A randomized controlled trial of sedation in the critically ill

A randomized controlled trial comparing: a) a combination of oral chloral hydrate and promethazine to b) a continuous intravenous midazolam infusion, for maintenance sedation in critically ill children, was carried out. The level of sedation was assessed four hourly using a specifically devized sedation scale. Forty-four children entered the study of whom two were subsequently excluded. The number of satisfactory assessments (desired and actual levels of sedation equal) was significantly greater in the chloral hydrate and promethazine group (Chi-squared P <0.01; confidence intervals of the difference 0.06 to 0.20). The number of assessments at level 5 on the sedation scale (patient restless/distressed) was significantly greater in the midazolam group (Chi-squared P <0.05). The total number of satisfactory assessments in the two groups were only 61 and 48% respectively, suggesting that sedation can be considerably improved. Chloral hydrate and promethazine are more effective than midazolam as maintenance sedation in critically ill children. It is possible to prospectively study the efficacy of sedative drugs in critically ill children.     

Dramatic improvement of severe dilated cardiomyopathy in an acromegalic patient after treatment with octreotide and trans-sphenoidal surgery

Severe congestive heart failure developed in an acromegalicpatient, and was successfully treated with octreotide followedby trans-sphenoidal surgery. Clinical, hormonal echocardiographicand haemodynamic findings as well as histological heart examinationbefore and after treatment revealed tliat over-production ofgrowth hormone may induce the myocardial cell degeneration responsiblefor mechanical heart dysfunction. In addition, this unique exampledemonstrates the reversibility of myocardial damage followingoctreotide and trans-sphenoidal surgery, leading to significantimprovement in cardiac function with minimal diastolic dysfunctionand moderate interstitial fibrosis.     

Ultrastructural, Protein, and Lipid Changes in Liver Associated with Chlordecone Treatment of Mice

Pretreatment of mice with chlordecone (CD) reduced hepatic accumulationof a subsequent dose of [¹⁴C]CD without significantly changing[¹⁴C]CD biotransformation. To determine if CD-induced changesin hepatic [¹⁴C]CD accumulation were coincident with alteredcell composition, we examined the effects of CD on hepatic proteinand lipid content, on fatty acid profiles of liver and kidney,and on the ultrastructure of hepatocytes. SDS-polyacrylamidegel electrophoresis detected an apparent CD dose-related increasein a microsomal protein with a molecular weight of about 23kDa. Total liver or kidney lipid contents were not altered byCD but relative amounts of several hepatic fatty acids werechanged. CD caused marked hepatic mitochondrial swelling, increasedamounts of endoplasmic reticulum, apparently increased numbersof peroxisome-like structures, and decreased numbers of lipiddroplets in cytoplasm of hepatocytes. Numbers of lipid dropletswere not decreased in perisinusoidal fat storage cells. In addition,the numbers of cytoplasmic lipoprotein vesicles were apparentlyincreased in some hepatocytes. Overall these changes indicatedan increased hepatocyte secretory activity and suggested thatCD changed hepatocellular lipid transport, storage, and metabolismpathways.     

A phase 1 ascending dose study of a subcutaneously administered factor IXa inhibitor and its active control agent

Summary. Background: The REG2 anticoagulation system consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous control agent, anivamersen. Objectives: To assess the safety, tolerability and pharmacokinetic and pharmacodynamic responses of REG2. Patients/Methods: In this phase 1a study, 36 healthy volunteers were enrolled into five cohorts and given one dose of pegnivacogin. Cohorts 1 (n = 6) and 1A (n = 4) received 0.5 mg kg^?1; cohort 2 (n = 6) received 1.0 mg kg^?1; cohort 3 (n = 6) received 3.0 mg kg^?1; and cohort 4 (n = 8) received 2.0 mg kg^?1. In cohorts 1–3, two subjects were randomized to placebo. Cohort 4 subjects were subsequently randomized to single‐dose (n = 4) or multidose (n = 4) anivamersen. Results: The mean maximum observed concentrations of pegnivacogin in cohorts 1, 1A, 2 and 3 at median time were 5.16 μg mL^?1 at 84 h, 5.19 μg mL^?1 at 72 h, 9.32 μg mL^?1 at 90 h, and 32.5 μg mL^?1 at 84 h, respectively. The maximum relative activated partial thromboplastin time and time needed to achieve this were 1.18 at 2 days, 1.16 at 2 days, 1.27 at 3 days, and 1.85 at 2 days, respectively. The calculated mean half‐life and mean residence times of pegnivacogin were 6.12 days and 9.6 days, respectively. There was rapid reversal with intravenous anivamersen, although subsequent reaccumulation of pegnivacogin was observed. Conclusions: In our first‐in‐human study, REG2 was well tolerated and provided dose‐proportional anticoagulation for several days after a single subcutaneous dose, with complete, although transient, reversal by its control agent. This study demonstrates the first application of a subcutaneously administered aptamer, and represents a potential advance in aptamer therapeutics.     

Tuberculous splenomegaly with the hypersplenism syndrome; a case report

A case of tuberculous splenomegaly with leukopenia and anemia followingmiliary tuberculosis has been presented. Splenectomy was required after streptomycin failed to control the cytopenias, progressive emaciation, and splenic infection. However, following what appeared to be six weeks of marked improvement,the patient developed a fulminating tuberculous meningitis and died.

Note: ACKNOWLEDGMENTThe authors are indebted to Dr. Byrd S. Leavell for his suggestions in the preparation of this paper.

     

Abnormal Automaticity as Mechanism of Atrial Tachycardia in the Human Heart—Electrophysiologic and Histologic Correlation:

Abnormal Automaticity in Human Atrium, introduction: A 32-year-old woman was operated upon because of drug refractory atrial tachycardia.
Methods and Results: Electrophysiologic study was performed prior to operation. During surgery, epicardial mapping of the electrical activity of the left atrium was performed. The left atrial appendage was resected and studied in a tissue bath. Thereafter, histologic examination was performed. Polarity of the P wave in the surface ECG suggested that the tachycardia originated high in the left atrium. Epicardial mapping disclosed earliest activation in the apex of the left atrial appendage. Intracellular recordings from surgical specimen made at the site of origin, which was marked during surgery, revealed cells with phase 4 depolarization at cycle lengths ranging from 360 to 540 msec. Exit block prevented spread of activation from the spontaneously firing cells to surrounding tissue. Histology showed that spontaneous activity arose in an area with abnormal cells-characterized by an amorphous, pale eosinophilic staining cytoplasm and absence of nuclei-surrounded by normal myocytes.
Conclusion: The observations indicate that the mechanism of the atrial tachycardia was based on abnormal automaticity in an area consisting of a conglomeration of normal and abnormal myocytes.     

HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment

This study compares the injecting and sexual risk-taking behaviour among injecting drug users (IDUs) currently, previously and never enrolled in methadone maintenance treatment (MMT). All subjects had injected during the 6 months prior to the day of interview. The current MMT group showed significantly lower injecting risk-taking behaviour subscale scores on the HIV Risk-taking Behaviour Scale (HRBS) of the Opiate Treatment Index than the previous MMT and non-MMT groups together. The current MMT group differed from the other two groups in the frequency of injecting and cleaning of injection equipment with bleach. There was no difference between the current MMT group and the other two groups combined in sexual risk-taking behaviour scores on the HRBS. There were no differences between the previous MMT and non-MMT groups in injecting and sexual risk-taking behaviour. HIV seroprevalence was low and there was no difference in seroprevalence between groups. Thus, IDUs currently enrolled in MMT are at reduced risk for HIV infection when compared with IDUs who have previously or never been enrolled in MMT. However, the absence of a difference between the current MMT and other two groups in frequency of sharing behaviours suggests the need for additional strategies among MMT clients to reduce needle-sharing. Possible strategies include the application of relapse prevention interventions and the availability of sterile injecting equipment in MMT clinics. Further research is needed to identify factors which increase attraction and retention of IDUs to MMT.