC1) and -2 (PC2), gene products of PKD1 and PKD2, leads to uncontrolled tubule lumen size.² The molecular mechanism of tubule lumen size restriction, however, is still unclear.Most of our major organs, including lung, kidney, mammary gland, and vasculature, are composed primarily, sometimes exclusively, of tubules.³ During tubule growth, cell polarity must be precisely controlled and cellular adherens junctions need to be continuously remodeled without losing cell–cell contacts. This is a complex two-step process in which cells depolarize and migrate away to form elongated tubules and repolarize once they have reached their new position.⁴ At least in postnatal kidneys, maturation of tubules requires substantial elongation, involving an intense proliferation phase. This type of tubule elongation is associated with oriented cell division in which mitotic cells are oriented along the tubular axis. This process determines the diameter of a tubule and likely requires intrinsic planar cell polarity (PCP) signaling,⁵ a noncanonical Wnt signaling pathway. PCP was first described in Drosophila and is defined as the process in which epithelial cells become polarized in the plane of a tissue, perpendicular to the apical-basal axis.⁶ The core PCP components Frizzled (Fz), Dishevelled (Dvl), Prickle, Van Gogh, Diego, and Flamingo were first identified in Drosophila, where they function in regulating tissue organization.^6,7 In mammals, PCP signaling also regulates convergent extension movements that are required for neural tube closure and lengthening of embryos and kidney tubules.^8,9 Recently, a group of PCP genes, Fat, Dachsous, and Four-jointed (Fj), were identified in Drosophila as an upstream cassette of transmembrane proteins, providing an initial cue at the cell surface to induce asymmetrical localization of the core PCP components. Interestingly, loss of the vertebrate Fat homolog, Fat4, disrupts oriented cell division and tubule elongation during kidney development, causing tubule dilation. This cystic phenotype in Fat4 mutants is enhanced by loss of the core PCP component Vangl2 as well as loss of the Fj ortholog, Fjx1.¹⁰In this study, we demonstrated that Pkd1 inactivation affects oriented cell division in precystic Pkd1-inactivated developing and injured kidneys. Moreover, the PCP components Fz3 and CDC42 are significantly upregulated and activated in cystic kidneys. Interestingly, we found that Fz3 localizes to the cilia and the centrosomes in renal tubules. We also showed that Fz3 and PC1 antagonize each other to regulate CDC42 expression and cell migration in kidney cells, suggesting that the polycystin pathway interacts with the Fz3 pathway.     

Change in Nutritional Status and Dysphagia after Resection of Head and Neck Cancer

Nutritional status is well-known to influence patient recovery after resection of head and neck cancer (HNC). The influence of preoperative nutritional status on dysphagia was assessed in patients who underwent surgical resection of HNC along with the assessment of nutritional status during the acute and subacute phases. Eighty-six patients underwent surgical resection and dysphagia assessments (repetitive saliva-swallowing test, water-swallowing test, and functional oral intake scale) and had their tongue pressure assessed five times (before surgery, after 1–2 weeks, and 1, 2, and 3 months after surgery). The nutritional status was assessed according to the body mass index, total protein, and albumin. The prognostic nutritional index was calculated from preoperative data, and the subjects were classified into three groups: Low-risk, Attention and High-risk groups. After surgery, the nutritional status index values were low, and the High-risk group showed significantly lower values in comparison to the other two groups. The water-swallowing test and functional oral intake scale findings were worse than they had been preoperatively until 2 months after surgery, and a significant correlation was noted between the postoperative nutritional status and the presence of dysphagia. The results indicated that the preoperative nutritional status of HNC patients influenced their ability to ingest/swallow, which in turn influenced their nutritional status after HNC resection.     

Oral administration of cilnidipine to patients with hypertensive intracerebral hemorrhage in the acute stage: significance and role of an N-type calcium channel blocker

Background

Elevated blood pressure (BP) causes re-bleeding or enlargement of intracerebral hematomas.

Aims

How a long-acting oral calcium channel blocker, cilnidipine, could control BP in the acute stage of cerebral hemorrhage was evaluated.

Methods and results

Cilnidipine given within 3 days of hospitalization has more benefit than cilnidipine given after 4 days of hospitalization; it can reduce the amount of intravenous nicardipine, and it can help to maintain the BP below 80% of the initial BP. Surgical removal of the hematoma has no benefit in reducing the amount of intravenous nicardipine and maintaining the BP below 80% of the initial BP.

Conclusion

In order to reduce the total amount of intravenous nicardipine and to maintain the BP below 80% of the initial BP, oral administration of a long-acting N-type calcium channel blocker, cilnidipine, is useful and important, independent of whether the hematomas are surgically removed.     

The persistent elimination of B cells responding to blood group A carbohydrates by synthetic group A carbohydrates and B-1 cell differentiation blockade: novel concept in preventing antibody-mediated rejection in ABO-incompatible transplantation

We demonstrated a novel strategy for specific and persistent inhibition of antibody (Ab) production against blood group A or B carbohydrate determinants necessary for successful ABO-incompatible transplantation. Similar to human blood group O or B individuals, mice have naturally occurring Abs against human blood group A carbohydrates in their sera. B cells with receptors for A carbohydrates in mice belonging to the CD5(+)CD11b(+)B-1a subset have phenotypic properties similar to those of human B cells. These cells could be temporarily eliminated by injecting synthetic A carbohydrates (GalNAcalpha1-3, Fucalpha1-2Gal) conjugated to bovine serum albumin (A-BSA) and anti-BSA Abs. In mice that received the injection of A-BSA/anti-BSA Abs, the serum levels of anti-A IgM were reduced, but immunization with human A erythrocytes resulted in increased serum levels of anti-A Abs. When combined with cyclosporin A (CsA) treatment, which blocks B-1a cell differentiation, and treatment with A-BSA/anti-BSA Abs, the serum levels of anti-A Abs were persistently undetectable in the mice even after the immunization. B cells with receptors for A carbohydrates were markedly reduced in these mice. These results are consistent with the hypotheses that treatment with A-BSA/anti-BSA Abs temporarily depletes B cells responding to A determinants, and CsA treatment prevents the replenishment of these cells.     

Inhibitory effects of nicorandil, a K ATP channel opener and a nitric oxide donor, on overactive bladder in animal models

OBJECTIVES

To investigate the effects of nicorandil, an ATP‐sensitive potassium (K_ATP) channel opener with a nitric oxide (NO) donor property, on overactive bladder (OAB) in animal models. Nicorandil is currently used clinically to treat ischaemic heart disease.

MATERIALS AND METHODS

Three animal OAB models were used: (i) C‐fibre mediated bladder overactivity by infusion of a low concentration of acetic acid (AA) into the bladder in female Wistar rats; (ii) bladder outlet obstruction (BOO) created by partial urethral obstruction in female Wistar rats; and (iii) neuronal NO synthase (nNOS) knockout (KO) mice with urinary frequency. The effects of nicorandil and KRN2391, both of which act as K_ATP channel openers and NO donors, on the OAB models were examined.

RESULTS

Cystometry showed that intravesical instillation of nicorandil and KRN2391 successfully inhibited OAB induced by intravesical instillation of AA. In the BOO model compared with untreated BOO rats, both nicorandil (1 and 3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency. Compared with wild‐type mice, nNOS KO mice had urinary frequency with no change in the total urine volume. Nicorandil (3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency in nNOS KO mice.

CONCLUSIONS

Our in vivo results show that nicorandil, a K_ATP channel opener with a NO donor property, can suppress OAB from both neurogenic and myogenic causes. Nicorandil appears to be a promising candidate for clinical use in patients with OAB.     

Human T and natural killer cells possess a functional renin-angiotensin system: further mechanisms of angiotensin II-induced inflammation

The renin-angiotensin system (RAS) plays an important role in the regulation of inflammation and in the progression of chronic kidney disease. Accumulation of inflammatory cells into the renal parenchyma has been a hallmark of chronic kidney disease; however, little is known concerning the presence and the function of RAS elements in T and natural killer (NK) cells. Here is reported a co-stimulatory effect of angiotensin II (AngII) by showing an augmentation of mitogen and anti-CD3-stimulated T and NK cell proliferation with AngII treatment. Angiotensinogen and AngI also generated the same effect, suggesting that NK and T cells have functional renin and angiotensin-converting enzyme activity. Indeed, they express renin, the renin receptor, angiotensinogen, and angiotensin-converting enzyme by mRNA analysis. Flow cytometric analysis and Western blot revealed angiotensin receptor 2 (AT(2)) expression in T and NK cells, whereas AT(1) expression was found in T and NK cells and monocytes by Western blot. These receptors were shown to be functional in calcium signaling, chemotaxis, and proliferation. However, AT(1) and AT(2) antagonists alone or in combination were unable to abrogate completely the effects of AngII, suggesting that another AngII receptor may also be functional in leukocytes. This is the first study to show that T and NK cells are fully equipped with RAS elements and are potentially capable of producing and delivering AngII to sites of inflammation. Because their chemotaxis is enhanced by AngII, this creates a potential inflammatory amplification system.