Calculating endocardial potentials from epicardial potentials measured during external stimulation. This paper presents a boundary integral method for calculating the potential field generated by external stimulation at locations within the heart using realistic heart geometry and samples of the potential taken from the epicardial surface. This method assumes the heart is homogeneous and isotropic. To test the method we made epicardial and endocardial measurements in dogs during transthoracic pacing stimuli. From the epicardial potential measurements we predicted the endocardial potential values and compared them with the measured data. Despite the seemingly gross assumptions, the mean correlation coefficient between the measured and predicted potentials for three dogs and eleven stimulation electrode configurations was 0.985, and the mean rms error was 17%.


The effect of measurement conditions on MCG inverse solutions. A magnetic inverse solution that uses a single current dipole in a homogeneous volume conductor with realistic torso shape was tested numerically to establish the effect of magnetic noise, number of measurement points, and torso size on the localization accuracy. Seven different sites of cardiological interest were selected as locations for the source dipole. The three components of the magnetic field were calculated as if measured by second order gradiometers, Gaussian noise was added, and Monte Carlo tests performed for inverse solutions using a single field component, or all three combined. It was found that for any of the single component solutions, and a signal-to-noise ratio of 100, 25 measuring points are sufficient for good accuracy; just 12 points are needed if all three components are used together. If, however, the torso size of the inverse solution is different from that of the field data by 10 or 20%, a larger error occurs, even for 56 measurement points and no noise. In this case, the field component orthogonal to the measurement grid, Bz, yields better results than the other two components, or even all three combined. We conclude that a multichannel system measuring the z component of the magnetic field in about 30 locations would be the best choice to locate a dipolar source, provided the torso of the field data is closely matched by the model used in the inverse solution. To this effect, scaling of the torso model can easily be included in the computation. Imaging techniques could be used to accommodate different torso shapes.


The effects of metals on a transcutaneous energy transmission system. The effects of metal objects on the mutual inductance, self-inductance, and effective series resistance (ESR) of the coaxial coils of a transcutaneous energy transmission system (TETS) were investigated theoretically and experimentally. The theory considers a thin conducting sheet of infinite size aligned parallel to a current-carrying coil. Results of the theory indicate that coil parameters vary with the distance from the sheet to the coil. Changes in mutual and self inductance are independent of the conductivity and thickness of the sheet, with a larger percentage change for mutual inductance than for self inductance. Changes in ESR are proportional to the surface resistivity of the sheet. Experimental measurements using several aluminum sheets and a titanium alloy can in the presence of the TETS coils used for the Penn State artificial heart showed excellent agreement with the theory for inductance parameters and agreed within a factor of 2 for ESR measurements when skin effect was considered. It was generally observed that mutual inductance drops to 65% of its initial value as a metal sheet is moved to within 1-2 cm of the coil, while self-inductance drops to 80% of its initial value when the sheet is 2 cm from the coil. Measured changes in ESR tended to be higher than the calculated values with the discrepancy depending on distance to the metal object. Theory and measurements were extended to the case of lateral misalignment of the coils.


An eccentrically coated asymmetric antenna applicator for intracavitary hyperthermia treatment of cancer. In this paper a model based on transmission line theory is used to predict the behavior of an eccentrically coated asymmetric antenna applicator for use in intracavitary hyperthermia. Theoretical results for the heating rate (HR) of the applicators are compared to experimental results. The experimental results were obtained at City of Hope National Medical Center using four different 915-MHz applicators, each with a different antenna size and eccentricity of the coating. A parameter delta is defined where delta << 1.0 is a thin wire approximation; delta is primarily a function of the eccentricity of the coating, the antenna diameter, and the coating diameter. It is found that when delta approximately less than 0.5, the theoretical model works well. In particular, it predicts the directivity due to the eccentricity of the coating. However, as this eccentricity is increased or as the antenna diameter is increased (delta approximately greater than 0.6), the model no longer accurately predicts directivity. Thus, the model that can be used to predict the HR profiles for an eccentrically coated asymmetric antenna only when delta approximately less than 0.5.


Topographic mapping of single sweep evoked potentials in the brain. Single trial analysis of brain-evoked potentials via stochastic parametric identification and filtering is here extended to multichannel recordings, leading to the topographic mapping of the brain activity elicited by a single stimulus, instead of the usual averaged mapping. The temporal dynamics of the subsequent sweeps in the protocol of a neurophysiologic experiment can thus be recovered and quantified also on its spatial characteristic.


On the tracking of rapid dynamic changes in seizure EEG. Estimation of autospectra and coherence and phase spectra of seizure EEG, using the FFT technique, will cause "smearing" of the rapid dynamic changes which occur during the seizure. This is inherent to FFT spectral estimation, due to the averaging process which is necessary in order to get consistent spectral estimates. A different approach suggested in the present study is to carry out multivariate autoregressive modeling of the multichannel seizure EEG, combined with adaptive segmentation. In order to obtain good estimates in cases of short record length, the vectorial AR modeling was based on residual energy ratios. The method has been tested on multichannel seizure EEG recordings from rats with focal epilepsy, caused by intracerebral administration of Kainic acid, and in depth EEG recordings in patients with temporal lobe epilepsy.


Analysis of knee vibration signals using linear prediction. Clinical methods used at present for the diagnosis of cartilage pathology in the knee are invasive in nature, and carry some risks. There exists a need for the development of a safe, objective, noninvasive method for early detection, localization, and quantification of cartilage pathology in the knee. This paper investigates the possibility of developing such a method based on an analysis of vibrations produced by joint surfaces rubbing against one another during normal movement. In particular, the method of modeling by linear prediction is used for adaptive segmentation and parameterization of knee vibration signals. Dominant poles are extracted from the model system function for each segment based on their energy contributions and bandwidths. These dominant poles represent the dominant features of the signal segments in the spectral domain. Two-dimensional feature vectors are then constructed using the first dominant pole and the ratio of power in the 40-120 Hz band to the total power of the segment. The potential use of this method to distinguish between vibrations produced by normal volunteers and patients known to have cartilage pathology (chondromalacia) is discussed.


Mathematical modeling and spectrum analysis of the physiological patello-femoral pulse train produced by slow knee movement. Analysis of vibration signals emitted by the knee joint has the potential for the development of a noninvasive procedure for the diagnosis and monitoring of knee pathology. In order to obtain as much information as possible from the power density spectrum of the knee vibration signal, it is necessary to identify the physiological factors (or physiologically relevant parameters) that shape the spectrum. This paper presents a mathematical model for knee vibration signals, in particular the physiological patello-femoral pulse (PFP) train produced by slow knee movement. It demonstrates through the mathematical model that the repetition rate of the physiological PFP train introduces repeated peaks in the power spectrum, and that it affects the spectrum mainly at low frequencies. The theoretical results also show that the spectral peaks at multiples of the PFP repetition rate become more evident when the variance of the interpulse interval (IPI) is small, and that these spectral peaks shift toward higher frequencies with increasing PFP repetition rates. To evaluate the mathematical model, a simulation algorithm was developed, which generates PFP signals with adjustable repetition rate and IPI variance. Signals generated by simulation were seen to possess representative spectral characteristics typically observed in physiological PFP signals. This simulation procedure allows an interactive examination of several factors which affect the PFP train spectrum. Finally, in vivo measurements of physiological PFP signals of normal volunteers are presented. Results of simulations and analysis of signals recorded from human subjects support the mathematical model's prediction that the IPI statistics play a very significant role in determining the low-end power spectrum of the physiological PFP signal.(ABSTRACT TRUNCATED AT 250 WORDS)


Accuracy of drug infusion pumps under computer control. Prototype systems implementing algorithms for automated drug infusions are typically constructed by coupling a microcomputer to a drug infusion pump through a serial communications interface. Infusion rates demanded of the infusion pump in many computed-controlled drug delivery applications are made to change at intervals much shorter than those encountered under routine clinical use. Because the ability of infusion pumps to maintain accurate flow rates during high frequency rate changes has not been documented, the purpose of this study was to validate the volumetric accuracy of three commercially available infusion pumps operating in a demanding computer-controlled application. In independent 2-h evaluations, the infusion rate demanded of each pump changed as often as every 5, 10, or 15 s using an algorithm for computer-controlled pharmacokinetic model-driven intravenous infusion. Accuracy of the infusion devices was determined gravimetrically. At all measurement times, each of the infusion pumps was accurate to within approximately +/- 5% of the expected volumetric output under each of the infusion rate intervals tested. Flow rate accuracy of +/- 5% is equal to the nominal expected accuracy of these infusion pumps in conventional clinical use.


Biotelemetry of cardiovascular hemodynamic measurements in miniswine. A three-channel biotelemetry system has been designed and implemented for use in a chronically instrumented animal model of cardiovascular disease. A dual-channel ultrasonic transit-time micrometer allows monitoring of left-ventricular wall motion for the regions perfused by the left circumflex and left anterior descending coronary arteries. A third channel provides left ventricular blood pressure obtained from a high-fidelity blood pressure transducer implanted in the left ventricle. The biotelemetry system features a high voltage dc-dc converter for improved ultrasonic signal strength, a time-to-voltage converter that is highly immune to synchronization frequency variations, low power consumption (approx. 100 mW), small size (4 x 6 x 12 cm), and low weight (approx. 200 g). This three-channel system has enabled our laboratory to continuously monitor untethered animals for 24-h periods. Data obtained from this miniature biotelemetry system can be utilized to quantify myocardial oxygen demand and regional left-ventricular wall thickening.


A linear discretization of the volume conductor boundary integral equation using analytically integrated elements. A method is presented to compute the potential distribution on the surface of a homogeneous isolated conductor of arbitrary shape. The method is based on an approximation of a boundary integral equation as a set linear algebraic equations. The potential is described as a piecewise linear or quadratic function. The matrix elements of the discretized equation are expressed as analytical formulas.


A PC-based imaging system for automated platelet identification. In this communication, a PC-based imaging system was developed for automatically identifying fluorescence-labeled individual platelets adherent to protein-coated surface under flow conditions. It is to eliminate the laborious and time-consuming task, and the subjective error of manual measurements. Based upon the features of adherent platelets, three passes of the image processing were developed for platelet identification. From the results, 90-95% accuracy could be routinely obtained. The platelet distribution and other related parameters could be easily extracted and investigated.


Platelet function in chronic leukemias.

Platelet function in chronic leukemias. Bleeding time, clot retraction, platelet factor 3 availability and platelet aggregation in response to ADP, epinephrine, collagen and ristocetin were studied in 12 cases of chronic leukemia which included eight of chronic myeloid leukemia, two of chronic lymphatic leukemia and two of CLL related disorders. One or more abnormalities in platelet function were detected in all the cases. Among the cases of CML, bleeding time was prolonged in one, clot retraction was impaired in one and PF3 availability was decreased in one case. Defects in platelet aggregation were variable. Among the cases of CLL and CLL related disorders, bleeding time was prolonged in two, clot retraction was impaired in one and PF3 availability was decreased in three cases. Platelet aggregation responses were significantly impaired in all the cases.


Cytological diversity of osteosarcoma.

Cytological diversity of osteosarcoma. Sixty three cases of clinically and radiologically diagnosed osteosarcomas were evaluated by fine needle aspiration cytology over a five year period. Adequate material was obtained in 59 cases. The sites aspirated were femur, tibia, humerus, fibula, scapula and clavicle. The mean age was 16 years. The most frequent morphological type encountered was the pleomorphic tumor (42) the other cytological types were sclerotic (10), chondroid (6), and small cell osteosarcoma (1). Hematoxylin and Eosin stain was better suited for detection of osteoid than routinely done cytological stain. The awareness of this cytological diversity is essential to avoid misinterpretation of osteosarcomas.


Mast cell reactivity in lymphoma: a preliminary communication. Fifty nodes of Hodgkin's disease, 50 of non-Hodgkin's lymphoma and 20 of reactive hyperplasia revealed varying degree of mast cell reactivity. It was maximum in reactive lymph nodes, sinuses and interfollicular areas being infiltrated more than zones. The number of mast cells was more in nodular sclerosis variety of Hodgkin's disease than other Rye-subtypes, and more in Hodgkin's group than non-Hodgkin's, out of the latter, the diffuse histiocytic lymphoma revealed higher number. Analysis of a larger series and follow-up of these patients are indicated to establish the possible reactionary nature of mast cell reactivity in lymphomas, and the prognostic bearing, if any.


CT staging of pancreatic and periampullary carcinoma. Sixteen cases of carcinoma head pancreas and seven cases of periampullary carcinoma are staged together on CT scan because of their morphological similarity and similar parameters. Following parameters are considered for CT staging: tumour mass, involvement of splanchnic vessels, locoregional lymph nodes and presence or absence of hepatic metastases. Findings were confirmed on surgical exploration. A contrast enhanced CT scan was 58.3 percent sensitive and 100 percent specific for the involvement of lymph nodes and 100 percent sensitive and 93.4 percent specific for hepatic metastases. The cases diagnosed as non-resectable on CT staging were found inoperable on exploration. Authors believe that for all practical purposes, pancreatic and periampullary malignancies can be grouped together and a contrast enhanced CT scan can provide reliable information for the staging of the tumor.


Bone metastases in the patients of carcinoma cervix. Seventeen of 620 patients (2.7%) of cancer cervix were diagnosed to have bone metastasis (BM). In three bone metastasis were seen at initial presentation; remaining 14 developed BM in 3 to 36 months after the diagnosis of cancer cervix. Backache (8), localised pain (8), in thigh/hip/neck paraparesis (1) were main symptoms. The duration of symptoms ranged from 1 to 4 (median 2.5) months. Lumber spine, pelvic bones and long bones were the commonest site of involvement. The lesions were single in 12 and at multiple sites in five patients. Radiologically the lesions were osteolytic in all except three where Tc99m bone scan showed increased uptake of radionuclide. Palliative radiotherapy resulted in significant symptomatic relief.


Metastasising congenital subcutaneous sacrococcygeal ependymoma. A case of myxopapillary ependymoma located subcutaneously in sacrococcygeal area of a 18 months male child with metastasis to right inguinal lymph nodes is described; the tumour was present since birth. Histological examination of the tumour besides myxopapillary structures, also revealed an ependyma lined cystic space, resembling ventricular cavity. So far only two cases of congenital metastasising subcutaneous sacrococcygeal ependymoma have been described. However, the present case had a very aggressive post-operative biological behaviour.


Long term survival in a patient with multiple myeloma. A case report with review of literature. A 37 year old man with symptomatic multiple myeloma diagnosed in April 1968 presented with generalised bony pains, extensive skeletal osteolytic lesions, monoclonal gammopathy and 90 percent atypical plasma cells in the marrow. He was given cyclophosphamide for six months with minimal response and then initiated on melphalan for one year. He was asymptomatic for 15 years thereafter and presented again in 1985 with a relapse of the disease. Over the next four years he was given various combinations of chemotherapy including cyclophosphamide, vincristine, melphalan and carmustine. He responded well on two more occasions only to relapse again. Recently, he has developed a symptomatic relapse with 36 percent plasma cells. This case report highlights the fact that there is a subset of patients with myeloma who survive beyond ten years, but remain symptomatic and respond slowly to chemotherapy.


Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease)--a case report with review of the literature. Dysplastic gangliocytoma of the cerebellum is an uncommon malformative lesion and clinically manifest as a slow growing space occupying lesion. In this report, the characteristic clinical and histopathological features of a case of dysplastic gangliocytoma of the cerebellum are described.


Extragonadal malignant teratoma of the foot. This report documents the occurrence of an extragonadal malignant teratoma on the sole of the foot, in a young male. The patient also developed a groin nodule showing the same histology. The testes, retroperitoneum and mediastinum, which are usual sites of germ cell tumours were all normal, and no other primary could be detected. A teratoma growing in the tip of an extremity is a unique occurrence, biologically difficult to explain, and, which to the best of our knowledge has never been reported in literature.


Immunoglobulin profile in schizophrenia. The present study was conducted on 40 new consecutive schizophrenic patients admitted in the psychiatry ward. The diagnosis of schizophrenia was done by Research Diagnosis Criteria (RDC). Serum immunoglobulins were were estimated in schizophrenic patients and were age and sex matched with 40 healthy individuals, comprising the control group. The IgG and IgA mean levels of schizophrenic patients were found to be significantly higher (p < 0.01) than the normal healthy individuals. There were however no significant differences between the schizophrenic patients and control group regarding total proteins, albumin and globulin levels. In subtypes of schinophrenia based on phenomenology only, paranoid group scored significantly higher (p < 0.01) IgG and IgA mean values than other types of Schizophrenia (catatonic, disorganised and undifferentiated).


Blood pressure simulation model: a teaching aid. A mechanical blood pressure simulation model has been designed and developed by superimposing intermittent pressure on a steady pressure in a fluid filled closed rubber bladder. As a result, pulsatile pressure waves are generated in the bladder. By adjusting the magnitudes of constant pressure and intermittent pressure a 'simulated blood pressure' profile may be generated in the closed bladder with clearly three identifiable components i.e. systolic, diastolic and pulse pressure. The model consists of two bladders, a rubber bag and a motor which produces up and down movements. The pressure is recorded on a manometer and a biorite simultaneously. The device is simple, sturdy and inexpensive and may be used as adjunct for laboratory teaching in physiology and related sciences.


Steroidogenic inhibition in testicular tissue of formaldehyde exposed rats. Three groups of rats (n = 10) were subjected to intraperitoneal treatment of formaldehyde daily at doses of 5, 10 and 15 mg/kg body weight over a period of 30 days. Gradual diminution in body and testicular weight was observed in all treated groups. Leyding cell impairement was conspicuous in those given doses of 10 and 15 mg/kg. Inhibition of 3 beta-delta 5-hydroxy steroid dehydrogenase and accumulation of sudanophillic materials in testicular tissue of formaldehyde treated rats was recorded histochemically. Significant decline of serum testosterone was also observed in the same groups. Structural and functional impairement of Leydig cells after formaldehyde treatment caused steroidogenic inhibition.


Cigarette smoking and pressure-volume characteristics of the lung. This study was done to identify the immediate changes induced by cigarette smoking on the mechanical properties of the lung. Static compliance (C stat), static pressure-volume (Stat P-V) hysteresis, vital capacity (VC), frequency dependence of dynamic compliance (C dyn) and collateral ventilation (Coll V) of the lung were studied in six mongrel dogs. The smoking of one cigarette induced a fall in VC and static P-V hysteresis of the lungs. These changes indicate an increase in elastic recoil of the lung probably caused by inactivation of pulmonary surfactant. Frequency dependence of C dyn did not develop after smoking. Extensive collateral ventilation was seen in the lungs of all the experimental animals and in those of five other normal dogs, who had not been exposed to cigarette smoke. The significance of these findings are discussed.


Alterations in feeding and sexual behaviour during reproductive cycle in female rats. Alterations in feeding and sexual behaviour were studied in adult female rats. During estrous phase there was decrease in food intake and increased sexual behaviour, as manifested by increased lordosis quotient. During met-and diestrous phases, increase in food intake and depressed sexual behaviour were observed, indicating inverse relationship between these two behaviours. Multisensory hypothalamic neurons may explain interactions among regulatory systems.


Bronchial lability in allergic rhinitis. The aim of this study was to assess the relationship between exercise bronchial lability and the changes in pulmonary function over a one year period in allergic rhinitis. Eighty four nonsmoking male medical students of whom twenty two were allergic rhinitics were studied. Pulmonary function status was significantly lower and exercise bronchial lability significantly higher in the allergics. Over a one year period the mean decline in the forced expiratory volume in one second (FEV1) was three times greater and in the forced expiratory flow rate in the middle half of the vital capacity (FEF 25-75%) 50% greater among the allergics. The change in FEV1 was positively related to the bronchial lability, indicating that greater bronchial lability was associated with less decline in pulmonary function in these subjects.


Influence of calcium removal from bath solution on isolated rat duodenum contractions. In this study whether extracellular Ca++ is essential to produce an increase of tension of isolated rat duodenum by ACh, 5-HT, AVP and KCl-, was examined. KCl- and AVP-evoked contractions were almost totally prevented by Ca++ removal from bath solution. The increase of tension of isolated duodenum caused by ACh or 5-HT was totally prevented after adding nifedipine, a Ca++ channel blocker, into Ca free solution. Our results suggest that ACh or 5-HT utilizes intracellular as well as extracellular sources of Ca++ to produce contraction in rat duodenum, whereas AVP-or KCl evoked contraction was mainly due to influx of Ca from extracellular sources.


Receptor mechanisms in vasoconstrictor responses to choline esters in Bufo melanostictus. Choline esters have been found to cause vasoconstriction of perfused systemic blood vessels of common Indian toad, Bufo melanostictus. The vasoconstriction appears to be mediated through atropine sensitive receptors and nicotinic mechanisms appear unlikely to be involved.


Adverse reactions to gentamycin in patients with ear, nose or throat infections. Eighty four patients requiring treatment with Gentamycin were selected from Otorhinolaryngology outpatient and those admitted to the hospital. Patients suffering from hepatic or renal disorders, pregnant women and children were excluded from the study. Seventy three were administered gentamycin 40 mg BD intramuscularly for 7-10 days and in 11 the drug was applied topically as ear drops for 6-12 weeks. Adverse reactions were observed in 9 (13.3%) and 11 (100%) patients given the drug parenterally and topically respectively. In parenteral group incidence was higher in females as compared to males and profile included nausea and vomiting, headache, cough, tinnitis, albuminuria, diminition of hearing and vertigo. Whereas diminition of hearing acuity was observed in all those who had topical application as evidenced by pure tone audiometry.


Functional recovery following reptilean (Calotus calotus) spinal cord transection. Various approaches to remedy the effects of spinal cord injury have been suggested from time to time. One of these is to study the regeneration following spinal cord transection in phylogenetic lower species in order to gain some information from this for its application in non-regenerating spinal cord injuries in higher species. In the present study the functional recovery following spinal cord transection in a reptile (Calotus calotus) was studied in 30 animals, and it was observed that functional recovery was quite marked by 4 weeks and more or less comple by 6 weeks.


Effect of soman administration on beta-esterases in blood, liver microsomes and brain regions of rats. Activities of enzymes cholinesterase (ChE) and carboxylesterase (CaE) were assayed in serum, liver microsomes and three regions of brain, viz; cerebrum, cerebellum and brain stem (with mid brain) in male albino rats at 0.5 and 2 h periods after administration of 1/2 LD 50 dose of soman (0.22 mg/kg) intraperitoneally in olive oil as vehicle. At 0.5 h, in serum, ChE activity declined to 33% of its initial level whereas CaE activity was almost completely inhibited. However, in the liver microsomes at this period, ChE activity was greatly inhibited (18% of initial level) whereas CaE activity was nearly unaffected. At 2 h period, both the enzymes in the serum were almost completely inhibited. In the brain regions (excepting in cerebellum), both the enzymes were nearly similarly inhibited (by 55% to 65% of the initial level) at both the periods. The time related differential response of these two beta-esterases in acute soman intoxication probably occurred in the peripheral tissues like blood and liver but not in the CNS.


Influence of selenium supplementation during chelation of lead in rats. The influence of selenium supplementation during chelation therapy to reduce body burden and toxicity of lead was investigated in rats. Selenium had marginal effects on liver, kidney and blood lead decorporation by calcium disodium ethylenediamine tetra acetic acid (CaNa2EDTA) and activation of inhibited delta- aminolevulinic acid dehydratase (ALAD) activity by calcium trisodium diethylenetriamine penta acetic acid (CaNa3DTPA). Selenium supplementation however, had no influence on lead induced inhibition of renal and hepatic transaminases and alkaline phosphatase. The results suggest that selenium supplementation slightly augments lead mobilization by chelating drugs.


Comparison of bioavailability and pharmacodynamics of diltiazem from two pharmaceutical preparations. Diltiazem, a calcium channel blocker, is used in multiple divided doses daily, due to its short elimination half-life. Hence, administration as a modified release (MR) formulation is suggested. In this double blind cross-over trial, the pharmacokinetics and pharmacodynamics of diltiazem was studied in eight healthy Indian adults. Diltiazem was administered as single dose (60 mg) of the two formulations viz immediate release (IR) and MR. Venous blood samples, for estimation of diltiazem by HPLC, were collected at frequent intervals and BP, HR and ECG were monitored during the 12h study period. With MR formulation, plasma half-life was significantly (P < 0.05) prolonged (6.25 +/- 1.2 h vs. 2.69 +/- 0.2 h), the extent of alterations in BP, HR and PR interval was significantly less, while the duration of prolongation of PR interval was significantly more as compared to IR formulation. Therefore, MR formulation of diltiazem has better pharmacokinetic and pharmacodynamic profile as compared to IR formulation.


A preliminary study on the interaction between ethanol and propranolol in normal human subjects. Ethanol significantly increased the steady-state peak concentration of propranolol while propranolol significantly reduced the total body clearance of ethanol in healthy human volunteers. Ethanol per se caused tachycardia and rise in systolic blood pressure while propranolol administration resulted in bradycardia. In combinations, ethanol and propranolol caused significant fall in diastolic blood pressure without any significant changes in the heart rate and systolic blood pressure compared to the control readings of four healthy male volunteers. The kinetic and haemodynamic interactions observed between ethanol and propranolol in the preliminary study are of clinical relevance and need further exploration.


A simple technique for hemoglobin estimation to screen for anaemia. Drabkins method has been modified enabling detection of anaemia in a large population. 132 samples of EDTA blood were subjected to hemoglobin estimation by (1) Direct Drabkin (DD) (2), Filter Drabkin (FD) and (3) Special Filter Drabkin (SFD). Hemoglobin estimations by DD and FD compared well on statistical analysis. SFD with a punch diameter of 10.6 to 10.7 mm compared well with DD and is ideal for screening anaemia in field studies.


Effect of coingestion of paracetamol on glycaemic response. Rate of gastric emptying is a frequently measured variable in glycaemic response studies. One of the indices employed for measurement of the gastric emptying rate is the blood level of paracetamol at frequent intervals of time following coingestion of paracetamol with the meal. But the effect of paracetamol itself on glycaemic response is not known. The present study was performed on ten healthy and five NIDDM subjects. Each subject underwent two meal tolerance tests in random sequence. On one occasion the meal was white bread; on the other occasion, the meal consisted of the same quantity of white bread and 1.5 g paracetamol. The postprandial glycaemica following the two meals was not significantly different. Thus the results validate the use of the paracetamol technique for gastric emptying in glycaemic response studies.


Effects of topically applied sulphur mustard on tissue glycogen, blood glucose, lactate and pyruvate in mice. Bis-2-Chloroethyl sulphide, commonly known as sulphur mustard (SM) or mustard gas, an alkylating agent, is frequently used as a chemical warfare agent. Inhibition of glycolysis has been related to skin injury and cell death. The effects of SM on tissue glycogen, blood glucose, lactate/pyruvate ratio were investigated in the present study. After a single dermal application of 1.0 LD50 SM in mice, a significant hyperglycemia was observed at 24 hr post exposure. There was a corresponding decrease in liver glycogen content, with no alteration in glycogen content of brain, muscles and kidney. Blood pyruvate and lactate levels were not appreciably altered.


Measuring growth in the volume and intensity of Medicare physician services. Congress adopted a policy of Volume Performance Standards that will adjust Medicare fees downward (or upward) in direct relation to the amount that spending exceeds (or falls below) a preset target. Using data from the 1985 through 1989 Medicare Part B Annual Data (BMAD), we show there are wide differences in the rate of growth in volume and intensity across types of services, specialties, and geographic areas. This suggests the current policy that bases adjustments on two national standards for surgical and nonsurgical services could lead to inequitable fee rewards and penalties. A greater number of targets based on more homogeneous service categories could reduce these inequities.


Explaining the association between surgeon supply and utilization. This study uses Medicare enrollment and physician claims data to examine the effect of surgeon supply on the demand for surgeons' services. The specialties studied were ophthalmology, general surgery, orthopedic surgery, and urology. The study found that higher surgeon supply increases the demand for initial contacts with surgeons (first-occurrences demand) but does not affect the demand for services among surgeons' patients (intensity-of-care demand). These findings suggest that a high supply of surgeons improves access or is associated with stronger preferences for referrals to surgeons. The findings offer little support for the hypothesis that a substantial component of the additional utilization that occurs when surgeons are plentiful is due to increases in physician-induced demand.


Physician responses to fee-for-service and capitation payment. The ability to achieve reductions in health care costs is determined in part by physician payment mechanisms. This study observes the response to a change in the reimbursement mechanism by a group of physicians who participated in a fee-for-service plan and then formed an IPA using capitation payment for primary care physicians and a reduced fee schedule for specialists. Patient benefits were similar under the two plans. Analyses of data for a group of continuous enrollees show that the change in the physician payment mechanism was associated with a reduction in hospitalizations but increases in length of hospital stay and number of ambulatory visits. These increases may have occurred because capitation for primary care physicians and a reduced fee schedule for specialists led to a greater number of referrals with no incentive in place for reductions in length of stay for specialty admissions.


Medicare: looking for pareto optimal changes. Medicare enrollees are at risk for potentially unlimited out-of-pocket costs for acute care, defined here as prescription drug costs and copayments on covered services. As a result, many enrollees supplement Medicare with Medigap insurance, which increases their premium costs and their use of Medicare-covered services. The objective of this study was to limit enrollees' risk for acute care costs without increasing federal spending. The study found that savings from prohibiting Medigap would be sufficient to provide a copayment cap under Medicare. If Medicare's copayment requirements were also restructured, the savings would finance a prescription drug benefit as well. Most enrollees could expect lower expenses for premiums and out-of-pocket costs combined, but expenses would be significantly higher for 5% of enrollees, all current Medigap policyholders.


Time costs and informal social support as determinants of differences between black and white families in the provision of long-term care. This paper presents an economic model that predicts the observed racial difference in the mix of informal home and nursing home services used for long-term care by black versus white families. A cause of this difference in services used is a difference between black and white families in the relative prices they pay for particular services. Each group uses relatively more of the relatively less expensive (for that group) form of long-term care. The model indicates three specific hypotheses. The empirical analysis focuses on the Differential Opportunity Cost of Informal Caregiver Time hypothesis. Based on data from the 1982 and 1984 National Long-Term Care Surveys, two sets of results consistent with though not direct tests of this hypothesis are presented.


How restrictive are Medicaid's categorical eligibility requirements? A look at nine Southern states. Medicaid, as an existing program with federal matching dollars, remains attractive to state legislatures looking for a means to address the problems of the uninsured. However, the extent to which states can maximize coverage of the poor uninsured under Medicaid's present eligibility criteria is unknown. Surprisingly, this study of nine Southern states shows a modest 14.8% reduction in the uninsured population when the AFDC income eligibility threshold is moved up to the federal poverty level. This threshold is twice as high as the national mean and three times greater than the mean income eligibility threshold for the nine states that were the focus of this study. In sharp contrast, elimination of the categorical eligibility requirements under the same poverty-level threshold reduces the uninsured population by nearly 40%.


The impact of being uninsured on utilization of basic health care services. Recent proposals to increase access to health insurance suggest the need to know what the magnitude of responses would be if the one in five nonelderly persons uninsured for all or part of the year were to become insured. This paper finds that an additional commitment of resources to hospital and ambulatory care on the order of $26 billion (in 1989 dollars), or about 4% of total national health care spending, would be required if those now uninsured were to use these services on a par with the privately insured. The primary inputs to this result are new estimates of the impact of being uninsured which indicate a substantial potential response to insurance, particularly by adults.


Increased ambulatory utilization in IPA plans among children receiving hyposensitization therapy. There is concern that children with chronic conditions are less likely to be enrolled in managed care systems and that they may not receive optimal care. We studied the relationship between enrollment in an Independent Practice Association (IPA) plan and utilization of ambulatory services among children in a suburban pediatric practice with one mild chronic condition--those receiving hyposensitization therapy for allergic diseases. Ambulatory utilization by IPA patients (N = 102) was determined by medical chart review for one year before and one year after each patient switched from Blue Cross to IPA coverage. Blue Cross hyposensitization patients (N = 57) matched for age served as controls. Patients receiving hyposensitization were more likely to have enrolled in an IPA than those not receiving hyposensitization (70% vs 45%, p < .001). Before enrollment pre-IPA patients had 41% fewer well-child care (WCC) visits than Blue Cross patients (p < .01); both underutilized WCC visits according to established guidelines. Controlling for age and baseline utilization, we found a significant increase in WCC and acute care visits after IPA enrollment (p < .05), but no change in hyposensitization visits or referrals. In this setting, there was no evidence for reduced access to ambulatory services but rather evidence for improved utilization of primary care.


Cyclosporin and ketoconazole, drug interaction or therapeutic association? Coadministration of cyclosporin and ketoconazole results in marked elevation in blood levels of cyclosporin, which is believed to be the result of competition for hepatic P-450 mixed function oxidase enzymes. This requires a significant reduction in cyclosporin dosage regimen which may result in savings of nearly $5,000/year per transplant recipient. As a consequence, the idea of intentionally adding ketoconazole to cyclosporin for the purpose of decreasing toxicity and cost has been advanced. This article reviews the reported cases and studies of which the ketoconazole/cyclosporin interaction is the major concern. From a pharmaceutical standpoint, it is stressed that further investigations are needed to clarify the actual consequences of the inhibitory effect of ketoconazole on cyclosporin metabolism as well in short-term as in long-term treatments, before taking advantage of metabolic interaction to supply the two drugs as a unique preparation for clinical use. It is concluded that at the time of this review, individual monitoring of adjunctive ketoconazole therapy still remains the best therapeutic choice.


Effect of changing the bioequivalence range from (0.80, 1.20) to (0.80, 1.25) on the power and sample size. International harmonization of guidelines for bioequivalence assessment has led to a wide acceptance of the multiplicative model for the extent and rate characteristics AUC and Cmax and--in consistency with this--of the bioequivalence range (0.80, 1.25). The effect of this change from (0.80, 1.20) on the power of the two one-sided test procedure and the sample sizes based thereon is investigated as a function of the within-subject coefficient of variation (CV) and the ratio mu T/mu R of expected medians for test and reference. The relative reduction in sample size is practically zero for mu T/mu R < or = 0.9 and then gradually increases as mu T/mu R approaches 1.2. At mu T/mu R = 1, the reduction is up to 20%. For a fixed ratio mu T/mu R this reduction increases with the coefficient of variation, reaching a plateau at a CV of about 25%.


Prolonged release of morphine alkaloid from a lipophilic suppository base in vitro and in vivo. The in vitro release characteristics of four suppository formulations of morphine (15 mg) were investigated using the USP rotating basket dissolution apparatus. Morphine hydrochloride in polyethylene glycol (PEG), a hydrophilic suppository base, morphine alkaloid in PEG and morphine hydrochloride in Novata BBC (a lipophilic suppository base) completely released the drug within 25 min whereas, morphine alkaloid in Novata BBC (MAN) released the drug over 10 h. The absorption of the morphine hydrochloride/PEG (MHP) suppository was compared with that of a 15 mg oral solution in eight patients with malignant disease in a crossover design. Time of peak plasma morphine concentration (tmax) was similar for both preparations (1.8 +/- 1.6 h and 1.2 +/- 0.5 h, respectively; p > 0.05), showing that the MHP suppository was rapidly absorbed. The MAN and MHP suppositories were then compared in a further nine patients in a crossover design. Prolonged release of morphine from the MAN suppository was also evident in vivo as tmax (2.5 +/- 1.4 h) was significantly greater than that for the morphine hydrochloride/PEG suppository (0.7 +/- 0.3 h; p < 0.002). There was no significant difference in AUC (0-7 h) (34.5 +/- 19.2 versus 38.9 +/- 16.1 ng.h/ml, respectively; p > 0.05) indicating a similar amount of morphine absorbed. Plasma morphine concentrations were more sustained for 7 h after dosage with the MAN suppository, with lower peak (8.3 +/- 4.9 and 12.3 +/- 6.6 ng/ml, respectively) and higher 6 h plasma morphine concentrations (5.81 +/- 4.85 and 3.30 +/- 1.0 ng/ml, respectively; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Phytomenadione improves red cell deformability in laboratory animals. The deformability of red blood cells (RBC) is one of the factors that determine whole blood rheology. Derivatives of vitamin K (phytomenadione, menadione, menadione bisulfite) are electron-transporting substances. The aim of this study was to investigate the possible influence of derivatives of vitamin K on erythrocyte deformability in studies in vivo--on rats and rabbits. The influence of vitamin K antagonist on erythrocyte deformability (ethylbiscumacetate) was also determined. Pentoxifylline known to affect RBC deformability was also included in the study as the control treatment. The study was performed on white laboratory rats and domestic rabbits. The blood was obtained from animals after single and multiple dosing of drugs. Blood sample was prepared and RBC filterability was assayed with a gravity driven filtration technique. Pentoxyfylline did not change erythrocyte deformability after single dose, but significantly improved erythrocyte deformability of laboratory animals after multiple application. Filterability values of the RBCs of the rats and rabbits increased significantly after single and multiple treatment with phytomenadione, while the two other derivatives, menadione and menadione bisulfite, did not change RBC deformability. Ethylbiscumacetate did not change erythrocyte deformability in rats after single dose.


Serum and synovial fluid osteocalcin in rheumatic diseases. The mechanisms involved in juxta-articular bone destruction are poorly understood. Osteocalcin or gamma-carboxyglutamic acid (GLA) protein is a small non-collagenous bone protein. It is a sensitive marker of osteoblastic bone formation. Its seric variations in the serum in such rheumatisms as rheumatoid arthritis remain unclear. Further information on local osteoblastic activity may be obtained by assaying the level of osteocalcin in the synovium. Its serum level can be evaluated by radioimmunoassay. The same method can be used in the synovial fluid. Paired serum and synovial fluid samples have been assayed from 63 patients, 33 patients with inflammatory arthritis (rheumatoid arthritis, psoriasis, chondrocalcinosis, pyogenic arthritis) and 30 patients with mechanical joint effusion (osteoarthritis, meniscal lesions). Serum levels of osteocalcin were the same in the inflammatory group (m: 8.69 +/- 0.68 ng/ml) and in the mechanical group (m: 10.2 +/- 0.67 ng/ml). In the synovial fluid, the levels of osteocalcin were significantly lower in the inflammatory group (m: 3.27 +/- 0.40 ng/ml) than in the mechanical group (m: 6.91 +/- 0.47 ng/ml). The same results were obtained with the ratio of synovial fluid osteocalcin on serum osteocalcin. There was a significant correlation between serum and synovial fluid osteocalcin and an inverse correlation between synovial fluid osteocalcin and the number of synovial fluid cells. The present study suggests that periarticular osteoblastic depression, among patients with inflammatory arthritis, is likely.


Serum lipoprotein profile under different antihypertensive therapy. Serum lipids of 80 patients with moderately severe essential hypertension under four different antihypertensive therapies were compared to ten matched hypertensives on a placebo, after eight weeks of therapy. The results in the serum lipid parameters measured after therapy showed with enalapril a significant increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in the total cholesterol/HDL-C ratio. With benazepril a significant decrease in the total cholesterol/HDL-C ratio was obtained. With the diuretic combination Epitens the effect on serum sodium and potassium was minimal. No significant changes were found in the lipoprotein profile following the administration of the placebo. Both angiotensin converting enzyme inhibitors (enalapril and benazapril) induced a significant improvement in the atherogenic ratio; as well as the calcium antagonist (isradipine), though to a less extent. The diuretic Epitens induced an insignificant deterioration of the atherogenic ratio.


Protein binding of indomethacin, methotrexate and morphine in patients with cancer. The in vitro protein binding of indomethacin, morphine and methotrexate has been studied in two groups of ten patients each suffering from different types of cancers and compared with twenty normal adult subjects. One group of patients had active disease and the other group was in complete clinical remission. Serum samples were obtained from each subject and the concentrations of albumin and alpha-1 acid glycoprotein (AGP) were measured. Protein binding of drugs was determined using equilibrium dialysis. Alpha-1 acid glycoprotein levels were increased in patients and this effect was more pronounced in active disease (1802 +/- 1025 mg/l) than in remission (931 +/- 273 mg/l). Albumin levels were reduced in active disease (47.67 +/- 15.91 milligrams), but not in remission (61.86 +/- 6.62 milligrams), as compared to control values (58.98 +/- 9.9 milligrams). The protein binding of methotrexate and indomethacin were both reduced in active disease (34.17 +/- 7.12% and 96.26 +/- 0.93% respectively) in comparison with normal subjects (39.33 +/- 4.68% and 96.89 +/- 0.47% respectively), but that of morphine was not changed. In patients there was a strong negative correlation between albumin and alpha-1 acid glycoprotein levels (r = -0.75, p < 0.01) but the correlation in controls was not significant. This study found only weak association between the binding of the drugs studied and the protein levels. It is concluded that reduction in methotrexate dose levels may reduce toxicity in patients with active cancer.


Evaluation of monoclonal/polyclonal ratio in kidney-transplanted patients treated with cyclosporine. Fifty-seven kidney-transplanted outpatients, treated with cyclosporine alone or associated with azathioprine, prednisone, or methylprednisolone, were submitted to a monthly follow-up in order to determine cyclosporine blood levels and the monoclonal/polyclonal (M/P) ratio. Only methylprednisolone was able to modify the M/P ratio. This drug increased the M/P ratio, suggesting a cyclosporine metabolic inhibition. This effect disappeared in a few months in spite of the continuation of methylprednisolone treatment.


Pharmacokinetics of pramiracetam in healthy volunteers after oral administration. The pharmacokinetics of pramiracetam was assessed using an HPLC method after oral administration of two different formulations of 600 mg (a solution and a tablet) of pramiracetam to 11 fasting volunteers. The mean kinetic parameters were: t1 = 4.7 +/- 2.4 - 4.3 +/- 2.2 h, AUC = 57.6 +/- 43.6 - 47.2 +/- 33.9 micrograms h/ml, Cmax = 6.80 +/- 3.2 - 5.80 +/- 3.3 micrograms/ml for the solution and the tablet respectively. The plasma profile of pramiracetam proved to be not highly affected by the formulation, only that the absorption rate was faster after oral administration of the drug in solution than after administration as a tablet. The half-life was very variable between subjects [2-8 hours], but less variable within subjects and it was unaffected by the formulation.


Gastric tolerance of single dose unbuffered and buffered acetylsalicylic acid: a randomized comparative endoscopic study in 24 volunteers. A randomized, three-way crossover study by gastroscopic examination in 24 healthy male volunteers was performed to compare the gastric tolerance of a single dose of buffered or unbuffered acetylsalicylic acid. Gastroscopic assessment was made two hours after administration of the buffered (800 mg ASA) or unbuffered (500 mg ASA) tablets taken with 200 ml of water. Mucosal changes were rare and of a minor nature. Only two volunteers in the unbuffered ASA group presented minor changes (erythema and oedema). No pathological changes were observed after the buffered ASA. Subjective adverse reactions, e.g. epigastric complaints, were reported by four volunteers in the unbuffered group and by two in the buffered group. Based on the limited number and the minor extent of visible changes, statistical tests did not appear to be warranted. The results indicate that buffered ASA is better tolerated.


Betablocking drugs in essential hypertension: transdermal bupranolol compared with oral metoprolol. In the present study the antihypertensive efficacy and tolerability of transdermal bupranolol (30 mg once-daily) was compared with oral metoprolol (100 mg once-daily). Blood pressure measurements were performed in the office, at home, and with ambulatory 24-h blood pressure devices. Systemic and local side-effects, as well as compliance and acceptance, were evaluated every two weeks. The treatment period lasted eight weeks. The results showed a significant decrease in blood pressure under the bupranolol transdermal therapeutic system in the office, at home, and with 24-h blood pressure measurements day- (08h00-20h00) and night-time (20h00-08h00). Under oral metoprolol there was a significant blood pressure decrease in the office, at home, and in the mean daytime values of the 24-h blood pressure measurements. The night-time values, however, demonstrated only a slight decrease in blood pressure, being significant only for diastolic values. Systemic side-effects were comparable in both groups. 69% of the patients had local side-effects at the patch side (erythema, papulous exanthema, pruritus). Six patients dropped out because of localized urticarial exanthema (five patients treated with transdermal bupranolol, one patient treated with oral metoprolol). In comparison to the oral form, twice as many patients had admitted to have been non-compliant with the patches (13 versus 7 patients). At the end of the study, 24 out of 32 patients preferred to be treated with capsules.


Polygonal triple osteotomy of the pelvis. A correction for dysplastic hip joints. A new triple osteotomy, polygonal pelvic osteotomy (PPO), is described for use in dysplastic hips. The hip joint must be congruous with a centre-edge (CE) angle between +20 degrees and -10 degrees. Templates are used before and during operation which allow precise correction of the position of the acetabulum. The geometry of the osteotomy and a special compression plate achieve sufficient stability to permit early mobilisation. Surgery is indicated in adolescents and young adults if pain persists for at least two months. The surgical exposure, operative technique and postoperative management are presented, with the two-year results in nine cases.


Pelvic deformity in experimental dislocation of the growing hip. The hip joints of growing rats have been dislocated experimentally to determine how this affects pelvic shape and acetabular orientation. After hip dislocation the innominate bone tilts laterally in the frontal plane. It bends anteriorly in the sagittal plane and rotates contralaterally in the coronal plane. No significant acetabular anteversion develops.


The fixateur interne for stabilising fractures of the thoracolumbar and lumbar spine. Between 1986 and 1988, 27 patients with fractures of the thoracolumbar and lumbar spine were treated by fixateur interne (FI) instrumentation, and 24 were followed up for a mean of 25 months. Complications occurred in 13 cases, mostly due to loosening and corrosion. The results were compared with plate fixation. The radiological parameters and differences between the preoperative and postoperative indices were well within the normal range. The inferiority of FI instrumentation compared to plate fixation during follow up was mainly attributable to the complications. Reduction of the posterior wall fragments by the intact posterior longitudinal ligament was not consistent, so instrumented reduction is usually the method of choice.


[One stage revision of infected total hip replacements with replacement of bone loss by allografts. Study of 90 cases of which 46 used bone allografts]. We usually manage infected total hip replacements by a one stage revision. We have reviewed 90 cases operated on before 1988. Notable bone loss was frequently encountered and reconstructed using allografts. In all cases complete surgical debridement was performed and a cemented total hip replacement implanted. Bone allografts were used in 46 cases. Systemic antibiotics and antibiotic loaded cement were utilised. There were 17 failures (19%); one patient died soon after operation, there were 8 obvious infections (9%), 1 hip was thought to be infected although the prosthesis was not loose, and 7 femoral prostheses became loose of which 3 were due to mechanical failure and the remainder had no obvious explanation. Infection with staphylococcus aureus and pseudomonas had a statistical correlation with failure, but other factors including the preoperative status and the use of allografts did not appear to influence the result. Allograft femoral heads from the bone bank were found to be reliable for reconstruction of the acetabulum and small femoral defects. With major femoral bone loss we preferred massive irradiated cortical allografts. The quality of the bone reconstruction was probably the most important factor in the good functional results observed in 79% of cases. Effective surgical debridement and an appropriate antibiotic regime will allow a successful one stage revision procedure. The use of allografts gave a reliable reconstruction of the bone loss and was not associated with an increased rate of failure.


A scoring system to determine radiological loosening in cemented total hip arthroplasty. A radiological scoring system was developed to identify grades of loosening of the components of a cemented hip replacement. In grade 1, there are mild changes, usually of minor significance; in grade 2 moderate changes which need regular observation, and in grade 3 severe changes which indicate impending failure. Three parameters are used for the socket, giving a score of 10 points, and 5 for the stem, with a score of 15 points. This method can be used to provide a comparison between different series with a long-term follow up.


The Exeter bipolar prosthesis in the active elderly patient: the results at 7 years. Seventy one Exeter bipolar hemiarthroplasties were reviewed after a mean follow up of 3.2 years (range 1-7 years). Patients with displaced subcapital fractures were selected for operation on the basis of good mobility before the fracture. The operation was well tolerated and the mortality at 1 month and 6 months was 3.7% and 6.5% respectively. Using a newly devised hip scoring system 89% had a good or excellent result and 94% had no or only occasional pain. There was no radiological evidence of acetabular erosion.


Microscopic analysis of autograft bone applied at the interface of porous-coated devices in human cancellous bone. This study describes the response of human cancellous bone when autologous bone chips are added at operation to the interface between host bone and porous-coated implants. During the first operation of a staged bilateral total knee arthroplasty, seven patients consented to have paired porous-coated devices implanted into their opposite medial femoral condyle. One device of each pair had autologous bone chips applied to the porous-coating, and the other was not grafted and was a control. The devices were removed en bloc at the second total knee arthroplasty 6 to 49 weeks later. Backscattered electron imaging showed significantly more bone (p < or = 0.05) in the porous-coating of the implant treated with autologous bone chips which significantly increased (p < or = 0.05) the amount of bone available at the interface. The grafted devices had a mineral apposition rate of 1.04 +/- 0.20 microns/day for the interface and 0.81 +/- 0.09 microns/day for the peripheral bone. This compared with corresponding figures of 1.03 +/- 0.38 microns/day and 0.79 +/- 0.19 microns/day at the ungrafted devices. The mineral apposition rate at the interface of the porous-coated implants was significantly increased (p < or = 0.05) relative to the host bone in the periphery. Our results support the view that autologous bone chips are effective in attaching cementless porous-coated total knee replacements to the human skeleton by bone ingrowth.


A prospective randomized study of the use of sliding hip screws and Ender nails for trochanteric fractures of the femur. The functional outcome of trochanteric hip fractures was investigated prospectively in a group of 92 patients treated at random with either Ender nails or a sliding hip screw. Apart from clinical variables, the walking ability of the patients was assessed by gait analysis performed on an electronic walkway. No perioperative complications were noted. The patients in the Ender group had significantly less blood loss and a shorter operation time than the patients treated with the sliding hip screw, indicating that the former method is more gentle as a primary intervention. However, over time there were more reoperations in the Ender group and the functional outcome, including gait analysis after 6 months, showed more favourable results for fractures treated with the sliding hip screw. We therefore recommend the sliding hip screw for an optimal functional result.


The healing of flexor tendons in chickens. The healing of flexor tendons was studied in chickens using transmission electron microscopy. After resecting the flexor sheath between the proximal and distal pulleys in zone II, the profundus tendon was severed and sutured. Intermittent passive motion was carried out 35 times daily immediately afterwards. The chickens were sacrificed at 3, 6 and 9 weeks. In vivo healing was shown to be much more rapid than in in vitro studies. There was marked proliferation of endoplasmic reticulum and phagocytosis at 3 weeks, collagen synthesis at 6 weeks and remodelling at 9 weeks. Healing was by a combination of extrinsic and intrinsic mechanisms.


The third metacarpal boss.

The third metacarpal boss. A swelling and ache on the dorsum of the wrist in relation to the base of the 3rd metacarpal bone may indicate a bony lesion or an enlarged styloid process. It may also be due to an old fracture of the process or an accessory ossicle (os styloideum). Approximately half the 14 patients (15 wrists) had a history of an injury, usually a hit with the fist. Recurrent occupational strain may also produce symptoms at this site. Excision of the metacarpal base with the adjacent capitate or trapezoid, and repair of the periosteum and extensor tendon, will remove the lump and usually relieve symptoms.


The patella thinning osteotomy. An experimental study of a new technique for reducing patellofemoral pressure. The authors describe an original procedure, the patella thinning osteotomy, as an alternative to advancement of the tibial tuberosity or patellectomy in cases of severe anterior knee pain. They present an experimental study on cadaveric knees prior to a clinical trial. This study on 13 knee specimens, using Fujifilm Prescale barosensitive film, shows that thinning of the patella by 7 mm diminishes to a significant degree the patellofemoral contact areas from 16.07% at 60 degrees of flexion to 27.90% at 30 degrees of flexion. Patellofemoral joint reacting forces, measured in 12 knees, also diminish in both medial and lateral surfaces at 30 degrees, 60 degrees and 90 degrees of flexion, the level of statistical significance being over 0.05, except for the lateral surface at 60 degrees of flexion. This technique decompresses the patellofemoral joint, and produces the biological effects found after other osteotomies.


Vascular changes in the ruptured Achilles tendon and paratenon. Thirty patients with ruptures of the Achilles tendon were studied. There were 21 men and 9 women with an average age of 36 years. Specimens from the tendon and paratenon in 24 were examined histologically. Tissue samples of 20 were studied by electron microscopy. Marked degenerative, obliterative and/or inflammatory vascular changes were found in all the ruptured tendons and their paratenon. Our findings indicate that poor vascularity play a role in the aetiology of rupture of the Achilles tendon.


Amputation for occlusive arterial disease. A prospective multicentre study of 177 amputees. All major amputations of the lower limb due to occlusive arterial disease were studied prospectively and consecutively during one year in the 5 hospitals in Malmöhus county, Sweden. The patients were followed for 6 months after the primary amputation of which 136 were through the tibia, 6 through the knee and 35 through the femur. One hundred and seventy-seven patients (92 men and 85 women) were included; 49% were 80 years or older and 40% were diabetic. At 6 months, 85 of the surviving 109 patients had healed stumps, 10 were not healed and 14 had been revised or reamputated. Half the survivors used a prosthesis daily. There was no significant difference in healing related to sex, age, diabetes or the level of amputation, but diabetics were more often bilateral amputees. The mortality at 6 months was 38% and at 4 years 72%.


The effect on low back pain of shortening osteotomy for leg length inequality. This study evaluates the effect on low back pain of shortening osteotomy in patients with leg length inequality (LLI). Twenty-two patients were followed up after an average of 5 years. The mean preoperative LLI was 32 mm and was 4.3 mm at follow up. The degree of low back pain was significantly reduced after the operation.


Osteomyelitis and septic arthritis in sickle cell disease in the eastern province of Saudi Arabia. Patients with sickle cell disease are more susceptible to osteomyelitis and septic arthritis than the population at large. Seventy eight patients with these conditions were admitted to our hospital from April 1988 to March 1991. Thirty had sickle cell disease, 14 had the sickle cell trait and 34 had normal electrophoresis. The tibia, followed by the femur and humerus were the bones most commonly affected, and the knee was the joint most often involved. Salmonella was the commonest organism in osteomyelitis and septic arthritis in sickle cell disease, whereas staphylococcus was commonest in normal patients and those with the sickle cell trait. Antibiotics that cover these two organisms must be considered in patients with sickle cell disease who are suspected of having osteomyelitis or septic arthritis.


Bioactivity of cis and dicis isomers of vitamin A esters. In order to declare the accurate vitamin A effectiveness of foodstuffs and synthetic vitamin A preparations, the biological activity of the individual isomers has to be known. Total activity is expressed as all-trans vitamin A equivalents which are calculated by multiplication of analytical content of each isomer with the corresponding biopotency factor. The biological activity of four cis and three or four dicis isomers of vitamin A acetate and palmitate was determined by means of rat vaginal smear assays. The purity of the compounds, the content and isomerisation in stock solutions were checked by HPLC methods prior to their dilution and application to the experimental animals. Based on analytical contents the following activities were found for vitamin A acetate isomers: all-trans 1.00, 13-cis 0.76, 11-cis 0.31, 9-cis 0.19, 7-cis 0.18, 9,13-dicis 0.16, 11,13-dicis 0.18, 9,11-dicis approx. 0.03. The corresponding values for vitamin A palmitate were: all-trans 1.00, 13-cis 0.73, 11-cis 0.34, 9-cis 0.19, 7-cis 0.14, 9,13-dicis 0.21, 11,13-dicis 0.20, 9,11-dicis approx. 0.04, 7,11-dicis approx. 0.12. The vitamin A activity of the cis isomers ranged from about 0.75 for 13-cis to about 0.05 for 9,11-dicis. For the cis series, a biopotency relationship depending on the distance between the beta-ionone ring system and the cis configuration could be observed.


Assessment of the vitamin A status of preschool and school age Senegalese children during a cross-sectional study. The increasing concern about vitamin A deficiency in even its mild subclinical form has created the need for a mass screening test. Various clinical, biochemical and cytological methods for assessing the vitamin A status have been widely used but all are unsatisfactory for technical, ethical or public health reasons. The two prevalence criteria defined by the World Health Organization (WHO) for a vitamin A deficiency problem of public health significance are xerophthalmia and serum retinol concentrations. Recently we proposed a prevalence criterion for impression cytology with transfer (ICT) at the level of 50% of ICT results being abnormal. We conducted a cross-sectional survey of the prevalence of vitamin A deficiency and also undernutrition during the dry season in a random sample of 1,259 children (n = 442 for the 2-6 years and n = 817 for the 7-14 years) from a rural area in Senegal. Prevalence was 0 times and 4.2 times the WHO criteria for xerophthalmia and deficient serum retinol levels, respectively in preschool children. Abnormal ICT results were more frequent in preschool than in school children (53.4% versus 21.0%). There was an association between abnormal ICT results and stunting. Vitamin A deficiency was a public health problem in preschool children as assessed by the biochemical criterion (20.9% of serum retinol values under 0.35 mumol/l) or the cytological cut-off (53.4% of abnormal ICT results) but was also found in school children (21.0% of abnormal ICT results).


Annual assessment of the vitamin A and nutritional status of children during two cross-sectional surveys. The changes in the vitamin A and nutritional status of children from a rural area in Senegal were determined by the same team during two cross-sectional surveys distant from exactly one year. At baseline (T = 0 year) 1,259 children were chosen at random. One year later (T = 1 year), 1,008 children were re-examined. Vitamin A and nutritional status were assessed by clinical and cytological methods, and by anthropometrical indicators for the 1,008 participants, respectively. No signs of xerophthalmia were recorded at T = 0 and T = 1 year. The proportions of children deficient in vitamin A as defined by abnormal cytology and suffering from stunting were similar at these two measuring points. Even though these percentages remained similar at T = 0 and T = 1 year, there existed little movement between the abnormal and normal eye cytology group and the stunted and non-stunted group. Since vitamin A is required for normal growth, we calculated the mean linear gain in height according to the eye cytological changes assessed between the two examinations. We found that mean linear growth increments were higher in the groups of children who remained abnormal or reverted to abnormal cytology than in those who remained normal or reverted to normal cytology.


A new spectrophotometric assay for the determination of vitamin A and related compounds in serum. A new, direct multicomponent spectrophotometric assay for determining the vitamin A, lycopene, the total beta-carotene+beta-cryptoxanthin, the total lutein+alpha-carotene content of human serum is reported. The new method has been validated by performing parallel HPLC assays and is likely to be especially useful for use in population screening programmes. It is also suitable for screening paediatric samples.


Concentration of plasma and milk vitamin E and plasma beta-carotene of mastitic and healthy cows. Variation of vitamin E in blood plasma and milk and beta-carotene in blood plasma of 38 healthy and 38 mastitic cows was studied. Cows were assigned to one of the two treatment groups: control and vitamin E supplemented. Vitamin E supplementation was started when cows were dried-off at the end of lactation and continued until 3 months post partum at the rate of 1000 IU per cow daily and then reduced to 500 IU for the remaining lactation. A cow was considered mastitic when somatic cell count of milk was greater than 500 x 10(3) cells/ml. Milk samples with somatic cell counts below 100 x 10(3) cells/ml were from healthy cows. Data on vitamin E concentration of plasma and milk and beta-carotene in plasma were analyzed by a least squares procedure. The model included the effects of treatment, mastitis status, stage of lactation, and all first order interactions. Mean vitamin E levels in plasma and milk of supplemented cows were significantly higher than of the non-supplemented cows. Plasma and milk levels of vitamin E as well as beta-carotene in plasma were significantly lower in mastitic than healthy cows. When data were analyzed with loge, of somatic cell count in milk as an independent regression variable, results were similar. There was a negative correlation of mastitis status with vitamin E levels in plasma (-0.48), milk (-0.24), and beta-carotene in plasma (-0.38).(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of nitrite ingestion on the bioavailability of folate in the rat. The effect of nitrite ingestion on the intestinal deconjugation and absorption of folic acid (PGA) and brewers yeast folate was investigated using a rat bioassay and liver folate uptake as the response parameter. Male weanling Sprague Dawley rats were depleted on a low folate AIN-76A formulated basal diet for 21 days. During a 14 day repletion period, folic acid (PGA) and brewers yeast were added to provide 0.25, 0.5 and 1.0 mg of folate per kg of diet. Potassium nitrite was administered as part of the diet at 0.5%. All diets were made isonitrogenous and isocaloric. Based on a parallel line assay, the relative bioavailability of folate in the brewers yeast diet (109) was significantly higher than in the standard diet (PGA = 100). When combined with nitrite, the relative bioavailability of the PGA diet was not significantly different (101), while that of the brewers yeast diet was significantly lower than the standard diet. Concomitant ingestion of nitrite significantly reduced the bioavailability of brewers yeast folate but not that of PGA in rats. This appeared to be a direct effect of oxidation by nitrite on the more susceptible substituted folates in brewers yeast.


Epidemiology of vitamins A, E, D and C in rural villages in Finland: biochemical, nutritional and socioeconomical aspects. We carried out an extensive health profile analysis in spring-winter 1986 in four Eastern Finnish rural villages as a part of the Healthy Village Study. Altogether, 793 people at working age (20-64 years of age, 427 men and 366 women) participated (80%). Serum lipids (total cholesterol, HDL-cholesterol and triglycerides) and plasma vitamins (vitamin A, D, E and C) were measured as biochemical indicators of health. The dietary habits were reflected in high serum total cholesterol, and in low plasma vitamin C (ascorbic acid, mean 34.4 mumol/l in men, and 51.2 mumol/l in women). The plasma levels of the other vitamins studied were, in general, satisfactory. The mean plasma concentration of vitamin A (retinol) was 2.70 mumol/l in men, and 2.23 mumol/l in women. The gender, high body weight and the use of animal fats had the strongest association to apparent plasma retinol concentrations. The corresponding plasma concentrations of vitamin D (25-hydroxy-D) were 34.1 nmol/l and 35.4 nmol/l, and vitamin E (d-alpha-tocopherol) 22.1 mumol/l and 22.2 mumol/l. Vitamin D deficiency (plasma 25-OHD less than 12.5 nmol/l) was seen in 5% of the subjects. A good vitamin D status was correlated with the use of vitamin supplements, and, surprisingly, with the frequent consumption of alcohol.


A cross-sectional study of vitamin C intake and blood pressure in the elderly. Data collected as part of a study designed to examine the nutritional status of non-institutionalized elderly individuals, ages 60-100 years, residing in the Boston area were used to investigate the relationship between blood pressure (BP) and vitamin C intake reported by three-day diet records. Four hundred and ten subjects not taking antihypertensive medications were grouped into 5 categories of vitamin C intake: < 60, 60-119, 120-179, 180-239, > or = 240 mg/day. Relative differences in systolic and diastolic BP between subjects consuming > or = 240 mg/day compared to those consuming < 60 mg/day were -6.9% (p < 0.05) and -6.6% (p < 0.05), respectively. The prevalence of elevated BP (systolic > or = 160 mmHg or diastolic > or = 100 mmHg) was approximately 50% lower (p < 0.05) across this range of vitamin C intake. Adjustment of these associations for age, sex, body mass, smoking, dietary sodium:potassium ratio, and other dietary factors did little to alter the relationship between vitamin C and BP. These results lend support to the hypothesis that vitamin C and BP are related, but further research is required to test whether the relationship is causal.


Effects of purified eicosapentaenoic acid ethyl ester on plasma lipoproteins in primary hypercholesterolemia. We investigated the effects of purified eicosapentaenoic acid (EPA) ethyl ester capsules (90% purity), which are free from cholesterol, saturated fatty acids and docosahexaenoic acid (DHA), on plasma lipoproteins and cholesteryl ester transfer protein (CETP) activity. We administered 2.7 g of EPA per day as capsules for 6 months to 14 primary hypercholesterolemic subjects. Total cholesterol, triglyceride and low density lipoprotein (LDL)-cholesterol levels in plasma were significantly reduced. The LDL cholesterol/apoB ratio and LDL particle size did not change. The ratio of high density lipoprotein (HDL)2/HDL3 cholesterol increased from 1.04 to 1.35 (p < 0.05), while the HDL cholesterol level did not change. CETP activity was significantly reduced. The reduction of CETP activity may explain the increase in the HDL2/HDL3 cholesterol ratio. These results suggest that purified EPA not only reduces LDL cholesterol levels but also acts on HDL metabolism in patients with hypercholesterolemia and therefore will be useful for the treatment of hypercholesterolemia.


Plasma lipid composition in an elderly population: correlation with dietary fat. The effects of dietary fat on plasma lipid composition were studied in a population of 51 elderly subjects (19 men, 32 women) who lived in a retirement home in the province of Jaén (southern Spain). Dietary intake of fat was elevated (106 and 115 g/day in men and women respectively), and fatty acid intake consisted of 40% oleic acid, 17% linoleic acid and 0.7% linolenic acid. Cholesterol intake was 506 and 518 mg/day in men and women respectively, whereas the plasma level of cholesterol was approximately 250 mg/dl in both sexes. In men and women, HDL-cholesterol levels were 71.5 and 62.2 mg/dl, and LDL-cholesterol levels were 153.5 and 152.3 mg/dl. The most abundant circulating fatty acid was palmitic acid (25%) in both sexes, followed by oleic (23%) and linoleic acid (15-16%), whereas linolenic acid represented only 0.3% of the plasma fatty acids. To determine whether plasma levels of fatty acids served as reliable biological markers of dietary fatty acid intake, we compared the two sets of values, and found that higher intake was reflected in higher plasma levels, although a significant linear correlation (p < 0.05) was found only for linolenic acid.


Glycemic index of selected foodstuffs commonly used in south India. To assess the true physiological basis of carbohydrate exchange of food, commonly eaten in South India, the "Glycemic Index", defined as the area of the glucose tolerance test, under 3 hr, for each food item, expressed as percentage of the area after taking the same amount of carbohydrate as glucose (75 gms) was studied, in healthy fasting human volunteers. Thirteen articles of food items were fed to groups of 12 to 15 healthy fasting volunteers and their glucose tolerance test values up to 3 hr, were measured. The highest glycemic index values were shown by starchy tubers, Raggi and fleshy fruits, while relatively lower values were obtained for pulses and rice; whole wheat showed the smallest glycemic index.


Statistical analysis of relationship between net protein utilization in rat and amino acid composition in cooked foods. To determine the relation between protein nutritive value and amino acid composition of protein in cooked food, statistical analysis was carried out on thirty cooked foods selected from Japanese daily meal. The food samples were cooked, and powdered after freeze-drying. The amino acid composition was determined by liquid chromatography and colorimetry. The Wistar rats were put on the 7% cooked food protein diet and NPU (net protein utilization) was determined. Linear multiple regression analysis was made between NPU and the ratio of individual essential amino acid in the cooked food protein (mg/Ng)/the corresponding amino acid in the reference protein (mg/Ng). The regression equation for the predicted net protein utilization (NPUp) reads as follows: [formula: see text] Highest correlation coefficient (r = 0.93, p < 0.01) was obtained between NPU and NPUp of the protein in the cooked food.


Nutritional status of a group of self-sufficient institutionalized elderly people in Perugia (Italy). The nutritional status of forty-six self sufficient institutionalized elderly people of Perugia was assessed. The diet of this group is slightly better than that of other groups of elderly people previously examined. As observed in other studies, the diet of the elderly from this region of Italy does not seem to be of the Mediterranean type. The location of subcutaneous fat in elderly men is prevalent in the upper trunk and in women in the arms. The clinical signs of nutritional status among this group of self-sufficient institutionalized elderly people are in general not specific and mostly associated with old age. The pathological conditions observed and the administration of drugs do not appear to substantially influence the nutritional status of this group.


Effect of prone versus supine patient positioning on pelvic magnetic resonance image quality. Magnetic resonance imaging (MRI) of the pelvis in the prone position has been proposed as a means of reducing motion-related image blurring. The authors performed a randomized controlled trial to determine if patient positioning affects image quality. All women undergoing pelvic MRI during a 7-month period, who could lie both prone and supine, were randomized to the supine or prone position. The quality of axial T2-weighted spin-echo images was rated by two radiologists using a 1-to-4 scale (1 = marked blurring to 4 = sharp definition of pelvic structures). Of 78 eligible women, 61 were randomized. Two patients could not complete the examination. The mean image quality rating of 2.8 for the 32 patients imaged prone was not significantly different from the mean rating of 2.9 for the 27 patients imaged supine (P = .5, Mann-Whitney U test). Patient positioning did not significantly affect pelvic MRI quality. The choice of patient position should be based on other considerations, such as patient comfort or ease of patient positioning.


Venography of the lower limbs. Pitfalls of the diagnostic standard. The ETTT Trial Investigators. Phlebography is considered the diagnostic standard for suspected deep venous thrombosis. The authors studied the inter-observer variability of phlebogram interpretation in the setting of a multicenter therapeutic trial of the thrombolytic agent alteplase. The interpretation of 31 pairs of venograms (before and after thrombolytic therapy) was studied by comparing the quantitative Marder's scores which were computed by three experts and the qualitative assessment of phlebographic changes induced by thrombolysis by the panel of experts and by the investigators. Although the scores of the three experts correlated fairly well (r = .67-.82; P < .001), they differed significantly from each other (P < .0001). Substantial differences also were found between local (by investigators) qualitative evaluation of the venographic changes induced by the treatment and central evaluation by the panel of experts (coefficient of agreement kappa = 0.19), local assessment being significantly more optimistic (P = .002) than central judgment. Significant differences were observed between assessment of changes in venographic scores after thrombolytic treatment both among three expert radiologists, and between the panel of experts and the local investigators of the multicenter trial. This observation points to the need for an a priori definition of well-characterized decision criteria to allow a valid interpretation of the effects of the therapeutic intervention.


Risks associated with intestinal perforation during experimental percutaneous drainage. The authors evaluated the complication rate of transgressing small or large bowel during intraperitoneal percutaneous catheter placement in an animal model. Twenty-four 8-F catheters were percutaneously placed through the small and large bowel of 12 pigs. In six animals, the catheters were left in place until autopsy, whereas in the remaining six animals, the catheters were withdrawn 5 days after insertion. Computed tomographic (CT) scans were performed on days 1 and 8 after catheter placement in pigs in which catheters were in place at time of autopsy, and on days 1, 5, and 8 in pigs in which catheters were removed. CT results showed no abscess or peritoneal effusion, but a pneumoperitoneum was present in four animals whose signs resolved on subsequent studies. Autopsy was performed in all animals 9 days after catheter placement. No clinical complication occurred, and no significant biochemical changes were observed. At autopsy, no bowel leakage, peritonitis, or abscess was visible. Bowel and peritoneal adhesions were found around the catheter tract. There was no difference between the animals with catheters in place at the time of autopsy and the animals without catheters. There also was no difference between the group of animals with small or large bowel transgression. This study suggests that traversing the intestine during percutaneous placement of an intra-abdominal catheter should not be considered an absolute contraindication when no other approach is available.


Deformation characteristics of a bioabsorbable intravascular stent. Biodegradable polymeric stents offer an alternative to metallic stents, which have a significant compliance mismatch with blood vessels and have the potential for long-term complications. In the current study, the deformation characteristics of polymeric stents have been investigated. Stents were subjected to radial compressive pressure by inserting them in a wrap-around collar, one end of which was loaded in tension using dead-weights. The resulting decrease in stent diameter was measured under an optical microscope. Deformation curves for the stents were plotted, and an effective stiffness, E', was determined for each. The deformation curves exhibited two different regions: an initial linear region, followed by a steep nonlinear region. The transition from the linear region occurred at a fractional decrease in stent diameter of approximately 0.5. E' decreases with increasing stent diameter and filament draw-ratio. The relationship between E' and the initial stent diameter is not linear. The deformation curves can be used for choosing the appropriate stents for specific applications.


Variation in hemostatic parameters after intra-arterial and intravenous administration of iodinated contrast media. A few case reports have suggested a possible thrombogenic effect of nonionic contrast media. In vitro investigations have lead to conflicting results. The authors performed three ex vivo studies to evaluate the influence of an ionic, ioxaglate, and a nonionic, iopamidol, low-osmolality contrast medium on a series of clotting and fibrinolytic parameters, after intravenous or intra-arterial administration, during routine diagnostic procedures. In the first study, iopamidol was given to 20 consecutive patients through an arterial catheter for digital subtraction arteriography (DSA). In the second study, iopamidol was compared with ioxaglate. The media were randomly and blindly administered intravenously to 21 consecutive patients undergoing brain computed tomography (CT). Finally, ioxaglate was administered intra-arterially to 20 consecutive patients, in a situation comparable with that of the first study. In the first study, a weak anticoagulant effect and an activation of fibrinolysis were found, associated with indirect markers of thrombin generation, such as increased plasma levels of fibrinopeptide A (FpA) and thrombin-antithrombin III complexes (TAT). In the second study, no significant changes were seen with either contrast medium, for thrombin or fibrinolysis activation parameters. In the third study, the intra-arterially administered contrast medium elicited a marked increase of FpA and TAT, together with an anticoagulant effect. Both ionic and nonionic contrast media are able to interfere with the clotting/fibrinolytic system in the general circulation when they are administered to patients at the usual dosages. Ioxaglate shows more marked anticoagulant and thrombin-generating effects than iopamidol. The procedure (ie, arterial catheter versus intravenous infusion) seems to be more important than the category of contrast medium in conditioning the magnitude of these effects.


Comparison of vascular opacification after bolus injection of iodixanol-320 iohexol-350. The vascular opacification characteristics of a new nonionic, dimeric contrast agent, iodixanol, have been compared with a nonionic, monomeric agent, iohexol, using ultrafast computed tomography (UFCT). In 10 experiments with mongrel dogs, the contrast agents were alternately injected into the animal's left atrium, and UFCT images were obtained at four cross-sectional levels through the carotid arteries. Time-density curves were then obtained for each carotid artery and each agent. The peak height and area under the curves were compared for each agent. Iohexol provided significantly (P < or = .05) greater opacification, determined by paired Student's t tests. This result was predicted from the greater iodine concentration of iohexol (350 mg/mL) compared with iodixanol (320 mg/mL); the difference was greater than expected based on iodine content alone.


Hydrostatic pulmonary edema in sheep. Effects of bronchial artery embolization on the plain chest radiograph. The bronchial circulation may influence pulmonary edema. This study evaluates possible effects of bronchoesophageal artery embolization on the plain film manifestations of hydrostatic pulmonary edema in sheep. Anteroposterior and lateral chest radiographs were obtained during the induction of pulmonary edema both before and after embolization of the bronchoesophageal artery in six adult sheep. Interstitial lines and perivascular, segmental bronchial, proximal bronchial, carinal, tracheal, and parenchymal edema were evaluated. Only parenchymal edema was graded consistently. Though edema increased with left atrial pressure before embolization (P < .001), there was no similar change afterward. The embolized animals tended to be more edematous by the first film. Rather than any protective effect, bronchoesophageal artery embolization may increase edema. This model may be inappropriate for further investigation of the bronchial circulation in the development of human pulmonary edema.


In vitro dissolution of cholesterol gallstones. Methyl tert-butyl ether (MTBE) is the solvent most commonly used for in vivo dissolution of cholesterol gallstones. Its limitations, however, include high volatility and flammability along with potential toxicologic concerns. Therapy may take several hours. This study was initiated to identify alternate solvents which may be superior to MTBE in one or more of these areas. MTBE was compared with several other solvents for cholesterol-dissolving capacity. Groups of human cholesterol gallstones were placed in test tubes, and, without agitation, subjected to mixtures of MTBE:ethanol or another solvent:ethanol. Six other solvents were found to have higher capacities. In several cases, other solvent mixtures dissolved gallstones up to twice as fast as the MTBE:ethanol mixture. These faster solvents were cyclic ethers (tetrahydrofuran [THF], methyl tetrahydrofuran [MTHF], tetrahydropyran [THP], methyl tetrahydropyran [MTHP], and possibly dimethyl tetrahydrofuran [DMTHF]) and limonene. Some of these solvents also have lower volatility and higher flash points than MTBE, resulting in safer storage and handling. THF and pyridine, however, were found to precipitate bile components when mixed with bile. The authors describe solvents that may be superior to MTBE for rapid dissolution of gallstones in vivo.


Laminar submerged jets by color Doppler ultrasound. A model of the ureteral jet phenomenon. The authors developed and tested a technique to noninvasively measure ureterovesical junction (UVJ) pressure gradients. Such a technique could be used to evaluate ureteral reflux and obstruction. Color Doppler ultrasound measurements of an in vitro model of the ureteral jet were performed. The authors show that the orificial rate of momentum transfer of the ureteral jet (from which the intraluminal pressure in the ureter can be calculated) can be determined to within 45% to 94% of its true value depending primarily on the flow sensitivity of the color flow imager. Marked improvement in the momentum calculation (> 80%) is achieved when a low-flow sensitivity is used. Such noninvasive measurements could replace more invasive techniques (eg, the Whitaker test or cystoscopy with or without ureteral cannulation), which seriously perturb the system of interest.


Arteriosclerosis obliterans in a rabbit model. The authors induced atherosclerotic occlusions in a rabbit model, using and comparing different experimental methods. Lesions were induced in 40 femoral arteries in 20 rabbits. Four combinations of lesion induction methods were used: 1) drying of the endothelium with carbon dioxide gas; 2) gas-drying of the artery plus mechanical injury; 3) gas-drying plus induced thrombosis of the treated segment using thrombin; and 4) gas-drying, mechanical injury, and induced thrombosis. All rabbits were fed a high-fat, high-cholesterol diet for 1 to 2 months after lesion induction. Seventeen rabbits were available for follow-up. Sixty-eight percent (13 of 19) of femoral arteries treated with thrombin-induced thrombosis demonstrated atherosclerotic occlusions, compared with 27% of those that did not receive this treatment (4 of 15; P < .01). Thrombin-induced thrombotic occlusion of a segment of artery which has been de-endothelialized, followed by a high-fat, high cholesterol diet, results in a higher yield of experimental occlusive atherosclerosis in rabbits than is achievable by other methods.


Comparative effects of neutral dipolar compounds and lipophilic anions on technetium 99m-hexakis (2-methoxyisobutyl isonitrile) accumulation in cultured chick ventricular myocytes. Non-flow-dependent myocellular accumulation and uptake kinetics of the myocardial perfusion and viability imaging agent, hexakis (2-methoxyisobutyl isonitrile) technetium 99m(I) (Tc-SESTAMIBI), are thermodynamically driven by large negative sarcolemmal and mitochondrial membrane potentials, and can be enhanced by addition of the lipophilic anion, tetraphenylborate (TPB). To further understand the general properties required of a co-administered compound for increasing the kinetic response of Tc-SESTAMIBI to membrane potential, a systematic appraisal of additional candidate lipid-soluble anions and neutral dipolar compounds was undertaken. Each compound was biologically tested for its ability to enhance Tc-SESTAMIBI accumulation in a cultured heart cell model, and electronic dipole moments were evaluated using semi-empirical molecular orbital calculations. Of this series, phloretin (100 microM), TPB (10 microM), and to a lesser degree, 8-anilino-1-naphthalene sulfonate (100 microM) enhanced myocellular accumulation of Tc-SESTAMIBI. Phloretin enhancement was pH-dependent, showing maximal effect at pH 7.4, and was not additive to the augmentation induced by TPB. A series of additional lipid soluble anions and structural analogues of phloretin were without effect. Although selected compounds enhanced Tc-SESTAMIBI accumulation, overall, no direct relationship of dipole moment to biologic enhancement was demonstrated.


Contrast media-induced renal morphologic lesions during experimental hemorrhagic necrotizing pancreatitis. Contrast media-induced renal morphologic changes were studied in rats. Hemorrhagic pancreatitis was induced as a means of sensitizing the animals to the effects of contrast media. The histologically verified hemorrhagic pancreatitis was induced in Wistar rats (n = 66) by injecting 6% sodium taurocholate into the pancreatic duct. After 2 hours, the animals received intravenously 1.0 or 3.0 g iodine/kg of high-osmolal osmolal diatrizoate, low-osmolal iopromide or iohexol, iso-osmolal iotrolan or 0.2 or 0.6 g/kg of high-osmolal magnetic resonance contrast agent, gadolinium-DTPA (Gd-DTPA). Control animals received physiologic saline. The kidneys were fixed by perfusion 2 hours later, and the morphologic changes were reviewed by two independent observers blinded to the injected agent. The smaller dose of iohexol and the larger dose of all the contrast media induced a statistically significant (P < .001 or .01) cytoplasmic vacuolization in the proximal convoluted tubule (PCT) cells. The nonionic, low- and iso-osmolal contrast media caused as much or even significantly more vacuolization than diatrizoate. Hemorrhagic pancreatitis potentiates the contrast media-induced renal morphologic changes, which depend on the type and dose of the injected contrast media.