Sir William Osler--contrasts between the saint-like legend and the rough-edged man.

Sir William Osler, the first physician-in-chief of the Johns Hopkins Hospital and later Regius Professor of Medicine at Oxford, is judged by many to be the greatest clinician of the modern era. His life history of distinguished service to medicine and to society is well known. What is not so well known is his mischievous streak.


T1 snapshot FLASH measurement of rat brain glioma: kinetics of the tumor-enhancing contrast agent manganese (III) tetraphenylporphine sulfonate.

The ultrafast inversion recovery snapshot FLASH technique was used to determine the kinetics of the contrast agent manganese (III) tetraphenylporphine sulfonate (MnTPPS) in experimental brain tumors in rats. In the first part of the investigation this technique was validated with the conventional inversion recovery spin-echo method by comparing in vivo T1 data of a normal rat brain. Agreement between T1 values obtained from both techniques was complete, as tested for a large number of pixels in identical coronal slices. In the second part the fast IR snapshot FLASH method was applied to study the effect of the NMR contrast agent MnTPPS on the T1 relaxation time of experimental gliomas in rat brains. T1 of normal brain tissue (1024-1035 ms), tumor (1217 ms), and edema (1199 ms) was determined with the inversion recovery version of the snapshot FLASH imaging technique. After intraperitoneal injection of MnTPPS (0.25 mmol/kg body wt) T1 decreased exponentially to 56% of control in tumor and to 62% in muscle. In normal and edematous brain tissue no significant changes in T1 were observed up to 5 h after injection of the contrast agent. Once the T1 contrast between tumor and peritumoral brain tissue had reached a saturation, the enhancement persisted for several hours to days. Therefore application of this contrast agent resulted in a sharp demarcation between glioma and peri-tumoral edema.


Nuclear magnetic resonance velocity spectra of pulsatile flow in a rigid tube.

Velocity spectra can be derived from velocity-encoded nuclear magnetic resonance (NMR) images. Velocity spectra are histograms showing the amounts of fluid flowing at different velocities in the sensitive volume of the measurement. Velocity spectra may prove to be useful in characterizing the flow of blood in small vessels, for example, in detecting the presence of stenoses and in evaluating their severity. NMR velocity spectra acquired in vivo are sufficiently complicated that a model system was designed and tested to investigate the velocity spectra of pulsatile flow. This study measured the NMR velocity spectra of pulsatile flow in a rigid tube and compared them to velocity spectra derived from Doppler ultrasound measurements and to velocity spectra inferred from a theoretical model driven by the measured pressure difference function. The experimental results from each technique agree.


Tissue characterization and assessment of preoperative chemotherapeutic response in musculoskeletal tumors by in vivo 31P magnetic resonance spectroscopy.

This study investigates the potential of in vivo 31P magnetic resonance spectroscopy (MRS) to characterize musculoskeletal tumors and to determine preoperative levels of histological necrosis, which is an important clinical indicator of patient response. Pretherapy MRS was performed on 28 patients with large musculoskeletal tumors: 13 with osteosarcoma, 3 with chondrosarcoma, 5 with malignant fibrous histiocytoma, 1 with desmoid tumor, 1 with Ewing's, 2 with hemangioendothelioma, 1 with myxoid liposarcoma, 1 with synovial cell sarcoma, and 1 with rhabdomyosarcoma. Fifteen patients had follow-up MRS examinations after commencement of chemotherapy (mean of five/patient), eight of whom have now had surgery. Elevated levels of PMEs (P < 0.01), P(i) (P < 0.01), and PDEs (P < 0.02) as well as elevated tumor pH (P < 0.05) were observed in all patients. The synovial cell sarcoma was characterized by high levels of PMEs (> 20%) and low pH (pH 6.76). This contrasted with the spectra obtained from the malignant fibrous histiocytomas which had high levels of PDEs (17 +/- 5%). Reductions in PDE levels postchemotherapy were associated with a high degree of necrosis (> 90%) at surgery, while an increase in PDE levels was associated with a low level of histological necrosis. Likewise, reductions in the ratios PDE/NTP and PDE/PCr and an increase in P(i)/PDE were also associated with a high level of necrosis.


Spin-echo M-mode NMR imaging.

A nuclear magnetic resonance (NMR) imaging and display method for the observation of the continuous motion of objects is presented. By modifying a line scan technique, the spin-density distribution along a line is displayed in succession. Although spatial information is limited to only one dimension, the motion of the object is recorded at intervals of 55 ms by using a commercially available NMR imaging system. In a phantom study, this method yielded accurate velocity measurements along a single axis. When the method was applied to the human chest, an image analogous to that of M-mode echocardiography was obtained. This method, which can be called spin-echo M-mode NMR imaging, approaches the functional analysis of cardiac wall motion in regions where echocardiography is not possible. The effects of respiratory motion on the left ventricular wall were recorded in addition to its intrinsic contractile motion in an image obtained along a line parallel to the cranio-caudal axis of the body. The advantages of this method to assess cardiac wall motion in a patient with an arrhythmia were also demonstrated.


Signal-to-noise, resolution, and bias function analysis of asymmetric sampling with zero-padded magnitude FT reconstruction.

This report describes NMR image effects due to sampling asymmetry when using zero-padded magnitude FT reconstruction. With this method, the MTF is not flat over the spatial frequency passband, so resolution cannot be accurately described by a single variable such as voxel size. At small to moderate asymmetry, shortened (reduced window duration) asymmetry provides increased S/N and decreased resolution, whereas shifted (constant window duration) asymmetry yields essentially constant S/N with simultaneously increased and decreased resolution. A bias function expression describes image distortion due to sampling in terms separable from the imaged object. The analyses are consistent with previous descriptions of perceived image differences related to data asymmetry.


Characteristics of extracellular sodium relaxation in perfused hearts with pathologic interventions.

Sodium spectroscopy and imaging sequences designed to emphasize fast T2 decay or the multiple quantum signal have previously demonstrated a high contrast between normal and pathologic tissue which may be due to changes in intracellular versus extracellular sodium distribution. Since alterations in the amount of signal with fast T2 decay have previously been shown to occur with changes in intracellular sodium content, this study investigated the fast T2 relaxation characteristics of extracellular sodium during pathologic interventions on nonsubmerged perfused rat hearts. T2 data on total sodium content were obtained while global ischemia (stopping all perfusate flow) and extracellular edema (due to long perfusion times) were induced in the heart. The data were fit to a biexponential, with Mf(T2f) the magnitude (time constant) of the fast component of decay. Mf increased significantly in both pathologies (to 319 +/- 26%, n = 3, of baseline for ischemia and to 527 +/- 284%, n = 3, of baseline for edema); the increase with edema was demonstrated to be due to extracellular sodium by intermittently perfusing the heart for a short period with shift reagent. When shift reagent was not used until the conclusion of the edema experiment, Mf increased to 169 +/- 35% of baseline, also due mainly to extracellular sodium. T2f did not exhibit any trends with these experiments, with values ranging from 1.7 to 5.5 ms. We believe that these results indicate that compartmental sodium content will most likely not be quantifiable in pathologic states in the heart with relaxation-based techniques. However, correlations between the pathologic state of the tissue and the sodium NMR signal obtained with pulse sequences or images that emphasize a particular aspect of relaxation may prove to be useful.


31P NMR spectroscopic study of the effects of gamma-irradiation on RIF-1 tumor cells perfused in vitro.

In order to examine the mechanisms underlying radiation-induced changes in phosphorus metabolite levels observed in RIF-1 tumors in vivo, RIF-1 cells in culture were perfused for up to 70 h following gamma-irradiation with 0-25 Gy and monitored continuously by 31P NMR spectroscopy at 8.5 T. Cells immobilized in the sample volume by incorporation into calcium alginate beads were bioenergetically stable, but did not replicate at the cell density used. Following an initial increase in PCr and NTP, which occurred in both control and irradiated cells, a dramatic decline in high-energy phosphates was detected beginning 24-30 h after irradiation with 15 or 25 Gy. In contrast, unirradiated cells or cells treated with 10 Gy remained metabolically stable for up to 72 h. The metabolic changes induced by irradiation of the cultured cells, which reflected cell death and lysis, were distinctly different from those observed in RIF-1 tumors in vivo during the same postirradiation time interval--an increase in high-energy relative to low-energy phosphates. This suggests that the spectral changes in vivo do not result from direct modification of cellular energy metabolism by radiation injury.


Automatic in vivo NMR data processing based on an enhancement procedure and linear prediction method.

A new data processing method for in vivo NMR data quantitation is presented. This method (EPLPSVD) is based on the enhancement procedure (EP) proposed by J. A. Cadzow (IEEE Trans. Acoust. Speech Signal Process. 36, 49, 1988) followed by the usual linear prediction method using the singular value decomposition (LPSVD). The evaluation of this protocol is performed using synthesized 31P signals with different signal-to-noise ratios. A Monte-Carlo simulation as a function of signal-to-noise ratio (SNR) has proved that EPLPSVD leads to unbiased estimated values of parameters. Then the Cramer-Rao method yields reliable confidence intervals for the estimated parameters. The estimates of NMR parameters using EPLPSVD are reliable and accurate for SNR > or = 1.2 while the LPSVD method failed for SNR < or = 4. This protocol is applied to analyze automatically a series of 31P free induction decays obtained from the human gastrocnemius muscle during exercise. Spectral parameters with their confidence intervals, curves of relative intensity variations in phosphocreatine and inorganic phosphate, and pH curves are automatically provided.


Improved cardiac gating and ventilation timing in animal experiments.

In this work we present an improved solution for cardiac gating and ventilation timing in in vivo spectroscopic and imaging experiments. This approach makes use of a pulse conditioner to extract primary timing signals from noisy and fluctuating input signals. A timing controller is then used to set all additional timing outputs. Full feedback control is utilized in this timing controller to optimize both magnetic resonance and respiratory timing. Feedback control also helps ensure that timing errors will not occur during acquisition.


A piezoelectric respiratory monitor for in vivo NMR.

This report describes a simple electronic device employing a piezoelectric element which serves as a sensitive detector of motion. The device is useful as a monitor of respiratory motion for nuclear magnetic resonance animal experiments in vivo. It can also provide a trigger pulse for respiratory gating experiments.


Changes in probe sensitivity during NMR spectroscopic studies of the perfused rat heart: a warning.

During NMR experiments on isolated, perfused rat heart, we observed a 57% change in probe sensitivity when the perfusion buffer surrounding the heart was replaced by either a low-ionic-strength mannitol solution or air and the heart was made ischemic. Such changes in sensitivity, should they go unrecognized, would result in substantial quantification errors.


A simple procedure for obtaining high-quality NMR spectra of semiquantitative value from small tissue specimens: cervical biopsies.

The handling of small tissue biopsy samples (< 100 microliters) for NMR investigations poses special problems. Optimal and stable positioning of the samples within the sensitive volume of the radiofrequency coil can be achieved by inserting the sample in a capillary. Methods for quantitation of the spectral information from samples requiring histological evaluation after the NMR experiment are discussed, in particular with respect to cervical biopsies.


Real-time observation of transient focal ischemia and hyperemia in cat brain.

Gradient-recalled echo-planar (T2*-weighted) imaging was used to noninvasively monitor regional blood oxygenation state changes in real time during transient episodes of focal ischemia in cat brain. Varying ischemic intervals (12 s to 30 min) were caused by middle cerebral artery occlusion. A rapid signal drop was noted upon occlusion, due to deoxygenation of static blood in the ischemic tissues. Upon successful reperfusion, the signal intensity recovered immediately and increased above (overshot) the baseline level before slowly returning to normal. The "overshoot" response was strongly dependent on the duration of the ischemic interval and is thought to reflect reactive hyperemia.


Shaping the signal response during the approach to steady state in three-dimensional magnetization-prepared rapid gradient-echo imaging using variable flip angles.

A theoretical algorithm for shaping the signal response during the approach to steady state in three-dimensional magnetization-prepared rapid gradient-echo (3D MP-RAGE) pulse sequences has been developed and implemented. This algorithm derives the flip angle series required to produce specifically chosen time evolutions of the signal intensities during the data acquisition segment of 3D MP-RAGE sequences. Theoretical predictions for the cases of unshaped, uniform, and mono-exponential decay signal responses were quantitatively validated with a doped-water phantom on a 1.5-T whole-body imager and in all cases there was excellent agreement between the theoretical and experimental values. The effects of RF inhomogeneities and eddy currents on the signal response shaping were also investigated. To demonstrate the potential utility of the technique, the signal response shaping algorithm was applied to a T1-weighted 3D MP-RAGE sequence to derive the acquisition flip angle series which theoretically yields the maximum white matter/gray matter signal difference (WGSD) consistent with the chosen response shape. Images obtained from a healthy volunteer using this variable flip angle sequence were compared with 3D RF-spoiled steady-state gradient-echo images obtained in the same total imaging time. The 3D MP-RAGE images demonstrated a 41% increase in the WGSD-to-noise ratio. These initial very promising results indicate that with further refinement to eliminate some intensity artifacts, the variable flip angle 3D MP-RAGE technique may, with respect to certain image properties, provide considerable improvements over currently available 3D gradient-echo imaging techniques.


RF current density imaging in homogeneous media.

MRI has proven capable of imaging quasistatic volume current densities in electrolytic and biological media. In this paper, the feasibility of extending the method to image RF current density at the Larmor frequency is studied. RF current imaging could be relevant to MR power absorption and safety and to hyperthermia analysis, as well as creating dielectric and conductivity-dependent tissue contrast. The approach is to deliberately induce or inject RF currents in a sample synchronous with an MR pulse sequence and measure the resulting transverse RF magnetic field components. Current density is extracted by computing the curl of the magnetic fields. The preliminary theory has been developed for uniform media where both displacement and conduction currents exist while skin effects or eddy currents are absent. If the derivative in the B0 direction of the RF magnetic field component parallel to B0 is negligible, then sufficient information exists to reconstruct the RF current density component that is parallel to B0 without rotating the sample. The relative phase of the current can also be estimated. The method has been proven feasible by successfully imaging a uniform 85.6-MHz current density in a salt water phantom. The experiment conforms closely to capacitively coupled hyperthermia heating.


Fast spiral coronary artery imaging.

A flow-independent method for imaging the coronary arteries within a breath-hold on a standard whole-body MR imager was developed. The technique is based on interleaved spiral k-space scanning and forms a cardiac-gated image in 20 heartbeats. The spiral readouts have good flow properties and generate minimal flow artifacts. The oblique slices are positioned so that the arteries are in the plane and so that the chamber blood does not obscure the arteries. Fat suppression by a spectral-spatial pulse improves the visualization of the arteries.


A new frontier of blood imaging using susceptibility effect and tailored RF pulses.

In MRI, image contrast can be controlled by use of the susceptibility effect if an object contains paramagnetic substances. The localized linear gradient dephases spins in the voxel, leading to phase cancellation and thus reduced signal. This signal void phenomenon, can be exploited if the intrinsic linear gradient is either enhanced or compensated by externally applied RF generated phase distributions. In this paper, a new concept which utilizes the susceptibility effect through the use of tailored RF pulses is proposed. As potential applications of the method, two different types of tailored RF pulses are introduced: one for the enhancement of the susceptibility effect and the other for the correction of the susceptibility artifact, respectively. The former, for example, can be applied to angiography utilizing the paramagnetic property of deoxygenated blood, suggesting a new avenue for the angiography which, for the first time, is not based on flow, although the method is currently limited to imaging of venous blood or venography. Both a theoretical study of the method and experimental results are reported.


Sodium ion transport in rat hearts during cold ischemic storage: 23Na and 31P NMR study.

The success of heart transplantation is limited by the negative correlation between the length of the cold ischemic storage period and the quality of functional recovery. We use 23Na, 31P NMR spectroscopy, and hemodynamic parameters to describe temperature-dependent changes in sodium influx and the concentration of phosphorus high-energy compounds during different storage periods. Perfusion with Krebs-Henseleit solutions containing Dy(TTHA)3- permitted discrimination of intra- and extracellular sodium during cold ischemic storage. The 23Na NMR visibilities under the acquisition and processing parameters used in our experiments were 40 +/- 4% for the intracellular compartment and 97 +/- 11% for the extracellular compartment. At 4 degrees C, the intracellular Na+ accumulation exceeded that observed at 15 and 22 degrees C. The ATP and PCr depletion rates were much lower at 4 degrees C and the left ventricular contractility was higher after longer periods of storage, as the storage temperature decreased. The intracellular Na+ concentration cannot serve as a marker for the postischemic recovery probability. The relative activity of the Na/K ATPase pumps is not correlated with the preservation success. However, intracellular sodium ion accumulation is a major factor in the time lag of the reperfusion recovery.


Projection reconstruction techniques for reduction of motion effects in MRI.

Projection reconstruction (PR) techniques are shown to have intrinsic advantages over spin-warp (2DFT) methods with respect to diminished artifacts from respiratory motion. The benefits result from (1) portrayal of artifacts as radial streaks, with the amplitude smallest near the moving elements; (2) streak deployment perpendicular to the direction of motion of moving elements and often residing outside the anatomic boundaries of the subject; (3) inherent signal averaging of low spatial frequencies from oversampling of central k-space data. In addition, respiratory-ordered view angle (ROVA) acquisition is found to diminish residual streaking significantly by reducing interview inconsistencies. Comparisons of 2DFT and PR acquisitions are made with and without ROVA. Reconstructions from magnitude-only projections are found to have increased streaks from motion-induced phase shifts.


Phase-scrambled RF excitation for 3D volume-selective multislice NMR imaging.

An RF excitation technique with which one can improve the effective dynamic range of the receiver and reduce the interference between slices for 3D volume-selective multislice MRI is described. The basic idea of the technique is to use phase scrambling in conjunction with slice encoding through the use of RF pulses. The spins in each slice are encoded by RF pulses which have the scrambled as well as slice-encoded phase components along the slice-selection direction. The scrambled, or randomly distributed, phase reduces the peak signal intensity, thereby reducing the dynamic range of the signal. Since the proposed technique utilizes RF slice encoding together with phase scrambling, interslice image interference is greatly reduced and the dynamic range is improved. In addition, the method has several advantages such as a reduction in the power requirement for the RF pulses and the elimination of the necessity for hardware such as nonlinear gradient coils.


31P transverse relaxation times of the ATP NMR signals of human skeletal muscle in vivo.

31P MRS examinations of the calf muscles of 12 healthy volunteers were performed to determine T2 of the coupled ATP signals by using the 90 degrees-TE/2-2662-TE/2-acq selective spin-echo sequence for elimination of phase and intensity distortions. The T2 relaxation times obtained are much longer than those usually assumed: gamma-ATP, 93 ms; alpha-ATP, 74 ms; beta-ATP, 75 ms.


Phosphoarginine-adenosine triphosphate exchange detected in vivo in a microscopic nematode parasite by flow 31P FT-NMR spectroscopy.

In vivo flow 31P NMR spectroscopy of a microscopic nematode, Steinernema carpocapsae, is described. Long-term viability was maintained during analysis by continuous circulation of an oxygenated suspension of the parasite through an NMR spectrometer. Saturation transfer and inversion recovery were employed under flowing conditions to investigate the kinetics of phosphoarginine<-->adenosine triphosphate exchange. The kinetic constants for the forward and reverse reactions were 0.37/s and 1.45/s, respectively. This report is the first to demonstrate a functional phosphagen kinase in the metabolism of a parasitic helminth.


Cardiac tagging with breath-hold cine MRI.

A method is presented for measuring myocardial deformation in a breath-hold with tagged cine MRI. Tagged cine images of human hearts are obtained in arbitrary oblique planes on a standard imager with as few as four heartbeats. The scan time has been reduced 16- to 64-fold from previous techniques.


Magnetic resonance neurography.

We have made cross-sectional image "neurograms" in which peripheral nerve has a greater signal intensity than that of other tissue. Neurographic images of the rabbit forelimb were obtained using a spin-echo magnetic resonance imaging (MRI) technique that combines fat suppression and diffusion weighting. After fat suppression the nerve shows up in relative isolation and is brighter than the surrounding tissue due to its longer T2 relaxation time of approximately 50 ms compared to approximately 27 ms for muscle. The addition of pulsed gradients for diffusion weighting of the MR signal further enhances the intensity of the nerve signal relative to that of surrounding muscle tissue. The greater diffusional anisotropy of nerve tissue (D parallel/D perpendicular = 3.1) compared to that of muscle (D parallel/D perpendicular = 1.9) allows further enhancement of the nerve by a subtraction of two diffusion-weighted images, one with the gradients oriented parallel and one with the gradients oriented perpendicular to the nerve orientation. We show that by manipulation of the MRI parameters, either echo time or pulsed gradient strength, the nerves can be made to show up as the most intense feature. This verifies the feasibility of generating three-dimensional "neurographic" images, analogous to angiograms, but which demonstrate the peripheral nerve tracts in apparent isolation.


Pulmonary arterial brain natriuretic peptide concentration and cardiopulmonary hemodynamics during exercise in patients with essential hypertension.

Brain natriuretic peptide (BNP) is secreted through the coronary sinus of the human heart. The purpose of this study was to determine whether BNP secretion from the heart is stimulated by exercise and to examine the relationship between pulmonary arterial BNP concentrations and hemodynamic measurements, especially cardiopulmonary hemodynamics, during exercise in patients with essential hypertension. The exercise protocol consisted of three fixed workloads (25, 50, 75 W) on a bicycle ergometer in the supine position. The mean pulmonary arterial BNP level at rest was 14.8 +/- 4.1 pg/mL, and BNP values gradually increased with higher stages of exercise. At the maximum exercise stage, the BNP value increased to 40.9 +/- 6.5 pg/mL. Close correlations of pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) with pulmonary arterial BNP level were observed at four points at rest and during each stage of exercise. In contrast, heart rate, mean blood pressure, cardiac index (CI), and stroke index (SI) were not correlated with BNP values. Results suggest that cardiac secretion of BNP was increased during exercise in essential hypertensive subjects, and the observed increase of BNP may be related to elevated PAP and PAWP. The enhancement of BNP secretion during exercise in these patients may reflect increased redistribution of blood to the cardiopulmonary compartment.


Effects of different lipid substrates on glucose metabolism in normal postabsorptive humans.

We investigated the effects on glucose metabolism of the infusion of either long-chain triglycerides (LCT), a mixture of long-chain and medium-chain triglycerides (MCT/LCT), D-beta-hydroxybutyrate (D-beta-OHB), or saline in normal postabsorptive subjects. Plasma insulin, C-peptide, and glucagon concentrations were unchanged in all groups. LCT and MCT/LCT infusions increased levels of plasma free fatty acids (FFA) compared with those of the saline group, whereas D-beta-OHB decreased them. Plasma ketone body concentrations were higher during the D-beta-OHB and triglyceride infusions than during the saline test. Glucose concentrations and appearance (Ra) and disappearance (Rd) rates were not modified during saline infusion. Glucose levels decreased only in the D-beta-OHB and MCT/LCT groups (P < .05), whereas they were unchanged during LCT infusion. Glucose Ra decreased slightly by 15% to 17% in LCT, MCT/LCT, and D-beta-OHB groups (P < .05 v saline). Glucose Rd decreased by 14% to 16% in each lipid-infusion group (P < .05 v saline). Glucose clearance rates decreased by 14% only in the LCT group (P < .001). Glucose oxidation rates did not change significantly during the lipid substrate infusions compared with saline infusion. In conclusion, (1) the effects of fatty acids on glucose metabolism appear to depend on the fatty acid chain length, since only LCT infusion significantly impaired glucose utilization; and (2) in subjects with normal endocrine pancreas function, we found no adverse effects of a short-term increase in lipid substrate availability on glucose production rate and concentration.


Metabolic availability of oral glucose during exercise: a reassessment.

The purpose of this study was to reassess the metabolic availability of oral glucose during prolonged exercise in man, using 13C-labeling and a computation procedure (J Appl Physiol 69:1047-1052, 1990) that correctly takes into account changes in isotopic composition of CO2 arising from oxidation of endogenous substrates (Rendo). These changes are due to glucose ingestion associated with exercise. Each of the seven subjects completed three 2-hour periods of exercise at 67% maximum oxygen consumption (VO2max) on an ergocycle, with ingestion of water (1,000 mL) or 60 g (in 1,000 mL water) of 13C-labeled glucose at two levels of enrichment (13C/12C = 1.11482% and 1.13303%). As expected, Rendo significantly increased from rest to exercise with water ingestion (1.09888% +/- .00196% to 1.09970% +/- .00175%) and with glucose ingestion (1.10002% +/- .00159%) due to changes in the respective contributions of endogenous carbohydrates and fat to energy requirements as assessed by the respiratory exchange ratio (RER). When changes in Rendo were taken into account, the estimated amount of exogenous glucose oxidized was 38.8 +/- 10.3 g. Much higher values were found when Rendo at rest or during exercise with water ingestion were used in the computation (42.3 +/- 10.3 to 65.1 +/- 20.5 g) according to the commonly used method. Examination of data in the literature indicates that the reported oxidation rate of exogenous glucose (g/min) is significantly related to oxygen consumption (VO2) (L/min; r = .592) and that exogenous glucose contributes approximately 14% to 17% to the energy requirement.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of acute elevations in plasma cortisol levels on alanine metabolism in the conscious dog.

The present study was undertaken to determine whether an acute physiological increase in plasma cortisol level had significant effects on alanine metabolism and gluconeogenesis within 3 hours in conscious, overnight-fasted dogs. Each experiment consisted of an 80-minute tracer and dye equilibration period, a 40-minute basal period, and a 3-hour experimental period. A primed, continuous infusion of [3-3H]glucose and continuous infusions of [U-14C]alanine and indocyanine green dye were initiated at the start of the equilibration period and continued throughout the experiment. Dogs were studied with (1) a hydrocortisone infusion ([CORT] 3.0 micrograms.kg-1.min-1, n = 5), (2) hydrocortisone infused as in CORT, but with pancreatic hormones clamped using somatostatin and basal intraportal replacement of insulin and glucagon (CLAMP+CORT, n = 5), or (3) saline infusion during a pancreatic clamp (CLAMP, n = 5). Glucose production and gluconeogenesis were determined using tracer and arteriovenous difference techniques. During CLAMP, all parameters were stable except for a modest 67% +/- 6% increase in gluconeogenic conversion of alanine to glucose and a 53% +/- 26% increase in gluconeogenic efficiency. When plasma cortisol levels were increased fourfold during CLAMP+CORT, there was no change in the concentration, production, or clearance of glucose. Gluconeogenic conversion of alanine to glucose increased 10% +/- 34% and gluconeogenic efficiency increased 65% +/- 43%, while net hepatic alanine uptake (NHAU) increased 60% +/- 19% and hepatic fractional extraction of alanine increased 38% +/- 12%. Cortisol did not cause an increase in the arterial glycerol level or net hepatic glycerol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)


Beta-cell hypersecretion and not reduced hepatic insulin extraction is the main cause of hyperinsulinemia in obese nondiabetic subjects.

Obesity is characterized by peripheral hyperinsulinemia, for which either beta-cell hypersecretion, diminished hepatic insulin extraction, or both may be responsible. To clarify this issue, we investigated insulin secretion and hormone hepatic extraction in 18 nondiabetic obese patients (body mass index [BMI], 39 +/- 1.3 kg/m2) and 18 healthy, lean control subjects (BMI, 21.3 +/- 0.7 kg/m2). Body fat distribution was calculated by measuring the waist to hip ratio (WHR). A highly reduced tissue insulin sensitivity (2.4 +/- 0.5 v 9.5 +/- 1.5 10(4).min-1/[microU/mL], P > .0005) and glucose effectiveness, ie, glucose's ability to stimulate its own disappearance at basal insulin (16 +/- 2 v 30 +/- 3 10(3).min-1, P > .005), were found in the overweight subjects compared with the controls. The basal (76 +/- 14 v 37 +/- 4 pmol/L/min) and total (377,848 +/- 5,562 v 16,864 +/- 1,850 pmol/L) prehepatic insulin secretion and the basal (15 +/- 2 v 7 +/- 0.7 pmol/L/min) and total (8,286 +/- 2,009 v 2,840 +/- 210 pmol/L) posthepatic insulin delivery were significantly higher in the overweight subjects compared with the controls (P < .005), whereas the mean hepatic insulin extraction did not differ (77.8% +/- 2.6% v 79.5% +/- 2.6%). A significant inverse correlation was found between the hepatic insulin extraction and the WHR (r = .5, P > .04), signifying the importance of fat distribution in insulin metabolism. The obese patients were subdivided into two subgroups according to their glucose tolerance; eight patients exhibited a normal tolerance and the remaining 10 were intolerant.(ABSTRACT TRUNCATED AT 250 WORDS)


Polydisperse low-density lipoproteins in hyperalphalipoproteinemic chronic alcohol drinkers in association with marked reduction of cholesteryl ester transfer protein activity.

Long-term heavy alcohol intake is well known to increase serum high-density lipoprotein (HDL) cholesterol concentrations. Epidemiologic studies have shown that the protective effect of alcohol intake against coronary heart disease (CHD) is observed in moderate alcohol drinkers, but not in heavy ones. To clarify whether heavy alcohol intake may cause abnormalities in lipoprotein metabolism, we analyzed the plasma lipoproteins in eight male chronic heavy alcohol drinkers with marked hyperalphalipoproteinemia. Although their serum HDL cholesterol levels were remarkably high, ranging from 2.67 to 3.58 mmol/L, three patients had CHD and corneal arcus was present in seven patients. Cholesteryl ester transfer protein (CETP) activity was reduced in all subjects (7.3% +/- 4.2%/10 microL/18 h in alcohol drinkers v 20.5% +/- 2.4%/10 microL/18 h in control; mean +/- SD, P < .001). The CETP mass levels were also markedly reduced in these subjects. The analysis of low-density lipoprotein (LDL) on nondenaturing polyacrylamide gradient gel electrophoresis revealed that four subjects with severely low CETP activity (< 25% of control) had polydisperse LDLs, similar to those observed in genetic CETP deficiency. The other four subjects with approximately half the normal CETP activity had homogeneous but smaller-sized LDLs, as compared with control subjects. Particle size of HDL was larger than that of normal control HDL in all subjects. After cessation of alcohol intake, plasma HDL cholesterol levels were decreased and LDLs became more homogeneous and normal in size, in parallel with elevation of CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum cholesterol and lipoprotein concentrations in mothers during and after prolonged exclusive lactation.

The effect of exclusive lactation on lipid levels was investigated by evaluating serum concentrations of total and lipoprotein cholesterol, triglyceride (TG), and apoprotein (apo) B in mothers during and after exclusive, prolonged lactation. Serum total cholesterol concentrations were measured at delivery (n = 195), at 2 (n = 165), 6 (n = 119), 9 (n = 74), and 12 months (n = 32) of lactation, and 2 months (n = 27) after ending this exclusive lactation. In a subgroup of 34 mothers, serum levels of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein 2 (HDL2), HDL3, and LDL apo B were determined at 2, 6, 9, and 12 months of lactation. The mean value of serum total cholesterol concentrations decreased from 6.2 +/- 0.12 (SEM; n = 195) at delivery to 4.8 +/- 0.1 mmol/L (n = 116) at 6 months of exclusive lactation (P < .001). The average decrement in total cholesterol level was 0.80 mmol/L (P < .001) from delivery to 2 months of lactation and 0.55 mmol/L (P < .001) from 2 to 6 months of lactation, and levels were stable thereafter. In the 27 mothers who were exclusively breast-feeding their infants at 9 months of lactation and whose serum cholesterol levels were measured 2 months after the end of lactation, cholesterol levels increased rapidly to 5.7 +/- 0.21 mmol/L (P = .001). In the subgroup of 34 mothers who were examined more closely, the course just described was also true for serum TG, LDL and VLDL cholesterol, and LDL apo B levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of dietary composition on energy expenditure during recovery of body weight in the rat: implications for catch-up growth and obesity relapse.

The influence of dietary composition on whole-body energetics was examined during the first 2 weeks of isocaloric refeeding after low food intake in a rat model. The high energetic efficiency and energy partitioning toward fat accretion characteristic of this refeeding period were unaltered by (1) dietary fat levels varying between 6% and 30% of energy intake; (2) protein levels between 15% and 40%; (3) carbohydrate types (glucose v fructose v sucrose v starch v unrefined carbohydrate); and (4) diets containing 30% fat but differing in fatty acid composition (long-chain triglycerides [LCT] v medium-chain triglycerides [MCT] v oleic v linoleic v alpha-linolenic metabolites eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] omega-3 fatty acids). Changes were only observed for extreme diets, ie, those deficient in protein or very high in fat. Low-protein diet was the only condition in which the high metabolic efficiency characteristic of the refeeding period was partially suppressed, and this occurred despite a lack of concomitant reduction in body fat deposition. On the contrary, with high-fat diets (> 30% of dietary energy consumption) the elevated efficiency was further increased, an effect that was only partially accounted for by the lower energy cost of body fat gain from high-fat diets. These studies indicate that during body weight recovery, the mechanisms underlying the adaptive increase in metabolic efficiency favoring the replenishment of body fat stores override any effect of food type on thermogenesis, and suggest some convergence in the controlling neural pathway. The implications of these findings vis-a-vis nutritional rehabilitation (catch-up growth) and obesity relapse are discussed.


Partial enterectomy in the rat does not diminish muscle glutamine production.

The hypothesis was posed that consumption of the amino acid glutamine by the splanchnic tissues is an important regulating mechanism for its production in muscle. Therefore, glutamine consumption or production in portal-drained viscera (PDV), liver, and hindquarter was measured by determining fluxes and intracellular concentrations after 80% enterectomy or SHAM operation in rats. Moreover, fluxes and intracellular concentrations of several other amino acids, ammonia, and liver urea production were determined concomitantly. After enterectomy, arterial glutamine concentration was increased, PDV glutamine consumption was decreased by 77%, and liver glutamine consumption was unchanged compared with values in SHAM-operated rats. Although hindquarter glutamine production remained unchanged after enterectomy, intracellular glutamate concentration (glutamine precursor) was lower, suggesting that enterectomy induces changes in muscle metabolism without changing the flux of glutamine. For the remaining gut, it was calculated that after enterectomy glutamine consumption per gram remaining gut tissue increased. These results cast doubt on the hypothesis that diminished splanchnic glutamine uptake can reduce muscle glutamine production.


Resting energy metabolism and cardiovascular disease risk in resistance-trained and aerobically trained males.

The objectives of this study were (1) to examine differences in resting metabolic rate (RMR) and cardiovascular risk factors among aerobically trained (n = 36), resistance-trained (n = 18), and untrained (n = 42) young males; and (2) to investigate the influence of body composition, dietary intake, and VO2max as possible modulators of differences in cardiovascular risk among groups. Results showed that RMR, adjusted for differences in fat-free weight (FFW), was 5% higher in aerobically trained males compared with resistance-trained males (P < .01), and 10% higher than that in untrained males (P < .01). Plasma levels of cholesterol and low-density lipoprotein cholesterol (LDL-C) were comparable between resistance-trained and aerobically trained males, but were lower (P < .05) than those in untrained males. (The percent intake of dietary fat was related to plasma cholesterol [r = .32, P < .01] and LDL-C [r = .30, P < .01].) When compared with untrained males, fasting triglyceride (TG) levels were 39% and 43% lower (P < .01) in resistance-trained and aerobically trained males, respectively. When compared with untrained males, the fasting insulin to glucose ratio (I/G) was 45% and 53% lower (P < .01) in resistance- and aerobically trained males, respectively. Mean arterial pressure (MAP) was 7% lower (P < .01) in aerobically trained compared with untrained males. Statistical control for differences in percent body fat or percent intake of dietary fat diminished the differences among the groups for plasma lipids, blood pressure, and the I/G ratio. We conclude that aerobically trained and resistance-trained males have higher resting energy requirements independent of FFW compared with untrained males. Aerobically trained and resistance-trained young males have comparable and favorable cardiovascular disease risk profiles compared with untrained males, and this appears to be related to their low level of adiposity and low intake of dietary fat.


Postprandial lipoprotein(a) response to a single meal containing either saturated or omega-3 polyunsaturated fatty acids in subjects with hypoalphalipoproteinemia.

We have recently reported that the apolipoprotein (apo) B-100-apo(a) complex, the protein moiety of lipoprotein(a) [Lp(a)], has a high affinity for triglyceride(TG)-rich particles (TRP) and that this complex can affiliate with endogenous TG-rich lipoproteins. To shed more light on the apo B-100-apo(a) complex associated with plasma TRP during postprandial lipidemia, we fed five male subjects presenting with primary hypoalphalipoproteinemia (HP) and four male controls a single fat meal (60 g/m2) containing saturated fatty acids (SFA) and, 6 weeks later, an isocaloric meal containing omega-3 polyunsaturated fatty acids. The subjects were phenotyped for plasma Lp(a) and apo C-III levels, apo(a) and apo E isoforms, and lipoprotein lipase and hepatic lipase activities. Vitamin A was included in the meal as a marker of intestinally derived TRP. Following the SFA meal, three of the HP subjects showed a decrease in plasma levels of Lp(a) that lasted 10 to 12 hours in the presence of an increased hypertriglyceridemic response. Two HP subjects who had low preprandial lipoprotein lipase activity and elevated plasma apo C-III levels showed an increase in plasma Lp(a) levels along with the hypertriglyceridemic excursion. However, in all cases, inclusive of the controls, there was an elevation in plasma levels of TRP of Sf greater than 1,000 that contained apo B-100-apo(a) 6 to 8 hours after the meal. This TRP excursion appeared not to be related to the basal levels of plasma Lp(a), high-density lipoprotein (HDL) cholesterol, TGs, or apo(a) and apo E isoforms, and it did not coincide with the retinyl ester peak.(ABSTRACT TRUNCATED AT 250 WORDS)


Intrapancreatic islet transplantation in experimental diabetes in the rat.

Pancreatic islets have been transplanted successfully to a variety of organs except the pancreas. Since this organ is the most physiologic recipient for islets in rodents with chemically induced diabetes, we have placed neonatal islets intrapancreatically in highly inbred Lewis rats with streptozotocin (ST) diabetes. Transplantation of 2,000 neonatal islets into the pancreas of diabetic rats reversed diabetes within 2 weeks in all of the treated rats (seven of seven). The same success rate was obtained using the same number of islets placed under the kidney capsule in 11 recipients. Although cured of their diabetes, rats in both groups with inadequate islet-cell mass were not able to produce glucose tolerance tests equal to those observed in normal animals. Higher insulin levels were measured in the rats receiving islets under the kidney capsule, as compared with those placed intrapancreatically. In summary, syngeneic islet transplants to the pancreas of ST-diabetic rats are successful in reversing the diabetic state. This model may be useful to the study of islet function after islet transplants into their natural environment.


Normal plasminogen activator inhibitor levels at long-term follow-up after jejuno-ileal bypass surgery in morbidly obese individuals.

Forty-five patients who had been subjected to jejuno-ileal bypass (JIB) surgery for morbid obesity and 10 obese nonsurgery subjects were studied. The former group was examined 14 to 20 years after surgery, and was found to have lower mean plasminogen activator inhibitor type 1 (PAI-1) activity (8.4 v 32 U/mL, P < .001), tissue plasminogen activator (tPA) antigen concentrations (7.2 v 12 micrograms/L, P < .01), body mass index (BMI), and fasting plasma insulin, triglyceride, and cholesterol levels. The PAI-1 levels were correlated with BMI, waist to hip ratio, and insulin, triglyceride, and cholesterol levels. Thus, previously obese subjects have normal PAI levels 14 to 20 years after treatment with JIB surgery, in contrast to the high PAI-1 levels in nonsurgery obese subjects.


A high-monounsaturated-fat/low-carbohydrate diet improves peripheral insulin sensitivity in non-insulin-dependent diabetic patients.

It is commonly believed that high-carbohydrate (CHO) diets improve peripheral insulin sensitivity; however, this concept is based on anecdotal evidence. Furthermore, it has been demonstrated that in non-insulin-dependent diabetic patients treated with insulin, a high-monounsaturated-fat (MUFA) diet is more effective than a high-complex-CHO diet in reducing blood glucose levels. The aim of our study was to compare the effect of a high-MUFA diet and a high-CHO diet on peripheral insulin sensitivity and metabolic control in non-insulin-dependent diabetic patients. Ten non-insulin-dependent diabetic patients aged 52 +/- 8 years with a body mass index (BMI) of 26.7 +/- 3.5 kg/m2 who were being treated with diet alone (n = 5) or with diet plus glibenclamide (n = 5) were randomly assigned to a 15-day period of either a high-MUFA/low-CHO diet (CHO, 40%; fat, 40%; protein, 20%; fiber, 24g) or a low-MUFA/high-CHO diet (CHO, 60%; fat, 20%; protein, 20%; fiber, 24g) and were then crossed-over to the other diet. Diets were similar in their content of monosaccharides, disaccharides, and saturated fats, and were administered to the patients in a metabolic ward. The dosage of hypoglycemic drugs was maintained at a constant level throughout the study. With the high-MUFA/low-CHO diet, a decrease in both postprandial glucose (8.76 +/- 2.12 v 10.08 +/- 2.76 mmol/L; P < .05) and plasma insulin (195.0 +/- 86.4 v 224.4 +/- 75.6 pmol/L; P < .02) levels was observed. Furthermore, fasting plasma triglyceride levels were reduced after the high-MUFA fat/low-CHO diet (1.16 +/- 0.59 v 1.37 +/- 0.59 mmol/L; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)


Correlation between residual beta-cell function and age at onset of spontaneous diabetes in Long Evans Tokushima lean rats.

We studied the natural course of disease in spontaneously diabetic rats, Long Evans Tokushima Lean (LETL) rats, to determine whether it showed similar pathogenetic heterogeneity to that of patients with insulin-dependent diabetes mellitus (IDDM) with regard to the relationships between age at onset, rapidity of disease progress, and degree of beta-cell function at the time of its manifestation. Type 1 diabetes developed in 35 rats (6.3%) between 40 and 140 days of age. Eight rats that became diabetic at age 69 days or less were more severely ketotic at the time of first detection of glycosuria and showed more rapid deterioration than seven rats that became diabetic later after birth (mean plasma 3-hydroxybutyrate levels, 4,707 +/- 1,215 pmol/L v 1,390 +/- 859 pmol/L; mean +/- SEM, P < .01). The mean plasma levels and pancreatic content of immunoreactive insulin (IRI) of the early onset rats, 47 +/- 13 pmol/L and 19 +/- 12 pmol/g tissue weight, were significantly lower (P < .01) than the corresponding values of the late-onset rats, 262 +/- 52 pmol/L and 348 +/- 87 pmol/g tissue weight, respectively. Both values were markedly lower than the mean values of 25 nondiabetic LETL rats, 976 +/- 122 pmol/L and 3,488 +/- 628 pmol/g tissue weight. Plasma immunoreactive glucagon (IRG) levels were significantly increased in the diabetic groups (early onset, 57 +/- 13 pmol/L; late-onset, 51 +/- 12 pmol/L; nondiabetic, 18 +/- 1 pmol/L; P < .01). These changes in pancreatic hormone levels of the early onset and late-onset rats were compatible with the histological features of their pancreatic islets.(ABSTRACT TRUNCATED AT 250 WORDS)


High-density apolipoprotein A-I and A-II kinetics in relation to regional adiposity.

High-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations decrease with increasing central adiposity. The present study investigated possible mechanisms for these effects by examining the relationship between body mass index, regional adiposity, and HDL apo A-I and A-II metabolism. Fifteen sedentary men and 10 male endurance athletes aged 22 to 44 served as subjects. HDL apo A-I and A-II metabolism was examined using 125I-labeled autologous HDL. Chest and thigh skinfold thickness and the ratio of chest to thigh skinfold thickness were used as indices of regional adiposity. The relationship of adiposity to HDL metabolism was examined using correlational and multiple regression analysis. In both subject groups, the fractional catabolic rate of apo A-I and A-II increased with increasing chest skinfold thickness and chest to thigh skinfold ratio (.43 < r2 < .66). This effect was partially independent of triglyceride or HDL cholesterol concentrations. Apo A-I and A-II fractional catabolic rates increased with increasing body mass index only in the sedentary men. Concentrations and synthetic rates (mg.d-1.kg-1) of apo A-I and A-II were not consistently related to body mass index or regional adiposity. Peripheral adiposity assessed by thigh skinfold thickness was not correlated with any parameter of apo metabolism. We conclude that HDL apo A-I and A-II catabolism increases with increasing central adiposity.


Naturally occurring SLE anti-DNA antibodies recognize unique conformation on DNA-lysine photoadduct.

Native calf thymus DNA has been covalently modified with lysine under UV-A light. Human autoantibodies on purification through affinity column of native DNA linked to polylysyl-Sepharose 4B showed almost equal recognition of DNA and photoadduct. The recognition of DNA-lysine photoadduct by the affinity-purified autoantibodies might be helpful in understanding their origin in SLE vis-à-vis the role of positively charged amino acids in the pathogenesis of autoimmune diseases.


Temperature-sensitive immunoglobulin A-binding and dimerization of C-terminus-impaired protein Arp4 produced in Escherichia coli.

A gene for protein Arp4, an IgA receptor protein derived from Streptococcus pyogenes AP4, was expressed in Escherichia coli. The product was demonstrated to be accumulated in a periplasmic space as a polypeptide with an apparent molecular weight of 40 kDa with the deleted C-terminal membrane anchor portion of protein Arp4. This 40-kDa peptide of the C-terminus-impaired recombinant protein Arp4 produced in E. coli, designated ir-protein Arp4, was purified from a periplasmic fraction of transformants and its IgA-binding activity was analyzed. The IgA binding of ir-protein Arp4 was temperature-sensitive, that is, ir-protein Arp4 bound IgA at 4 and 25 C, but did not at 37 C. In addition, the dimerization of ir-protein Arp4 was also temperature-sensitive in parallel with temperature-dependent binding activity, suggesting that the dimerization of ir-protein Arp4 may be required for its active binding to IgA. In contrast, ir-protein Arp4 immobilized on Sepharose 4B did bind to IgA even at 37 C as well as 4 and 25 C. The immobilized ir-protein Arp4 might acquire the temperature-resistant IgA binding activity in part through the formation of a stable dimerized ir-protein Arp4 on the solid support.


Involvement of calcium in germination of coat-modified spores of Bacillus cereus T.

The effect of calcium on germination of coat-modified Bacillus cereus T spores was investigated. Coat-modified spores produced either by chemical extraction (SDS-DTT-treated spores) or by mutagenesis (10LD mutant spores) were unable to germinate in response to inosine. While SDS-DTT-treated spores could germinate slowly in the presence of L-alanine, 10LD mutant spores could not germinate at all. The lost or reduced germinability of coat-modified spores was restored when exogenous Ca2+ was supplemented to the germination media. The calcium requirement of coat-modified spores for germination was fairly specific. The simultaneous presence of germinant with Ca2+ was also required for germination of coat-modified spores. The optimal recovery of germinability was observed in the presence of 1.0 mM of calcium acetate. The calcium requirement itself was remarkably diminished under the condition in which L-alanine and a certain purine nucleoside analog, adenosine or inosine, coexisted. The lost or diminished germinability observed in SDS-DTT-treated spores or 10LD mutant spores may be attributed to the loss of calcium associated with the spore integuments.


Phage pattern and antibiotic resistance pattern of coagulase-negative staphylococci obtained from immunocompromised patients.

A total of 152 coagulase-negative staphylococcal strains were isolated from clinical samples of 14 patients hospitalized after bone-marrow transplantation in a specialized hospital ward in Hungary, during an 18-month period between 1987 and 1989. Two species, Staphylococcus epidermidis and Staphylococcus haemolyticus, predominated (each, 45%). Using Pulverer and co-workers' phage set for typing, 68% of the isolates were typable; 16 phage patterns were observed. A characteristic long pattern with phages Ph10/Ph13/Ph15/U4/U15/U16/U20/U33 /U46 appeared only in S. epidermidis, among 5 of 11 colonized patients (8.5% of all strains). Single lysis with phage Ph13 was observed in 7 of the 14 patients (49% of all strains), in species S. capitis, S. epidermidis, S. haemolyticus, S. hominis, and S. warneri. In S. haemolyticus, non-typable strains predominated (66%); this character occurred only in 2% among other species. The strains colonizing the immunocompromised patients differed from each other in phage pattern, antibiotic resistance pattern, and/or slime production. No hospital infection was suggested. On the other hand, high incidence of two well-definable phage patterns raises some relationship between phage receptors or some regulatory systems in phage multiplication and factors responsible for special colonization as common surface properties.


Structural studies of peptidoglycans in Campylobacter species.

Peptidoglycans (PG) from Campylobacter coli, Campylobacter jejuni, and Campylobacter fetus were composed of muramic acid, glucosamine, alanine, glutamic acid, and diaminopimelic acid in a molar ratio of 1.1:1:1.7:1.1:09. Thirty percent of the amino groups of diaminopimelic acid were involved in cross-linkages between peptides. During cultivation, C. coli and C. jejuni changed from a spiral to a coccoid form. In C. coli, we could isolate PG only from the spiral forms in yields of 0.8-1.2% by dry weight. C. fetus did not change to a coccoid form, and always contained PG. Thus, it is possible that the morphological transformation from the spirals to the coccoid forms of C. coli and C. jejuni is accompanied by, and probably due to, the degradation of PG.


Characterization of the dextranase purified from Streptococcus mutans Ingbritt.

We purified dextranase from the culture supernatant of Streptococcus mutans Ingbritt by procedures including ammonium sulfate precipitation, ion-exchange chromatography, and gel filtration. The molecular weight of the enzyme was estimated as 78 kDa by SDS-PAGE. The enzyme degraded dextran at the optimum pH of 5.5, but not other glucans and fructans at all. Paper chromatographic analysis revealed that the enzyme cleaved dextran by an endo-type mechanism. The enzyme was inhibited by Hg2+, Fe3+, Zn2+, and anionic detergents SDS and deoxycholic acid, but not inhibited by non-ionic detergents Triton X-100, Lubrol PX, Nonidet P-40, and Tween 80. SDS-blue dextran-PAGE analysis of the culture supernatant revealed that the enzyme activity detected in the 96 kDa band shifted gradually to the 78 kDa band during handling the supernatant. This shift was inhibited by phenylmethylsulfonyl fluoride, suggesting that the shift of the molecular size is due to proteolytic degradation of the enzyme by serine protease.


IgG subclass alterations in adult asthma.

Immunoglobulin levels were measured in serum samples of 12 black adult non-smoking asthmatic patients, 11 females and 1 male, and compared with 15 age-, sex-matched normal controls. Their total IgG, IgA and IgM levels were within the normal range. However, on quantitation of subclasses, IgG1 levels were significantly above normal, while IgG2 and IgG3 levels were significantly lower than those of controls. No significant differences were found between the two groups when IgG4 levels were compared. These studies as well as those of others suggest that immunoglobulin administration, particularly of individual subclasses, might prove to be a beneficial addition in the management of this condition.


The protective activity of tea catechins against experimental infection by Vibrio cholerae O1.

Tea catechins inhibited the fluid accumulation induced by cholera toxin in sealed adult mice. The catechins also reduced fluid accumulation by Vibrio cholerae O1 in ligated intestinal loops of rabbits. These findings suggest that tea catechins may possess protective activity against V. cholerae O1.


Should medical students be selected only from recent school-leavers who have studied science?

This study was undertaken to investigate the apparently widespread belief that in order to be successful at medical school, aspiring candidates must have a sound academic background based predominantly on the study of the natural sciences, be school-leavers aged about 18 (in the non-college educational environments such as Australia or the United Kingdom) and preferably be men. The demographic background and prior academic achievement of individual students entering the University of Newcastle Medical School between 1978 and 1989 has been reviewed and compared with their progress in medical studies. The data show that in the Newcastle medical school environment there is no significant correlation between outcome and previous study of any of the natural sciences. However, significant correlations between outcome and performance in the humanities in general, and English in particular, were found. In this regard a weak background in these subjects correlated with an increased tendency not to complete the medical course. There were no significant correlations found between outcome and age at entry, sex or levels of prior academic achievement (within the top 10% achievement band studied). In summary, the study offers no support for the current selection criteria dominating medical school admissions processes.


A comparison of the interviewing skills of first- and final-year medical students.

This study compared the communication skills of randomly chosen first- and final-year medical students. The intention was to follow up previous research, conducted over 10 years ago, into the effects of the medical curriculum on communication skills. It was hypothesized that there would be little improvement in such skills over the period of training, with the possibility that the final-year students might be less caring, empathic and supportive, more directive, and less concerned with psychosocial information. All students interviewed a simulated patient in the role of a mother of a child with cerebral palsy, where the main problems were psychological and social. The interviews were recorded on videotape and analysed by an independent observer for the presence or absence of a set of communication behaviours considered important in facilitating an effective relationship and in the exploration and understanding of the problem. The results failed to support the hypotheses. The final-year students were superior to their juniors on several measures, indicating improvements in relating to the patient in a caring, empathic, facilitative and listening manner. They also elicited more information relevant to the problem. The indications were that these final-year students were more skilled than in earlier studies, suggesting that the general change in attitudes to communications skills and the limited, but increased input into the curriculum may be having effect, even though there remains a need for considerably more training.


A skills programme for preclinical medical students.

An education programme in which preclinical medical students are introduced to common procedural skills is described. This programme is presented by a multidisciplinary health care team using short lectures, demonstrations, mannequin practice, and, in selected instances, practice on class-mate volunteers. The programme was evaluated by the students immediately following the presentation and for one class during their clinical activities one year later. The students' support for this programme was generally enthusiastic and remained undiminished upon reflection 12 months later.


Learning, retention and recall of clinical information.

A representative group of 33 medical students who were entering the junior year clerkships was tested for retention and recall of clinical information 3 months after taking an examination on the same subject. The students were not given an opportunity to review the subject. On 39 identical multiple choice test questions, the students' mean score declined 10 percentile points (P < 0.05) from that on the original examination. On 40 comparable but previously unseen questions, the mean score fell 19 percentile points from that attained 3 months earlier. On open-ended questions of clinical reasoning, a third component of the assessment, the students performed at a level similar to those on the two multiple choice tests, but with greater variability. These assessments give data on retention and recall that have not previously been reported in the literature. Correlations among individual test components were moderate (r = 0.52-0.63). There was inconsistency of individual students in scores on the component tests, and, thus, variability in performance by students was marked. Retention and recall were weakly predicted by results on an initial multiple choice examination. In addition, on a subsequent assessment of knowledge, results from different types of tests were inconsistent, suggesting that these tests evaluate different forms of competence.


Students' written reports as an essential part of a case-based learning programme in anatomy.

This paper reports on second-year medical students' views and performance on the written reports for the cases that were studied in a case-based learning programme in anatomy at the University of Otago in 1988. The mean marks for the reports for the three main categories of student entry are presented. Differential performance on the written reports relative to the case-based component of the examination held at the end of the year has been determined for each student in the class and ranked in order. The proportions of students falling in the top and bottom quartiles for the class are given. The data taken together indicate that with an intensive programme of case-based learning in 1988, optimal performance in the written reports was reached at an early stage by the graduates whereas the two undergraduate categories improved their performance towards the end of the programme.


Active and problem-based learning: two years' experience in physiology at the Medical School of the University of Barcelona.

Traditional educational methods are used in most medical schools. The introduction of new methods including active and problem-solving learning in traditional medical schools is difficult. The aims of this experiment were: (1) to introduce a self-learning system with a problem-solving approach in physiology; (2) to promote active student participation; (3) to introduce early clinical exposure; (4) to evaluate the response of the students to this experiment; and (5) to evaluate the feasibility and usefulness of a self-learning and problem-solving approach in only one discipline. Our experience has shown that it is possible to change the learning system in a traditional medical school, with good acceptance by the students and with a high level of satisfaction on the part of the teachers.


Education in family and community health: the challenge faced by a new medical school.

This paper describes the efforts of the Department of Family and Community Health at Sultan Qaboos University in providing opportunities for the development of 'hands-on' problem-solving skills appropriate for Oman. The curriculum of the Department is discussed, highlighting the unusual emphasis of this discipline in both the preclinical and clinical curriculum of the College of Medicine. The importance of continuous assessment and supervision of students is discussed. Course-work in the preclinical curriculum of the Department is kept to a minimum. Field-work forms an important part of preclinical training, where application and problem-based learning are emphasized. During the clinical years the students are exposed to an integrated series of lectures and practicals covering core knowledge in clinical medicine. Practical clinical training, over a total period of 15 weeks, takes place at a variety of sites where common problems in primary health care in Oman are handled by students under supervision.


The development and evaluation of Basic Epidemiology: Student's Text.

This paper describes the development and evaluation of a World Health Organization book Basic Epidemiology: Student's Text. This book was a response to a need identified by members of the WHO Global Environmental Epidemiology network. A draft was commented on by members of the Network and then at an editorial meeting. Two thousand copies of a pre-publication version were prepared and this version was formally evaluated by 13 teachers of introductory courses of epidemiology and less formally by members of the Epidemiology Network. A high response was received to the evaluation questionnaires; 45% of the students rated the test overall as 'very useful' and another 54% as 'useful'; many useful comments were received and were incorporated into the final version which will be published by WHO in 1993.


The contribution of general practice to medical education: expectations and fulfillment.

The aim of this study was to discover what students expected to learn during their fourth-year general practice attachment, to compare this with their GP tutors' expectations and to determine the extent to which the students' expectations were fulfilled. Questionnaires were used to gather this information; students completed them on the first and last days of the 4-week attachment and tutors shortly after the attachment. Students and their tutors had the highest expectations of the course in helping to raise awareness of the psychological and social aspects of ill health and develop clinical decision-making and management skills. At the end of the course students thought that they had gained most in these areas. Both students and tutors had lower expectations of the course helping to develop physical examination and practical skills and to improve knowledge in certain clinical areas. These were also rated lowest in terms of fulfillment. This study was carried out at a time when it is being suggested that more undergraduate teaching should take place in general practice and that this could include the teaching of practical skills and clinical subjects traditionally associated with hospital-based teaching. The results suggest that the expectations of students and GP tutors would need to be modified, as well as extra resources provided, if there is to be a shift in teaching towards the community.


Independent learning among general practice trainees: an initial survey.

Self-directed learning is a natural way for adults to learn. Vocational training for general practice is a preparation for unsupervised clinical work that will be supported, in the main, by continuing medical education. This study uses the Self-Directed Learning Readiness Scale to investigate factors influencing readiness for such learning among a sample of general practice trainees. Three principal factors emerged from analysis: enjoyment and enthusiasm for learning; a positive self-concept as a learner and a factor suggesting the possibility of a 'reproducing' orientation to learning. These factors may reflect approaches to learning in general rather than these adopted for professional learning, but offer helpful pointers for the development of both vocational training and of continuing medical education.


Assessing clinical competence at the undergraduate level.

This booklet aims to provide relevant background information and guidelines for medical school teachers in clinical departments charged with assessing the clinical competence of undergraduate students. It starts by emphasizing the difference between clinical competence and clinical performance. An approach to defining what should be assessed is outlined. The technical considerations of validity, reliability and practicability are discussed with reference to the ward- or practice-based setting and to the examination setting. The various methods available to assess aspects of competence are described and their strengths and weaknesses reviewed. The paper concludes with a discussion of the important issues of scoring and standard setting. The conclusion is reached that the quality of many current assessments could be improved. To do so will require a multi-format approach using both the practice and examination settings. Some of the traditional methods will have to be abandoned or modified and new methods introduced.


A factor in the increased risk of colorectal cancer due to ingestion of animal fat is inhibition of colon epithelial cell glutathione S-transferase, an enzyme that detoxifies mutagens.

Dietary animal fat increases the risk of colorectal cancer. A factor in the increased risk is hypothesised to result from the inhibition of isoforms of a colonic epithelial cell enzyme that detoxifies genotoxins, glutathione S-transferase, by one of the major secondary bile acids produced in the colon by fat digestion, lithocholic acid. The inhibition allows mutagens to persist in colonic epithelial cells while proliferation is stimulated by secondary bile acids, with a concomitant greater frequency of neoplasia-associated mutations than when proliferation is stimulated in the absence of the mutagens. Elements in the hypothesis include the ability of relatively low concentrations of lithocholic acid to inhibit isoforms of glutathione S-transferase found in colon epithelial cells, entry of lithocholic acid into the epithelial cells, and the correlation of neoplasia-associated colon pathology with high levels of lithocholic acid in fecal water. Higher pH values in the colonic stream are identified as exacerbating the effects of lithocholic acid by increasing its solubility. Lithocholic acid is suggested to be more inhibitory to glutathione S-transferase than the other major colonic secondary bile acid, deoxycholic acid, on the basis of inhibition-structure relationships.


Could diet be one of the causal factors of Alzheimer's disease?

Recent developments show that the brains of persons who have died from Alzheimer's Disease (AD) have a deficiency of Essential Fatty acids in one of the principal classes of phospholipids. It is hypothesized that faulty brain cell membranes resulting from this deficiency may allow passage of an enzyme into the bilayer membrane space which cuts beta amyloid precursor proteins attached to such cells at a critical intramembrane position releasing a complete sequence of beta amyloid protein into the extracellular space. Beta amyloid protein appears to be the principal active constituent of senile plaques thought to be a probable cause of brain damage resulting in AD. Treatment of persons suffering from AD with desferrioxamine, a trivalent ion chelator to remove aluminium has shown results in slowing the progression of this disease, implicating aluminium and/or other chelated substances in its etiology. Both EFA deficiency and aluminium build-up may be prevented by dietary precautions.


Sudden infant death syndrome (SIDS) and the immune response.

Vitamin E pretreatment significantly prevented E. coli-induced Disseminated Intravascular Coagulation (DIC) in rats (1). DIC, a reduction in fibrinogen and a falling platelet count and diffuse haemorrhage are part of the clinical features of Haemorrhagic Shock Encephalopathy Syndrome (HSES), recognised as a disease entity in the 1980s (2). At the SIDS Conference 1974 Reisinger described the effect of Escherichia coli (E. coli) endotoxin on the rabbit (3). An early effect was a reduction in fibrinogen and a falling platelet count, resulting in the release of relatively large amounts of the neuro-transmitter serotonin, stored in platelets (3, 4). Fibrinogen inhibited the release of serotonin from platelets (24). Serotonin is released from platelets during platelet aggregation (14). Platelet aggregation is inhibited by vitamin E (1). Serotonin is a neuro-transmitter associated with deep sleep, respiratory movements and cardiovascular collapse (3). Death at a later stage involved vascular permeability, edema and haemorrhage. After fibrin-platelet clots had formed DIC was present in lungs, kidneys and other organs (3). Medical researchers in Australia linked almost half of SIDS victims with a poisonous strain of intestinal E. coli bacteria (5). Dietary selenium in the intestinal villous tip is considered a daily modulator of cytochrome P450-dependent metabolism of drugs and toxins absorbed by intestinal mucosa (6). Villous atrophy occurs in HSES (2).


Hypotensive drugs and the cellular energetic potential.

Clinical and experimental investigations have revealed changes of the Na, K, Ca and Mg concentration in serum and cells in patients with essential arterial hypertension (EAH). Some hypotensive drugs correct, more or less, the electrolytic abnormalities at the same time as the decrease of arterial pressure. Epidemiological studies have shown a lower arterial blood pressure in populations with decreased intake of Na and an increased intake of K, Ca and Mg. However the most frequently encountered electrolyte anomaly in patients with EAH is hypophosphatemia, mainly induced by a shift of inorganic phosphate from serum into the cells. Probably the increased influx of inorganic phosphate from the serum, increases the arterial cellular energetic potential. As hypotensive drugs lead to a reduction of the inorganic phosphate shift from serum into the cells one may suggest that the obtained decrease of arterial blood pressure may be at least partially due to a diminished energetic potential of certain cells.


Understanding the role of oxyradicals in general and in toxic hepatic damage can help safer drug design.

The existence and importance of free radicals are well established both theoretically and in in vivo experiments. Methods and techniques are now available to demonstrate the formation of free radical metabolites of natural substances and xenobiotics. Theories of the biological effects of free radicals could be unified and used for a better understanding of the complex processes of the organism. Pharmacology can gain profit from this multidisciplinary approach, which helps to design safer drugs. The theories of free radicals and the results of experiments with antioxidants could help to decrease the oxidative stress caused by pharmaceutical chemicals.


Hormonal therapy for stomach cancer.

Stomach cancer is one of the major cancers in Asia. Recent advances in diagnosis and surgical techniques have improved the survival of patients with gastric cancer. But radiation and chemotherapy had limited value in promoting the outcome of patients with gastric cancer. Hormonal therapy with tamoxifen had been tried with conflicting results. Previously, we have found that estrogen receptors (ER) were present in 50% cases of Chinese patients with gastric cancers. Recently, the amplification of c-erbB-2 oncogene and its overexpression have been found to correlate with the advancement of lung, ovarian, breast and gastric cancers. In addition, estrogen has been found to inhibit the expression of c-erbB-2 through ER in breast cancer cell lines. A hypothesis is that the same event may occur in ER-positive gastric cancer cell. Thus patients with gastric cancers whose tumors were positive for both ER and c-erbB-2 gene expression, may benefit from estrogen therapy rather than tamoxifen therapy.


Nitric oxide-mediated neuronal injury in multiple sclerosis.

Although several explanations have been proposed for destruction of myelin and oligodendrocytes in multiple sclerosis, there is no proven mechanism of injury. We postulate that the autoimmune response seen in multiple sclerosis results in a cytokine-mediated increase in nitric oxide production by macrophages/microglia, smooth muscle cells and/or endothelium of the central nervous system. 3 mechanisms of cellular damage due to nitric oxide are proposed: 1. direct nitric oxide cytotoxicity; 2. injury due to peroxynitrite formation from superoxide anion and nitric oxide; and 3. nitric oxide-mediated elevations of cellular cGMP that enhance tumor necrosis factor-alpha toxicity. In support of these hypotheses, the anti-inflammatory effectors, dexamethasone and transforming growth factor-beta, ameliorate symptoms seen in clinical multiple sclerosis and experimental allergic encephalitis, respectively. These 2 immunomodulators also inhibit induction of cytokine-mediated nitric oxide production by macrophages. An experimental design and therapeutic interventions which will evaluate the role of nitric oxide in the pathophysiology of experimental allergic encephalitis are presented.


The role of lipid peroxidation in McArdle's disease: applications for treatment of other myopathies.

Experimental therapies for McArdle's disease have been directed toward increasing substrate availability to exercising muscle. Such therapies to date have proven largely unsuccessful. These include administration of isoproterenol to increase blood flow, glucagon treatment to elevate serum glucose and increased dietary fat intake. Each of these therapies also results in greater levels of unesterified fatty acids in blood. More recently, a high protein diet is suggested to provide increased amounts of amino acids which would be available as fuel sources. We hypothesize that the absence of myophosphorylase in McArdle's disease creates an imbalance between the enzymes of the redox systems that control the generation, propagation and inactivation of free radicals. This occurs because muscle cells are forced to rely more heavily on fatty acid oxidation. The resulting free radical damage to cellular components disrupts metabolic control and increases the permeability of membranes. Elevated levels of Ca2+ in the sarcoplasm activate proteases, phospholipases and other catabolic enzymes initiating muscle fatigue and cramping. Lipid peroxidation is a consequence of normal muscle activity and may occur unchecked in individuals with McArdle's disease. Continued muscle activity in the absence of a favorable nutritional environment may promote the progression of the disease by increasing susceptibility to oxidative stress.


Bioregulatory roles for fibrin(ogen) on blood coagulation.

A high plasma fibrin(ogen) concentration is a known risk for thrombosis and cardiovascular disease. Because fibrin(ogen) binds alpha-thrombin with high affinity, it has potential to modulate the interactions of the enzyme with its inhibitors and other substrates in plasma. In particular, fibrin moderates the inhibition of thrombin by antithrombin III and antithrombin III/heparin. Recently, we have demonstrated a novel regulatory role for fibrin(ogen) on plasma coagulation. A push-pull hypothesis is proposed for bioregulation of coagulation by fibrin(ogen). The experimental work which led to the formulation of this hypothesis is outlined.


Turner syndrome as a candidate pseudoautosomal disorder.

Turner syndrome has been clearly associated with the absence of an X chromosome, but it remains uncertain how this deletion produces either the range of defects regularly associated with the syndrome or those only occasionally seen. It is of particular interest in this regard that the pseudoautosomal portion of the X chromosome has recently been identified as the location for the GM-CSF receptor gene. It is submitted that Turner syndrome, with its hemizygosity for the psuedoautosome, may be an important model for studying the GM-CSF receptor gene as well as other associated genetic material.


Clues to prolific productivity among prominent scientists.

In a survey based on the biographical sketches, obituary notes and eulogies of notable scientists, eight were identified as belonging to an elite group, having authored more than 1000 research publications, which include books, monographs and patents. They were, in chronological order, Thomas Alva Edison, Paul Karrer, Margaret Mead, Giulio Natta, Hans Selye, Herbert C Brown, Tetsuji Kametani and Carl Djerassi. Among these, Karrer, Natta and Brown were Nobelists in chemistry. Four criteria which can be identified as clues to their prolific productivity are, 1) enthusiasm for compulsive work and eccentric life style, 2) physical and/or environmental handicap, 3) pioneering efforts in a new research field, and 4) selection of research area, predominantly organic chemistry.


Infant colic: the effect of serotonin and melatonin circadian rhythms on the intestinal smooth muscle.

It is hypothesized that in the evening, peak serotonin concentration causes intestinal cramps associated with colic because serotonin increases intestinal smooth muscle contractions. Melatonin has the opposite effect of relaxing intestinal smooth muscles. Both serotonin and melatonin exhibit a circadian rhythm with peak concentrations in the evening. However, serotonin intestinal contractions are unopposed by melatonin during the first 3 months because only serotonin circadian rhythms are present at birth. Melatonin circadian rhythms appear at 3 months of age. The cramps of colic disappear at 3 months of age.


The cytokine theory of headache.

Immune cell cytokines are proposed as the common mediators of headache. This unifying concept can not only account for headache, but also the prostaglandins, leukotrienes, platelet activating and vasoactive substances linked with headache, the varied symptoms associated with headache and the high incidence of headache with depression, infectious disease, trauma and in premenopausal women. The immune system as the central mediator of headache is consistent with the promoting effect of estrogen, the abortive activity of cortisol and the prophylactic properties of fish oil and evening primrose oil. This hypothesis provides a unified mechanism to explain headache triggered by food, infectious disease or trauma.


An overview of the effects of convergent magnetic ionizing radiation on biological function.

This paper provides new theoretical premises for understanding issues in 'bio-electromagnetics'. It firstly explains how converging magnetic fields, e.g. dipoles, can exert pressure on electrolyte distribution in an aqueous medium, and then it expands on this point to explain how this magnetic pressure is, in one extreme, a potential cancer causing force in the environment, and is, in another sense, a powerful new technique in cancer treatment. Included in this examination is a short analysis of the importance of this force in the morphogenesis of the fetus, and in the control of chromatic expression after the fact.


Models of cell population in tumours and possibility of their application to optimization of radiotherapy.

Two models of cell population in tumours are analyzed and used to explain some experiments on the influence of radiation on tumours. There is a proposal to remove disagreements between these models and experiments by the assumption that cells under the influence of a destructive factor may reduce their degree of differentiation.


Fatigue syndromes: new thoughts and reinterpretation of previous data.

Recently, the author has identified 19 patients who have complained of marked fatigue that had abnormal responses to copper test bracelets or necklaces. At this time, 8 have been shown to have at least one enzyme deficiency in the heme pathway. These patients have been diagnosed with multiple sclerosis, chronic fatigue syndrome and other non-specific diagnoses. A lengthy but still limited review of the literature was performed regarding the following conditions: multiple sclerosis (MS), hepatic porphyria (HP), chronic fatigue syndrome (CFS) and paralytic polio (PP). The text will focus on similar epidemiologies, laboratory findings and clinical courses. Copper as a common but not unique etiologic agent will be discussed; as will the heme pathway, a biologic process that may be disordered in all.


Precipitous stem cell (SC) differentiation and 1/f noise.

After a brief digression on certain types of noise of generic interest, it is concluded that 1/f noise offers interesting interpretations for unusual modes of SC differentiation such as the precipitous maturation of a subset of the macrophage lineage. Functionally equivalent to weak, spurious sources these specialized cells support the proliferation and maturation of erythroid cells extending thus the stimulatory influence of true, strong sources although in a rather indirect fashion.


Estimating left ventricular work by gated blood pool ventriculogram.

Utilizing simplifying assumptions and a formula for ventricular radioactivity versus time, a method is presented for the estimation of systolic ventricular work. This value in MKS units is calculated from data available from the radionuclide blood pool ventriculogram.


Five cases of pleural mesothelioma with endemic pleural calcifications in a rural area in Greece.

The authors describe 5 cases of pleural mesothelioma in a rural population of Macedonia, Greece. This population had been covered by an X-ray study over a 3-year period to detect pleural calcifications compatible with asbestos exposure. The study revealed a 24.2% prevalence of pleural plaques among the inhabitants aged over 40 years of 7 rural villages. High contents of asbestos (chrysotile and tremolite)--up to 90% by volume--were found in the material that was used for whitewashing the houses up to 1935. Even now, environmental concentrations of 0.01 fibres/ml were recorded in the houses. The prevalence of pleural mesothelioma in this rural population is high compared to the general population. A possible explanation of the phenomenon may be a cumulative environmental exposure to asbestos which, even though presumably within the acceptable limits for occupational exposure, lasted over a much longer time period, in terms of both daily exposure and total duration.


[Use of statistics in occupational medicine. Analysis of papers presented at the national congresses of the Italian Society of Occupational Medicine and Industrial Hygiene].

The statistical methods used in occupational health studies were evaluated by analyzing the papers published from 1986 to 1990 in the proceedings of the annual meetings of the Italian Society of Occupational Medicine and Industrial Hygiene, in order to calculate the degree of understanding of the readers provided with only one-sided knowledge of statistical subjects and to improve the educational objectives in postgraduate schools of occupational health. Almost 70% of the 1151 articles reviewed contained some kind of statistical analysis: methods more complicated than descriptive statistics were used in about 35%. Student's t test (15%) and chi square (12%) were the most common methods. Other methods were less frequently used, so that it was possible to estimate that the learning of any new method would improve the understanding of about 1-2% of the articles. A wider use of statistical methods in data analysis is recommended; the attainment of a higher level of statistical knowledge should be a priority target in occupational health training.


[Ocular hypertension in radiologists and radiology technicians].

Ionizing radiations (IR) produce changes in the eye and, above all, in the lens. Several studies on radiotherapy in neoplastic diseases and dangerous nuclear accidents like Chernobyl have indicated the percentage and the exposure level at which the eye becomes the target organ of IR. The aim of the study was to establish the association between ocular tension and low-level IR exposure. The incidence of ocular hypertension in the general population is about 1-2% in persons aged 30-40 years and 10% in the 70-80 years age group; the frequency of glaucoma is 0.2-0.5% in persons aged 50-55 years and 2% in those aged 70 years and over; after 15 years of disease, conversion from ocular hypertension to glaucoma is observed in 40% of the cases. We examined 128 subjects occupationally exposed to IR (42 radiologists and 86 radiology technicians) and 130 non-exposed. For each subject we recorded age, length of employment, job titles, dosimetry, ocular tension, refraction and motility impairments. The data obtained from a complete ophthalmologic test was analyzed by the t-Student test, Chi-square and Pearson's test. The ocular tension of 33 occupationally exposed subjects and 2 non-occupationally exposed subjects was higher than the cut-off value of 18 mmHg. There was no analogy between age distribution of ocular hypertension in the groups under study and the general population. There seems to have been a relationship between ocular tension and job titles since a higher incidence was observed among the radiology technicians than among the radiologists and also in the 30-40 years age class.(ABSTRACT TRUNCATED AT 250 WORDS)


[Postural tenosynovitis caused by misuse of a computer input device (mouse)].

Several reports of postural problems among video display unit workers are available, most frequently involving the back, neck and shoulder. The case described is an example of tenosynovitis of the right wrist at the point where the wrist rests on the work surface while operating the mouse in a computer workstation (2-3 hours/day 6 days/week). The alteration was caused by a combination of friction and pressure on the wrist joint tendon due to the faulty positioning of the hand and wrist. This is the normal resting position for the wrist (inclined towards the ulnar side), and is thus the most natural position to adopt. The reported alteration, which responded to a short period of rest and treatment with non-steroid anti-inflammatory drugs for 2-3 days, is described as an example of common injury caused by an unusual faulty posture of the hand. The preventive measures suggested to avoid the occurrence of this type of injury include: (i) instead of resting the weight of the hand on the ulnar side of the wrist it should be distributed between the two pads of fatty tissue which form the base of the palm, (ii) the mouse button could be clicked with the third finger instead of the index finger in order to avoid the tendency of hand to roll into the faulty rest position.


[Alcohol consumption by refuse collection workers: a problem of public health].

A total of 485 workers were interviewed employed by the municipal urban refuse collection corporation of Venice; 87.6% consumed alcoholic beverages, 24.5% of whom exceeded 1 litre of wine per day. Only 9.7% of the interviewees thought that an acceptable alcohol consumption level should not exceed 1 litre, whereas more than 23% thought that 2 or more litres of wine per day was not harmful. The variables associated with a high alcohol consumption in this working community were mainly: level of education and of specific knowledge about alcohol and long-term residence in the historical centre of Venice. The authors discuss the possible factors connected with the type of job which could influence the incentive to drink and the public hygiene actions that could be taken. The need for community medicine programmes is emphasized.


Current status of physical measurements of the skeleton.

An overview is presented of some of the major methods of measuring the skeleton in the past 30 years. These include single photon absorptiometry (SPA), dual photon absorptiometry (DPA), quantitative computed tomography (QCT), and recently dual energy radiographic absorptiometry (DRA), also called DEXA (dual energy x-ray absorptiometry). In addition to these methods, all attempting to measure bone mineral density, regional and total body calcium have been determined by in vivo neutron activation analysis (IVNAA). An attempt to determine bone quality as contrasted with bone quantity has been made using ultrasound, with measurements of speed of sound and of attenuation as useful parameters to characterize bone tissue. While the various methods for measuring bone density have been most useful, no one method includes all the features required to be entirely satisfactory: excellent precision and accuracy and the ability to measure volumetric density in gm/cm3. Least successful has been the ability to predict fracture risk, an essential goal in helping the patient.


[Sudden death caused by freon 22?].

Case report of a plumber's fatal work accident. Investigations on the causes of death made at post mortem showed that the worker had absorbed a large quantity of freon 22 (chlorodifluoromethane) which is known to be a narcotic agent and capable of inducing cardiac arrhythmia. It is believed freon inhalation was the cause of loss of consciousness with consequent death from drowning in the water issuing from the pipes. It is concluded that preventive measures need to be reinforced by adequate information to the workforce on the risks connected to this type of gas.


Biological effects of the Auger emitter iodine-125: a review. Report No. 1 of AAPM Nuclear Medicine Task Group No. 6.

The biological implications of Auger electron cascades following inner shell ionization of atoms have been of interest for over 25 years. By virtue of their decay via orbital electron capture and/or internal conversion, several biomedical radionuclides emit numerous low-energy electrons spontaneously. The biological effects of such radionuclides incorporated into tissues cannot be predicted a priori because of the highly localized patterns of energy deposition by the electrons. Results of extensive research using Iodine-125 as a model Auger electron emitter are now available. This article presents an up-to-date review of the physical and radiobiological data on this Auger emitter. Valuable concepts concerning the action of internal Auger emitters are identified phenomenologically, and questions that need to be answered are indicated. The present understanding provides a scientific basis toward estimation of risk associated with Auger emitters used in diagnosis, and suggests potential applications to therapy.


Radiation spectra for Auger-electron emitting radionuclides: report No. 2 of AAPM Nuclear Medicine Task Group No. 6.

Radiation spectra for radionuclides currently provided by the MIRD Committee and ICRP do not include the very low-energy N- and O-shell Auger electrons. These electrons, emitted in large numbers by radionuclides decaying by electron capture and/or internal conversion, are important for determining the absorbed dose in microscopic volumes. Accordingly, the present AAPM Report employs Monte Carlo computational methods to obtain a self-consistent set of complete radiation spectra for a variety of radionuclides including 55Fe, 67Ga, 99mTc, 111In, 113mIn, 115mIn, 123I, 125I, 193mPt, 195mPt, 201Tl, and 203Pb. Although the conventional spectra provided by MIRD and ICRP are adequate for most dosimetry calculations, the Auger electron spectra provided in this report are recommended for calculating the dose to target volumes < 1 microns in diameter.


Analytic microdosimetry for radioimmunotherapeutic alpha emitters.

Analytic microdosimetry using Fourier transform techniques has been applied to internal alpha emitters. These techniques need revision and simplification for use with short-lived radionuclides such as those which may be useful for radioimmunotherapy. Analytic methods may have advantages over Monte Carlo methods in some cases (e.g., where time is important). Applications to eight different source geometries show the usefulness of these techniques. Comparisons of some of the results of Monte Carlo calculations prove its accuracy. For a uniform source of 5.867-MeV alphas spread throughout the volume outside a cell surface, the two methods agree well. Results are within 1% both for the average specific energy and for the number of hits. Analytic microdosimetry provides an alternate method to use for the critical evaluation of models that seek to predict the relation between alpha energy deposition and cell survival data. Similarly, it may be helpful to point the way toward the rational interpretation of general biological results for antibodies labeled with alpha emitters.