Consultation about violent students.

Violence in the schools is a growing problem. Psychiatrists consulting to schools can play an important role in helping school-based professionals with early identification, diagnostic evaluations, program planning, and prevention. They can also serve as educators and child advocates and help to coordinate and to organize a team approach.

Patient reading ability: an overlooked problem in health care.

Health care workers often assume that patients who have completed a certain grade in school can read at that level. This study examines the relationships between patient reading ability, the last grade completed, and the reading ability necessary to comprehend commonly used written materials. We tested 528 patients during regular visits to seven outpatient clinics serving a predominantly indigent population. In addition, we analyzed the readability of 280 brochures and consent forms used in these clinics. Most patients had reading abilities on a level far below their last grade completed, while almost all materials tested were written on a level far above average patient reading ability. We conclude that patient reading ability should be routinely tested and that written materials should be developed on a level commensurate with patient reading ability.

Higher plasma Na+,K+-ATPase inhibitory activity in essential hypertensive patients.

The ability of plasma to inhibit 86 rubidium uptake in rat aorta and to displace [3H]-ouabain from hog brain Na+,K+-ATPase was used as a measure of plasma Na+,K+-ATPase inhibitory activity in seven normotensive and eight hypertensive subjects. Rat aortae rings were incubated in oxygenated plasma containing 86 rubidium (2 microCi/mL) for 30 mins at 37 degrees C and uptake measured and expressed as mumol/kg wet weight/min. Plasma was extracted with a mixture of chloroform and methanol (2:1) and the extract separated by silicic acid column followed by thin layer chromatography and fractions assayed for ouabain displacement using digoxin as a standard. Total ouabain displacement was calculated as the sum of all fractions. There was a strong correlation between the two methods for total plasma Na+,K+-ATPase inhibitory activity (r = 0.761, P less than 0.01). There was a significant positive correlation between plasma Na+,K+-ATPase inhibitory activity and blood pressure in all subjects. Na+,K+-ATPase inhibitory activity was significantly higher in plasma of hypertensives by both methods (P less than 0.001). The increased Na+,K+-ATPase inhibitory activity in plasma from hypertensives was due to the nonesterified fatty acid, long chain acylcarnitine and diphosphatidylglycerol fractions.

BioSYNTHESIS: bridging the information gap.

BioSYNTHESIS is a prototype intelligent retrieval system under development as part of the IAIMS project at Georgetown University. The aim is to create an integrated system that can retrieve information located on disparate computer systems. The project work has been divided in two phases: BioSYNTHESIS I, development of a single menu to access various databases which reside on different computers; and BioSYNTHESIS II, development of a search component that facilitates complex searching for the user. BioSYNTHESIS II will accept a user's query and conduct a search for appropriate information in the IAIMS databases at Georgetown. For information not available at Georgetown, such as full text, it will access selected remote systems and translate the search query as appropriate for the target system. The search through various computer systems and different databases with unique storage and retrieval structures will be transparent to the user. BioSYNTHESIS I is complete and available to users. The design work for BioSYNTHESIS II is under development and will continue as a multiyear technical research effort of the proposed Georgetown IAIMS implementation project.

Recurrent hemoperitoneum in women receiving continuous ambulatory peritoneal dialysis.

Of 27 women in the reproductive age group receiving continuous ambulatory peritoneal dialysis for more than 3 months, 4 of 7 who menstruated developed recurrent hemoperitoneum. Tubal ligation had been done in 3 of these 4 women. There were 37 episodes of hemoperitoneum; 22 occurred at midcycle and 15 with menstruation. One patient required repeated blood transfusion, but after oral anovulant therapy no further bleeding occurred and no transfusion was required. Two patients needed laparotomy: one for heavy intraperitoneal bleeding originating from a luteal cyst, and the other for severe lower abdominal pain from follicular and luteal cysts. Ultrasound examinations suggested the presence of small ovarian cysts in the two remaining patients. Recurrent midcycle hemoperitoneum in women on continuous ambulatory peritoneal dialysis may be triggered by ovulation and associated ovarian cyst formation. Suppression of ovulation should be considered.

The effect of ethanol on serum cyclosporine A levels in renal transplant recipients.

Following an alcohol binge, cyclosporine A (CyA) levels rose by 100% in a 51-year-old transplant recipient treated with CyA. As CyA and ethanol are both metabolized by the cytochrome P-450 enzyme system, ethanol could theoretically interfere with CyA metabolism. Therefore, eight male renal transplant recipients were assessed in a crossover study to determine the effects of acute ethanol ingestion on CyA serum concentrations. CyA serum concentrations did not rise following 50 mL of 100% alcohol. We conclude that heavy alcohol intake may increase CyA levels but that acute moderate intake does not.

Interpretation of serum digoxin values in renal failure.

We have studied three circumstances that have been reported to make interpretation of the serum digoxin concentration difficult in patients with renal failure: increased biotransformation; endogenous digitalis-like factors (DLF); and sudden, unexpected increases in serum digoxin values, even after the discontinuation of digoxin. Biotransformation, as estimated by the percent true digoxin in serum, was comparable in patients with renal failure who were dependent on dialysis and in control subjects (76% vs. 73%). Certain commercial immunoassays did not, or rarely, gave values for DLF of clinical significance (greater than 0.2 ng/ml digoxin equivalents) in patients with a wide range of renal dysfunction who were not receiving digoxin. With a sensitive method, values for DLF did not exceed 0.23 ng/ml in 22 dialysis patients dependent on dialysis, but were significantly increased in comparison with values in control subjects. The case histories of two patients with renal failure, acute illness, and sudden unexpected marked increases in serum digoxin concentrations are presented and possible explanations are discussed.

The outcome and complications of the DiaTAP bioCarbon button-graft vascular access device in haemodialysis patients: a two-year experience.

The outcome and complications which developed in 8 hemodialysis patients who received 12 DiaTAP bioCarbon button vascular-access devices were reviewed. All patients had a poor vascular access history. Three of twelve devices have been replaced because of thrombosis and two because of infection. Four patients have had 10 episodes of reduced blood flow. Streptokinase infusion into the DiaTAP button led to improved blood flow in 8 of 10 episodes. The 6-month survival rate of the DiaTAP access device was 67% and the average functioning life was 9.4 months. It was a valuable form of access when others had failed.

Digoxin-rifampin interaction.

Digoxin doses required to maintain therapeutic serum concentrations rose substantially in two patients dependent on dialysis with the commencement of rifampin therapy. When rifampin was discontinued, doses fell to requirements before rifampin. Serum digoxin concentration may fall to ineffective levels with rifampin therapy and rise to potentially toxic levels when rifampin is discontinued.

Digoxigenin biotransformation.

Two healthy subjects took 3H-digoxigenin-12 alpha and unlabeled digoxigenin. Metabolites were assayed by high-pressure liquid chromatography (HPLC) in serum and urine. Of the tritium activity in the serum at 30 min, less than 26% chromatographed with digoxigenin; the rest chromatographed as metabolites, most of which were polar. The main polar metabolites identified were glucuronides of 3-epidigoxigenin. An important route of biotransformation to polar metabolites appears to be from 3 beta-digoxigenin through 3-keto-digoxigenin to 3-epidigoxigenin. Several HPLC peaks remain unidentified. There was extensive cross reactivity between metabolites and antisera to digoxin. The digoxigenin route of digoxin biotransformation to polar metabolites may be important in some patients receiving digoxin and such metabolites could contribute an important fraction to the serum digoxin concentration measured by radioimmunoassay.

Influence of gastric pH on digoxin biotransformation. II. Extractable urinary metabolites.

High-performance liquid chromatography (HPLC) analysis was performed on methylene chloride extracts of urine from six subjects after administration of 3H-digoxin-12 alpha and unlabeled digoxin by nasogastric tube under four conditions: pentagastrin and control saline infusions, each in the supine and ambulatory states. There were no differences with change in position. With pentagastrin stimulation of acid secretion, there was extensive intragastric hydrolysis, mainly to digoxigenin; there was further extensive biotransformation leading to an increase in both extractable and unextractable metabolites in urine, particularly the latter. In the first 5 hr mean digoxin was only 17% and unextractable metabolites were 54% of total urine radioactivity. Extractable radioactivity was found under HPLC peaks with retention times of digoxin, digoxigenin, and its mono- and bis-digitoxosides. There were also three other peaks that were not identified; two correlated with gastric H+ activity and with the peak for digoxigenin, which is probably their precursor since similar peaks were found after ingestion of digoxigenin. The third unidentified peak eluted immediately after the digoxin, with which it correlated; it may have a close structural relationship to digoxin. Gastric acid stimulation induced a major increase in the production of urinary metabolites and may prove a useful model for the study of digoxin biotransformation, which is not yet well defined.

Influence of gastric pH on digoxin biotransformation. I. Intragastric hydrolysis.

3H-digoxin-12 alpha and unlabeled digoxin were administered down a nasogastric tube and digoxin, digoxyigenin and its mono- and bis-digitoxosides, and pH were assayed in gastric fluid of 6 healthy subjects at intervals for 90 min each under 4 conditions: pentagastrin infusion 6 micrograms/kg/hr with the subjects ambulatory and supine, and saline infusion ambulatory and supine. Intragastric hydrolysis occurred at roughly the same rate as reported in vitro. At 90 min, an average of 12.5% of the radioactivity that remained in the gastric fluid was recovered as digoxin for the 2 conditions when pentagastrin was infused, compared with 52.5% for th 2 conditions when saline was infused. The main glycosidic metabolite was digoxigenin and the amount correlated closely with the hydrogen ion activity in gastric fluid at 90 min (r = 0.83, p less than 0.01). Only minor differences were found between the supine and ambulatory conditions. The clinical significance of these results remains to be determined.

Hemodialysis for methanol intoxication.

We describe nine patients with methyl alcohol poisoning who were treated with hemodialysis. The time from ingestion to dialysis varied from 4 to 100 hours. Predialysis blood methanol levels ranged from 3 to 570 mg/dl. All patients were acidotic and had an increased anion gap. Two patients died, seven recovered, but three had permanent visual impairment. There was little correlation between the blood methanol level or anion gap and visual outcome. The interval from ingestion to treatment appears to be more important than the initial biochemical status. We recommend prompt hemodialysis if the blood methanol level is above 50 mg/dl, when an amount of methanol exceeding the minimal lethal dose (30 ml) is known to have been ingested, when there is evidence of acidosis or when an abnormality has developed in vision, funduscopic examination or mental state. Concurrent therapy with alkali and ethanol is vital.

Cryoablation of drug-resistant ventricular tachycardia in a patient with a variant of scleroderma.

A 37-year-old man with a benign variant of scleroderma (CRST syndrome: calcinosis circumscripta, Raynaud's phenomenon, sclerodactyly, and telangiectasia) presented with recurrent ventricular tachycardia. Preoperative electrophysiologic study suggested that the mechanism of tachycardia was an ectopic pacemaker focus in the right ventricle. Right ventricular dilatation, tricuspid insufficiency, normal pulmonary pressures, and normal coronary arteries were also demonstrated. At surgery, epicardial mapping localized the site of origin of ventricular tachycardia to the anterior right ventricle near the crista supraventricular. Intramural recordings of the site of tachycardia demonstrated autonomous activity unreflected on the peripheral ECG during brief periods of sinus rhythm. Local epicardial cooling of this area with a cryoprobe promptly terminated ventricular tachycardia with resumption of tachycardia on warming. The focus was ablated by freezing the area at -60 degrees C. The patient remained free of dysrhythmia on no anti-arrhythmic agents for eight months at which time he had a single recurrence of ventricular tachycardia from a different site in the right ventricle. This technique offers a method for ablating sites of dysrhythmia arising in diffusely diseased myocardium.

Virus-like particles in Australia antigen-associated hepatitis. An immunoelectron microscopic study of human liver.

IN A PREVIOUS REPORT (HUANG SN: Hepatitis-associated antigen hepatitis: an electron microscopic study. Am J Pathol 64:483-500, 1971) liver biopsies of renal transplant patients who developed chronic progressive viral hepatitis associated with persistence of Australia antigenemia [Au(1)] while under immunosuppressive therapy were studied. Predominantly intranuclear 210-250 A spherical, virus-like particles were revealed in 12 of 13 biopsies examined by electron microscope. No such particles were found in biopsies from Australia antigen negative patients. To investigate the relationship of these virus-like particles to Australia antigen, 2 of the Au(1) hepatitis renal transplant patients were restudied 6 to 8 months later. Liver biopsy material was prepared for light microscopy, immunofluorescent microscopy, electron microscopy and immunoelectron microscopy. The specificity of the anti-Au(1) serum used in this study was ascertained by immunodiffusion and immunoelectrophoresis, and by immunoelectron microscopic studies of the antigen-antibody complex prepared in vitro by mixing the ferritin-conjugated anti-Au(1) reagent with the purified Au(1) particles. Electron microscopy of biopsies from liver not treated with antibody showed that virus-like particles persisted in liver cells. Immunofluorescent microscopy of teased liver biopsy suspensions showed nuclear and some cytoplasmic fluorescence, indicating the cellular localization of Au(1). The immunoelectron microscopic preparations showed agglutination of the virus-like particles and the presence of antibody coupled ferritin in the intranuclear and cytoplasmic particle agglutinates. No virus-like particles were seen in the biopsy from a control patient without Au(1) antigenemia, and results of the immunoelectron microscopic procedure were negative. Our observations that massive amounts of Au(1)-associated particles are located in liver cell nuclei of individuals with chronic active hepatitis strengthen the hypothesis of Blumberg et al that Au(1) is an infectious agent and/or the antigenic determinant of a hepatitis virus.