A case of under-dosing after raltegravir formulation change in an elderly patient treated for HIV.

Our case was a 70-year-old male (height: 168 cm, weight: 74.3 kg) with polypharmacy (total 15 drugs including 10 tablets) who was treated for HIV infection. His dosing schedule of raltegravir was changed from BID (a 400 mg tablet, twice) to QD (2x600 mg tablet, once). After a month, we found that he miss-took raltegravir for 1x600 mg tablet at once. His HIV-1 RNA increased from undetectable levels to < 20 copies per mL. Pharmaceutical companies should therefore carefully consider swallowing difficulties in old patients, such as by reformulating medications so that only one dosing is required per day and decreasing the size of tablets to 7-8 mm in diameter or orally distinguish tablet.

Telescience testbed for biomedical experiments in space morphological and physiological experiments of rat musculoskeletal system.

As the second telescience testbed experiment we were examined sophisticated processes of biomedical experiment, such as an implantation of a transmitter into the hamster's abdominal cavity, non-stressful blood sampling, large amount of blood collection, muscle extirpation and biopsy from the hamsters on February 6-8, 1990. To make clear the differences between successful results obtained by an experienced hand and by a non-experienced one, three operators were selected for three successive experimental days; an engineer who had never experienced any biological experiment, a non-biology student, who experienced on biological experiments, and a veterinary surgeon. Surgical procedures need much experiences on maneuvering and understanding of theory to shorten the elapse time. Especially for a non-experienced hand, graphic instructions were much helpful to understand and to maneuver the procedures. Continuous recordings of ECG from a operator and PIs were of an advantage to grasp an extent of the mental strain, which was compared with their reports requested after end of each experimental day. The mental strain was not related to degrees of scientific achievement, but showed faithfully difficulty of each experimental procedure. Training effects on PIs in successive experimental days were found in their instructions for the operator to let understand the procedures.

Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin.

Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay.

Evaluation of complex congenital ventricular anomalies with magnetic resonance imaging.

Complex ventricular anomalies are frequently associated with abnormalities of thoracic and abdominal situs, arterioventricular connection, and venous connection. The definition of all components of these anomalies is difficult to accomplish with imaging techniques. This study compared the effectiveness of electrocardiographic (ECG) gated spin-echo magnetic resonance imaging (MRI) with cardiac angiography for the evaluation of all components of central cardiovascular anatomy in patients with the clinical diagnosis of single or common ventricle or complete atrioventricular (AV) septal (canal) defect. MRI studies and angiograms of 29 patients were evaluated independently. A sequential approach was used to define cardiac anatomy assessing nine anatomic features in each patient. MRI provided 261 observations and angiography provided 209 observations. In the mutual 209 observations, only 17 discrepancies were found. Comparison of MRI and angiography in individual cases showed that MRI was as effective as angiography in the depiction of ventricular anomalies, including determination of morphology and evaluation of the size of the ventricles, the orientation of the ventricular septum relative to the AV valves, as well as the origins and spatial relationships of the great arteries. MRI was more informative for the determination of thoracic and abdominal situs and systemic and pulmonary venoatrial connections, but was not as effective for the evaluation of semilunar valves. Thus MRI provides complete evaluation of central cardiovascular anatomy and is effective in the anatomic assessment of most components of complex ventricular anomalies.

Should parents of children with congenital heart disease and life-threatening dysrhythmias be taught cardiopulmonary resuscitation?

In conclusion, CPR at home can be successfully performed by parents who have been given adequate training. As a result of the findings of this study, our recommendation is that training in CPR should be taught to all parents of children with life-threatening dysrhythmias and complex congenital heart disease.

Magnetic resonance imaging of congenital heart disease: sensitivity and specificity using receiver operating characteristic curve analysis.

MRI has shown promise for the evaluation of various congenital heart lesions. The current study was designed to assess the sensitivity and specificity of the technique for the evaluation of all major anatomic elements of the heart affected in simple and complex congenital heart disease. MR images of 51 patients (31 males and 20 females, ages 3 to 69 years) with a total of 110 congenital heart lesions were reviewed by a panel of two cardiac radiologists and one pediatric cardiologist, who assessed the cardiac pathoanatomy without knowledge of clinical details and assigned a confidence level to each diagnosis. The true diagnosis was established independently by the findings of angiocardiography and catheterization as well as by surgery, where applicable. ROC curves were generated from the responses, and the sensitivity at a specificity level of 90% was determined. MRI was shown to have a high sensitivity in evaluating great vessel relationships (100%), thoracic aorta abnormalities (94%), ASDs (91%) and VSDs (100%), visceroatrial situs (100%), and loop (100%). Three of five anomalies of the pulmonary and systemic veins were diagnosed by MRI. Right ventricular outflow obstructions (95%) were detected with a much higher sensitivity than lesions of the other valves (aortic valve 52%, mitral valve 62%, tricuspid valve 76%). Spin-echo MRI is a sensitive and specific method for the noninvasive assessment of congenital heart disease, with limitations in the evaluation of some valvular anomalies.

Coarctation of the aorta: MR imaging.

Thirteen patients, aged 3-31 years, with coarctation of the thoracic aorta were examined by magnetic resonance (MR) imaging (total of 14 studies). Eight studies were performed preoperatively and six postoperatively. Catheterization data were available on 12 patients for verification of MR imaging findings. Electrocardiographically gated sagittal and left anterior oblique images best depicted the coarctations; however, involvement of arch vessels was best evaluated on transaxial images. MR imaging readily identified all coarctations but one, their site and extent, and involvement of the arch vessels. In addition, MR images depicted poststenotic dilatation and dilated collateral vessels. In patients studied postoperatively, restenosis could be evaluated, and complications such as postoperative aneurysm and perianastomotic hematoma were identified. MR imaging provides excellent anatomic detail of coarctation of the aorta, potentially obviating the need for angiography.

Inadequate erythroid response to hypoxia in cystic fibrosis.

An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.

Intercellular communication and tissue growth : IV. Conductance of membrane junctions of normal and cancerous cells in culture.

Epithelial cells of normal rat (adult) liver and hamster embryo in tissue culture communicate through membrane junctions: the membrane regions of cell contact are highly ion-permeable. Cancerous counterparts of these cells, cells from Morris' and Reuber's liver tumors and from x-ray-transformed embryo cultures, do not communicate under the same experimental conditions. These cells also fail to communicate with contiguous normal cells. Cancerous fibroblastic cells from a variety of tissues, including cells transformed by virus, x-radiation and chemicals, communicate as well as their normal counterparts; this is so for long- and short-term cell cultures. Communication in some fibroblastic cells is sensitive to components of blood serum: normal and transformed hamster embryo fibroblasts, which communicate when cultured in medium containing fetal calf serum, appear to lose communication in medium containing calf serum; the converse holds for hamster (adult) fibroblasts and 3T3 cells.

Uncoupling of an epithelial cell membrane junction by calcium-ion removal.

Calcium takes part in maintaining ion communication between salivary gland cells (Chironomus thummi). Its withdrawal from the cell systems results in virtual disconnection of ion communication, at Ca(++) concentrations which do not noticeably affect cell adhesion. The junctional membrane surfaces. which are normally quite freely permeable to ions, become as impermeable as the nonjunctional membrane surfaces; each cell seals itself off irreversibly as a unit. In maintaining ion communication Mg(++) substitutes for Ca(++)