Mucinous carcinomas of the colorectum have distinct molecular genetic characteristics

We compared the frequency of CpG island methylation phenotype (CIMP), inactivation of APC, p53 and DCC genes and K-ras and BRAF mutations in 39 mucinous carcinomas (MC) and 34 non-mucinous carcinomas (NMC) of the colorectum with different microsatellite instability (MSI) status. The higher incidence of MSI (36% vs. 18%) was observed in MC compared with NMC. APC inactivation and K-ras mutations occurred more frequently in NMC (APC, 88%, p<0.001; K-ras, 58%, p=0.01) than in MC (APC, 24%; K-ras, 28%) regardless of MSI status. BRAF mutation occurred at a higher frequency in MC (18%, p=0.01) than in NMC (0%). However, with respect to inactivation of p53 and DCC, MSI status did matter and in both NMC and MC, more frequent inactivation of p53 and DCC was observed in MSS tumors than in MSI tumors. MSS tumors of NMC had a higher frequency of p53 (58% by IHC, p=0.03 and 83% by LOH, p=0.02) and DCC inactivation (83%, p=0.02) compared to MSI tumors of NMC (p53, 33% by IHC and 20% by LOH; DCC, 20%). MSS tumors of MC also showed a higher frequency of p53 and DCC inactivation (p53, 45% by IHC, p=0.02 and 53% by LOH, p=0.005; DCC, 82%, p=0.001) compared to MSI tumors of MC (p53, 0% by IHC and 0% for LOH; DCC, 17%). MC showed a higher frequency of CIMP compared with NMC (41% vs. 11%, p=0.01). These results indicate that mucinous carcinomas of the colorectum exhibit distinct molecular genetic characteristics and may arise from distinct pathogenic pathways.     

Inpatient rehabilitation of patients requiring hemodialysis: improving efficiency of care

OBJECTIVE: To determine if reducing missed therapy sessions by patients requiring hemodialysis will reduce the length of stay (LOS) and improve the efficiency of care in an inpatient rehabilitation unit. DESIGN: Retrospective study. SETTING: Inpatient rehabilitation unit at a university medical center. PARTICIPANTS: All patients discharged from the Albany Medical Center rehabilitation unit between January 1, 2003, and June 30, 2004. The total number of patients was 955, 40 of whom required hemodialysis. INTERVENTION: On January 1, 2003, Albany Medical Center began providing hemodialysis in the late afternoon, allowing patients to complete a full 3-hour program without missing therapy sessions to attend dialysis. We compared the outcomes of 915 patients who did not require hemodialysis with the outcomes of 40 patients who required hemodialysis. We also compared the outcomes of patients treated on the rehabilitation unit in 2003-2004 to the outcomes of patients treated on the rehabilitation unit before dialysis was available at times that did not conflict with therapy (calendar year 2001). MAIN OUTCOME MEASURES: LOS, improvement on the FIM instrument, and FIM efficiency score. RESULTS: The LOS of the hemodialysis patients changed from 16.0 in 2001 to 12.1 in 2003-2004 (P<.05), and the FIM efficiency score of the hemodialysis patients improved from 1.8 in 2001 to 2.9 in 2003-2004 (P<.05). The FIM efficiency score of the nondialysis group in 2003-2004 was 4.0. This was significantly greater (P<.05) than that of dialysis patients in 2003-2004. CONCLUSIONS: A program to reduce conflicts between medical treatments such as hemodialysis and therapy sessions may result in reduced LOS and improved efficiency on an inpatient rehabilitation unit.     

Respiratory motion prediction by using the adaptive neuro fuzzy inference system (ANFIS)

The quality of radiation therapy delivered for treating cancer patients is related to set-up errors and organ motion. Due to the margins needed to ensure adequate target coverage, many breast cancer patients have been shown to develop late side effects such as pneumonitis and cardiac damage. Breathing-adapted radiation therapy offers the potential for precise radiation dose delivery to a moving target and thereby reduces the side effects substantially. However, the basic requirement for breathing-adapted radiation therapy is to track and predict the target as precisely as possible. Recent studies have addressed the problem of organ motion prediction by using different methods including artificial neural network and model based approaches. In this study, we propose to use a hybrid intelligent system called ANFIS (the adaptive neuro fuzzy inference system) for predicting respiratory motion in breast cancer patients. In ANFIS, we combine both the learning capabilities of a neural network and reasoning capabilities of fuzzy logic in order to give enhanced prediction capabilities, as compared to using a single methodology alone. After training ANFIS and checking for prediction accuracy on 11 breast cancer patients, it was found that the RMSE (root-mean-square error) can be reduced to sub-millimetre accuracy over a period of 20 s provided the patient is assisted with coaching. The average RMSE for the un-coached patients was 35% of the respiratory amplitude and for the coached patients 6% of the respiratory amplitude.     

Ropinirole in the treatment of restless legs syndrome

Ropinirole is an original nonergoline dopamine agonist indicated for the treatment of Parkinson's disease. However, recent developments in the study of restless legs syndrome have demonstrated another role for this drug. The symptoms of restless legs syndrome are responsive to dopaminergic agents such as ropinirole. The dosage of ropinirole needed to treat the symptoms of restless legs syndrome appears to be much smaller than what is necessary for Parkinson's disease therapy. The liver is primarily responsible for the metabolism of ropinirole, which has an elimination half-life of approximately 6 h. Ropinirole is generally well tolerated, with no serious adverse effects. Clinical studies have indicated that ropinirole can effectively reduce the motor symptoms of restless legs syndrome and improve overall sleep quality.     

Accuracy of liver fat quantification at MR imaging: comparison of out-of-phase gradient-echo and fat-saturated fast spin-echo techniques--initial experience

PURPOSE: To retrospectively determine the relative accuracy of liver fat quantification with out-of-phase gradient-echo magnetic resonance (MR) imaging and fat-saturated fast spin-echo MR imaging in patients with and without cirrhosis, with histologic analysis as the reference standard. MATERIALS AND METHODS: Committee on Human Research approval was obtained. Patient consent was not required. Data collection ended before HIPAA regulations were implemented, but patient anonymity was maintained. Twenty-seven patients, 16 with cirrhosis, were retrospectively identified who underwent MR imaging before histopathologic evaluation of liver fat at biopsy or surgery. The patient population consisted of 15 male and 12 female patients (mean age, 55 years; range, 16-75 years). One radiologist blinded to the histopathologic results recorded mean signal intensity derived from three regions of interest placed in the right and left lobes of the liver on three sections and signal intensity of the spleen from one region of interest within the same section. Liver fat was quantified with the relative loss of signal intensity on out-of-phase images compared with that on in-phase T1-weighted gradient-echo images and with relative loss of signal intensity on T2-weighted fast spin-echo MR images obtained with fat saturation compared with those obtained without fat saturation. Hotelling t test was used to compare correlation coefficients between relative signal intensity differences and histopathologically determined percentage of fat. RESULTS: In patients without cirrhosis, liver fat quantification with fat-saturated fast spin-echo MR imaging was significantly better than it was with out-of-phase gradient-echo MR imaging (r = 0.92 vs 0.69, P < .01). In patients with cirrhosis, liver fat quantification was correlated only with fat-saturated fast spin-echo MR imaging (r = 0.76, P < .01); the relative signal intensity loss on out-of-phase gradient-echo MR images was not correlated with histopathologically determined percentage of fat (r = 0.25, P = .36). CONCLUSION: Preliminary results suggest liver fat may be more accurately quantified with fat-saturated fast spin-echo MR imaging than with out-of-phase gradient-echo MR imaging, especially in patients with cirrhosis.     

Thiazide use and the risk of cholecystectomy in women

As part of a case-control study of gallstone disease conducted among the female members of Group Health Cooperative of Puget Sound, the authors investigated the possible etiologic role of prior use of thiazide diuretics. One hundred fifty-three women who underwent gallstone surgery between January 1979 and September 1980, and 156 controls selected from membership files, were interviewed about their past use of certain medications, their reproductive history, and physical and demographic characteristics. The risk of gallstone disease which required surgery among women who had used thiazides relative to those who had not used this drug, after controlling for age, race, pregnancy, and body mass index, was 1.9 (95% confidence interval (CI) = 1.0-3.7). However, this association was present only among women who were not overweight, i.e., those with body mass index less than or equal to 36, for whom the relative risk was 5.0 (95% CI = 1.8-13.5). Among overweight women, the relative risk was 1.0 (95% CI = 0.5-2.2). Among women who were not overweight, there was no further increase in risk with increasing duration or recency of thiazide use. These data fail to agree with data from earlier studies which show a possible thiazide-gallstone disease association. The results of the present study suggest that if thiazide use has any influence on the occurrence of gallstone disease in women, that influence exists primarily in those who are not overweight.     

Development of cystic glandular hyperplasia of the endometrium in Mullerian inhibitory substance type II receptor-pituitary tumor transforming gene transgenic mice

The pituitary tumor transforming gene (PTTG)/securin is an oncogene that is involved in cell cycle regulation and sister chromatid separation. PTTG is highly expressed in various tumors including ovarian tumors, suggesting that PTTG may play a role in ovarian tumorigenesis. Overexpression of PTTG resulted in induction of cellular transformation in vitro and tumor formation in nude mice. To ascertain PTTG function in ovarian tumorigenesis, we generated a transgenic mouse model of PTTG by cloning PTTG cDNA downstream of Mullerian inhibitory substance type II receptor gene promoter (MISIIR) in order to target the ovarian surface epithelium. By screening of transgenic animals, we identified five founders (four males and one female). Using the four male founders, we developed four transgenic lines. PTTG expression was increased in ovarian surface epithelium, ovarian granulosa cells, as well as in the pituitary gland. Transgenic females did not develop any visible ovarian tumors at 8-10 months of age; however, there was an overall increase in the corpus luteum mass in transgenic ovary, suggesting increased luteinization. These changes were associated with an increase in serum LH and testosterone levels. In addition, there was a generalized hypertrophy of the myometrium of MISIIR-PTTG transgenic uteri with cystic glandular and hyperplasia of the endometrium. Based on these results, we conclude that the overexpression of PTTG may be required to initiate precancerous conditions but is not sufficient to induce ovarian tumorigenesis and may require another partner to initiate cellular transformation.