Evidence for adaptive radiation from a phylogenetic study of plant defenses

One signature of adaptive radiation is a high level of trait change early during the diversification process and a plateau toward the end of the radiation. Although the study of the tempo of evolution has historically been the domain of paleontologists, recently developed phylogenetic tools allow for the rigorous examination of trait evolution in a tremendous diversity of organisms. Enemy-driven adaptive radiation was a key prediction of Ehrlich and Raven''s coevolutionary hypothesis [Ehrlich PR, Raven PH (1964) Evolution 18:586–608], yet has remained largely untested. Here we examine patterns of trait evolution in 51 North American milkweed species (Asclepias), using maximum likelihood methods. We study 7 traits of the milkweeds, ranging from seed size and foliar physiological traits to defense traits (cardenolides, latex, and trichomes) previously shown to impact herbivores, including the monarch butterfly. We compare the fit of simple random-walk models of trait evolution to models that incorporate stabilizing selection (Ornstein-Ulenbeck process), as well as time-varying rates of trait evolution. Early bursts of trait evolution were implicated for 2 traits, while stabilizing selection was implicated for several others. We further modeled the relationship between trait change and species diversification while allowing rates of trait evolution to vary during the radiation. Species-rich lineages underwent a proportionately greater decline in latex and cardenolides relative to species-poor lineages, and the rate of trait change was most rapid early in the radiation. An interpretation of this result is that reduced investment in defensive traits accelerated diversification, and disproportionately so, early in the adaptive radiation of milkweeds.     

Upper Gastrointestinal Symptoms and Associated Disorders in Morbidly Obese Patients: A Prospective Study

Objective To prospectively evaluate the frequency of upper gastrointestinal symptoms and associated disorders in morbidly obese patients with endoscopy and histology prior to their gastric bypass surgery in comparison with age- and sex-matched nonobese control subjects. Methods All patients who were scheduled to undergo laparoscopic gastric bypass for treatment of morbid obesity (body mass index, BMI > 40 kg/m²) during a 1-year period (n = 101) were included in the study. Age- and sex-matched nonobese patients who were seen in the medical clinics during the study period were enrolled as control subjects. The demographic data, total body weight, body mass index, and gastrointestinal symptoms were recorded, and the results of upper endoscopy and histology were tabulated. Endoscopic documentation of hiatal hernia, esophagitis, gastritis, gastric polyps, and peptic ulcer disease was also noted along with the histologic findings of the mucosal biopsies from the upper gastrointestinal tract. Results The prevalence of heartburn as a symptom was significantly higher (P < 0.05) in the morbidly obese patients (32.6%) compared with in the control group (18.8%). Endoscopically, the prevalence of hiatal hernia was also significantly higher (P < 0.05) in the morbidly obese group (38.6%) compared with in the control group (13.8%). Similarly the frequency of endoscopically and histologically identified gastritis was significantly higher (P < 0.01) in the morbidly obese patient group. However, the frequency of histologically identified Helicobacter pylori was not statistically different in the two groups. Conclusion These observations suggest a significant increase in the frequency of heartburn, hiatal hernia, and histologically identified gastritis in morbidly obese patients.     

Abdominoanterior sagittal approach for sphincter-saving low anterior resection for carcinoma of the rectum in females: a modified anatomical approach

Safe access to the lower rectum is of the utmost importance when performing sphincter-saving resection for rectal cancer. We describe an abdominoanterior sagittal approach for low anterior resection in females. The abdominal part of the procedure is similar to conventional low anterior resection. The perineal part includes making an anterior sagittal incision from the posterior fourchette to the anterior edge of the anus. The use of a muscle stimulator allows identification of the external sphincters. The rectum and both puborectal slings are identified. Lower margin division and completion of total mesorectal excision is done from below, under vision. The specimen is delivered and mobilized colon is brought down, a hand-sewn end-to-end colorectal anastomosis is formed, and a diverting colostomy is fashioned. Seven patients underwent low anterior resection via the abdominoanterior sagittal approach. Two patients (29%) developed anastomotic stricture, one in association with a rectovaginal fistula and still had a defunctioning stoma, while the other responded to dilatation. The six patients who underwent stoma closure achieved continence to solid stools with a mean Kelly score of 5. The abdominoanterior sagittal approach for low anterior resection is an alternative option for sphincter-saving resection in female patients as it defines the sphincteric anatomy, and minimizes the risk of sphincter injury.     

Cyclophosphamide-associated complications: we need to be aware of SIADH and central pontine myelinolysis

SIR, We report a case highlighting a rare complication thatrheumatologists might come across while using cyclophosphamide. A 49-yr-old lady with dcSSc for 2 yrs, presented with coughand dyspnoea on exertion of 4 months duration. Clinical examination,HRCT-thorax and pulmonary function test     

Pregnancy and rheumatic disease: “by the book” or “by the doc”

Pregnancy is an important condition that can affect and be affected by rheumatic disease. Overall, pregnancy is viewed as a Th2-predominant state, but several Th1-related cytokines are vital to early pregnancy. In rheumatoid arthritis for example, the majority of women improve by the beginning of the second trimester, but the majority (90%) will flare in the first 3 to 4 months postpartum. In contrast, systemic lupus erythematosus has an unpredictable course in pregnancy, leaving most rheumatologists to recommend a disease-quiescent state prior to conception. Other diseases such as scleroderma are less clear because the disease less commonly presents in the childbearing period. Many immunosuppressive medications for the rheumatic diseases are contraindicated in pregnancy because of their mechanisms of action leaving only a select few “safe” medications. Significant heterogeneity between the Food and Drug Administration (FDA) category for a medication and what a rheumatologist does in clinic leads to confusion on how a patient should be treated for active rheumatic disease both peripartum and postpartum, particularly if the patient is breastfeeding. We review the general state of pregnancy and how it is affected by prototypical rheumatic diseases including rheumatoid arthritis and systemic lupus erythematosus. In addition, we present the most commonly used disease-modifying antirheumatic drugs and immunosuppressants and explain the difference between the FDA category and clinical practice among rheumatologists. Finally, we provide some general recommendations on how to manage a rheumatic disease during pregnancy including: (a) preconception planning to ensure no teratogenic medications on board, (b) early disclosure of pregnancy to all caregivers including the rheumatologist, family physician, obstetrician, and maternal–fetal medicine specialist, and (c) planning of safe medication use for acute flare-ups and disease suppression peripartum and postpartum. Presented as Medical Grand Rounds at the University of Alberta.     

Coronary vein graft disease: Pathogenesis and prevention

Not long after coronary artery bypass grafting surgery was described, several reports presented follow-up angiographic data on large cohorts of patients, demonstrating that approximately one-half of saphenous vein grafts fail within 10 to 15 years of surgery and that graft failure is associated with worse clinical outcomes. Three processes are responsible for vein graft failure. Thrombosis, intimal hyperplasia and accelerated atherosclerosis contribute to graft failure in the acute, subacute and late postoperative periods, respectively. Studies have shown that perioperative antiplatelet therapy can reduce early thrombosis and graft failure. As in native coronaries, intensive lipid lowering can attenuate the process of atherosclerosis in vein grafts. Intimal hyperplasia in the vein graft is thought to be an adaptation of the vein to higher pressures in the arterial circulation. This process is further promoted by the loss of inhibition from the endothelial layer, which is injured during surgery. A new ‘no-touch’ technique for harvesting grafts may be effective in preventing disruption to the endothelial layer, and subsequent intimal hyperplasia and graft loss. Off-pump surgery and endoscopic vein harvesting, which are known to reduce surgical morbidity, have been shown to be no worse than on-pump surgery and open vein harvesting, respectively, in terms of vein graft patency. Various gene therapies can prevent intimal hyperplasia in animal models, but human data obtained so far have been disappointing. Placing an external stent around a vein graft may reduce tangential wall stress and subsequent intimal hyperplasia.     

Clinical profile of dasatinib in Asian and non-Asian patients with chronic myeloid leukemia

Resistance and intolerance to imatinib are of particular clinical relevance to Asian patients because of their lower body surface area. Dasatinib is 325-fold more potent than imatinib in inhibiting BCR-ABL in vitro and is indicated for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to imatinib. Data from a series of phase I/II research trials were analyzed to compare the efficacy, safety and pharmacokinetic profile of dasatinib 70 mg twice daily in Asian and non-Asian patients. Results from 55 Asian and 615 non-Asian patients demonstrated that the efficacy and safety of dasatinib was comparable. Dasatinib was well tolerated, with no observed toxicities exclusive to Asian patients. A higher incidence of adverse events and lower rate of response observed among Asian patients with myeloid blast phase CML reflected the aggressive nature of the disease. Analyses of noncompartmental pharmacokinetics (5 Asian and 49 non-Asian patients) and population pharmacokinetics (17 Asian and 382 non-Asian patients) were also comparable. The efficacy, safety and pharmacokinetic profile of dasatinib 70 mg twice daily is similar in Asian and non-Asian patients with CML. Dasatinib is therefore an important therapeutic option for this patient population.