Effects of sitagliptin on peritoneal membrane: The potential role of mesothelial cell tight junction proteins.

BACKGROUND: The roles of tight junction (TJ) proteins in peritoneal membrane transport and peritoneal dialysis (PD) require further characterisation. Dipeptidyl peptidase-4 is expressed in mesothelial cells, and its activity may affect peritoneal membrane function and morphology. METHODS: Human peritoneal mesothelial cells (HPMCs) were isolated and cultured from omentum obtained during abdominal surgery, and paracellular transport functions were evaluated by measuring transmesothelial electrical resistance (TMER) and dextran flux. Sprague-Dawley rats were infused daily with 4.25% peritoneal dialysate with and without sitagliptin administration for 8 weeks. At the end of this period, rat peritoneal mesothelial cells (RPMCs) were isolated to evaluate TJ protein expression. RESULTS: In HPMCs, the protein expression of claudin-1, claudin-15, occludin and E-cadherin was decreased by TGF-ß treatment but reversed by sitagliptin co-treatment. TMER was decreased by TGF-ß treatment but improved by sitagliptin co-treatment. Consistent with this, dextran flux was increased by TGF-ß treatment and reversed by sitagliptin co-treatment. In the animal experiment, sitagliptin-treated rats had a lower D2/D0 glucose ratio and a higher D2/P2 creatinine ratio than PD controls during the peritoneal equilibration test. Protein expression of claudin-1, claudin-15 and E-cadherin decreased in RPMCs from PD controls but was not affected in those from sitagliptin-treated rats. Peritoneal fibrosis was induced in PD controls but ameliorated in sitagliptin-treated rats. CONCLUSION: The expression of TJ proteins including claudin-1 and claudin-15 was associated with transport function both in HPMCs and in a rat model of PD. Sitagliptin prevents peritoneal fibrosis in PD and can potentially restore peritoneal mesothelial cell TJ proteins.

Sodium bicarbonate buffer for weaning from venovenous extracorporeal membrane oxygenation in patients with hypercapnic respiratory failure and acute renal failure.

Although the routine use of alkali buffer is not recommended in patients with respiratory acidosis, some patients may benefit from its administration. A 42-year-old man was treated with venovenous extracorporeal membrane oxygenation (VV-ECMO) and continuous venovenous hemodiafiltration (CVVHDF) due to necrotizing pneumonia and emphysematous cystitis with Klebsiella pneumoniae. Although the sweep gas flow rate of the VV-ECMO was gradually reduced, he failed to wean off VV-ECMO due to respiratory acidosis, followed by tachycardia and tachypnea on the 63rd day of VV-ECMO. Therefore, we mixed sodium bicarbonate in the replacement fluid of CVVHDF for 5 days to avoid an intolerable decrease in blood pH after discontinuing the VV-ECMO sweep gas. When the serum bicarbonate concentration was >30 mmol/L and pH was maintained at >7.30 with a PCO2 of >60 mmHg, VV-ECMO was finally decannulated. Sodium bicarbonate buffer through the replacement of CVVHDF fluid facilitated VV-ECMO weaning in a patient with hypercapnic respiratory failure.

Anti-Leukemic Properties of Aplysinopsin Derivative EE-84 Alone and Combined to BH3 Mimetic A-1210477.

Aplysinopsins are a class of marine indole alkaloids that exhibit a wide range of biological activities. Although both the indole and N-benzyl moieties of aplysinopsins are known to possess antiproliferative activity against cancer cells, their mechanism of action remains unclear. Through in vitro and in vivo proliferation and viability screening of newly synthesized aplysinopsin analogs on myelogenous leukemia cell lines and zebrafish toxicity tests, as well as analysis of differential toxicity in noncancerous RPMI 1788 cells and PBMCs, we identified EE-84 as a promising novel drug candidate against chronic myeloid leukemia. This indole derivative demonstrated drug-likeness in agreement with Lipinski's rule of five. Furthermore, EE-84 induced a senescent-like phenotype in K562 cells in line with its cytostatic effect. EE-84-treated K562 cells underwent morphological changes in line with mitochondrial dysfunction concomitant with autophagy and ER stress induction. Finally, we demonstrated the synergistic cytotoxic effect of EE-84 with a BH3 mimetic, the Mcl-1 inhibitor A-1210477, against imatinib-sensitive and resistant K562 cells, highlighting the inhibition of antiapoptotic Bcl-2 proteins as a promising novel senolytic approach against chronic myeloid leukemia.

Psychotropic drugs upregulate aquaporin-2 via vasopressin-2 receptor/cAMP/protein kinase A signaling in inner medullary collecting duct cells.

Psychotropic drugs may be associated with hyponatremia, but an understanding of how they induce water retention in the kidney remains elusive. Previous studies have postulated that they may increase vasopressin production in the hypothalamus without supporting evidence. In this study, we investigated the possibility of drug-induced nephrogenic syndrome of inappropriate antidiuresis using haloperidol, sertraline, and carbamazepine. Haloperidol, sertraline, or carbamazepine were treated in inner medullary collecting duct (IMCD) suspensions and primary cultured IMCD cells prepared from male Sprague-Dawley rats. The responses of intracellular cAMP production, aquaporin-2 (AQP2) protein expression and localization, vasopressin-2 receptor (V2R) and AQP2 mRNA, and cAMP-responsive element-binding protein (CREB) were tested with and without tolvaptan and the protein kinase A (PKA) inhibitors H89 and Rp-cAMPS. In IMCD suspensions, cAMP production was increased by haloperidol, sertraline, or carbamazepine and was relieved by tolvaptan cotreatment. In primary cultured IMCD cells, haloperidol, sertraline, or carbamazepine treatment increased total AQP2 and decreased phosphorylated Ser261-AQP2 protein expression. Notably, these responses were reversed by cotreatment with tolvaptan or a PKA inhibitor. AQP2 membrane trafficking was induced by haloperidol, sertraline, or carbamazepine and was also blocked by cotreatment with tolvaptan or a PKA inhibitor. Furthermore, upregulation of V2R and AQP2 mRNA and phosphorylated CREB was induced by haloperidol, sertraline, or carbamazepine and was blocked by tolvaptan cotreatment. We conclude that, in the rat IMCD, psychotropic drugs upregulate AQP2 via V2R-cAMP-PKA signaling in the absence of vasopressin stimulation. The vasopressin-like action on the kidney appears to accelerate AQP2 transcription and dephosphorylate AQP2 at Ser261.NEW & NOTEWORTHY It is unclear whether antipsychotic drugs can retain water in the kidney in the absence of vasopressin. This study demonstrates that haloperidol, sertraline, and carbamazepine can produce nephrogenic syndrome of inappropriate antidiuresis because they directly upregulate vasopressin-2 receptor and aquaporin-2 (AQP2) via cAMP/PKA signaling. We showed that, in addition to AQP2 trafficking, AQP2 protein abundance was rapidly increased by treatment with antipsychotic drugs in association with dephosphorylation of AQP2 at Ser261 and accelerated AQP2 transcription.

Predictive Role of Lung Injury Prediction Score in the Development of Acute Respiratory Distress Syndrome in Korea.

PURPOSE: Early recognition and therapeutic intervention are important in patients at high risk of acute respiratory distress syndrome (ARDS). The lung injury prediction score (LIPS) has been used to predict ARDS development; however, it was developed based on the previous definition of ARDS. We investigated the predictive role of LIPS in ARDS development according to its Berlin definition in the Korean population. MATERIALS AND METHODS: This was a retrospective study that enrolled adult patients admitted to the intensive care unit (ICU) at a single university-affiliated hospital in Korea from September 1, 2018, to August 31, 2019. LIPS at the time of ICU admission and the development of ARDS were evaluated. RESULTS: Of the 548 enrolled patients, 33 (6.0%) fulfilled the Berlin ARDS definition. The LIPS for non-ARDS and ARDS groups were 4.96±3.05 and 8.53±2.45, respectively (p<0.001); it was significantly associated with ARDS development (odds ratio 1.48, 95% confidence interval, 1.29-1.69; p<0.001). LIPS >6 predicted the development of ARDS with a sensitivity of 84.8% and a specificity of 67.2% [area under the curve (AUC)=0.82]. A modified LIPS model adjusted for age and severity at ICU admission predicted ICU mortality in patients with ARDS (AUC=0.80), but not in those without ARDS (AUC=0.54). CONCLUSION: LIPS predicted the development of ARDS as diagnosed by the Berlin definition in the Korean population. LIPS provides useful information for managing patients with ARDS.

Two women presenting aborted sudden cardiac arrest as the first event of mitral valve disease

Mitral valve prolapse (MVP) is a relatively common valvular heart disease and is known to have a benign course. However, a certain subtype of MVP has a pathologic prognosis and can be accompanied by malignant cardiac arrhythmia causing sudden cardiac arrest, which can be characterized by bileaflet mitral valvular thickening and prolapse and frequent premature ventricular ectopic activity upon electrocardiography. Herein, we present two patients with bileaflet mitral prolapse who survived aborted sudden cardiac arrest. These cases show a precise MVP diagnosis that may prevent a devastating life event with the unique MVP subtype.

Roles of claudin-2, ZO-1 and occludin in leaky HK-2 cells.

BACKGROUND: Claudin-2, ZO-1, and occludin are major components of tight junctions (TJs) in the proximal tubule. However, their roles in maintaining paracellular permeability as leaky epithelia have yet to be defined. METHODS: To investigate the contributory role of TJ proteins in the leaky proximal tubule, we xamined the effect of inhibiting claudin-2, occludin, and ZO-1 expression on transepithelial electrical resistance (TER) and paracellular permeability using the immortalized human proximal tubule epithelial cell line HK-2. For this, small-interfering RNAs (siRNAs) against claudin-2, occludin and ZO-1 were transfected into HK-2 cells. TER and transepithelial flux rates of dextrans (4 and 70 kDa) were determined after 24 h. RESULTS: Transfection of siRNAs (25 nM) knocked down TJ protein expression. Control HK-2 monolayers achieved a steady-state TER of 6-8 Ω·cm2 when grown in 12-well Transwell filters, which are compatible with leaky epithelia. Knockdown of claudin-2 decreased in TER and increased occludin expression. Transfection with siRNA against either occludin or ZO-1 increased TER and decreased claudin-2 expression. TER was decreased by co-inhibition of claudin-2 and ZO-1 but increased by co-inhibition of claudin-2 and occludin. TER was suppressed when claudin-2, occludin, and ZO-1 were all inhibited. Dextran flux rate was increased by claudin-2, occludin, or ZO-1 siRNA transfection. Increased dextran flux was enhanced by co-transfection of claudin-2, ZO-1, and occludin siRNA. CONCLUSIONS: The depletion of claudin-2, occludin and ZO-1 in HK-2 cells had differential effects on TER and macromolecule flux. We demonstrated that integration of claudin-2, occludin and ZO-1 is necessary for maintaining the function of the proximal tubular epithelium.

Fulminant lymphocytic myocarditis associated with orbital myositis and diaphragmatic paralysis.

Although the clinical presentation of myocarditis is very diverse, ranging from mild dyspnea to hemodynamic collapse, myocarditis accompanied with extracardiac myositis is extremely rare. We report a single case of fulminant myocarditis associated with orbital myositis and diaphragmatic paralysis in a 40-year-old man, which was successfully managed by immunosuppressive therapy with steroid.

Unexpected Pathologic Diagnosis of the Mitral Valvular Mass.

A 59-year-old man with multifocal cerebral infarction was found to have the large obstructive mitral valvular mass. Although benign tumor was under suspicion before surgery, he was finally diagnosed as chronic infective endocarditis by microscopic evaluation. The precise diagnosis and the proper management of a cardiac mass are very important since even the benign tumor may cause fatal complications. However, primary cardiac mass has the broad spectrum from pseudo-tumor to malignancy and the differential diagnosis using non-invasive methods is not easy even with the currently available imaging techniques.

Should preoperative chest CT be recommended to all colon cancer patients?

OBJECTIVE: The aim of this study was to evaluate the efficacy of preoperative chest computed tomography (CT) and the risk factors for lung metastasis in colon cancer patients without liver metastasis who had negative findings on initial chest X-ray (CXR). BACKGROUND: Preoperative staging with chest CT is recommended in colon cancer patients. However, there have been only scant data on the clinical efficacy. METHODS: Three hundred nineteen consecutive colon cancer patients without liver metastasis were retrospectively reviewed and analyzed. The patients had negative findings on preoperative CXR, and they underwent surgery for colon cancer during the period of January 2008 to April 2010. RESULTS: Lung nodule on chest CT was found in 136 patients (42.6%). Twenty of those were definitely diagnosed with lung metastasis (6.3%) by follow-up chest CT or pathologic confirmation. There was no case of delay in surgery due to findings of lung nodule. Comparing the group with lung metastases to that without lung metastases, postoperative pathologic findings reported more advanced T and N status (P = 0.004, P < 0.001, respectively), and lymphatic invasion was more frequent (P = 0.003) in the group with lung metastasis. By multivariate analysis, CT-predicted lymph node metastases and pathologic lymph node metastases were risk factors for lung metastases. CONCLUSIONS: Preoperative staging chest CT is not beneficial to colon cancer patients without liver metastasis and lymph node metastasis suggested on abdominal and pelvic CT who had negative finding on initial CXR.

Presence of preoperative diastolic dysfunction predicts postoperative pulmonary edema and cardiovascular complications in patients undergoing noncardiac surgery.

OBJECTIVE: The aim of this study was to evaluate the impact of left ventricular diastolic dysfunction on predicting postoperative pulmonary edema and major cardiovascular events (MACE) in patients who underwent low- or intermediate-risk noncardiac surgery. METHODS: A total of 692 patients aged >60 years who underwent transthoracic echocardiography (TTE) before undergoing elective low- or intermediate-risk noncardiac surgery were prospectively enrolled. The medical history and TTE variables were assessed. Each patient was clinically evaluated for postoperative pulmonary edema and MACE. The presence of postoperative pulmonary edema and MACE were evaluated during a 30-day follow-up period after surgery. RESULTS: We identified 166 patients with pulmonary edema and 49 patients with MACE. After adjusting for clinical and TTE variables, multivariate analysis demonstrated that a ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/e') >15, pulmonary artery systolic pressure (PASP) ≥35 mmHg, and left ventricular hypertrophy (LVH) were significantly associated with postoperative pulmonary edema (E/e', P < 0.001: PASP, P = 0.005; LVH, P = 0.017). The multivariate analysis for MACE after adjusting for clinical risk factors indicated that MACE were significantly associated with an E/e' > 15 (P < 0.001). CONCLUSION: E/e' > 15, PASP elevation, and LVH on preoperative TTE predicted postoperative pulmonary edema, and E/e' > 15 predicted MACE in the patients who underwent low- or intermediate-risk noncardiac surgery. Thus, we believe that clinicians need to be cautious when providing perioperative care to patients with high E/e' ratios who are indicated for TTE.

Enhanced systemic exposure of saquinavir via the concomitant use of curcumin-loaded solid dispersion in rats.

The present study aimed to evaluate the effect of curcumin-loaded solid dispersion on the pharmacokinetics of saquinavir in rats. Solid dispersion (SD) formulation was prepared with Solutol® HS15 to improve the solubility and bioavailability of curcumin. Subsequently, its inhibition effect on P-gp mediated cellular efflux was examined by using NCI/ADR-RES cells overexpressing P-gp. Compared to the untreated curcumin, SD formulation enhanced the cellular uptake of rhodamine-123, a P-gp substrate by approximately 3 folds in NCI/ADR-RES cells. The oral and intravenous pharmacokinetics of saquinavir were also determined in rats with/without curcumin in the different formulations. Compared to the control given saquinavir alone, curcumin-loaded solid dispersion significantly (p<0.05) increased the oral exposure of saquinavir in rats, while it did not affect the intravenous pharmacokinetics of saquinavir. The AUC and Cmax of oral saquinavir increased by 3.8- and 2.7-folds, respectively in the presence of curcumin-loaded solid dispersion. In contrast, the untreated curcumin did not affect the oral pharmacokinetics of saquinavir. These results suggest that SD formulation of curcumin should be effective to improve the in vivo effectiveness of curcumin as an absorption enhancer, leading to the improved oral exposure of saquinavir.

Acute and chronic effects of dietary sodium restriction on renal tubulointerstitial fibrosis in cisplatin-treated rats.

BACKGROUND: Renal interstitial fibrosis is a major complication of cisplatin (CP) treatment, and increased sodium intake may accelerate its progression by stimulating transforming growth factor (TGF)-ß/Smad signaling. However, it is not clear whether a low-sodium diet has beneficial effects on the development of interstitial fibrosis because it activates the renin-angiotensin-aldosterone system. Here, we tested whether the TGF-ß/Smad signaling pathway is stimulated in CP-treated rats, and whether the development of tubulointerstitial fibrosis in CP nephropathy can be checked by dietary sodium restriction. METHODS: Male Sprague Dawley rats were randomly divided into controls, CP treatment and CP treatment with low-sodium diet. The acute experiment lasted 7 days with a single intraperitoneal injection (6 mg/kg) of CP, and the chronic experiment involved weekly injections (2 mg/kg) for 7 weeks. RESULTS: In both sets of experiments, CP treatment produced pronounced tubulointerstitial injury, increased infiltration of ED1-positive cells and increased expression of monocyte chemotactic protein-1 (MCP-1), α-smooth muscle actin (SMA), TGF-ß1, phosphorylated Smad3, fibronectin and collagen III proteins. In the acute experiment, the increases in expression of osteopontin, MCP-1, α-SMA, TGF-ß and collagen III were significantly reduced by dietary sodium restriction. In the chronic experiment, however, none of the measurements were improved by a low-sodium diet. Examination of CP-treated rat kidneys revealed de novo vimentin expression in tubular epithelial cells and invasion of α-SMA-positive tubular epithelial cells through the basement membrane into the interstitium. CONCLUSIONS: The pro-fibrotic effect of TGF-ß in CP nephropathy appears to be associated with the epithelial-mesenchymal transition and is ameliorated by dietary sodium restriction only during the acute phase.

Overweight is associated with a favorable survival in patients with colorectal cancer: a prospective cohort study in an Asian population.

BACKGROUND: The influence of body mass index (BMI) on the outcome of patients with colorectal cancer (CRC) is largely unknown, particularly in an Asian population. Therefore, we investigated the influence of BMI on survival of patients who underwent surgical treatment for CRC in Korean population. METHODS: This prospective cohort study included CRC patients who underwent surgery between June 2003 and May 2005. Study participants were divided into two BMI groups: normal weight (<23 kg/m(2)) and overweight (≥23 kg/m(2)). RESULTS: A total of 509 CRC patients were included in this study. Of these, 318 patients (62.5%) were male, and the mean ± SD age was 59.1 ± 11.3 years. Two hundred eighteen patients (42.8%) were included in the normal-weight group and 291 (57.2%) were included in the overweight group. During a follow-up of 62.8 ± 27.2 months, 100 (19.6%) of the 509 eligible patients died, and 72 (15.0%) of 479 experienced recurrence. The overall survival of overweight group was more favorable compared with that of the normal-weight group (P = 0.001), while there was no significant difference in recurrence (P = 0.735). Compared with the normal-weight group, the hazard ratios of death and recurrence, respectively, were 0.615 (95% confidence interval 0.408-925; P = 0.020) and 0.992 (95% confidence interval 0.613-1.604; P = 0.973) for the overweight group. CONCLUSIONS: Overweight is not associated with an increased risk of cancer recurrence but rather is associated a favorable overall survival in Asian CRC patients undergoing surgery.

The clinical and laboratory characteristics of patients with chronic hepatitis B using current or past antiviral therapy in Korea: a multi-center, nation-wide, cross-sectional epidemiologic study.

BACKGROUND/AIMS: The proper assessment of the current disease status of patients with chronic hepatitis B would be valuable for establishing optimal management strategies. METHODS: The clinical and laboratory characteristics of 2,954 patients with current or previous antiviral treatment (46.2±10.8 years, 69.7% male) enrolled from 46 referral hospitals and 129 local hospitals or clinics throughout Korea were analyzed. RESULTS: The disease status included chronic hepatitis, cirrhosis, and hepatocellular carcinoma in 79.9%, 16.4%, and 3.7% of the patients, respectively. The major mode of hepatitis B virus (HBV) infection was vertical transmission. The hepatitis C virus (HCV) co-infection rate was 1.5%; however, only 50.8% of patients were evaluated for HCV. The use of herbal or complementary medicines was reported in 33.5% of the patients. The majority of patients (97.6%) were treated with oral nucleoside/nucleotide analogues. Several characteristics were different between the patients treated at referral hospitals and local hospitals/clinics, including the disease state, choice of antiviral drug, and methods of HBV DNA measurement. CONCLUSIONS: This study provides a comprehensive picture of the clinical and laboratory characteristics of patients treated in Korea. Efforts to optimize management strategies are warranted.

Successful retrieval of a fractured and entrapped 0.035-inch terumo wire in the femoral artery using biopsy forceps.

A 0.035-inch guide wire fracture and entrapment in a peripheral artery is a very rare complication, but when it does occur it may lead to life-threatening complications, such as perforation, thrombus formation, embolization, and subsequent limb ischemia. We describe our experience of successfully retrieving a fractured 0.035-inch Terumo guide wire in the external iliac artery using a biopsy forcep.

Association between colorectal cancer and colonic diverticulosis: case-control study based on computed tomographic colonography.

BACKGROUND: The association between colorectal cancer (CRC) and diverticulosis is uncertain, and there is little data reported in Asia. This study examined the association of both diseases based on the computed tomographic colonography (CTC). METHODS: This study was designed as a case-control study. Korean subjects undergoing CTC between April 2002 to April 2008 in Samsung Medical Center were eligible. Patients with histologically proven colorectal cancer (case group) and asymptomatic age and gender matched controls (control group) were analyzed retrospectively. RESULTS: A total of 604 subjects were enrolled in this study (Case group N = 302, Control group N = 302). The case group was 54.6% male and the median age was 56.9 years old. Among them 24.5% of CRC patients had diverticulosis compared to 29.5% of controls (P = 0.169). The distribution of diverticulosis between the two groups was similar. Subset analysis revealed no difference in the location of diverticulosis in patients with right colon cancer and left colon cancer (P = 0.781). CONCLUSIONS: This study indicates that CRC is not associated with diverticulosis.

New-onset diabetes patients need pancreatic cancer screening?

OBJECTIVE: Because patients with new-onset diabetes mellitus (DM) have a significantly increased likelihood of association with pancreatic cancer, we need to select the subgroup of diabetic patients who have more chance of association with pancreatic cancer. METHODS: We retrospectively reviewed medical records of case group (151 patients with pancreatic cancer with new-onset DM) and control group (302 patients with new-onset DM without cancer). RESULTS: Compared with the control group, pancreatic cancer group were older, had more weight loss, lower usual body mass index (BMI), more family history of pancreatic cancer (3.3% vs. 0.7%; P=0.044), and had less family history of DM (13.9% vs. 37.4%; P<0.001). If a new-onset DM patient did not have family history of DM, he was of age older than or equal to 65 years or had weight loss of >2 kg or had premorbid usual BMI <25 kg/m(2), pancreatic cancer associated DM could be discriminated from new-onset type 2 DM with 80.8% sensitivity, 67.6% specificity, 2.5% and 99.7% of positive and negative predictability for pancreatic cancer, respectively. CONCLUSIONS: Among patients who meet criteria for diabetes within 2 years, those who are elderly, have lower premorbid BMI, weight loss, no family history of DM, need screening of pancreatic cancer.

The role of proximal nephron in cyclophosphamide-induced water retention: preliminary data.

Cyclophosphamide is clinically useful in treating malignancy and rheumatologic disease, but has limitations in that it induces hyponatremia. The mechanisms by which cyclophosphamide induces water retention in the kidney have yet to be identified. This study was undertaken to test the hypothesis that cyclophosphamide may produce water retention via the proximal nephron, where aquaporin-1 (AQP1) and aquaporin-7 (AQP7) water channels participate in water absorption. To test this hypothesis, we gave a single dose of intraperitoneal cyclophosphamide to male Sprague-Dawley rats and treated rabbit proximal tubule cells (PTCs) with 4-hydroperoxycyclophosphamide (4-HC), an active metabolite of cyclophosphamide. In the short-term 3-day rat study, AQP1 protein expression was significantly increased in the whole kidney homogenates by cyclophosphamide administration at 48 (614 ± 194%, P < 0.005), and 96 (460 ± 46%, P < 0.05) mg/kg BW compared with vehicle-treated controls. Plasma sodium concentration was significantly decreased (143 ± 1 vs. 146 ± 1 mEq/L, P < 0.05) by cyclophosphamide 100 mg/kg BW in the long-term 6-day rat study. When primary cultured rabbit PTCs were treated with 4-HC for 24 hours, the protein expressions of AQP1 and AQP7 were increased in a dose-dependent manner. Quantitative polymerase chain reaction revealed no significant changes in the mRNA levels of AQP1 and AQP7 from cyclophosphamide-treated rat renal cortices. From these preliminary data, we conclude that the proximal nephron may be involved in cyclophosphamide-induced water retention via AQP1 and AQP7 water channels. Further studies are required to demonstrate intracellular mechanisms that affect the expression of AQP proteins.

Bronchoscopic features and bronchoscopic intervention for endobronchial hamartoma.

BACKGROUND AND OBJECTIVE: Bronchoscopic resection of endobronchial hamartomas has been reported to have a favourable outcome. This study describes the bronchoscopic features of endobronchial hamartoma and reports the clinical outcome of bronchoscopic intervention. METHODS: A retrospective analysis was conducted of patients with histologically proven endobronchial hamartomas, diagnosed in the 10-year period 1999-2009 to elucidate the clinical, radiological and bronchoscopic features of hamartoma and to describe the clinical outcomes. RESULTS: Seventeen of the 135 patients with pulmonary hamartomas were diagnosed as having endobronchial hamartomas. CXR was abnormal in 11 of the 17 patients. On chest CT (n = 16), the median diameter of the lesion was 15.6 mm. Calcification and areas of focal fat in the lesion, the diagnostic CT findings of pulmonary hamartoma, were found in two of 16 (12.5%) patients. At bronchoscopy (n = 16), all tumours had a mass appearance and most were smooth surfaced round masses (50.0%) with 18.8% having a 'stalk'. Bronchoscopic forceps biopsies were performed in 13 patients, which resulted in five patients (38.5%) being diagnosed with endobronchial hamartoma. Fifteen patients were treated with rigid or flexible bronchoscopic resection, one had lobectomy, and one had no intervention. No procedure-related mortalities or late complications developed. CONCLUSIONS: Bronchoscopic intervention appears to be a safe and effective method to resect endobronchial hamartomas.