Acaricidal effect of herbal extracts against cattle tick Rhipicephalus (Boophilus) microplus using in vitro studies.

The crude methanolic extract of Datura stramonium, Azadirachta indica, and Calotropis procera leaves, Allium sativum (AS) cloves, and Carica papaya (CP) seeds collected from Banaskanta, Gujarat (India) was tested for its acaricidal properties against Rhipicephalus (Boophilus) microplus. The percent adult mortality within 15 days, reproductive index, percentage inhibition of oviposition, hatching of laid ova, and percentage larval mortality were studied at concentrations of 12.5, 25, 50, and 100 mg/ml. At the highest concentration (100 mg/ml), the adult tick mortality was 66.67, 73.33, 80.00, and 93.33% for C. procera, D. stramonium, A. sativum, and C. papaya extracts, respectively, and it was statistically significant (P < 0.001). However, for A. indica, mortality was low and estimated to be 33.33%. Inhibition of oviposition at the highest concentration of A. indica, C. procera, D. stramonium, A. sativum, and C. papaya extract-treated ticks was 20.73, 71.34, 77.17, 85.83, and 100.00%, respectively. Inhibition of fecundity of treated groups differed significantly from the control and was concentration dependent. Larvae treated with all the tested concentrations of A. indica, C. procera, D. stramonium, A. sativum, and C. papaya extracts by larval packet test showed significant mortality (P < 0.001) than that of control tick larvae, and at the highest concentration, it was 55.2, 63.2, 71.8, 69.0, and 82.2%, respectively. Garlic cloves and papaya seed extract produced complete failure of eclosion of eggs from the treated ticks even at lower concentrations; however, neem, calotropis, and datura was capable of reducing hatchability by 20, 50, and 70%, respectively. The results pointed that the crude extracts of A. sativum cloves and C. papaya seeds have very good acaricidal properties and could be a potential component of alternative R. (B.) microplus tick control strategy.

Hyperfractionated Cyclophosphamide and Dexamethasone Alone or in Combination with Daratumumab and/or Carfilzomib for the Treatment of Relapsed or Refractory Multiple Myeloma: A Single-Center Retrospective Analysis.

BACKGROUND: Hyperfractionated cyclophosphamide and dexamethasone (HyperCd) alone, or with carfilzomib(K) and/or daratumumab(D), represents a potential treatment option when rapid disease control is needed for patients with aggressive presentations of relapsed/refractory multiple myeloma (RRMM). PATIENTS AND METHODS: This is a single-center, retrospective analysis of adult patients with RRMM who received HyperCd with or without K and/or D between May 1, 2016 and August 1, 2019 at the University of Texas MD Anderson Cancer Center. We here report treatment response and safety outcomes. RESULTS: Data from 97 patients, 12 with plasma cell leukemia (PCL), were reviewed in this analysis. Patients had had a median of 5 prior lines of therapy and received a median of 1 consecutive cycle of hyperCd-based therapy. The overall response rate (ORR) of all patients was 71.8% (HyperCd 75%, HyperCdK 64.3%, D-HyperCd 73.3%, and D-HyperCdK 76.9%). Median progression-free survival and overall survival among all patients was 4.3 months (HyperCd 3.1 months, HyperCdK 4.5 months, D-HyperCd 3.3 months, and D-HyperCdK 6 months) and 9.0 months (HyperCd 7.4 months, HyperCdK 9.0 months, D-HyperCd 7.5 months, and D-HyperCdK 15.2 months), respectively. Grade 3/4 hematologic toxicities were common, thrombocytopenia being the most frequent at 76%. Notably, 29-41% of patients per treatment group had existing grade 3/4 cytopenias at initiation of hyperCd-based therapy. CONCLUSION: HyperCd-based regimens provided rapid disease control among MM patients, even when heavily pre-treated and with few remaining treatment options. Grade 3/4 hematologic toxicities were frequent, but manageable with aggressive supportive care.

Single-step endoscopic ultrasonography-guided drainage of peripancreatic fluid collections with a single self-expandable metal stent and standard linear echoendoscope.

Endoscopic ultrasonography (EUS)-guided drainage of peripancreatic fluid collections (PFCs) is a well described alternative to surgery or percutaneous drainage. However, it is limited by the requirement for a large working channel that allows multiple plastic stent placement, which is only commercially available on therapeutic linear echoendoscopes. Herein, we describe the drainage of PFCs with a single self-expandable metal stent (SEMS) using a single-step technique and standard linear echoendoscope. Seven cases were identified during a retrospective chart review, and included all patients who had undergone EUS-guided drainage of PFCs during a 6-month period. The mean age was 46 years (range 25 - 70 years) and all patients were symptomatic. The mean diameter of PFCs was 8 cm (range 4.1 - 12.5 cm). Previous percutaneous drainage had failed in three patients. A total of 10 PFCs were drained. Three patients had two cysts drained by the same stent and one patient had two separate procedures to drain two distinct cysts. The SEMS was in place for a mean of 13 weeks (range 4 - 34 weeks). Successful placement of SEMS was achieved in all seven cases. Patients were followed for a mean of 18 weeks (range 7 - 35 weeks), and symptom improvement was achieved in all cases. Complete resolution of PFC was achieved in 9 /10 cysts. No complications were encountered. Single-step EUS-guided drainage of PFCs using a single 10-mm SEMS and a standard linear echoendoscope appears to be a feasible endoscopic technique with excellent technical and clinical success rates.

Outcome of patients with metastatic renal cell carcinoma treated with targeted therapy without cytoreductive nephrectomy.

BACKGROUND: Cytoreductive nephrectomy (CN) became a standard procedure in metastatic renal cell carcinoma (mRCC) in the immunotherapy era. Historically, median overall survival (OS) of patients treated with interferon alpha (IFN-α) without CN was 7.8 months. Median OS in patients treated with targeted therapy (TT) without CN is unknown. PATIENTS AND METHODS: We retrospectively reviewed records of patients with mRCC who received TT without CN. Kaplan-Meier methods and Cox regression analysis were used to estimate median OS and identify poor prognostic factors. RESULTS: One hundred and eighty-eight patients were identified. Most patients had intermediate-risk (54.8%) or poor-risk (44.1%) disease. Median OS for all patients was 10.4 months [95% confidence interval (CI) 8.1-12.5]. By multivariable analysis, elevated baseline lactate dehydrogenase and corrected calcium, performance status of two or more, retroperitoneal nodal metastasis, thrombocytosis, current smoking, two or more metastatic sites, and lymphopenia were independent risk factors for inferior OS. Patients with four or more factors had increased risk of death (hazard ratio 8.83, 95% CI 5.02-15.5, P < 0.001) and 5.5-month median OS. Nineteen patients (10.0%) survived for 2+ years. CONCLUSIONS: These data highlight the improved OS of patients with mRCC treated with TT without CN, compared with historical IFN-α treatment, and may guide the design of trials investigating the role of CN in the TT era.

The stem cell niche.

Virtually every tissue of the adult organism maintains a population of putatively slowly-cycling stem cells that maintain homeostasis of the tissue and respond to injury when challenged. These cells are regulated and supported by the surrounding microenvironment, referred to as the stem cell 'niche'. The niche includes all cellular and non-cellular components that interact in order to control the adult stem cell, and these interactions can often be broken down into one of two major mechanistic categories--physical contact and diffusible factors. The niche has been studied directly and indirectly in a number of adult stem cell systems. Herein, we will first focus on the most well-understood niches supporting the germline stem cells in the lower organisms Caenorhabditis elegans and Drosophila melanogaster before concentrating on the more complex, less well-understood mammalian niches supporting the neural, epidermal, haematopoietic and intestinal stem cells.

Investigation of association between bovine viral diarrhoea virus and cervid herpesvirus type-1, and abortion in New Zealand farmed deer.

This study tested for association between bovine viral diarrhoea virus (BVDv) and cervid herpesvirus type-1 (CvHV-1) exposure and abortion in New Zealand farmed red deer. Rising two-year-old (R2, n = 22,130) and mixed-age (MA, n = 36,223) hinds from 87 and 71 herds, respectively, throughout New Zealand were pregnancy tested using ultrasound early in gestation (Scan-1) and 55-89 days later (Scan-2) to detect mid-term abortion. Sera from aborted and non-aborted hinds at Scan-2 were tested for BVDv and CvHV-1 using virus neutralisation tests. Available uteri from aborted hinds and from hinds not rearing a calf to weaning were tested by PCR for herpesvirus DNA. In herds with aborted hinds, 10.3% of 639 R2 and 17.2% of 302 MA hinds were sero-positive for BVDv and 18.6% of 613 R2 and 68.5% of 232 MA hinds were sero-positive for CvHV-1. There was no association between BVDv sero-status and abortion at animal level (R2 p = 0.36, MA p = 0.76) whereas CvHV-1 sero-positivity was negatively associated with abortion in MA hinds (p = 0.01) but not in R2 hinds (p = 0.36), MA). Eleven of 108 uteri from aborted R2 hinds but no MA hinds were positive for herpesvirus DNA. Vaginal samples from four R2 and one MA aborted hinds tested were negative for herpesvirus DNA. A Cervid Rhadinovirus type-2 (CRhV-2) was identified in seven PCR positive uteri samples. Findings suggest that BVDv and CvHV-1 may not be associated with abortion in R2 hinds, but association needs to be tested further in MA hinds. The role of CRhV-2 requires clarification.

Lack of association between Leptospira spp. serovars Hardjobovis and Pomona and pregnancy and mid-term abortion in New Zealand farmed red deer.

This paper investigates Leptospira borgpeterseni serovar Hardjobovis and L. interrogans serovar Pomona as potential causes of sub-optimum pregnancy rates and mid-term abortion in farmed red deer. Rising two-year-old (R2, n = 22,130) and mixed-age (MA, n = 36,223) hinds from 87 and 71 herds, respectively, throughout New Zealand were ultrasound scanned early in gestation (Scan-1) and a sub-sample re-scanned (Scan-2) 55-89 days later and mid-term daily abortion rate calculated. A sub-sample of sera from pregnant and non-pregnant hinds at both scans, both with (case herds) and without aborted hinds was tested for Leptospira using the microscopic agglutination test with titre cut-point ≥1:48 as positive. At Scan-1, 44.3% of 661 and 4.6% of 647 hinds were sero-positive for Hardjobovis and Pomona, respectively. The geometric mean titre (GMT) for Pomona was higher in pregnant than non-pregnant MA hinds (p = 0.015) but not in R2 hinds. At Scan-2 in case herds, 40.3% of 2242 and 7.1% of 2243 hinds were sero-positive for Hardjobovis and Pomona, respectively. There was no association between Hardjobovis or Pomona serology and non-pregnancy (Scan-1) or mid-term abortion (Scan-2) at animal or herd level. In case herds, GMT was higher in non-aborted than aborted hinds for Hardjobovis (p = 0.018) in MA herds and for Pomona in R2 herds (p = 0.006). No uteri from hinds not pregnant or aborting at either scan, or not rearing a calf to weaning, and fetuses as available, were positive on PCR. Evidence is insufficient to confirm that Leptospira Hardjobovis and Pomona play a significant role in sup-optimum early pregnancy or mid-term abortion rates in deer.

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization.

BACKGROUND: Previous investigators have shown that systemic markers of inflammation may be increased in patients with acute ischemic syndromes or after percutaneous coronary revascularization and that persistent elevation in these markers is predictive of excess risk of subsequent adverse cardiac events. By virtue of its cross-reactivity with the glycoprotein IIb/IIIa, avbeta3, and alphaMbeta2 receptors, abciximab may reduce inflammatory processes. Methods and Results-- Assays for the inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were performed on serum samples obtained from 160 patients in a placebo-controlled, randomized trial of abciximab during angioplasty. Eighty patients each had received a placebo or abciximab bolus plus a 12-hour infusion. Serum samples were drawn at baseline (before revascularization), 24 to 48 hours after study drug administration, and 4 weeks after study drug administration. Between baseline and 24 to 48 hours, the increase in C-reactive protein was 32% less in patients receiving abciximab than placebo (P=0.025); the rise in interleukin-6 levels was 76% less in the abciximab group (P<0.001); and the rise in tumor necrosis factor-alpha levels was 100% less with abciximab therapy (P=0.112). By 4 weeks, most marker levels had returned to baseline, with no significant differences between placebo and abciximab groups. CONCLUSIONS: Systemic markers of inflammation increase in the first 24 to 48 hours after angioplasty, but the magnitude of that rise is diminished by periprocedural abciximab. Some of the long-term clinical benefit derived from this agent may be related to an anti-inflammatory effect.

In Vitro Detection of Acaricidal Resistance Status of Rhipicephalus (Boophilus) microplus against Commercial Preparation of Deltamethrin, Flumethrin, and Fipronil from North Gujarat, India.

Rhipicephalus (Boophilus) microplus is the most common tick species in India infesting cattle and buffaloes and causing significant economic losses to dairy and leather industries by adversely affecting the milk production and quality of hides. A study to evaluate the acaricide resistance status of Rhipicephalus (Boophilus) microplus to deltamethrin, flumethrin, and fipronil was conducted on the samples collected from organized and unorganized farms of North Gujarat state, where treatment failures were reported frequently. Adult Immersion Test (AIT) and Larval Packet Test (LPT) were conducted using field strain for determination of 50 and 95% lethal concentration of deltamethrin, flumethrin, and fipronil. Results obtained by the Adult Immersion Test showed low grade resistance (level I, RF > 5) has been developed against both deltamethrin and fipronil. However, deltamethrin by performing Larval Packet Test showed moderate grade resistance (level II, RF > 25). Larval packet performed by flumethrin also revealed low grade resistance, level I. The data on field status of acaricide resistance from the area with diversified animal genetic resources will be helpful to adopt suitable strategy to overcome the process of development of resistance in ticks.

Pressure-flow specificity of inspiratory muscle training.

The inspiratory muscles (IM) can be trained by having a subject breathe through inspiratory resistive loads or by use of unloaded hyperpnea. These disparate training protocols are characterized by high inspiratory pressure (force) or high inspiratory flow (velocity), respectively. We tested the hypothesis that the posttraining improvements in IM pressure or flow performance are specific to training protocols in a way that is similar to force-velocity specificity of skeletal muscle training. IM training was accomplished in 15 normal subjects by use of three protocols: high inspiratory pressure-no flow (group A, n = 5), low inspiratory pressure-high flow (group B, n = 5), and intermediate inspiratory pressure and flow (group C, n = 5). A control group (n = 4) did no training. Before and after training, we measured esophageal pressure (Pes) and inspiratory flow (VI) during single maximal inspiratory efforts against a range of external resistances including an occluded airway. Efforts originated below relaxation volume (Vrel), and peak Pes and VI were measured at Vrel. Isovolume maximal Pes-VI plots were constructed to assess maximal inspiratory pressure-flow performance. Group A (pressure training) performed 30 maximal static inspiratory maneuvers at Vrel daily, group B (flow training) performed 30 sets of three maximal inspiratory maneuvers with no added external resistance daily, and group C (intermediate training) performed 30 maximal inspiratory efforts on a midrange external resistance (7 mm ID) daily. Subjects trained 5 days/wk for 6 wk. Data analysis included comparison of posttraining Pes-VI slopes among training groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Innovative approaches to educating medical students for practice in a changing health care environment: the National UME-21 Project.

In today's continually changing health care environment, there is serious concern that medical students are not being adequately prepared to provide optimal health care in the system where they will eventually practice. To address this problem, the Health Resources and Services Administration (HRSA) developed a $7.6 million national demonstration project, Undergraduate Medical Education for the 21st Century (UME-21). This project funded 18 U.S. medical schools, both public and private, for a three-year period (1998-2001) to implement innovative educational strategies. To accomplish their goals, the 18 UME-21 schools worked with more than 50 organizations external to the medical school (e.g., managed care organizations, integrated health systems, Area Health Education Centers, community health centers). The authors describe the major curricular changes that have been implemented through the UME-21 project, discuss the challenges that occurred in carrying out those changes, and outline the strategies for evaluating the project. The participating schools have developed curricular changes that focus on the core primary care clinical clerkships, take place in ambulatory settings, include learning objectives and competencies identified as important to providing care in the future health care system, and have faculty development and internal evaluation components. Curricular changes implemented at the 18 schools include having students work directly with managed care organizations, as well as special demonstration projects to teach students the knowledge, skills, and attitudes necessary for successfully managing care. It is already clear that the UME-21 project has catalyzed important curricular changes within 12.5% of U.S. medical schools. The ongoing national evaluation of this project, which will be completed in 2002, will provide further information about the project's impact and effectiveness.

Sentinel surveillance of HIV infection among new inmates and implications for policies of corrections facilities.

Seroprevalence surveys of incoming inmates provide useful sentinel information on human immunodeficiency virus (HIV) infection rates among groups that practice HIV-associated high-risk behaviors. In addition, such data are beneficial to corrections officials in the formulation of institutional policies to prevent HIV infection. Inmates entering the Michigan corrections system from December 1987 to March 1988 participated in blind, anonymous serosurveys for HIV infection. Eight of 802 entering inmates (1.0 percent) were seropositive; most seropositive persons reported intravenous drug use. The most common risk behaviors reported by study participants were intravenous drug use (20.0 percent), multiple sexual partners (37.1 percent), and infrequent (that is, never or seldom) use of condoms (82.6 percent). Women reported the highest rates of intravenous drug use (35.1 percent) and needle-sharing (19.4 percent). Results from this study indicate that in spite of wide-spread HIV-associated risk behaviors, the extent of HIV-seropositivity among incoming inmates in Michigan is relatively low. Such data suggest that there is still time to impact the course of the AIDS epidemic among high-risk groups in States where the prevalence of HIV infection is relatively low. The data also indicate that the potential for HIV spread in correctional facilities is noteworthy and that HIV prevention education and substance abuse treatment services are needed in corrections facilities.

A "round block" purse-string suture in facial reconstruction after operations for skin cancer surgery.

Removal of skin cancers in the head and neck region usually results in a circular or oval defect, which must be reconstructed immediately using one of several techniques. Larger defects can present a difficult aesthetic problem. The purse-string suture is particularly suited to such large defects where the skin is lax. We report 51 cases where this technique was used in the head and neck region. All defects were considerably reduced in size and some required a small skin graft to complete the reconstruction. Initially many redundant skin folds and considerable local distortion were seen but these improved with time. The technique is simple, inexpensive, and the results are satisfactory in appropriately selected cases. Comprehensive discussion to prepare patients for the gross initial distortion and the long period of retention of the suture makes the procedure acceptable to patients.

Protection of the lip from the activator arm of maxillary distractors.

The long spring-loaded distractor arms of maxillary distraction devices can cause pain and ulceration of the upper lip. We describe a simple method to relieve the tension and discomfort on the soft tissues using Silastic tubing.

Pharmacological screening of Coriandrum sativum Linn. for hepatoprotective activity.

OBJECTIVE: Coriandrum sativum (Linn.), a glabrous, aromatic, herbaceous annual plant, is well known for its use in jaundice. Essential oil, flavonoids, fatty acids, and sterols have been isolated from different parts of C. sativum. The plant has a very effective antioxidant profile showing 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, lipoxygenase inhibition, phospholipid peroxidation inhibition, iron chelating activity, hydroxyl radical scavenging activity, superoxide dismutation, glutathione reduction and antilipid peroxidation due to its high total phenolic content with the presence of constituents like pyrogallol, caffeic acid, glycitin, etc. MATERIALS AND METHODS: This study was aimed at investigating the hepatoprotective activity of C. sativum against carbon tetrachloride (CCl4), with estimation of serum serum glutamyl oxaloacetic acid transaminase (SGOT), serum glutamyl pyruvate transaminase (SGPT), alkaine phosphatase (ALP) and bilirubin, and with liver histopathology. RESULTS: Ethanolic extract was found to be rich in alkaloids, phenolic compounds and flavonoids, and high performance liquid chromatography (HPLC) fingerprinting showed the presence of iso-quercetin and quercetin. C. sativum signifies hepatoprotection by reducing the liver weight, activities of SGOT, SGPT, and ALP, and direct bilirubin of CCl(4) intoxicated animals. Administration of C. sativum extract at 300 mg/kg dose resulted in disappearance of fatty deposit, ballooning degeneration and necrosis, indicating antihepatotoxic activity. CONCLUSION: The results of this study have led to the conclusion that ethanolic extract of C. sativum possesses hepatoprotective activity which may be due to the antioxidant potential of phenolic compounds.

Future implications: compliance and failure with antiretroviral treatment.

HIV management is currently in an era of effective, potent antiretroviral therapy. Modern drug discovery and development have transformed HIV-1 disease into a treatable, chronic infectious disease. Complete suppression of viral replication is critical for long-term durability of antiretroviral therapy. Partial suppression, even at very low levels, is likely to lead to virologic failure and ultimately to the appearance of drug resistance. The relationship between adherence and resistance to HIV antiretroviral therapy is more complex than to state 'non-adherence increases the risk of drug resistance.' In many patients who fail to respond to initial therapy, the primary reason for failure is their inability to take the prescribed drug regimen or nonadherence.