Mixed evidence for early bursts of morphological evolution in extant clades.

Macroevolutionary theory predicts high rates of evolution should occur early in a clade's history as species exploit ecological opportunity. Evidence from the fossil record has shown a high prevalence of early bursts in morphological evolution, but recent work has provided little evidence for early high rates in the evolution of extant clades. Here, I test the prevalence of early bursts in extant data using phylogenetic comparative methods. Existing models are extended to allow a shift from a background Brownian motion (BM) process to an early burst process within subclades of phylogenies, rather than an early burst being applied to an entire phylogenetic tree. This nested early burst model is compared to other modes of evolution that can occur within subclades, such as evolution with a constraint (Ornstein-Uhlenbeck model) and nested BM rate shift models. These relaxed models are validated using simulations and then are applied to body size evolution of three major clades of amniotes (mammals, squamates and aves) at different levels of taxonomic organization (order, family). Applying these unconstrained models greatly increases the support for early bursts within nested subclades, and so early bursts are the most common model of evolution when only one shift is analysed. However, the relative fit of early burst models is worse than models that allow for multiple shifts of the BM or OU process. No single-shift or homogenous model is superior to models of multiple shifts in BM or OU evolution, but the patterns shown by these multirate models are generally congruent with patterns expected from early bursts.

Supervised exercise training for intermittent claudication: lasting benefit at three years.

OBJECTIVES: To assess the long-term outcome of supervised exercise training for intermittent claudication. METHODS: A prospective study was undertaken of all patients referred to a single centre with intermittent claudication (>46 m). Patients underwent supervised exercise training twice weekly for 10 weeks, with regular follow-up to 3 years. Actual Claudication Distance (ACD), Maximum Walking Distance (MWD) and ankle-brachial pressure indices (ABPI) were measured. RESULTS: In 202 patients the initial median ACD and MWD were 112 m and 197 m. Following exercise therapy both the median ACD and MWD increased to 266 m and 477 m at three months, increases of 237% and 242% respectively (p<0.001). At three years the median ACD and MWD were 250 m and 372 m, increases of 223% and 188% respectively (p<0.001). There was no significant change in ACD or MWD at 3 months compared to 1, 2 or 3 years. ABPI remained unchanged throughout. CONCLUSIONS: Supervised exercise training has long term benefit in patients with intermittent claudication. Results seen at 12 weeks are sustained at three years.

Intraperitoneal hypothermia during surgery enhances postoperative tumor growth.

BACKGROUND: Recent work has shown that intraoperative hypothermia is a significant source of surgical trauma, with wide-ranging physiological and immunological sequelae. The aim of this study was to examine the effects of intraperitoneal hypothermia during laparoscopy on tumor growth in an animal model. METHODS: Thirty WAG rats were randomized to undergo anesthesia alone (n = 10), insufflation with cold carbon dioxide (CO2) (n = 10), or insufflation with warm CO2 (n = 10). During insufflation, 1 x 105/ml CC531s colon cancer cells in suspension were injected into the peritoneal cavity. The control group was anesthetized and tumor cells were injected without insufflation. After 3 weeks, total tumor weight and the extent of tumor spread, as assessed by the modified Peritoneal Cancer Index (PCI), were compared at autopsy. RESULTS: Laparoscopy with cold CO2 resulted in a significant reduction in local and core body temperatures (p <0.05). Tumor growth in both groups that underwent CO2 pneumoperitoneum was significantly increased compared with the group that did not (p <0.0001, control vs warm CO2 and cold CO2). There was significantly more tumor growth in the rats insufflated with unwarmed CO2 than in the normothermic group (mean total tumor 0.01 g +/- 0.03 vs. 0.043 g +/- 0.07; p = 0.025 Mann-Whitney U test). Tumor spread as shown by the PCI scores was less in the warm gas group than it was in the animals insufflated with cold gas (151 vs 266). CONCLUSIONS: These data demonstrate that the peritoneal insufflation of CO2 enhances tumor growth and that the prevention of perioperative hypothermia during laparoscopy attenuates tumor growth. This effect may be partially mediated by the increased peritoneal trauma that results from insufflation with cold gas.

Oncologic implications of laparoscopic and open surgery.

Although instrumental manipulation and mechanical tumor cell spillage seem to play the major role in port-site metastases from laparoscopic cancer surgery, minimally invasive procedures are used more and more in the resection of malignancies. However, port-site metastases also have been reported after resection of colon cancer in International Union Against Cancer (UICC) stage I [2, 14]. Therefore, changes in the peritoneal environment during laparoscopy also might influence intra- and extraperitoneal tumor growth during laparoscopy and pneumoperitoneum. Different results of experimental studies presented at the Third International Conference for Laparoscopic Surgery are analyzed and discussed.

Comparison of immunologic and physiologic effects of CO2 pneumoperitoneum at room and body temperatures.

BACKGROUND: Prolonged and complex laparoscopic procedures expose patients to large volumes of cool insufflation gas. The aim of this study was to compare the effects of a conventional room temperature carbon dioxide (CO2) pneumoperitoneum with those of a body temperature pneumoperitoneum. METHODS: Patients were randomized to undergo laparoscopic cholecystectomy with a CO2 pneumoperitoneum warmed to either body temperature (n = 15) or room temperature (n = 15). The physiologic and immunologic effects of warming the gas were examined by measuring peroperative core and intraperitoneal temperatures, peritoneal fluid cytokine concentrations, and postoperative pain. RESULTS: The mean duration of surgery was 32 min in both groups. Core temperature was reduced in the room temperature group (mean, 0.42 degrees C; p < 0.05). No reduction in temperature occurred when the gas was warmed. Greater levels of cytokines were detected in peritoneal fluid from the room temperature insufflation group tumor necrosis factor alpha (TNF-alpha): mean, 10.9 pg/ml vs. 0.42, p < 0.05; interleukin 1 beta (IL-1beta): mean, 44.8 pg/ml vs. 15.5, p < 0.05; and IL-6: mean, 60.4 ng/ml vs. 47.2. There was no difference in postoperative pain scores or analgesia consumption between the two groups. CONCLUSIONS: The authors conclude that intraoperative cooling can be prevented by warming the insufflation gas, even in short laparoscopic procedures. In addition, warming the insufflation gas leads to a reduced postoperative intraperitoneal cytokine response.

Treatment of progressive rheumatoid interstitial lung disease with cyclosporine.

A 62-year-old man with longstanding rheumatoid arthritis (RA) presented with dyspnea. Active rheumatoid interstitial lung disease was documented by high resolution computed tomography, gallium scan, and bronchoalveolar lavage. He responded to high dose prednisone, but had unacceptable side effects. Chlorambucil and cyclophosphamide were not steroid sparing. After starting cyclosporine 3 mg/kg/day he was able to stop prednisone and his symptoms improved and stabilized. Pulmonary function showed sustained improvement during 2 years of followup. His RA has been well controlled. Side effects have been mild hypertension and increased serum creatinine.

Acute local reactions after intraarticular hylan for osteoarthritis of the knee.

OBJECTIVE: To describe acute local reactions following intraarticular hylan injection and determine their frequency. METHODS: Retrospective review of all patients with osteoarthritis of the knee treated with hylan by 3 rheumatologists. RESULTS: Twenty-two patients had 88 injections to 28 knees. Six patients had reactions within 24 h of injection characterized by pain, warmth, and swelling, lasting up to 3 weeks. This occurrence was unpredictable. Corticosteroid injections were sometimes required. Synovial fluid cell counts were 5.0-75.0 x 10(9)/l, often with a prominent mononuclear component. Crystal studies and cultures were negative. Radiographic chondrocalcinosis was present in only 1 patient. One patient had serum antibodies to chicken serum proteins. CONCLUSION: Intraarticular hylan was associated with significant local inflammatory reactions in 27% of patients, or 11% of injections. The mechanism(s) and long term sequelae are unclear.

Soft tissue tuberculosis: a series of 11 cases.

OBJECTIVE: To describe the clinical characteristics of soft tissue tuberculosis (TB). METHODS: Retrospective review of all cases of soft tissue TB seen by the authors. RESULTS: Eleven cases were seen between 1988 and 1994. All patients but one were foreign born. Six patients had collagen vascular disorders and another had a kidney transplant. Five were taking immunosuppressive therapy and/or prednisone. Three had preceding trauma to the affected area. Five had evidence of previous TB by history or chest radiograph. Symptoms (mean duration 4.4 months) included swelling and pain and often mimicked the underlying disease. Six patients had definite or suspected active TB at other sites. Good initial responses were seen with debridement or drainage and multiple drugs for 6 to 12 months. Two patients have had possible relapses at other sites. Medication intolerance was frequent. CONCLUSION: TB should be considered in patients who present with unexplained soft tissue swelling and pain, particularly if they are immunosuppressed, were foreign born in an endemic area, have an abnormal chest radiograph, or have had trauma to the affected area.

Extracorporeal knot tying using an atraumatic Babcock clamp.

Extracorporeal knot tying is a method of avoiding the difficult and time-consuming skill of intracorporeal knot tying and can be equally effective. An endoscopic Babcock clamp can be used instead of the usual knot-pusher devices so that the suture material does not become dislodged. The Babcock clamp lays the knot flat and applies equal traction on each end of the suture.

Itraconazole: Precautions regarding drug interactions and bioavailability.

OBJECTIVE: To describe patients with fungal infections in whom drug interactions and bioavailability problems were associated with itraconazole treatment failure. DESIGN: Retrospective chart review. SETTING: Two tertiary care university-affiliated teaching hospitals. POPULATION STUDIED: Itraconazole-treated patients between 1990 and 1992. MAIN RESULTS: Four patients treated with itraconazole were identified in whom suboptimal serum itraconazole levels were associated with relapse of disseminated histoplasmosis, treatment failure of invasive aspergillosis or development of superficial mycoses. Low serum itraconazole levels were associated with concurrent therapy with rifampin or agents inhibiting gastric acid secretion, with administration of itraconazole capsule contents through a nasogastric tube or with the presence of aids. CONCLUSIONS: It is recommended that serum itraconazole levels be measured in patients with potentially life-threatening mycoses if coexistent factors may interfere with itraconazole therapy.