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.     

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.     

MODELING THE AIDS EPIDEMIC: PLANNING,POLICY AND PREDICTION.

Edward H. Kaplan and Margaret L. Brandeau (Eds), Raven Press, New York, 1994. No. of pages: xxix + 624. Price: $125. ISBN: 0-7817-0164-3     

High Rate of Late Dislodgements of an Active Fixation Atrial Lead

Between May 1985 and May 1991 we implanted 115 DFH-leads as unipolar atrial leads. The active fixation mechanism of this electrode consists of two sickle-shaped anchoring hooks which are placed at a distance of 0.9 mm parallel to the distal flat end of the electrode. All leads were affixed to the free wall of the right atrium. One hundred eight leads (93.9%) were implanted for dual chamber pacing and seven leads (6.1%) for single chamber atrial pacing. Parameters measured at implantation were (mean values): stimulation threshold 1.06 ± 0.42 V at 0.5 msec pulse width, P wave amplitude 5.12 ± 2.04 mV, and lead impedance 560 ± 76.1 Ohms. Within the first week after implantation, three early dislodgements occurred (2.6%). The follow-up period averaged 30.4 ± 16.2 months (range 2–76 months). During this time, 14 late macrodislodgements (12.2%) occurred after a mean period of 18.4 months (range 2–59 months). All of them required reoperation. The active fixation mechanism of the DEH-lead appears to be unreliable, if implanted in the free wall of the right atrium for dual chamber pacing.     

The effect of a basic home stimulation programme on the development of young children infected with HIV

Aims The human immunodeficiency virus (HIV) potentially causes a significant encephalopathy and resultant developmental delay in infected children. The aim of this study was to determine whether a home‐based intervention programme could have an impact on the neurodevelopmental status of children infected with HIV. Method A longitudinal, randomized, controlled trial was conducted. A total of 122 children aged less than 2 years 6 months were assigned to either a comparison or an experimental group. Children in the experimental group were given a home stimulation programme that was updated every 3 months. The home programme included activities to promote motor, cognitive, and speech and language development. Children in the comparison group received no developmental intervention. Children were assessed by a blinded assessor at baseline, 6 months, and 12 months using the Bayley Scales of Infant Development, 2nd edition. Results The children in this study came from poor socioeconomic backgrounds and their nutritional status was suboptimal. The experimental group included 60 children (30 males, 30 females) with a mean age of 18 months (SD 8.1mo). The comparison group included 62 children (32 males, 30 females) with a mean age 19 months (SD 8.2mo). Cognitive and motor development were severely affected at baseline, with 52% of the children having severe cognitive delay and 72% having severe motor delay at baseline. Children in the experimental group showed significantly greater improvement in cognitive (p=0.010) and motor (p=0.020) development over time than children in the comparison group. Interpretation A home stimulation programme taught to the caregiver can significantly improve cognitive and motor development in young children infected with HIV.