Extracellular volume regulation and growth

We have formalized extracellular and intracellular volume interaction with each other and the influence of these processes on the type of cell growth. The linearized model was verified by stereo metric solution and the results were compared with experimental data. Two theoretical solutions were found: Solution 1, extracellular volume (ECV) was calculated to be about 23% of total body volume (TV). Stereo metric solution suggested the cubic cell cluster formed by 8-cells. This hypothesis (Solution l) explains the ECV to be compatible with the widely accepted value (about 23% of TV). In addition, the 8-cell cluster hypothesis explains the existence of ECV oscillation with the period of about seven days. This hypothesis probably describes the dominant type of growth in humans. Solution 2, in this type of growth, ECV fills about 77% per cent of TV. Instead of the 8-cell cube, in this type of proliferation 4-cells could form a tetrahedron. This type of growth could be beneficial in processes where free space in tissue or organ must be filled for example in peptic ulcer healing and namely in repopulating of free space in a bone after high dose chemotherapy.     

Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease

Context  Elevated concentrations of B-type natriuretic peptide (BNP) at presentation in patients with acute coronary syndrome (ACS) are associated with long-term mortality. Few data exist regarding serial assessment of BNP levels during follow-up. Objective  To determine whether concentrations of BNP at study entry (prior to hospital discharge for ACS) and at outpatient follow-up at 4 months and 12 months are associated with subsequent clinical outcomes. Design, Setting, and Patients  Prospective observational substudy of 4497 patients with non–ST-elevation or ST-elevation ACS who were enrolled in phase Z of the A to Z trial, which was conducted in 41 countries at 322 acute care hospitals between 1999 and 2003. Main Outcome Measure  Death from any cause or new onset of congestive heart failure (CHF) through 2 years. Results  Levels of BNP were available in 4266 patients at study entry (prior to hospital discharge), 3618 patients at 4 months, and 2966 patients at 12 months. During follow-up there were 230 deaths and 163 incident cases of CHF. Adjusting for age, sex, index event, renal function, hypertension, prior heart failure, and diabetes, elevated levels of BNP (>80 pg/mL) were associated with subsequent death or new CHF when measured at study entry (111 [21%] vs 246 [7%]; adjusted hazard ratio [HR], 2.5; 95% confidence interval [CI], 2.0-3.3), at 4 months (34 [19%] vs 125 [4%]; adjusted HR, 3.9; 95% CI, 2.6-6.0), and at 12 months (19 [11%] vs 37 [1%]; adjusted HR, 4.7; 95% CI, 2.5-8.9). Patients with newly elevated levels of BNP at 4 months were at increased risk of death or new CHF (10 [15%] vs 105 [3%]); HR, 4.5; 95% CI, 2.3-8.6). Patients with elevated levels of BNP at study entry and with BNP levels lower than 80 pg/mL at 4 months tended to have only modestly increased risk (HR, 1.7; 95% CI, 1.0-2.9) compared with patients with BNP levels lower than 80 pg/mL at both visits. Conclusions  Serial determinations of BNP levels during outpatient follow-up after ACS predict the risk of death or new CHF. Changes in BNP levels over time are associated with long-term clinical outcomes and may provide a basis for enhanced clinical decision making in patients after onset of ACS. Clinical Trials Registration  ClinicalTrials.gov Identifier: NCT00251576      

Cystatin C as a marker of residual renal function during continuous hemodiafiltration

BACKGROUND: The level of residual renal function (RRF) has an important impact on follow-up in critically ill patients with renal failure. There is currently no clear marker of RRF. METHODS: Cystatin C (cysC) concentrations were measured before and during the first 48 h of CVVHDF in 33 mechanically ventilated patients suffering from renal failure. Samples were drawn both from the ports proximal and distal to the filter. Each of the two control groups consisted of 10 patients. RESULTS: The levels of cysC were significantly higher in the group where diuresis (Vu) remained low or decreased after 48 h of treatment (n = 21, Vu median 380 (80-935) ml/24 h, cysC range 4.44-3.42 mg/l) than in the group where Vu increased to the level of 1.5 ml.kg(-1).h(-1) or higher after 48 h of treatment (n = 12, Vu 4,570 (4,000-5,130) ml/24 h, cysC 3.17-2.46 mg/l, p < 0.01). Creatinine clearance taken before treatment was not different between the groups. Significant correlation between cysC levels and Vu was found (r = -0.44, p < 0.0001). CysC levels were significantly higher in non-survivors than in survivors (3.54 +/- 1.38 vs. 3.07 +/- 1.24, p < 0.03). CONCLUSION: The levels of cysC are inversely related to Vu. High levels of cysC are associated with low residual diuresis, longer duration of CVVHDF and higher intensive care unit mortality in patients treated with CVVHDF.     

5-aminolaevulinic acid-induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer

OBJECTIVE: To assess the influence of 5-aminolaevulinic acid-induced fluorescence cystoscopy (FC) during transurethral resection (TUR) on the recurrence rate and the length of tumour-free interval in stage Ta/T1 transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: In all, 122 patients with primary or recurrent stage Ta/T1 bladder TCC treated with TUR were enrolled in a prospective randomized study. In group A the TUR was performed with standard white-light endoscopy, and in group B with FC. The patients were followed using standard cystoscopy and urinary cytology. The recurrence-free interval was evaluated in whole groups, for single and multiple, and for primary and recurrent tumours separately. RESULTS: At the time of the first cystoscopy (10-15 weeks after TUR) tumour recurrence was detected in 23 of 62 patients (37%) in group A, but only in five of 60 patients (8%) in group B. The recurrence-free survival rates in group A were 39% and 28% after 12 and 24 months, compared to 66% and 40% respectively in group B (P = 0.008, log-rank test). In separate analyses, the recurrence-free survival rates were significantly higher using FC in multiple (P = 0.001) and in recurrent (P = 0.02) tumours. In solitary and primary tumours the median time to recurrence was also longer in group B, but the difference was not statistically significant. CONCLUSION: 5-aminolaevulinic acid-induced FC during TUR reduces the recurrence rate in stage Ta/T1 bladder TCC. The most significant benefit is in patients with multiple and recurrent tumours.     

Laparoscopic Colorectal Surgery in Obese Patients

Background: The aim of the study was to the evaluate results of laparoscopic colorectal surgery in obese patients. Methods: All patients who underwent elective laparoscopic colorectal surgery from January 1993 to December 2003 were included in the study. BMI >30 was used as an objective obesity criterion. The evaluated parameters included BMI, age, sex, diagnosis and associated diseases, American Society of Anesthesiologists classification score (ASA), type and duration of procedure, peroperative and postoperative complications, postoperative course, reoperation, length of hospitalization, morbidity and early mortality. Results: 435 patients were evaluated. There were 80 patients (18%) in the obese group, and 355 patients (82%) were non-obese. The samples were comparable in terms of age, gender, ASA, diagnosis and procedure. Peroperative complications occurred more frequently in the obese group of patients (4% vs 2.5%, P>0.05) and the operating time was longer as well (151 min vs 141 min, P>0.05), both statistically not significant. There was no difference in postoperative course in both groups with regard to intravenous administration of analgesics (2 days), start of solid diet (day 3) and first bowel movement (day 4). Morbidity was higher in the obese group of patients (33% vs 24%, P>0.05), and reoperations were also more frequent here (13% vs 7%, P>0.05), which was reflected in prolonged hospital stay (14 days vs 12 days, P>0.05). On the other hand, early mortality was surprisingly lower in the obese group of patients (2.5% vs 6%, P>0.05). However, none of these differences achieved statistical significance on the set significance level of P=0.05. Conclusion: With sufficient experience, laparoscopic colorectal surgery in obese patients is feasible and safe. It is associated with no increased risk of complications and preserves all benefits of the mini-invasive approach.     

Carcinoid-like pattern in sebaceous neoplasms: another distinctive, previously unrecognized pattern in extraocular sebaceous carcinoma and sebaceoma

This report emphasizes a carcinoid-like pattern, a previously unrecognized feature in cutaneous sebaceous neoplasms. We report 7 patients with sebaceous tumors in which neoplastic cells were arranged in a trabecular and ribbon-like pattern or formed rosettes/pseudorosettes. The cases included 6 men and 1 woman, with their ages at the diagnosis ranging from 43 to 87 years (median age, 59). All patients presented with a solitary lesion. Locations were the scalp (n = 6) and forearm (n = 1). The carcinoid-like arrangement of neoplastic cells was the sole pattern in 4 cases, and in 3 cases the so-called labyrinthine/sinusoidal and/or rippled patterns were seen in addition. Sebaceous differentiation in the form of mature sebocytes varied from almost none to approximately 10%. Although the neoplasm appeared benign architecturally, the presence of cytologic atypia qualified 2 tumors as low-grade carcinomas. Four lesions represented sebaceomas, and in 1 case microscopic delineation between a carcinoma and sebaceoma was difficult. No neuroendocrine differentiation was demonstrated immunohistochemically, histochemically, and ultrastructurally. Electron microscopic examination performed in 1 case of carcinoma revealed lipid vacuoles in a minority of cells. There were no membrane-bound neuroendocrine granules. Rare cells contained peculiar large helioid inclusions. We conclude that the carcinoid-like pattern is another distinctive pattern indicative of sebaceous neoplasms. This pattern seems to be closely related to the rippled and labyrinthine/sinusoidal patterns, as exemplified by our cases, in which these arrangements sometimes occurred simultaneously.     

Amplification of <Emphasis Type="Italic">NOTCH1</Emphasis> and <Emphasis Type="Italic">ABL1</Emphasis> gene loci is a frequent aberration in enteropathy-type T-cell lymphoma

We have shown previously that amplification of chromosomal region 9q34 is the most frequent aberration in enteropathy-type T-cell lymphoma (ETL). To determine the minimum amplified 9q34 region and identify possible candidate gene(s), we performed a detailed microsatellite screening and quantitative real-time PCR (QPCR) on 26 ETL cases. Microsatellite analysis revealed allelic imbalance in both ABL1 and NOTCH1 gene loci (microsatellites D9S290–D9S1847 and D9S158 flanking the former and latter genes, respectively) localized in the band 9q34. The results were confirmed by TaqMan-based QPCR showing amplification of ABL1 and NOTCH1 exons in 50% and 65% of cases, respectively. Amplifications of the NOTCH1 gene were more frequent than of the ABL1 gene; moreover, the analyzed NOTCH1 exon consistently displayed higher levels of amplification than ABL1 coding sequences. From 9q34 known genes, NOTCH1 could thus be the primary target of genomic DNA amplification in ETL.