Long-interval Group Research Articles

The Selection of Time Interval Between Surgery and Adjuvant Therapy in Early Stage Cervical Cancer.

ObjectivesThe optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages.MethodsWe performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2–IIA.ResultsFor patients with stage IA2–IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2–IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2–IIA.ConclusionsIn cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

Long- versus short-interval follow-up after resection of hepatocellular carcinoma: a retrospective cohort study

BackgroundAverage postoperative follow-up intervals vary in patients undergoing hepatocellular carcinoma (HCC) resection because of limited evidence regarding the optimal interval. We aimed to compare the associations of long-versus short-interval follow-up with survival and recurrence in risk-stratified HCC patients.MethodsWe performed a retrospective cohort study between 2007 and 2014. In total, 1227 patients treated by curative resection of Barcelona Clinic Liver Cancer stage A or B HCC were stratified as having a low (n = 865) or high (n = 362) risk of early recurrence (within the first 2 years after resection) based on prognostic factors identified by the least absolute shrinkage and selection operation algorithm. Patients were further classified into long-interval (every 4–6 months) and short-interval (every 2–4 months) follow-up subgroups based on follow-up within 2 years after resection (low risk, long vs. short: n = 390 vs. n = 475; high-risk, long vs. short: n = 149 vs. n = 213).ResultsThe short-interval follow-up did not prolong overall survival in either the low-risk (hazard ratio [HR] = 1.152; 95% confidence interval [CI] 0.720–1.843) or high-risk (HR = 1.213; 95% CI 0.702–2.094) patients. Early recurrence occurred in 401 patients. For high-risk patients, the short-interval follow-up subgroup exhibited smaller intrahepatic recurrence than did the long-interval group (2.6 vs. 3.5 cm, respectively, P = 0.045). However, no significant difference in the rate of Barcelona Clinic Liver Cancer stage 0/A recurrence was found between the long- and short-interval follow-up groups in either low- or high-risk patients (63.1% vs. 68.2%, respectively, P = 0.580; 31.3% vs. 41.5%, respectively, P = 0.280). The rate of curative intent treatment for recurrence (34.5% vs. 39.7%, respectively, P = 0.430; 14.6% vs. 20.3%, respectively, P = 0.388) was also similar between the follow-up groups for low- and high-risk patients.ConclusionsShortening the postoperative follow-up interval from every 4–6 months to every 2–4 months within the first 2 years after resection did not increase the rate of curative intent treatment or prolong the overall survival of patients with Barcelona Clinic Liver Cancer stage A or B HCC.

Temporal bone contrast-enhanced high-resolution CT evaluation of pulsatile tinnitus after sigmoid sinus wall reconstruction.

Sigmoid sinus wall reconstruction (SSWR) is a proven effective treatment for pulsatile tinnitus (PT) caused by sigmoid sinus wall dehiscence (SSWD) with or without sigmoid sinus diverticulum (SSD); however, comprehensive analysis of the postoperative imaging manifestations has not yet been reported. To analyze temporal bone computed tomography (CT) imaging features following SSWR in patients with PT. Following SSWR, temporal bone contrast-enhanced high-resolution CT (HRCT) images from 33 PT cases were retrospectively analyzed. Patients were divided into two groups based on follow-up interval: a short-interval group (≤18 months, 12 cases) and a long-interval group (>18 months, 21 cases). The mending material density and morphology was analyzed. Postoperative changes of the venous sinus were evaluated. Imaging manifestations of the normal temporal bone and mastoid air cells adjacent to the operative field were observed. The order of CT values of mending materials was significantly lower in the short-interval group than in the long-interval group (Z = -4.716, P < 0.001); the incidence of complete newly remodeled cortical bone on the rim of the mending materials was significantly higher in the long-interval group than in the short-interval group ( P < 0.001). Eleven patients (33.3%) showed varying degrees of remnant SSWD. The mending materials and normal mastoid bone structure showed complete fusion (n = 12, 36.4%), partial fusion (n = 16, 48.5%), or complete separation (n = 5, 15.2%). Temporal bone contrast-enhanced HRCT can be used to observe imaging features of the mending materials, venous sinus, adjacent normal temporal bone and mastoid air cells following SSWR.

The efficacy and safety of long- versus short-interval transarterial chemoembolization in unresectable hepatocellular carcinoma

Background: To compare the efficacy and safety of long- versus short-interval of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) patients.Methods: This retrospective analysis enrolled 574 patients with unresectable HCC who underwent at least two sessions of TACE between January 2007 and December 2014. The patients were divided into a short-interval group (SIG) and a long-interval group (LIG) based on the median TACE interval of the first two sessions. Propensity score matching (PSM) identified 476 patients for a comparison of overall survival (OS) and safety.Results: Before matching, the LIG had a longer OS than the SIG (Median: 12.1 vs. 8.7 months; P = 0.003). After matching, median OS in the SIG and LIG were 9.1 and 14.2 months (P < 0.001). The 1-, 2-, and 3-year survival rates were 37.5%, 17.1%, and 9.9% for SIG and 50.1%, 19.3%, and 11.6% for LIG, respectively. The TACE interval was an independent prognostic factor for OS. The LIG had a longer OS than the SIG in Barcelona Clinic liver cancer (BCLC) stage C patients (Median: 10.2 vs. 5.8 months; P < 0.001), but not in BCLC-A or B. The postoperative adverse rates were similar in matched SIG and LIG patients (29.4% vs. 33.6%, P = 0.324).Conclusions: A long interval between the first two sessions of TACE resulted in a better OS than a short interval in patients with unresectable BCLC C-stage HCC.

Impact of the Timing of Metoprolol Administration During STEMI on Infarct Size and Ventricular Function

BackgroundPre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI). ObjectivesThis study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-to-reperfusion interval. MethodsWe performed a post hoc analysis of the METOCARD-CNIC (effect of METOprolol of CARDioproteCtioN during an acute myocardial InfarCtion) trial, which randomized anterior STEMI patients to IV metoprolol or control before mechanical reperfusion. Treated patients were divided into short- and long-interval groups, split by the median time from 15 mg metoprolol bolus to reperfusion. We also performed a controlled validation study in 51 pigs subjected to 45 min ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (−25 min) or short (−5 min) pre-perfusion interval, IV metoprolol post-reperfusion (+60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed in the acute and chronic phases in both clinical and experimental settings. ResultsFor 218 patients (105 receiving IV metoprolol), the median time from 15 mg metoprolol bolus to reperfusion was 53 min. Compared with patients in the short-interval group, those with longer metoprolol exposure had smaller infarcts (22.9 g vs. 28.1 g; p = 0.06) and higher left ventricular ejection fraction (LVEF) (48.3% vs. 43.9%; p = 0.019) on day 5 CMR. These differences occurred despite total ischemic time being significantly longer in the long-interval group (214 min vs. 160 min; p < 0.001). There was no between-group difference in the time from symptom onset to metoprolol bolus. In the animal study, the long-interval group (IV metoprolol 25 min before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR). ConclusionsIn anterior STEMI patients undergoing primary angioplasty, the sooner IV metoprolol is administered in the course of infarction, the smaller the infarct and the higher the LVEF. These hypothesis-generating clinical data are supported by a dedicated experimental large animal study.

Increasing the Interval Between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer

The aim of this meta-analysis was to demonstrate whether a longer interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery is associated with a better rate of pathological complete response (pCR) in rectal cancer. The standard of care in locally advanced rectal cancer is preoperative, long course (5-fluorouracil-based) CRT. After this neoadjuvant CRT, surgical exploration is undertaken 6 to 8 weeks later. PubMed, EMBASE, the ISI Web of Science, and The Cochrane Library (CENTRAL) were searched systematically for prospective or retrospective studies reporting oncological results for intervals longer or shorter than 6 to 8 weeks between the end of CRT and surgery, in rectal cancer. The primary endpoint, reported as relative risk (RR), was the rate of pCR. Secondary endpoints were overall survival (OS), disease-free survival (DFS), R0 resection rates, sphincter preservations, and wound/anastomotic complications. A meta-analysis was performed, using the fixed- or random-effects model, with Review Manager 5.1. Thirteen trials, including 3584 patients, were identified, and overall, an interval longer than 6 to 8 weeks from the end of neoadjuvant CRT and surgery significantly improved the pCR (RR = 1.42, 95% confidence interval: 1.19-1.68; P < 0.0001). Pathological complete responses increased from 13.7% to 19.5% in the longer interval group, and the OS, DFS, R0 resection rates, sphincter preservation, and complication rates were similar in the 2 groups. A longer waiting interval (more than the classical 6-8 weeks) from the end of preoperative CRT increases the rate of pCR by 6% in rectal cancer, with similar outcomes and complication rates. These results should be validated prospectively in a randomized trial.

Hearing outcome does not depend on the interval of intratympanic steroid administration in idiopathic sudden sensorineural hearing loss.

We studied the effect of intratympanic steroid administration with different intervals on hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The subjects were 197 consecutive patients (197 ears) with ISSNHL (hearing level ≥40dB, interval between onset and treatment ≤30days). They received systemic administration of prednisolone (100mg followed by tapered doses) combined with intratympanic injection of dexamethasone (4mg/ml). Intratympanic injection was performed once a week for 4weeks in 105 patients (long-interval group), or 4 times in 1week in 92 patients (short-interval group). The hearing outcomes were evaluated at two points of time: 1week from the start of treatment, and 1-2months after the completion of treatment when the hearing level reached a plateau. There was no significant difference in the cure rate, marked-recovery rate, recovery rate, hearing gain, hearing level, or percent hearing improvement between the long- and short-interval groups at either point of time. Multiple regression analysis also showed that the final hearing level did not depend on the interval of intratympanic steroid injection. These results indicate that the hearing outcome of ISSNHL does not improve even if the interval of intratympanic injection is shortened. This implies that a lower total number of intratympanic steroid injections may be as effective as the present protocol.

Increasing the interval between neoadjuvant chemoradiotherapy and surgery in esophageal cancer: a meta-analysis of published studies

The aim of this meta-analysis was to clarify whether a longer interval between the end of neoadjuvant chemoradiotherapy (nCRT) and surgery is associated with better outcomes in esophageal cancer. nCRT followed by surgery is the most common approach for patients with resectable esophageal cancer. Operations are performed within 2-8 weeks after nCRT; however, the optimal interval between nCRT and surgery for esophageal cancer is unknown. We performed a systematic literature search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Clinical Trials database for studies published between January 2000 and December 2014. Eligible studies were prospective or retrospective studies of esophageal cancer that assessed the effects of intervals longer or shorter than 7-8 weeks between the end of nCRT and surgery. The primary end-points were the overall survival (OS) and pathologic complete response (pCR). Secondary end-points were anastomotic leak, R0 resection, and postoperative mortality rate. A meta-analysis was performed to estimate odds ratios (ORs) using fixed-effect and random-effect models, with Review Manager 5.2. The five studies that met the eligibility requirements included 1,016 patients: 520 in the shorter interval group (≤7-8 weeks) and 496 in the longer interval group (>7-8 weeks). The results of our meta-analysis indicate that a longer interval between nCRT and surgery may be disadvantageous for 2-year OS (OR = 1.40, 95% confidence interval [CI]: 1.09-1.80, P = 0.010) and R0 resection rate (OR = 1.71, 95% CI: 1.14-2.22, P = 0.009). The pCR, anastomotic leak rate, and postoperative morbidity were similar in the two groups. A longer interval (more than the standard 7-8 weeks) from the end of preoperative nCRT to surgery did not increase the rate of pCR in esophageal cancer, and the different intervals had similar effects on anastomotic leak rate and postoperative mortality rates. However, the longer interval between nCRT and surgery may be disadvantageous for long-term OS. These results should be validated prospectively in a randomized trial.

Impact of interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer on surgical and oncologic outcome.

The aim of this study was to evaluate the effect of a longer interval between long-course neoadjuvant chemoradiotherapy and surgery on surgical and oncologic outcome. A total of 233 consecutive patients with clinical stage II and III rectal cancer were divided into 2 groups according to the neoadjuvant-surgery interval: short-interval group (≤ 7 weeks, n = 111), and long-interval group (>7 weeks, n = 122). Data on neoadjuvant-surgery interval, operative time, perioperative complications, final pathology, disease recurrence, and mortality were prospectively collected and analyzed. The two groups were comparable in terms of demographics, tumor, and treatment characteristics. Operative time and perioperative complications were not influenced by a longer interval. Patients in the long-interval group had a significantly higher pathologic complete response (pCR) rate (27.1% vs. 15.3%, P = 0.029), and a decreased rate of circumferential resection margin involvement (1.6% vs. 8.1%, P = 0.020). After a median follow-up of 42 months (range 6-90 months), the 3-year local recurrence rate was 12.9% in the short-interval group versus 4.8% in the long-interval group (P = 0.025). A neoadjuvant-surgery interval >7 weeks is safe and is associated with a higher rate of pCR and R0 resection, and decreased local recurrence.

Effects of Intensity and Duration in Aerobic High-Intensity Interval Training in Highly Trained Junior Cross-Country Skiers

The purpose of this study was to test whether a long duration of aerobic high-intensity interval training is more effective than shorter intervals at a higher intensity in highly trained endurance athletes. The sample comprised of 12 male and 9 female, national-level, junior cross-country skiers (age, 17.5 ± 0.4 years, maximal oxygen uptake (V[Combining Dot Above]O2max): 67.4 ± 7.7 ml min kg), who performed 8-week baseline and 8-week intervention training periods on dry land. During the intervention period, a short-interval group (SIG, n = 7) added 2 weekly sessions with short duration intervals (2- to 4-minute bouts, total duration of 15-20 minutes), a long-interval group (LIG; n = 7) added 2 weekly sessions with long duration intervals (5- to 10-minute bouts, total duration of 40-45 minutes). The interval sessions were performed with the athletes' maximal sustainable intensity. A control group (CG; n = 7) added 2 weekly sessions with low-intensity endurance training at 65-74% of maximal heart rate. Before and after the intervention period, the skiers were tested for time-trial performance on 12-km roller-ski skating and 7-km hill run. V[Combining Dot Above]O2max and oxygen uptake at the ventilatory threshold (V[Combining Dot Above]O2VT) were measured during treadmill running. After the intervention training period, the LIG-improved 12-km roller ski, 7-km hill run, V[Combining Dot Above]O2max, and V[Combining Dot Above]O2VT by 6.8 ± 4.0%, 4.8 ± 2.6%, 3.7 ± 1.6%, and 5.8 ± 3.3%, respectively, from pre- to posttesting, and improved both performance tests and V[Combining Dot Above]O2VT when compared with the SIG and the CG (all p < 0.05). The SIG improved V[Combining Dot Above]O2max by 3.5 ± 3.2% from pre- to posttesting (p < 0.05), whereas the CG remained unchanged. As hypothesized, a long duration of aerobic high-intensity interval training improved endurance performance and oxygen uptake at the ventilatory threshold more than shorter intervals at a higher intensity.

Impact of Interval between Neoadjuvant Chemoradiotherapy and TME for Locally Advanced Rectal Cancer on Pathologic Response and Oncologic Outcome

The interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer has arbitrarily been set at 6-8 weeks. However, tumor regression is variable. This study aimed to evaluate whether the interval between neoadjuvant therapy and surgery had an impact on pathologic response and on surgical and oncologic outcome. A total of 356 consecutive patients with clinical stage II and III rectal adenocarcinoma were identified. Median age was 63 years, and 65 % were men. All patients received neoadjuvant chemoradiotherapy (45 Gy) with a continuous infusion of 5-fluorouracil. Data on neoadjuvant-surgery interval, type of surgery, pathology, postoperative complications, length of hospital stay, disease recurrence, and survival were reviewed. Patients were divided into two groups according to the interval between neoadjuvant therapy and surgery: ≤ 7 weeks (short interval, n = 201) and >7 weeks (long interval, n = 155). The complete pathologic response rate was 21 %. It was significantly higher after a longer interval (28 %) than after a shorter interval (16 %, p = 0.006). A longer interval did not affect morbidity or length of hospital stay. After a median follow-up of 4.9 years, the 5-year cancer-specific survival rate was 83 % in the short-interval group versus 91 % in the long-interval group (p = 0.046), and the free-from-recurrence rate was 73 versus 83 %, respectively (p = 0.026). In this retrospective analysis, there seems to be an association between a longer interval after neoadjuvant chemoradiotherapy and complete pathologic response without affecting postoperative morbidity and length of hospital stay, and with no detrimental effect on oncologic outcome.

Timing of elective laparoscopic cholecystectomy after endoscopic retrograde cholangiopancreaticography with sphincterotomy: a prospective observational study of 308 patients

Endoscopic retrograde cholangiopancreaticography (ERCP) with sphincterotomy is associated with higher rates of conversion to open surgery during subsequent laparoscopic cholecystectomy (LC). The mechanisms of this association are unclear. The aim of this study was to investigate whether the time interval between the two procedures can affect the course of LC in terms of conversion rate or complications. In this prospective observational study, 308 consecutive patients underwent ERCP with sphincterotomy followed at various intervals by elective LC. According to these intervals, the patients' data were assigned to one of three groups: short-interval (2 days or less), medium-interval (3-42 days), or long-interval (43 days or more). Groups were also defined in terms of whether gallstones were extracted during ERCP and in terms of the number of ERCPs performed (single or multiple) prior to LC. The main outcome measures for all groups were the frequency of complications during or after LC and the frequency of conversions to open surgery. Of the 308 patients, 43 required conversion to open cholecystectomy (14%). The short-interval (95 patients), medium-interval (100 patients), and long-interval (113 patients) groups did not differ significantly in terms of intraoperative complications, postoperative complications, or conversion to open surgery (p = 0.985, 0.340, and 0.472, respectively). The conversion rate also did not differ significantly according to the presence or absence of gallstones on ERCP (14.7% versus 12.8%, respectively, p = 0.392). However, compared with patients who underwent single ERCP (n = 290), those who underwent multiple ERCPs (n = 18) experienced significantly more conversion to open surgery (p = 0.026). The length of time between endoscopic sphincterotomy and LC did not affect the latter procedure in terms of complications or conversion to open surgery. However, the lack of an association between conversion rate and gallstone presence on ERCP and the higher conversion rate among patients who underwent multiple ERCPs, suggest that ERCP with sphincterotomy itself may be a factor in the higher conversion rates that have been observed after this procedure.

Rate of Pathologic Complete Response With Increased Interval Between Preoperative Combined Modality Therapy and Rectal Cancer Resection

Recent data suggest a favorable prognosis for rectal cancer patients with a pathologic complete response to preoperative combined modality therapy. Prolongation of the interval between preoperative combined modality therapy and surgery (RT-surgery interval) as a means of increasing pathologic complete response rate has not been fully examined. One hundred and fifty-five rectal cancer patients undergoing preoperative pelvic external beam radiation therapy and 5-fluorouracil-based chemotherapy followed by rectal resection were identified. All patients had endorectal ultrasound prior to combined modality therapy. Final pathology reports were reviewed for ypT and ypN stage and margin status. Medical records were reviewed for sphincter preservation, operative time, estimated blood loss, hospital stay, and morbidity (overall, anastomotic, and perineal). A pathologic complete response (ypT0N0) occurred in 24 patients (15 percent). Median RT-surgery interval was 44 (range, 15-206) days. A pathologic complete response occurred in 19 percent of patients with an interval >44 days, vs. 12 percent in those with an interval < or =44 days ( P = 0.27). Downstaging by three stages occurred more frequently in the long-interval group (15 percent vs. 6 percent, P = 0.11). The rates of sphincter preservation, positive margins, estimated blood loss, and operative time were not significantly different. Overall morbidity was similar between groups. Our results demonstrate a trend toward increased pathologic complete response rate and downstaging with increased RT-surgery interval. However, sphincter preservation is not increased. Until prospective analyses are conducted assessing the impact of prolonged RT-surgery interval on long-term outcome, the benefit of a prolonged interval between the completion of preoperative combined modality therapy and surgery remains unclear.

Reproducibility of early and late asthmatic responses to allergen challenge in a large group of asthmatics

The specific bronchial provocative test (sBPT) coupled with allergen is used to investigate asthma. Very few studies have examined the reproducibility of responses to allergen challenge. The aim of this study was to measure the reproducibility of PD20FEV1allergen and late asthmatic response (LAR) in 53 asthmatics and to relate the reproducibility to the time interval between two allergen challenges.Fifty-three atopic asthmatics performed two allergen challenges not less than 2 and not more than 26 weeks apart. Randomly, 19 subjects were assigned to a short-interval group (14–35 days between the two tests) and 34 to a long-interval group (40–180 days). In each challenge, the PD20FEV1was sought for and the maximum % fall in FEV1from 3 to 7 h after the allergen challenge was evaluated as a measurement of magnitude of the LAR.High intraclass correlation coefficients (RI) were found for both PD20FEV1(RI= 0·78) and LAR (RI= 0·77) in all subjects. PD20FEV1allergen showed a high RIin the long-interval group (RI= 0·80), but a low RIin the short-interval group (RI= 0·63). In contrast LAR showed a lower RIin the long-interval group (RI= 0·68) than in the short-interval group (RI= 0·77). Moreover, the RIfor PD20FEV1was particularly low in subjects with a dual pattern to the allergen challenge and a short interval between the two allergen challenges.Our study confirmed that asthmatic responses induced by allergen challenge have a good reproducibility. Moreover, we have demonstrated that the interval between two allergen challenges can determine a change in reproducibility in asthmatic responses induced by allergen challenge.

Time-dependent influence of sensorimotor set on automatic responses in perturbed stance.

These experiments tested the hypothesis that the ability to change sensorimotor set quickly for automatic responses depends on the time interval between successive surface perturbations. Sensorimotor set refers to the influence of prior experience or context on the state of the sensorimotor system. Sensorimotor set for postural responses was influenced by first giving subjects a block of identical backward translations of the support surface, causing forward sway and automatic gastrocnemius responses. The ability to change set quickly was inferred by measuring the suppression of the stretched antagonist gastrocnemius responses to toes-up rotations causing backward sway, following the translations. Responses were examined under short (10-14 s) and long (19-24 s) inter-trial intervals in young healthy subjects. The results showed that subjects in the long-interval group changed set immediately by suppressing gastrocnemius to 51% of translation responses within the first rotation and continued to suppress them over succeeding rotations. In contrast, subjects in the short-interval group did not change set immediately, but required two or more rotations to suppress gastrocnemius responses. By the last rotation, the short-interval group suppressed gastrocnemius responses to 33%, similar to the long-interval group of 29%. Associated surface plantarflexor torque resulting from these responses showed similar results. When rotation and translation perturbations alternated, however, the short-interval group was not able to suppress gastrocnemius responses to rotations as much as the long-interval group, although they did suppress more than in the first rotation trial after a series of translations. Set for automatic responses appears to linger, from one trial to the next. Specifically, sensorimotor set is more difficult to change when surface perturbations are given in close succession, making it appear as if set has become progressively stronger. A strong set does not mean that responses become larger over consecutive trials. Rather, it is inferred by the extent of difficulty in changing a response when it is appropriate to do so. These results suggest that the ability to change sensorimotor set quickly is sensitive to whether the change is required after a long or a short series of a prior different response, which in turn depends on the time interval between successive trials. Different rate of gastrocnemius suppression to toes-up rotation of the support surface have been reported in previous studies. This may be partially explained by different inter-trial time intervals demonstrated in this study.

Histological Observation of Bone Reaction with Relation to Surface Treatment of Titanium

The biocompatibility of the titanium has been estabilished through various experimental studies such as cell culture toxicity test, pyrogen test, mutagen test and others. In order to confirm biocompatibility after fabrication of titanium and to clarify the difference between the bone reaction after insertion of the lathed titanium rods and the bone reaction after insertion of the finished and polished rods, both rods were implanted into the proximal femur of a rabbit. Histologic reactions in the bone were observed according to the ASTM standards at the intervals of 6 weeks, 12 weeks and 26 weeks after implantation. The result were as follows : In 6 weeks after implantation of lathed titanium rods, inflammatory reactions, such as minimal degree infiltration of polymorphonuclear leukocytes and lymphocytes were observed in all cases. This was thought to he caused by surgical trauma. However, inflammatory cell infiltration was not seen after implantation of polished and finished rods in all cases. The cellular infiltration and the histologic reaction of the hone after implantation of lathed group were significantly more pronounced than those after implantation of the finished group. In 12 weeks after implantation of lathed rods, two of four cases revealed a minimal degree of cellular infiltration. No inflammatory cell infiltration was demonstrated after implantation of the finished group. The cellular infiltration and histologic reaction seemed to be more pronounced in the lathed group, but they were not significant statistically. At 26 weeks after implantation of the lathed and finished group, there was no cellular infiltration in both groups. New bone formation was observed up 26 weeks, and no difference between lathed titanium rods and finished titanium rods were apparent. Mild bone necrosis was observed in 1 case out of 11 cases in which lathed titanium rods were implanted. Bone necrosis was not observed in the finished titanium rod group. Fibrosis was observed in both groups, but differences were not significant between the experimental groups. In the lathed titanium rods group and the shorter interval group, inflammatory cell infiltration was significantly higher. Finished titanium rods and longer interval groups had markedly decreased tendences in histologic reaction ratings. As a conclusion, although certificated titanium might be safe to use, difference of biocompatibility were observed depending on the method of surface finish. By identifying biocompatibility as a long-term standardized animal study, we can develop progressed internal fixation device that is safe for human beings.

Hemostasis profile and lipid metabolism with long-interval use of a desogestrel-containing oral contraceptive

Thirty healthy women, aged 18 to 37, were randomly allocated to treatment with a desogestrel-containing oral contraceptive, with 20 women using a nine-week on, one-week off regimen, and 10 women using the traditional regimen. At 0, 3 and 12 months, blood samples were drawn for liver proteins, lipoproteins and hemostatic variables. No significant changes were observed between the two regimens. Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG, transcortin) were increased two- to four-fold, as a measure of estrogenicity. Minimal changes occurred within the lipoprotein cholesterol fractions, whereas there were some increases within the lipoprotein triglyceride fractions. Among the hemostatic variables, there were significant increases of fibrinogen, factor VII and thrombin/antithrombin III (TAT) complex. The coagulation inhibitors, antithrombin III, protein C and protein S, were essentially unchanged. A decrease of both tissue plasminogen activator antigen (t-PA) and tissue plasminogen activator inhibitor activity (PAI activity) of the fibrinolytic system was observed. A nine-week regimen does not seem to alter lipid metabolism and coagulation more than a three-week regimen.