Chronic eccentric cycling improves quadriceps muscle structure and maximum cycling power.

An interesting finding from eccentric exercise training interventions is the presence of muscle hypertrophy without changes in maximum concentric strength and/or power. The lack of improvements in concentric strength and/or power could be due to long lasting suppressive effects on muscle force production following eccentric training. Thus, improvements in concentric strength and/or power might not be detected until muscle tissue has recovered (e. g., several weeks post-training). We evaluated alterations in muscular structure (rectus-femoris, RF, and vastus lateralis, VL, thickness and pennation angles) and maximum concentric cycling power (Pmax) 1-week following 8-weeks of eccentric cycling training (2×/week; 5-10.5 min; 20-55% of Pmax). Pmax was assessed again at 8-weeks post-training. At 1 week post-training, RF and VL thickness increased by 24±4% and 13±2%, respectively, and RF and VL pennation angles increased by 31±4% and 13±1%, respectively (all P<0.05). Compared to pre-training values, Pmax increased by 5±1% and 9±2% at 1 and 8 weeks post-training, respectively (both P<0.05). These results demonstrate that short-duration high-intensity eccentric cycling can be a time-effective intervention for improving muscular structure and function in the lower body of healthy individuals. The larger Pmax increase detected at 8-weeks post-training implies that sufficient recovery might be necessary to fully detect changes in muscular power after eccentric cycling training.

Extreme enhanced myometrial vascularity following cesarean scar pregnancy: a new diagnostic entity.

OBJECTIVE: To define, illustrate and to follow-up the diagnosis, pathophysiology and treatment of a subset of the known enhanced myometrial vascularity (EMV): its extreme form, associated with cesarean scar pregnancies (CSP) and with some cases pf placenta accreta spectrum being at increased risk of significant bleeding complications. We also aim to provide guidance to the management of such cases. MATERIAL AND METHODS: This is an IRB-approved retrospective observational study of thirteen patients with an extreme form of EMV complicating CSPs. Patient's age, parity, number of cesarean deliveries, initial and time to negative serum hCG levels, primary and secondary diagnoses, blood flow peak systolic velocities, primary and secondary treatments, uterine artery embolization and outcomes were recorded. RESULTS: Gestational ages ranged 6-11 weeks at initial presentation. Initial serum hCG was 20.0-102.48 mIU/L (mean 44.4 mIU/L). Diameter of EMV reached 20-75 mm (mean 46.8 mm). The mean peak systolic velocity (PSV) was 84.2 cm/s (range 46.7-118.0). Primary treatments were: systemic methotrexate (MTX) alone; D&C alone; MTX and D&C; local and systemic intra-gestational MTX injection; double cervical ripening balloon with systemic MTX; misoprostol and D&C; emergent UAE. UAE and hysterectomy were the two main secondary treatments in 10 women except 1 having a D&C after UAE, and in 1 the lesion regressed without secondary treatment. Mean time to nonpregnant hCG levels was 21-122 days (mean 67.2). Mean follow-up was 110.2 days (range 26-160). Ten women were treated with UAE, 6 had one, 3 had two embolizations. Two women had hysterectomies, one of these for persistent bleeding. Based upon the common denominators of the clinical and the US pictures, our definition of extreme EMV is sustained form of EMV associated with treated or untreated CSP, with peak systolic velocities of blood flow over 50 cm/s, slow return or plateauing serum hCG, with or without clinically significant vaginal bleeding, unresponsive to initial or secondary treatment requiring uterine artery embolization or hysterectomy. CONCLUSION: The EMV developing in the background of retained placental tissue associated with CSP differs following the normal regression of the physiologically re-modelled, dilated vascular bed from the faulty "disrepair" of the vessel wall in in treated or untreated CSPs. The "threatening" appearance of the above EMVs warranted the term "extreme", creating their separate new sub-category." Extreme forms of CSP-related EMV pose significant diagnostic and management challenges. Prompt recognition and intervention, the proactive use of UAE, can maximize the outcome of women affected by this "extreme" form of EMV enabling to preserve reproductive potential. Obstetricians, gynecologists and interventional radiologists should be aware of this form of severe vascular complication.

Microbial persistence. II. Characteristics of the sterile state of tubercle bacilli.

The capability of tubercle bacilli to assume a long continued sterile state in the tissues when exposed to pyrazinamide and isoniazid is a highly specific drug-microbe phenomenon in which host participation is not critical. Although it is the pyrazinamide that possesses the sterilizing type of action, the role of the isoniazid is specific and essential. The isoniazid serves to convert a phenomenon that occurs irregularly with pyrazinamide alone into one that occurs with a high degree of uniformity. The observations suggest a competition between isoniazid and the pyrazinamide (or its parent nicotinamide) for a site or entrance in or on the tubercle bacilli and for sterilization, the isoniazid apparently must reach the site first. The rare failures to attain complete sterilization, appear to depend on the emergence of pyrazinamide-resistance which prevents the necessary dependent action of the two drugs. Populations already in the sterile state are nevertheless subject to a continued drug influence. Whether this represents a direct action on the sterile bacilli or an indirect effect produced by making the environment hostile to microbial revival, cannot be determined from the present observations.

Microbial persistence. I. The capacity of tubercle bacilli to survive sterilization in mouse tissues.

A previously reported form of microbial persistence whereby large populations of tubercle bacilli can be made to "vanish" uniformly from the tissues of mice has been shown to occur generally throughout each group of animals subjected to the experimental procedure; it does not reflect the eradication of the bacilli in the majority of animals with their persistence and ultimate revival in only a minority. The one demonstrable alteration of the tubercle bacilli while "vanished" is that they are sterile. Thus, they are undetectable by cell-free culture, tissue culture, and blind animal passage, i.e. by any method based on microbial multiplication. Whether they have also undergone alteration in morphology and persist in some unconventional form cannot be stated. Acid-fast forms similar to tubercle bacilli can be detected in small numbers by intensified microscopic search of tissue homogenates but the relationship of these forms to the sterile bacilli that ultimately revive is unclear. Thus, the persisting tubercle bacilli are more correctly designated as being in a "sterile state" than one of true latency. The uniform induction of the sterile state is a specific phenomenon requiring the participation of both the nicotinamide derivative, pyrazinamide, and isoniazid. Once assumed, this sterile state is relatively stable and the time required for revival of the tubercle bacilli in the spleens in one-half the animals is seven months. This process can be speeded up by the administration of large doses of cortisone in the third or fourth month after sterilization but revival is not significantly affected by the administration of cortisone earlier.

Pharmaceuticals: their role in developing societies.

The appropriate technology for control of diseases of economically underdeveloped countries happens to be mainly that applicable to groups as a whole; whereas that effective for most diseases of industrialized societies must be individually delivered. The latter area is where the pharmaceutical industry has scored its greatest triumphs, yet most of this technology does not fit the major disease problems as they now exist in the developing countries. The argument is presented that in order for the U.S. industry to do more in the developing countries, the most needed invention is not a new drug, but a new system for drug development--a new R & D system tailored specially to both the financial and the biologic needs of the problem.

Surgical innovation and its evaluation.

Early clinical trials, observational or randomized, hasten the prompt evaluation of new operations. Early clinical surveillance facilitates the design and implementation of randomized clinical trials when they are necessary. Of equal or greater importance, long-term surveillance of operations allows continuing evaluation when their use becomes widespread. Standards, coordination, review, and funding of the evaluation of new operations we believe should be centralized in a single national agency, for which an Institute of Health Care Assessment might be created. Implementation and regulation of the evaluation we believe should remain at the local or regional level with existing mechanisms and agencies being used, such as institutional human research committees and local health systems agencies.

Selective oxidative dehydrogenation of propane to propene using boron nitride catalysts.

The exothermic oxidative dehydrogenation of propane reaction to generate propene has the potential to be a game-changing technology in the chemical industry. However, even after decades of research, selectivity to propene remains too low to be commercially attractive because of overoxidation of propene to thermodynamically favored CO2 Here, we report that hexagonal boron nitride and boron nitride nanotubes exhibit unique and hitherto unanticipated catalytic properties, resulting in great selectivity to olefins. As an example, at 14% propane conversion, we obtain selectivity of 79% propene and 12% ethene, another desired alkene. Based on catalytic experiments, spectroscopic insights, and ab initio modeling, we put forward a mechanistic hypothesis in which oxygen-terminated armchair boron nitride edges are proposed to be the catalytic active sites.

Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.

Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC.

Age-related changes in upper body adaptation to walking speed in human locomotion.

Assessments of changes in gait stability due to aging and disease are predominantly based on lower extremity kinematic and kinetic data. These gait changes are also often based on comparisons at preferred speed only. The purpose of this experiment was to: (1) examine age-related changes in range of motion and coordination of segments of the upper body during locomotion; and (2) investigate the effects of a systematic walking velocity manipulation on rotational motion and coordination. Participants (n=30) walked on a motor driven treadmill at speeds ranging from 0.2 to 1.8m/s and were divided into three groups with mean ages of 23.3, 49.3 and 72.6 years, respectively. Seven high-speed infrared cameras were used to record three-dimensional kinematics of the pelvis, trunk and head. Dependent variables were amplitude of segmental and joint rotations, as well as relative phase to assess coordination between segments. Although no differences in stride parameters were found between the groups, age-related changes in movement amplitude in response to speed manipulations were observed for all segments and joints. Pelvic rotations in sagittal, frontal and transverse planes of motion were systematically reduced with age. Older individuals showed reduced trunk flexion-extension in the sagittal plane and increased trunk axial rotation in the transverse plane. Coordination analysis showed reduced compensatory movement between pelvis and trunk in older individuals. These findings support the importance of systematic manipulation of walking velocity and three-dimensional upper body kinematics in assessing age-related changes in locomotor stability and adaptability.

Absence of indicators of the influence of its physicians on a society's health; impact of physician care on society.

There are no established indicators for measuring the influence of its private physicians on a society's health. For a brief period the age-adjusted death rate, an important indicator of the public health effort, also served to reflect a portion of the influence of the personal physician system. Particular medical interventions could be linked to specific sites in the pathogenesis of microbial disease in a way not yet permitted by the available knowledge of the common nonmicrobial diseases. Our national allocations for health cannot be made rationally until we develop indicators for measuring incremental investments in either system, but especially for the personal physician system. For death rates per se fail to accurately reflect the workings of this system which is concerned primarily with prolonging effective life by preserving or restoring function in an individual person.

Orthovoltage intraoperative radiotherapy: a new look at an old idea.

A 300 kvp orthovoltage machine has been permanently installed in an operating room for delivering intraoperative radiation therapy (IORT). A historical review of orthovoltage IORT and our present approach are described. The preliminary experience with 38 patients treated with orthovoltage IORT indicates that this technique is feasible, has low acute morbidity, and can be useful for palliation. "Radical" radiation therapy consisting of IORT "boost" treatment combined with external beam was used in 24 patients with primary or recurrent cancer. Local failure in 27 patients treated with IORT +/- external beam radiation therapy was 56%, but varied from 11% (1/9) for patients with resected disease to 78% (14/18) for patients with unresected disease. Complications occurred in nine patients (24%) and have been acceptable. There are 17 patients alive and six are NED, with follow-up of 4-18 months. There appears to be a role for orthovoltage IORT especially when combined with surgical resection for local control of advanced cancer arising in the abdomen where the use of high doses of external radiation therapy are hazardous.

Amino acid clearance and prognosis in surgical patients with cirrhosis.

To measure the effects of cirrhosis on amino acid (AA) flux and to assess the value of the central plasma clearance rate of amino acids (CPCR-AA) as a hepatocyte function test, 35 patients with cirrhosis were studied before and after operation. Fourteen of these patients died after the operation. CPCR-AA measures the number of milliliters of plasma cleared of AA per minute by the liver and other visceral tissues. It is the ratio of AA entry rate into plasma (from peripheral tissues plus infusion) to the arterial AA plasma concentration. Preoperative CPCR-AA measurements in 21 fasted patients with cirrhosis who were not infected revealed a pattern of AA plasma concentration and exchange similar to that previously observed in patients with sepsis with normal liver function. Whereas the concentration of AA in both groups was slightly lower than normal, the CPCR-AA of each was more than four times that of normal postabsorptive people (p less than 0.01). However, preoperative values of CPCR-AA in patients with cirrhosis who survived was 220 +/- 26 ml/M2/min while that in those who died was 97 +/- 16 ml/M2/min (p less than 0.001). Postoperative measurements remained relatively unchanged: survivors 212 +/- 24 ml/M2/min and those who died 89 ml/M2/min (p less than 0.0005). Measurements in vitro of the hepatic protein synthetic rate in liver biopsy specimens taken at operation correlated well with CPCR-AA values obtained immediately before operation in 10 patients (r = 0.73; p less than 0.01). Thus in patients with cirrhosis visceral amino acid uptake and hepatic protein synthesis are maximally stimulated. Nevertheless, if the preoperative CPCR-AA does not approach the value of 284 +/- 76 ml/M2/min previously observed in patients with sepsis who recover, the patient with cirrhosis is prone postoperatively to die of overwhelming infection and multisystem failure.

Intraoperative radiation therapy for biliary tract carcinoma: results of a 5-year experience.

The results of a 5-year experience with use of intraoperative radiation therapy (IORT) in the management of locally advanced bile duct carcinoma are presented. Fifteen patients received IORT doses between 5 and 20 Gy for localized disease, which was either primary and resected with microscopic residual (2 patients), primary and unresected (10 patients), or recurrent (3 patients). Thirteen patients also received postoperative radiation therapy. The median survival of the 12 patients with primary disease was 14 months, with disease controlled in the porta hepatis in 5 of 10 evaluable patients. The three patients with recurrent disease survived 2, 9, and 11 months. There were two operative deaths, for an operative mortality of 13%. Acute and chronic complications are reviewed. Cholangitis is the most frequent in both categories. This aggressive approach in the therapy for advanced disease has an acceptable level of morbidity and may warrant the use of IORT as part of the management of biliary tract cancer.

The Budd-Chiari syndrome and hepatic veno-occlusive disease. Recognition and treatment.

In a review of 29 patients who were surgically treated by combined hepatic and portal decompression for intractable ascites, 18 were identified as falling into the category of the Budd-Chiari syndrome, with varying causes. Of this group, 2 patients were distinguished by the classical hepatic venous endophlebitis described by Chiari and later by Bras et al. Recently, this disease entity has been recognized as being due to the toxic effects of pyrrolizidine alkaloids contained in the Senecio and Crotolaria plants. In the first of these two cases the patient had emigrated from Jamaica and was exposed to "bush trees," but no chemical measurements were done. The second patient had consumed a large amount of comfrey teas, which were shown to contain high levels of pyrrolizidine alkaloids. These two cases add further weight to the existing evidence of the toxic effect of these alkaloids, and also demonstrate the effectiveness of hepatic and portal decompression.

Primary cancer of the liver. Evaluation, treatment, and prognosis.

Between 1970 and 1985, a diagnosis of primary hepatocellular carcinoma was established in 98 patients. Sixty-one cases developed in the presence of chronic liver disease, and only six of these were considered resectable. Of these, the median survival was 19 months. There was one perioperative death. Of the 98 tumors, 37 arose in normal livers. Of the 16 patients with tumors in normal livers that were resected, all survived operation. The long-term median survival was 32 months. Two subsets of the fibrolamellar and clear-cell variants appeared to carry a more favorable prognosis.

Surgical therapy for recurrent liver metastases from colorectal cancer.

Forty percent of patients whose disease recurs after hepatic resection for liver metastases from colorectal cancer initially will have liver-only metastases. We have retrospectively reviewed our experience with repeated surgical treatment for liver-only recurrence after previous hepatic resection for colorectal metastases. Repeated hepatic procedures were performed with no mortality in 10 patients. Intraoperative ultrasound allowed identification of three unsuspected metastases and determination of unresectability of two metastases during 11 procedures. Three patients were free of disease at 31, 41, and 48 months from the first hepatic procedure and at 15, 31, and 43 months from the second procedure. Five patients have remained free of hepatic disease. Patients whose initial metastases were less than 6 cm in diameter and had single liver recurrences after hepatic resection appeared to be the best candidates for further surgical therapy. These data and a review of the literature suggest that surgical treatment of recurrent liver metastases from colorectal cancer can be performed safely, and it is associated with long-term disease-free survival in up to 38% of highly selected patients.

Management of recurrent pelvic tumors.

The management of regional tumor recurrence in the pelvis traditionally has been a difficult problem for surgeons and oncologists. The only meaningful therapy for these patients is a potentially curative re-resection. The records and operative reports of 29 patients with regional pelvic tumor recurrence treated between 1981 and 1986 were reviewed. The operative procedures performed included three bowel resections, six abdominoperineal resections, eight pelvic exenterations, eight resections of tumor recurrence, and four conservative procedures. There was one operative death in this group. Significant morbidity was noted in the group but was clustered in a small number of patients operated on early in the series. The median follow-up in this series was 13 months (range, two to 51 months). Nineteen (65%) of the patients are surviving at a median follow-up of ten months (range, two to 51 months). The median survival (following resection) in the ten patients (35%) who died was 18 months. In 15 (52%) of the patients, a complete resection was performed. In this group, the survival is 80% with a median follow-up of 11 months. Seven (37%) are surviving with no evidence of disease. Palliation of symptoms occurred in 23 (79%) of the 29 patients. Radical resection of tumor recurrence in the pelvis can be performed with acceptable mortality and complication rates. This therapy should be considered for further clinical trials combining surgical and adjuvant therapy in patients with regional pelvic tumor recurrence.

Hepatic cryosurgery with intraoperative ultrasound monitoring for metastatic colon carcinoma.

We utilized cryosurgery with intraoperative ultrasound (IOUS) monitoring in ten patients to treat multiple unresectable hepatic metastases from colorectal carcinoma. The liver was exposed at laparotomy, and tumors were subjected to three cycles of freezing (eight minutes each) and thawing. Freezing was monitored by IOUS, which visualized frozen tumor as a hyperechoic rim with posterior acoustic shadowing. Frozen normal liver appeared hypoechoic after thawing compared with normal unfrozen liver. There were no significant complications. The follow-up ranged from four months to 17 months (median, 7.5 months). Tumor response was documented by pathologic findings (coagulative necrosis), progressive fall of carcinoembryonic antigen levels, and computed tomographic scan evidence of necrosis and shrinkage of tumor. One patient underwent repeated laparotomy five months after cryosurgery and had the frozen lesions resected; there was no residual tumor. This study establishes the technical feasibility and antitumor response of hepatic cryosurgery and the use of IOUS for precise localization and monitoring of cryoablations.

Amino acid clearance in cirrhosis. A predictor of postoperative morbidity and mortality.

The central plasma clearance rate of amino acids (CPCR-AA), the ratio of peripheral amino acid entry rate into blood plasma to arterial amino acid concentration, was measured preoperatively in 149 noninfected cirrhotic patients. In 50 survivors of shunting or general surgical procedures, the mean (+/- SEM) CPCR-AA was 201 +/- 17 mL/m2/min; in 39 subsequent deaths, the mean ratio was 87 +/- 14 mL/m2/min. Comparing Child's classification with CPCR-AA reveals the following values: class A (mortality, two of ten patients) survivors, 152 +/- 23 mL/m2/min; class A deaths, 96 +/- 54 mL/m2/min; class C (mortality, 13 of 19 patients) survivors, 214 +/- 47 mL/m2/min; class C deaths, 101 +/- 13 mL/m2/min. The preoperative CPCR-AA of 46 patients receiving liver transplants was 91 +/- 9 mL/m2/min; 69% of these patients survived. Preoperative CPCR-AA values correlated significantly with rates of hepatic protein synthesis in incubated liver slices obtained by biopsy at operation in 22 patients. Thus, CPCR-AA determination is a true liver function test, valuable in predicting surgical mortality and selecting transplantation or other operations for cirrhotic patients.

Surgical treatment of biliary cystadenoma. A report of 15 cases.

Mucinous biliary cystadenomas are rare intrahepatic or, less commonly, extrahepatic neoplasms that may produce massive enlargement, hemorrhage, rupture, secondary infection, jaundice, or vena caval obstruction. Radiologic criteria differentiate biliary cystadenomas from more common parasitic or simple cysts. Treatment has included sclerosis, marsupialization, internal drainage, or resection, but without resection the patient is at risk for enlargement, infection, or progression of an unrecognized malignant neoplasm. We report the course of 15 patients who underwent resection for biliary cystadenoma to elucidate the clinical presentation, preoperative evaluation, and surgical treatment. Nine patients had had previous radiologic or surgical intervention other than excision, and complications of sepsis and tumor recurrence had developed. Following complete resection, however, only five postoperative complications were encountered, and no patient experienced recurrence of tumor. Thus, we recommend complete surgical resection as the preferred therapy.