Effects of antihypertensive drugs on ultrasound production and cardiovascular responses in 15-day-old rats

When exposed to extreme cold or injected with the alpha(2)-adrenoceptor agonist, clonidine, infant rats emit ultrasonic vocalizations (USVs). Based upon the cardiovascular changes that accompany these two manipulations, especially decreased venous return, it was hypothesized that USVs are the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that increases venous return. If this hypothesis is correct, then other anithypertensive drugs that decrease venous return should evoke USVs. In Experiment 1, sodium nitroprusside (SNP, 400 microg/kg), a direct-acting dilator of arteries and veins, was administered to 15-day-old rats under thermoneutral conditions while cardiac rate and ultrasound production were monitored. In Experiment 2, femoral artery pressure was monitored after SNP administration. Infants responded to SNP administration with decreased arterial pressure and tachycardia and, in addition, significantly increased ultrasound production. In Experiment 3, chlorisondamine (5 mg/kg), a ganglionic blocker that causes vasodilation and bradycardia, and hydralazine (20 mg/kg), a selective dilator of arteries, was administered to 15-day-olds. As predicted, chlorisondamine evoked ultrasound production and hydralazine did not. These results introduce SNP and chlorisondamine as only the second and third known agents capable of independently evoking USVs in thermoneutral conditions, and provide further support for the notion that ultrasound production is triggered by decreased venous return.     

Adiponectin and future coronary heart disease events among men with type 2 diabetes

Adiponectin, predominantly synthesized in the adipose tissue, seems to have substantial anti-inflammatory properties and to be a major modulator of insulin resistance and dyslipidemia, mechanisms that are associated with an increased atherosclerotic risk in diabetic patients. However, it is unknown whether higher levels of adiponectin are associated with a reduced risk for coronary heart disease (CHD) among diabetic individuals. We investigated the association between plasma adiponectin levels and incidence of CHD among 745 men with confirmed type 2 diabetes in the Health Professionals Follow-up Study. Participants were aged 46-81 years and were free of diagnosed cardiovascular disease at the time of blood draw in 1993/1994. During an average of 5 years of follow-up (3,980 person-years), we identified 89 incident cases of CHD (19 myocardial infarction and 70 coronary artery bypass surgery), confirmed by medical records. Levels of adiponectin were inversely associated with BMI and directly associated with age, alcohol intake, and duration of diabetes (P < 0.05). After adjustment for age, BMI, smoking, alcohol consumption, duration of diabetes, and other lifestyle factors, adiponectin was associated with a decreased risk for CHD events. The multivariate relative risk for CHD for a doubling of adiponectin was 0.71 (95% CI 0.53-0.95). Further adjustment for HDL cholesterol attenuated this association (0.78 [0.57-1.06]). The inverse association between adiponectin and CHD was consistent across strata of aspirin use, family history of myocardial infarction, alcohol consumption, insulin use, duration of diabetes, and levels of HbA(1c), triglycerides, C-reactive protein, and HDL cholesterol. Our study suggests that increased adiponectin levels are associated with a moderately decreased CHD risk in diabetic men. This association seems to be mediated in part by effects of adiponectin on HDL cholesterol levels.     

The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia

The synaptosomal-associated protein of 25 kDa (SNAP-25) is an essential component of the core complex that mediates presynaptic vesicle trafficking. Thus, SNAP-25 is directly involved in the release of neurotransmitters. Quantitative alterations of SNAP-25 expression have been reported in brain regions and cerebrospinal fluid (CSF) of schizophrenics and in haloperidol treated rats. This observed altered expression may be influenced by genetic variants of SNAP-25. We hypothesized that polymorphisms of the SNAP-25 gene (sites DdeI, MnlI and TaiI in the 3'UTR) are associated with antipsychotic drug response and induced weight gain. A sample of 59 patients with prior suboptimal response to antipsychotic treatment and diagnosed with DSM-IV schizophrenia or schizoaffective disorder was examined. Patients were administered clozapine, haloperidol, olanzapine or risperidone for up to 14 weeks. Clinical response was defined as the difference between the baseline and the endpoint total scores on the Positive and Negative Syndrome Scale (PANSS). Weight was assessed at baseline and at study endpoint. ANOVA revealed that the MnlI and TaiI polymorphisms were associated with response (F[2,53] = 4.57, p = 0.01 and F[2,52] = 3.53, p = 0.03) and with weight gain (F[2,52] = 4.28, p = 0.01 and F[2,51] = 3.38, p = 0.04). When covariates were included, the MnlI polymorphism remained significantly associated with changes of PANSS scores, but not with weight gain. The DdeI polymorphism was not associated with response or weight gain. These findings suggest that SNAP-25 gene variants affect clinical response in patients with prior poor response to antipsychotics. Weight changes do not seem to be associated with polymorphism of the SNAP-25 gene, however, replication in independent samples is warranted.     

School absenteeism in children with asthma in a Los Angeles inner city school

OBJECTIVE: To investigate the pattern of school absenteeism in asthmatic children within a Los Angeles inner city school. STUDY DESIGN: Five hundred twenty-eight students of predominant Hispanic ethnicity, from a Los Angeles inner city school were divided into 3 groups: known asthma, high probability of asthma, and low probability of asthma using a previously validated instrument. Attendance records of these students were analyzed to determine total and respiratory absences over a year. School records were compared to the corresponding answers on 513 surveys to determine the accuracy of parental responses in regard to their children's absenteeism. RESULTS: Children with known asthma missed on average 2 more days of school than children with low probability of asthma and high probability of asthma. This was only significant in the younger age groups. Survey responses were found to have a 45.6% agreement with school attendance records. Underestimation occurred more often when school-recorded absentee rates were highest. Overestimation occurred more by parents of children with known asthma or a high probability of asthma. CONCLUSION: In a Los Angeles inner city population, younger children with known asthma miss more days of school than those with no asthma. Survey-reported absenteeism is less accurate than school attendance records.     

Susceptibility of Chinese rhesus monkeys to SIV infection

The use of China-derived monkeys in AIDS research has been limited by reports of reduced susceptibility to SIV. We performed a serial passage of SIV in Chinese macaques, which resulted in a viral stock capable of inducing simian AIDS and high levels of replication in these animals. Similar to HIV in humans, SIV pathogenesis in non-human primates is not limited by geographical origin. Chinese macaques are useful in pathogenesis, vaccine, and therapeutic studies in AIDS.     

Anesthetic considerations during liver surgery

This article demonstrates the broad range of considerations that affect the outcome of patients undergoing hepatectomy. The progressive improvements in survival, despite the increasing complexity of the surgery, area testament to advances in both surgery and anesthesia. The key elements include careful patient selection, appropriate monitoring, and mechanical and pharmacologic protection of the liver and other vital organs.     

Does Cryotherapy Improve Outcomes With Soft Tissue Injury?

Reference:

Bleakley C, McDonough S, MacAuley D. The use of ice in the treatment of acute soft-tissue injury: a systematic review of randomized controlled trials. Am J Sport Med. 2004; 32:251–261.

Clinical Question:

What is the clinical evidence base for cryotherapy use?

Data Sources:

Studies were identified by using a computer-based literature search on a total of 8 databases: MEDLINE, Proquest, ISI Web of Science, Cumulative Index to Nursing and Allied Health (CINAHL) on Ovid, Allied and Complementary Medicine Database (AMED) on Ovid, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effectiveness, and Cochrane Controlled Trials Register (Central). This was supplemented with citation tracking of relevant primary and review articles. Search terms included surgery,orthopaedics,sports injury,soft tissue injury,sprains and strains,contusions,athletic injury,acute,compression, cryotherapy,ice,RICE, andcold.

Study Selection:

To be included in the review, each study had to fulfill the following conditions: be a randomized, controlled trial of human subjects; be published in English as a full paper; include patients recovering from acute soft tissue or orthopaedic surgical interventions who received cryotherapy in inpatient, outpatient, or home-based treatment, in isolation or in combination with placebo or other therapies; provide comparisons with no treatment, placebo, a different mode or protocol of cryotherapy, or other physiotherapeutic interventions; and have outcome measures that included function (subjective or objective), pain, swelling, or range of motion.

Data Extraction:

The study population, interventions, outcomes, follow-up, and reported results of the assessed trials were extracted and tabulated. The primary outcome measures were pain, swelling, and range of motion. Only 2 groups reported adequate data for return to normal function. All eligible articles were rated for methodologic quality using the PEDro scale. The PEDro scale is a checklist that examines the believability (internal validity) and the interpretability of trial quality. The 11-item checklist yields a maximum score of 10 if all criteria are satisfied. The intraclass correlation coefficient and kappa values are similar to those reported for 3 other frequently used quality scales (Chalmers Scale, Jadad Scale, and Maastricht List). Two reviewers graded the articles, a method that has been reported to be more reliable than one evaluator.

Main Results:

Specific search criteria identified 55 articles for review, of which 22 were eligible randomized, controlled clinical trials. The articles'' scores on the PEDro scale were low, ranging from 1 to 5, with an average score of 3.4. Five studies provided adequate information on the subjects'' baseline data, and only 3 studies concealed allocation during subject recruitment. No studies blinded their therapist''s administration of therapy, and just 1 study blinded subjects. Only 1 study included an intention-to-treat analysis. The average number of subjects in the studies was 66.7; however, only 1 group undertook a power analysis. The types of injuries varied widely (eg, acute or surgical). No authors investigated subjects with muscle contusions or strains, and only 5 groups studied subjects with acute ligament sprains. The remaining 17 groups examined patients recovering from operative procedures (anterior cruciate ligament repair, knee arthroscopy, lateral retinacular release, total knee and hip arthroplasties, and carpal tunnel release). Additionally, the mode of cryotherapy varied widely, as did the duration and frequency of cryotherapy application. The time period when cryotherapy was applied after injury ranged from immediately after injury to 1 to 3 days postinjury. Adequate information on the actual surface temperature of the cooling device was not provided in the selected studies. Most authors recorded outcome variables over short periods (1 week), with the longest reporting follow-ups of pain, swelling, and range of motion recorded at 4 weeks postinjury. Data in that study were insufficient to calculate effect size. Nine studies did not provide data of the key outcome measures, so individual study effect estimates could not be calculated. A total of 12 treatment comparisons were made. Ice submersion with simultaneous exercises was significantly more effective than heat and contrast therapy plus simultaneous exercises at reducing swelling. Ice was reported to be no different from ice and low-frequency or high-frequency electric stimulation in effect on swelling, pain, and range of motion. Ice alone seemed to be more effective than applying no form of cryotherapy after minor knee surgery in terms of pain, but no differences were reported for range of motion and girth. Continuous cryotherapy was associated with a significantly greater decrease in pain and wrist circumference after surgery than intermittent cryotherapy. Evidence was marginal that a single simultaneous treatment with ice and compression is no more effective than no cryotherapy after an ankle sprain. The authors reported ice to be no more effective than rehabilitation only with regard to pain, swelling, and range of motion. Ice and compression seemed to be significantly more effective than ice alone in terms of decreasing pain. Additionally, ice, compression, and a placebo injection reduced pain more than a placebo injection alone. Lastly, in 8 studies, there seemed to be little difference in the effectiveness of ice and compression compared with compression alone. Only 2 of the 8 groups reported significant differences in favor of ice and compression.

Conclusions:

Based on the available evidence, cryotherapy seems to be effective in decreasing pain. In comparison with other rehabilitation techniques, the efficacy of cryotherapy has been questioned. The exact effect of cryotherapy on more frequently treated acute injuries (eg, muscle strains and contusions) has not been fully elucidated. Additionally, the low methodologic quality of the available evidence is of concern. Many more high-quality studies are required to create evidence-based guidelines on the use of cryotherapy. These must focus on developing modes, durations, and frequencies of ice application that will optimize outcomes after injury.