The Autosow raised miniature swine as a model for assessing the effects of dietary soy trypsin inhibitor.

Toxicological effects of dietary soy trypsin inhibitor (TI) were assessed in male miniature swine, a model chosen for its similarities to human digestive physiology and anatomy. The TI preparation was extracted from defatted raw soy flour. From 1 through 5 weeks of age, piglets were automatically fed either a TI liquid diet [Autosow TI group (ASTI)] or a control liquid diet [Autosow control group (ASC)]. From 6 to 39 weeks of age, these animals received either swine chow and TI or swine chow and control article. The TI diets were formulated to contain a TI activity of approximately 500 mg TI/100 g dry matter. A sow control (SC) group suckled from birth to 6 weeks of age and then fed as the ASC group with swine chow plus control article from 6 to 39 weeks of age. The SC piglets grew faster than ASC piglets during postnatal weeks 1 and 2; however, the ASC piglets were significantly heavier than the SC piglets (P=0.001) at 6 weeks of age. Compared with the ASC group, TI caused a moderate decrease in feed consumption and a moderate but reversible decrease in growth from 2 to 5 weeks of age, but not thereafter. Some control and TI-fed Autosow-reared piglets had loose stools until 6 weeks of age; the effect was significantly greater in the TI-fed group. Otherwise, all swine were active and had normal appearance and behavior.

alpha-Dicarbonyls increase in the postprandial period and reflect the degree of hyperglycemia.

OBJECTIVE: Chronic hyperglycemia is known to increase tissue glycation and diabetic complications, but controversy exists regarding the independent role of increased postprandial glucose excursions. To address this question, we have studied the effect of postprandial glycemic excursions (PPGEs) on levels of methylglyoxal (MG) and 3-deoxyglucosone (3-DG), two highly reactive precursors of advanced glycation end products (AGEs). RESEARCH DESIGN AND METHODS: We performed 4-month crossover studies on 21 subjects with type 1 diabetes and compared the effect of premeal insulin lispro or regular insulin on PPGEs and MG/3-DG excursions. PPGE was determined after standard test meal (STMs) and by frequent postprandial glucose monitoring. HbA1c and postprandial MG and D-lactate were measured by HPLC, whereas 3-DG was determined by gas chromatography/mass spectroscopy. RESULTS: Treatment with insulin lispro resulted in a highly significant reduction in PPGEs relative to the regular insulin-treated group (P = 0.0005). However, HbA1c levels were similar in the two groups, and no relationship was observed between HbA1c and PPGE (P = 0.93). Significant postprandial increases in MG, 3-DG, and D-lactate occurred after the STM. Excursions of MG and 3-DG were highly correlated with levels of PPGE (R = 0.55, P = 0.0002 and R = 0.61, P = 0.0004; respectively), whereas a significant inverse relationship was seen between PPGE and D-lactate excursions (R = 0.40, P = 0.01). Conversely, no correlation was observed between HbAlc and postprandial MG, 3-DG, or D-lactate levels. CONCLUSIONS: Increased production of MG and 3-DG occur with greater PPGE, whereas HbA1c does not reflect these differences. Reduced PPGE also leads to increased production of D-lactate, indicating a role for increased detoxification in reducing MG levels. The higher postprandial levels of MG and 3-DG observed with greater PPGE may provide a partial explanation for the adverse effects of glycemic lability and support the value of agents that reduce glucose excursions.

MRI of lightning injury: early white matter changes associated with cerebral dysfunction.

A previously healthy male was struck by lightning. He developed neurologic deficits, including mild cerebral brain dysfunction. Magnetic resonance imaging (MRI) showed numerous foci of hyperintensity on long TR images, scattered throughout the supratentorial white matter. To our knowledge, the early MRI findings of lightning injury have not been previously reported.

Mood and performance effects of caffeine in relation to acute and chronic caffeine deprivation.

The mood and performance effects of caffeine deprivation (either 90 min, overnight, or at least 7 days) and ingestion (70 and 250 mg) were compared in young adults who were normally either moderate consumers (n = 49) or nonconsumers of caffeine (n = 18). Overnight caffeine deprivation produced dysphoric symptoms characteristic of caffeine withdrawal that were reduced, but still present, after longer-term abstinence. Acute caffeine intake affected the withdrawn consumers, nonwithdrawn consumers, and nonconsumers similarly. It increased jitteriness and decrease tiredness and headache. Furthermore, hand steadiness decreased as caffeine dose increased, whereas 70 mg, but not 250 mg, of caffeine was found to enhance performance on a simple reaction time task. These findings support the view that the negative effects experienced after overnight and longer-term caffeine deprivation play a significant role in influencing consumption of caffeine-containing drinks. Therefore, it would appear that to avoid the dysphoric symptoms resulting from both under- and overconsumption, regular caffeine consumers would have to regulate their caffeine intake fairly precisely.

Adsorption of a novel fluorescent derivative of a poly(ethylene oxide)/poly(butylene oxide) block copolymer on octadecyl glass studied by total internal reflection fluorescence and interferometry.

We have used total internal reflection fluorescence (TIRF) to measure the adsorption kinetics of a newly synthesized fluorescent derivative of a triblock copolymer comprising two poly(ethylene oxide) arms connected by a poly(butylene oxide) segment. The composition is (EO)400 (BO)55 (EO)400, in which EO represents ethylene oxide, BO represents butylene oxide, and one or both of the terminal OH groups of the two (EO)400 arms are labeled with tetramethylrhodamine. The poly(butylene oxide) segment binds to hydrophobic octadecyl glass, used as a substratum. The TIRF signal is shown to be derived almost entirely from surface-adsorbed polymer. This facilitates calculation of adsorption isotherms from 0.1-0.005% bulk polymer solution by means of diffusion kinetics. Information about the effective thickness of the adsorbed polymer, determined by optical interference microscopy, corresponds with what is known about the conformation of similar molecules at interfaces and indicates monolayer adsorption on the glass.

Bleeding complications from warfarin anticoagulation in patients with malignancy.

Bleeding complications from warfarin anticoagulants were analyzed in 431 patients with carcinoma of the lung, colon, prostate and head and neck who were admitted to a randomized, controlled therapeutic trial of this agent. A total of 215 patients were randomized to the warfarin-treated group and 216 to the control groups. The mean prothrombin time was significantly prolonged (p = 0.0001) for warfarin-treated patients. The duration of warfarin administration was 64.9% of the total followup period providing 101 patient-years of experience with warfarin in cancer. Both the overall incidence of bleeding episodes (58% of warfarin-treated versus 30% of control) and the incidence of major bleeding episodes (42% versus 14%, respectively) were significantly increased in the warfarin-treated group (p = less than 0.001). The incidence of major bleeding was 1.86 per patient-year on warfarin. The most common sites of bleeding (in descending order) were the gastointestinal tract, the urinary tract, the nasal passages and skin. Hemorrhage occurred in association with the terminal event in 10 warfarin-treated and 12 control patients. Warfarin anticoagulation may have contributed to terminal bleeding in 3 (1.4%) patients. There was no difference in mean hemoglobin or hematocrit values for patients with versus patients without bleeding episodes.

A user-oriented information system for emergency medicine.

A user-oriented Emergency Medical Services Information System ( EMSIS ) has been developed in our medical center that can readily be established by any interested medical center. This minicomputer based system provides online registration of poison center calls, access to the Poisindex (C) data base, concise patient information sheets, access to EMS treatment protocols, assistance in the differential diagnosis of acute poisoning, dosage recommendations for drugs with a narrow therapeutic margin, and kinetic analysis of drug overdoses. Video terminals access EMSIS in the Emergency Department, pharmacy, outpatient medicine clinic, pediatric clinic, medicine wards, poison control center, and biomedical engineering. A PDP 11/70 with 256 Kb core and 48 ports running under RSTS /E V7 .0 supports an average of 20 simultaneous users.

Comparison of alphabetic and phonetic retrieval of online drug information.

Alphabetic, phonetic, and combined alphabetic and phonetic methods of retrieving online drug information were compared. Twenty-four volunteers participated in the study representing four user groups: physicians, nurses, pharmacists, and nonhealth-care hospital staff. Each subject performed 150 searches, 50 by each retrieval method. Using the alphabetic method, drug information was retrievable only if the drug name was spelled correctly. Using the phonetic method, searches were conducted based on the phonetic spelling of requests (e.g., "symetadine" for cimetidine). The combined method used a phonetic search only after an initial alphabetic search was unsuccessful. The elapsed time between the first entry and an indication that the information had been found or could not be found was determined, and the number of drug names not found and the number of excess tries were counted. There were no significant differences in elapsed time among the three methods. Pharmacists had the shortest mean elapsed time and physicians the longest. The average number of excess tries using the phonetic system was a third of the number required using the alphabetic method. The number of drugs not found showed only slight differences among the three methods. The subjects found the desired information on the first try 67% of the time with the alphabetic method, 66% with the combined method, and 90% with the phonetic method. The phonetic method had an average of 75 matches versus 20 for the alphabetic and combined methods. These results support use of a combined alphabetic and phonetic system for retrieving drug information.

Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75.

In a controlled, randomized study, survival of patients with small cell carcinoma of the lung (SCCL) was prolonged on addition of warfarin sodium to combination chemotherapy plus radiation therapy. Median survival for 25 control patients was 24 weeks and for 25 warfarin-treated patients was 50 weeks. This difference could not be accounted for by differences between groups in performance status, extent of disease, age, or sex. The survival advantage associated with warfarin administration was observed both for patients with extensive disease and for those who failed to achieve complete or partial remission. The warfarin-treated group also demonstrated a significantly increased time to first evidence of disease progression. These results suggest that warfarin may be useful in the treatment of SCCL and also support the hypothesis that the blood coagulation mechanism may be involved in the growth and spread of cancer in man.

Direct measurement of transepithelial force: an in vivo technique.

A technique for direct in vivo measurement of the intensity of absorptive force generated by an epithelial membrane is described. A quasirigid porous cartridge containing normal saline was placed in isolated intestinal segments of anesthetized rat and connected, via a catheter, to a Statham pressure transducer. Once excess fluid had been absorbed, further fluid absorption was hindered by the nonyielding character of the cartridge, leading to the development of negative (subatmospheric) pressures. Volume expansion with intravenously infused normal saline solution resulted in an abrupt fall in absorptive force, followed by a more gradual recovery to the pre-volume-challenge level. Contraction of intravascular volume by bleeding led to a prompt increment in absorptive force proportional to the amount of blood removed. Return of the blood to the circulation restored absorptive force to the prebleed level. Complete circulatory arrest (death) produced a temporary increment, lasting about 30 min, in absorptive force. Physical mechanisms that may be involved in these alterations of absorptive force are discussed.

Treatment of cholelithiasis in patients with sickle cell anemia.

The incidence of cholelithiasis and surgical risk of cholecystectomy in patients with sickle cell anemia is reviewed. Records of all patients with sickle cell disease currently attending the Medical University of South Carolina Hematology Clinic were reviewed. An oral cholecystogram has been part of the initial evaluation for the past year. The records of 16 patients having cholecystectomy from 1968 to 1977 were reviewed with regard to diagnostic studies, preoperative preparation, morbidity, and mortality. When the status of the gallbladder is known, the incidence of cholelithiasis is 67%. The morbidity of elective cholecystectomy was high (37%); there was one death. Cholecystectomy is not recommended for the discovery of asymptomatic gallstones because of the relatively poor surgical risk and short life expectancy of these patients.

Ultrastructural identification of acid complex carbohydrate in cytoplasmic granules of normal and leukaemic human monocytes.

Complex carbohydrate in granules of monocytes was compared with that in granules of neutrophils by ultrastructural cytochemical methods. The acid mucosubstance in granules of both cell types stained with dialysed iron after brief fixation with dilute glutaraldehyde, but that in monocyte granules differed in failing to stain after stronger fixation. Approximately 10% granules in normal blood monocytes stained with this method, whereas more than 90% of granules in leukaemic monocytes from two of seven patients with acute myelomonocytic leukaemia stained intensely. This difference presumably results from unmasking of acid groups in immature granules or increased synthesis of granule mucosubstance in some leukaemic monocytes. Granules of monocytes differed further from those of neutrophils in failing after either type of fixation to stain with a high iron diamine technique for for demonstration of sulphated mucosubstance. The absence of high iron diamine staining could reflect a lack of sulphate esters in monocyte granule mucosubstance, masking of the sulphate groups by other components, or extraction of the sulphated mucosubstance during specimen processing.

Use of nitroglycerin ointment in congestive heart failure. Results of acute and chronic therapy.

7 consecutive patients with congestive heart failure refractory to standard therapy were treated with nitroglycerin ointment (GTNO). The pulmonary wedge pressure decreased from a control value of 30+/-1 to 15+/-1 mm Hg (mean +/-SEM), and the arteriovenous oxygen difference narrowed from 6.8+/-0.5 to 5.5+/-0.3 ml%, after GTNO therapy. The heart rate decreased in 5 patients and the systolic blood pressure was either unchanged or decreased slightly. A reduction in the echocardiographic end diastolic dimension was noted in all patients. The transmyocardial gradient (systemic artery diastolic pressure - pulmonary artery wedge pressure) increased in all except 1 subject. The double product decreased in 5 of the 7 patients. Hemodynamic improvement was maintained for 4.5-7 h. All patients were symptomatically improved on chronic GTNO treatment. Our results indicate that GTNO is a useful agent in the management of heart failure which is unresponsive to standard therapy.

Circulating erythropoietic precursors assessed in culture: characterization in normal men and patients with hemoglobinopathies.

Circulating erythropoietic precursors in normal men and patients with hemoglobinopathies were characterized in culture. Blood mononuclear cells harvested with a modification of the Ficoll-Isopaque technique were cultured in methylcellulose for 14 days. The majority of erythropoietic colonies consisted of several subcolonies assuming the morphology of erythropoietic "bursts" described in murine marrow cultures. Time course studied of colony formation from marrow and blood nucleated cells confirmed that the circulating erythropoietic precursors represented only early stages of development. Peak sedimentation velocity of the circulating precursors analyzed using a Staput apparatus averaged 5.31 mm/hr and corresponded with that of the early erythropoietic precursors in human marrow. One ml of blood yielded an average of 153 colonies in normal men and 785 colonies in patients with hemoglobinopathies. No correlation was observed between colony formation and reticulocyte indices of individual patients. Examination of the proliferative state of the erythropoietic precursors using high specific activity tritium-labeled thymidine revealed that almost none of the cells in normal men or patients with hemoglobinopathies were in the DNA synthetic phase.