Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway.

The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.

Is total knee replacement more painful than total hip replacement?

BACKGROUND: During its use in pain management the patient-controlled analgesia (PCA) devices are capable of registering the course of treatment at patient request, the condition of drug delivery and total amount of drug being given. The patients could determine the need of medication to their own satisfaction while forced treatment by the bias of the health care personnel is avoided and the safety of patients is further warranted. In pain relief with this device, the number of requests for analgesia and the dose of analgesic used can be easily measured. Therefore, it is more objective to compare the pain intensity among different types of operation when PCA device is used. Using PCA morphine consumption as a parameter, we attempted to elucidate the difference of intensity of pain associated with total hip and total knee replacements by comparing their morphine requirement. METHODS: In this prospective cohort study, 50 patients who underwent either total hip replacement (THR, n = 24) or total knee replacement (TKR, n = 26) were enrolled. After recovery from general anesthesia when the patients first complained intense pain in the recovery room, morphine was given intravenously in titration with a calculated loading dose in 30 min to achieve an acceptable analgesia (VAS < or = 3) followed by morphine PCA at 1 mg bolus with a lockout interval of 6 min. The patients were then followed for 48 h. During and at the end of the course the data relevant to pain score, total dose, demand, delivery, and adverse effects were recorded for assessment. RESULTS: With the use of PCA, the pain scores were similar in both surgical groups in the 48 h observation. Total consumption of morphine in THR was 13.2 +/- 8.1 mg as against 19.7 +/- 5.7 mg in TKR in postoperative day 1 and 25.2 +/- 12.7 mg as against 34.1 +/- 13.9 mg in postoperative day 2 (P < 0.05, t-test). Demand/delivery ratio was not statistically significant between the 2 groups at 24 and 48 h (t-test). Minor adverse effects were seen in both groups but the differences were not significant. CONCLUSIONS: Using PCA morphine consumption as parameter, we can distinguish the magnitude of pain intensity between 2 major orthopedic surgeries. The deeper and more extensive operation would in total hip replacement does not mean that it is a more painful procedure than total knee replacement. Several speculations are proposed.

Patient-controlled analgesia with tramadol versus tramadol plus lysine acetyl salicylate.

UNLABELLED: By using a patient-controlled analgesia (PCA) delivery system, we compared the clinical advantages and disadvantages of PCA with tramadol and PCA with a mixture of tramadol plus lysine acetyl salicylate (a soluble aspirin). Fifty adult patients who had undergone major orthopedic surgeries were enrolled into a prospective, randomized, and double-blinded study. The general anesthesia was performed in a standard manner. At the beginning of wound closure, an equal volume dose of either tramadol 2.5 mg/kg (Group 1) or tramadol 1.25 mg/kg + lysine acetyl salicylate 12.5 mg/kg mixture (Group 2) was administered slowly IV. These solutions were continued postoperatively for IV PCA. Pain control, patient satisfaction, vital signs, and adverse effects were assessed for 48 h. Visual Analog Scale

The effects of tramadol versus fentanyl in attenuating hemodynamic response following tracheal intubation.

BACKGROUND: Tramadol is a novel central acting analgesic. It has been used as a complement to general anesthesia and an effective agent for postoperative analgesia. However, the influence of tramadol on the hemodynamic response following laryngoscopy and tracheal intubation is less known. METHODS: Forty patients of both sexes, 16-50 year old, ASA physical status I or II, scheduled for elective surgery were randomly divided into equal groups in this prospective, double blind study. After obtaining the baseline data, the patient was given 3 micrograms/kg fentanyl (Group F) or 3 mg/kg tramadol (Group T). Then induction of anesthesia in a uniform and standardized manner was carried out by an anesthesiologist who was blind to the medication. The hemodynamic parameters were measured and recorded immediately after induction but prior to laryngoscopy, 3, 6, and 9 min after intubation, and before incision. We also observed any unusual effect in the postoperative care unit. Chi-square test, Student's t-test and paired t-test were used for statistical comparison. A P less than 0.05 was considered statistically significant. RESULTS: All patients had a successful induction and intubation. Differences in baseline values were not significant, nor were the differences in the values following induction. After laryngoscopy and intubation, heart rate increased significantly above the baseline level in both groups. The increase of heart rate was significantly more at 6 and 9 min (P < 0.05) and lasted longer in the tramadol group. After intubation, systolic, mean and diastolic arterial pressure (SAP, MAP, DAP) increased significantly above baseline in both groups too, except for DAP in fentanyl group. At 6 and 9 min, the MAP and DAP were significantly higher in tramadol than in fentanyl group (P < 0.05). Six patients in tramadol group had mild pain on injection of tramadol. CONCLUSIONS: When administered right before thiopental induction, 3 mg/kg tramadol did not display a better attenuation against the increase of hemodynamic profiles than did 3 micrograms/kg fentanyl following tracheal intubation.

Immunoperoxidase staining in the differential diagnosis of parathyroid from thyroid origin in fine needle aspirates of suspected parathyroid lesions.

OBJECTIVE: To determine whether immunoperoxidase staining could be used for differential diagnosis of parathyroid from thyroid origin in fine needle aspirates of suspected parathyroid lesions. STUDY DESIGN: Immunoperoxidase staining of parathyroid hormone and thyroglobulin was performed on aspirated smears from 10 patients with parathyroid lesions (6 of 10 patients also associated with thyroid lesions) and 10 patients with thyroid lesions. All of them had surgical tissue proof of the diagnosis. RESULTS: Aspirated smears of six patients with parathyroid lesions had strong to moderate staining for parathyroid hormone and negative staining for thyroglobulin. Another four patients with parathyroid lesions had equivocal staining for parathyroid hormone and negative staining for thyroglobulin. All aspirated smears from the 16 thyroid lesions had negative staining for parathyroid hormone and positive staining for thyroglobulin. CONCLUSION: Immunoperoxidase staining of parathyroid hormone and thyroglobulin, done for each suspected parathyroid lesion, was helpful in the differential diagnosis of parathyroid vs. thyroid origin.

Value of immunoperoxidase staining of thyroglobulin in fine needle aspiration cytology of thyroid diseases.

To elucidate the value of thyroglobulin staining by the immunoperoxidase method in fine needle aspiration cytology of thyroid diseases, it was performed on fine needle aspiration smears of 57 cases of various thyroid diseases. Thirteen of 22 cases (59%) with benign nodular goiter were positive. Eight of 14 cases (57%) with papillary thyroid carcinoma were positive. Among these eight cases with positive staining, seven were at clinical stage II or less. Among the other six cases with negative staining, five cases were in clinical stage III or more. There was a significant relationship between clinical stage and thyroglobulin staining (P < .05). One of 10 cases with thyroid cysts was positive. One of four cases with anaplastic carcinoma was positive. One of two cases with follicular thyroid carcinoma was positive. Two cases of subacute thyroiditis were positive. One case of Hashimoto's thyroiditis was positive. Two cases of metastatic thyroid cancer from the ovary were negative. These results reveal that positive thyroglobulin staining was helpful in defining the source of tissue from the thyroid. However, negative staining could not definitively exclude a thyroid origin. Positive thyroglobulin staining in papillary thyroid carcinoma correlated with less advanced clinical stages.

Hormonal changes in elderly men with non-insulin-dependent diabetes mellitus and the hormonal relationships to abdominal adiposity.

To elucidate the hormonal changes in elderly men with non-insulin-dependent diabetes mellitus (NIDDM) and the hormonal relationship to abdominal adiposity, we measured serum insulin-like growth factor 1 (IGF-1), T3, T4, TSH, testosterone, LH, and FSH levels, body mass index (BMI), skinfold thickness and waist-to-hip circumference ratio (W/H) in 40 elderly men (aged over 60 years), 20 elderly men with NIDDM (aged over 60 years) and 30 men aged 21-40 years (controls). The results showed that elderly men with and without NIDDM had lower serum T3, testosterone and IGF-1 levels and higher serum LH and FSH levels compared with controls. Elderly men with NIDDM had even lower serum testosterone levels compared with elderly men without NIDDM. Elderly men had a higher W/H ratio compared with controls. Elderly men with NIDDM had a higher W/H ratio, BMI and skinfold thickness than elderly men without NIDDM. Age was positively correlated with the W/H ratio. Serum LH and FSH levels were positively correlated with the W/H ratio, and serum IGF-1, T3 and testosterone levels were negatively correlated with W/H ratio. Age, serum IGF-1, T3, T4, TSH, LH and FSH levels were not related to BMI or skinfold thickness. Only serum testosterone levels were negatively correlated with BMI or skinfold thickness. In conclusion, elderly men with NIDDM were associated with a marked decrease in serum testosterone levels and an increase of the W/H ratio compared to other groups in addition to the age-associated decrease of serum T3, IGF-1 and testosterone levels and increase of the W/H ratio and serum LH and FSH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison between the effects of epidural and spinal anesthesia for selective cesarean section].

This study is proposed to compare the analgesic and side effects of different types of anesthesia used for Cesarean section (CS). Based on the use of CS inpatients, of whom 27 were without and 20 with previous CS experience, 47 cases were randomized into two groups: 21 epidural and 26 spinal anesthesia. Visual analogue scale was used to measure the pain score in seven stages (p1-p7): skin incision, peritoneum incision, abdominal wall retraction, delivering neonate, uterus exteriorization, checking bleeding and suturing skin, respectively. Significantly higher pain scores were found in epidural than spinal anesthesia during p1 to p4. However no significant differences were found during p5 to p7. This may be due to post-delivery intravenous injection of other analgesics and sedatives. No significant differences in hypotensive rate were found between epidural and spinal anesthesia (RR = 1.04, 95% C.I. = 0.93-1.17). There were also no significant differences in occurrence of tachycardia either according to definition (PR > or = 100 beats/min or 120% of baseline pulse rate) or clinical judgement (tachycardia resulted from hypotension). (According to definition:RR = 1.08, 95% C.I. = 0.91-1.27; clinical judgement:RR = 0.83, 95% C.I. = 0.35-1.95). If clinical judgement is used as the gold standard, sensitivity and specificity were 100% and 12.5% respectively. The rate of nausea and vomiting in the epidural group was only half of that of spinal group, but was not statistically significant (RR = 0.5, 95% C.I. = 0.18-1.36). Based on the above, no significantly better effects on blood pressure and pulse rate in epidural, rather than spinal, anesthesia were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cranial irradiation on hypothalamus and pituitary functions.

Hypopituitarism can occur after cranial irradiation for tumors distant from the pituitary gland. Recent studies have suggested that this is hypothalamic in origin. Hypothalamic and pituitary functions were studied in 11 patients, 4 men and 7 women, 4.5 years or more after radiotherapy for nasopharyngeal carcinomas. The estimated average total dose was 5000 cGys for the hypothalamus and pituitary gland. Except for 2 women with amenorrhea and 4 men with impotency, the patients did not have evident endocrine deficiency. Baseline hormone profiles revealed normal T4, T3 and cortisol levels, 6 with elevated prolactin, 3 with reduced testosterone and 3 with slightly elevated basal TSH. The four menopausal women had impaired gonadotropin response to LHRH (100 micrograms, i.v.). Four (1 menstruating, 1 amenorrheic, 2 menopausal) women did not reach peak FSH response 4 hours after LHRH injection. The other amenorrheic woman had minimal FSH and LH response to LHRH which persisted even after 8 days of pulsatile infusion of LHRH (1 microgram/90min). TSH response to TRH (400 micrograms, i.v.) was delayed in 7 patients. GH response to human GRH (1 microgram/kg, i.v.) was impaired in 6 patients (maximal GH less than 5 mU/l). ACTH response to ovine CRH (1 microgram/kg, i.v.) was impaired in 3 patients (less than 50% elevation from baseline). Three patients who had normal GRH tests had impaired GH response to insulin hypoglycemia. Six patients had an empty sella on CT scan. From this study the following conclusions are drawn: (1) Among the four axes, GH is the most vulnerable. (2) The insulin tolerance test is still the best single test for evaluation of hypothalamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of levels of aminoglycosides and vancomycin in serum in the presence of new beta-lactam antibiotics.

We evaluated the effect of new beta-lactam antibiotics (azlocillin, mezlocillin, piperacillin, cefotaxime, moxalactam, and cefoperazone) on assays for aminoglycosides and vancomycin. These antibiotics produced no interference in an immunoassay for gentamicin and tobramycin. The new penicillins produced no interference in a bioassay of amikacin and vancomycin with penicillinase incorporated into the assay agar. Bioassay in the presence of the cephalosporins required predigestion with cephalosporinase. We describe a method for accurate bioassay in the presence of the available cephalosporins, with the exception of moxalactam.

Prevalence of cytoplasmic antibodies in systemic lupus erythematosus.

Prevalence of cytoplasmic antibodies--smooth muscle antibodies (SMA), gastric parietal cell antibodies (GPA), and mitochondrial antibodies (MTA)--was evaluated in 148 normal persons and 168 patients by indirect immunofluorescent method. Their prevalence in normal persons was 0%, 2% and 0% for SMA, GPA and MTA respectively, while SMA and MTA were positive in 5.7% and 8.6% of the 35 systemic lupus erythematosus (SLE) patients respectively. The difference in the prevalence of SMA and MTA between these two groups was statistically significant. The higher prevalence of these antibodies and the occurrence of various kinds of antibodies in SLE patients support the thesis that SLE is an autoimmune phenomenon.