Permeability of lipid membranes revised in relation to freeze-thaw processes.

Water and solute activity gradients created during freeze-thaw processes produce water and solute fluxes across the cell membrane resulting in volume changes. Under these conditions, osmotic and thermal stresses affect the curvature, the phase behavior, and the surface properties of the lipid bilayer. These structural changes are not considered by the classical formalisms describing permeability of lipid membranes to water and nonelectrolytes such as the Nernst-Planck equation, Eyring's absolute rate theory, and Kedem-Katchalsky's thermodynamic of irreversible processes approach. In this paper, the influence of such changes on the glycerol permeation kinetics are reported. The results indicate that osmotic and chemical effects of the cryoprotectant on the membrane properties affect the rate of volume swelling depending on whether the membrane is in the gel or in the liquid crystalline state.


Cryoprotective effect of polyols on rat embryos during two-step freezing.

The cryoprotective effect of polyols on rat embryos was measured after two-step freezing, and the mechanism of action of polyols on embryo survival was examined. Rat embryos frozen in solution of polyol by two-step method at the morula stage showed higher survival than that obtained using DMSO. As the number of hydroxyl groups increased, the cryoprotective effect of the polyol increased. However, this was true only when the additive could permeate the cell membrane. Of the additives tested, four or five carbon polyols were most effective at concentrations of 0.3 or 1.0 M than two, three, six, or seven carbon polyols. The highest survival rate was obtained with adonitol, which yielded 83% embryo survival at 1.0 M and 67% even at 0.3 M. Embryos frozen in 0.3 M adonitol and transferred directly into foster mothers without any dilution of the additive after thawing developed into live young. During slow cooling below -40 degrees C, embryonic blastomeres exhibited cell fusion only in the presence of adonitol. These findings suggest that one cryoprotective action of polyols is that the hydroxyl groups act both on the cell surface and the cytoplasm to stabilize the bound water on the embryonic membrane, and that the length of the C-chain determines the permeability of the membrane to the additive.


Effect of phosphoenolpyruvate on metabolic and morphological recovery of red cells after prolonged liquid storage and subsequent freezing in glycerol medium.

The present study was designed to determine the effects of (i) phosphoenolpyruvate (PEP) treatment of red blood cells (RBCs) previously cold stored for a prolonged period in a liquid medium and (ii) the freezing of these treated cells in glycerol. RBCs stored for 21 days at 4 degrees C were incubated for 30 min at 37 degrees C with rejuvenant solution containing 50 mM PEP, 60 mM mannitol, 30 mM sodium chloride, 25 mM glucose, and 1 mM adenine, pH 6.0, and then frozen at -80 degrees C for 4 weeks. Red cell recovery as frozen and thawed red cells (FTRCs) after deglycerolization was increased to 80 +/- 4% compared to 43 +/- 9% in units without rejuvenation; the percentage of PEP-treated FTRCs was similar to the percentage of FTRCs recovered from fresh RBCs within 5 days after donation. Incubation of RBCs with PEP solution restored ATP and 2,3-DPG to levels seen in fresh RBCs, and also facilitated transformation of crenated RBCs to discocytes. These results indicate that maximum recovery of viable RBCs can be attained when FTRCs are processed from cells stored in the frozen state after they had been rejuvenated with PEP even after prolonged liquid storage.


Cryoprotection of red blood cells by a 2,3-butanediol containing mainly the levo and dextro isomers.

A 2,3-butanediol containing 96.7% (w/w) racemic mixture of the levo and dextro isomers and only 3.1% (w/w) of the meso isomer (called 2,3-butanediol 97% dl) has been used for the cryoprotection of red blood cells. The erythrocytes were cooled to -196 degrees C at rates between 2 and 3500 degrees C/min, followed by slow or rapid warming. Up to 20% (w/w) of this polyalcohol, only the classical peak of survival is observed, as with up to 20% (w/w) 1,2-propanediol or 1,3-butanediol. Twenty percent 2,3-butanediol 97% dl can protect red blood cells very efficiently. The maximum survival, of 90%, as with 20% glycerol, is a little lower than with 20% 1,2-propanediol and higher than with 20% 1,3-butanediol. Fifteen percent 2,3-butanediol protects fewer red blood cells than 15% glycerol or 1,2-propanediol, with a maximum survival of about 80%. The best cryoprotection by 30% 2,3-butanediol 97% dl is obtained at the slowest cooling and warming rates, where survival approaches 90%. After a minimum, an increase of survival is observed at the fastest cooling rates, which would correspond to complete vitrification. These rates are lower than with 30%, 1,2-propanediol or 1,3-butanediol, in agreement with the higher glass-forming tendency of 2,3-butanediol 97% dl solutions. In agreement with the remarkable physical properties of its aqueous solutions, the present experiments also suggest that 2,3-butanediol containing mainly the levo and dextro isomers could be a very useful cryoprotectant for organ cryopreservation. However, it would perhaps be better to use it in combination with other cryoprotectants, since it is a little more toxic than glycerol or 1,2-propanediol at high concentrations.


Performance of a kinetic model for intracellular ice formation based on the extent of supercooling.

Cryomicroscopy was used to study the incidence of intracellular ice formation (IIF) in protoplasts isolated from rye (Secale cereale) leaves during subfreezing isothermal periods and in in vitro mature bovine oocytes during cooling at constant rates. IIF in protoplasts occurred at random times during isothermal periods, and the kinetics of IIF were faster as isothermal temperature decreased. Mean IIF times decreased from approximately 1700 s at -4.0 degrees C to less than 1 s at -18.5 degrees C. Total incidence of IIF after 200 s increased from 4% at -4.0 degrees C to near 100% at -15.5 degrees C. IIF behavior in protoplasts was qualitatively similar to that for Drosophila melanogaster embryos over the same temperature ranges (Myers et al., Cryobiology 26, 472-484, 1989), but the kinetics of IIF were about five times faster in protoplasts. IIF observations in linear cooling of bovine oocytes indicated a median IIF temperature of -11 degrees C at 16 degrees C/min and total incidences of 97%, 50%, and 19% at 16, 8, and 4 degrees C/min, respectively. A stochastic model of IIF was developed which preserved certain features of an earlier model (Pitt et al. Cryobiology 28, 72-86, 1991), namely Weibull behavior in IIF temperatures during rapid linear cooling, but with a departure from the concept of a supercooling tolerance. Instead, the new model uses the osmotic state of the cell, represented by the extent of supercooling, as the independent variable governing the kinetics of IIF. Two kinetic parameters are needed for the model: a scale factor tau 0 dictating the sensitivity to supercooling, and an exponent rho dictating the strength of time dependency. The model was fit to the data presented in this study as well as those from Myers et al. and Pitt et al. for D. melanogaster embryos with and without cryoprotectant, and from Toner et al. (Cryobiology 28, 55-71, 1991) for mouse oocytes. In protoplasts, D. melanogaster embryos, and mouse oocytes, the parameters were estimated from IIF times in the early stages of isothermal periods, while the osmotic state of the cell was relatively constant. In bovine oocytes, the parameters were estimated from linear cooling data. Without further calibration, the model was used to predict total IIF incidence under different cooling regimes. For protoplasts, D. melanogaster embryos, and bovine oocytes, the model's predictions were quite accurate compared to the actual data. In mouse oocytes, adjustment of the hydraulic permeability coefficient (Lp) at 0 degree C was required to yield realistic behavior.(ABSTRACT TRUNCATED AT 400 WORDS)


Biochemical modification of plasma ice nucleating activity in a freeze-tolerant frog.

Recently, we reported the presence of ice nucleating activity, apparently proteinaceous, in the plasma of a freeze-tolerant frog, Rana sylvatica, collected in autumn and spring. Although this protein has not been purified, its ice nucleating behavior can act as an internal reference for tests that attempt to modify its ability to nucleate ice formation. If the addition of a chemical reagent alters the temperature of ice crystallization compared with the control, it can be assumed that protein modification may have occurred. The ice nucleating protein in R. sylvatica showed resistance to proteolysis with four different proteases although there was a significant reduction in the temperatures of nucleation with these treatments (ANOVA P less than 0.001). However, ice nucleating activity was lost when plasma was treated with the addition of urea or N-bromosuccinimide. Modification of protein sulphydryl groups with iodoacetamide did not affect the crystallization temperature (Tc) but treatment with iodoacetic acid resulted in a significant increase in Tc of plasma. An abrupt loss of ice nucleating ability was observed in plasma samples after heating above 87 degrees C. Anomalous potentiation of ice nucleating activity occurred when the plasma was heated to and held at temperatures between 67-75 degrees C.


Cryoprotective effects of yeast extracellular polysaccharides and glycoproteins.

Eighteen yeast strains were tested for their ability to survive the freeze-thaw process while being cryoprotected. Cryoprotection was accomplished by combining penetrating and nonpenetrating cryoagents. Four nonpenetrating (two extracellular polysaccharides of yeast and two extracellular glycoproteins of yeast) and two penetrating agents were used together with the nutritive-rich medium. Eight different mixtures were tested. The highest survival rate was obtained with glycoproteins of Rhodosporidium toruloides together with DMSO and nutritive-rich medium.


A comparison of the heart rate at different ambient temperatures during long-term hibernation in the garden dormouse, Eliomys quercinus L.

Heart rate in hibernating garden dormice, Eliomys quercinus, was studied by means of permanently implanted electrodes; ambient temperatures (TA's) were maintained at 0, 4, 6.5, and 9 degrees C during the 6-month test period in each winter study. The animals were kept under constant conditions in darkness and without food or water. Heart rate remained at a low level during deep hibernation at all TA's studied. There were no differences in midwinter values between the TA's of 6.5 and 9 degrees C: the means were 9-12 beats/min during apnea. Heart rate thus differs from other hibernation parameters studied simultaneously, which were strongly TA dependent. However, the optimal TA of 4 degrees C could be distinguished and heart rate was significantly lower, 8-10 beats/min. At 0 degree C the values were slightly higher: 12-13 beats/min. The TA of 0 degree C was exceptional for all parameters studied. At the beginning of the hibernation season was a transition period with elevated heart rate values. Respiratory-related heart-rate changes appeared during periodic respiration, heart rate being significantly higher during respiratory periods at all TA's. At 0, 6.5, and 9 degrees C tachycardia occurred also during apnea, very close to the respiratory period. There are responses that are comparable to hypoxic environmental conditions during hibernation, diving, and pregnancy and under high-altitude conditions. Parallel adaptations appear in heart rate and respiration, i.e., bradycardia and periodic respiration. In conclusion, heart-rate values were low during deep hibernation, and compared with other parameters measured at different TA's heart rate is maintained inside narrow limits during deep hibernation.


Enhancement of cellular immune function during cold adaptation of BALB/c inbred mice.

The cell-mediated immune function of cold-adapted BALB/c inbred mice was studied in experiments of splenic lymphocyte blastogenesis, indicated by tritium-labeled deoxythymidine incorporation and SDS-PAGE autoradiography of synthetic proteins in lymphocytes. Male BALB/c inbred mice were randomly divided into two groups: control (living at 25 degrees C) and cold-exposed (living at 2 degrees C). Results are as follows: in contrast with the control group, there was an obvious fluctuation of cell-mediated immune function in the cold-exposed group at initial cold exposure because of transient stress to cold; then cell-mediated immune function gradually recovered to control level. From Day 15, the cell-mediated immune function of the cold-exposed group was remarkably enhanced. On Day 15, the lymphocyte blastogenesis rate was increased by 20.66% (P less than 0.05), which implies the onset of cold adaptation; on Days 21 and 31, the rates increased by 80.15% (P less than 0.05) and 40.36% (P less than 0.05), respectively. Two to six months later, with continuing cold exposure, the murine lymphocyte blastogenesis rate in the cold-exposed group remained higher than that in the control group. The lymphocyte protein synthesis of the cold-exposed group, indicated by tritium-labeled leucine incorporation, apparently increased on Day 15 and the stimulated rate was 101.47% (P less than 0.05). SDS-PAGE autoradiography of synthetic proteins in lymphocytes demonstrated that after 2 weeks of cold exposure, protein bands were enriched in both quantity and quality. These results are identical to the results obtained from lymphocyte blastogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of supercooling on the developmental capacity of mouse embryos.

The effect of supercooled storage (at subzero temperatures without ice formation) on compacted mouse morulae and early blastocysts was studied. The embryos were equilibrated with one of three storage solutions containing 1, 3, or 6% each of methanol and glycerol and cooled to -2, -5, -10, or -15 degrees C and stored for up to 24 h to assess the effect of subzero storage at different temperatures and concentrations of the permeating cryoprotectants on embryo survival. Early blastocysts showed substantially greater survival than morulae and, in general, survival of embryos of either stage increased with the concentration of cryoprotectant, while the proportion of embryos surviving decreased with decreasing storage temperature and with increased duration of storage.


Association of glycolytic enzymes with the cytoskeleton.

The diverse physical associations of the glycolytic enzymes with structural components of the cell suggest that the glycolytic enzymes are not entirely soluble in the cell. The relatively low affinities of the associations are likely responsible for the apparently transient interactions. The binding phenomenon is suggested to regulate metabolism through changes in enzymatic activity and facilitates localized enrichment of the enzymes.


Interactions between mitochondria and cytoplasm in isolated hepatocytes.

Results from a wide variety of metabolic studies have provided indirect support for conclusions derived from enzymological approaches that the enzymes of the so-called soluble cytoplasm (and the mitochondrial matrix) exist within the cell and function in the form of multienzyme complexes and that metabolite channeling takes place between the enzymes of each complex. Our studies support the possibility that the enzymes of glycolysis in liver are segregated from those of gluconeogenesis. Thus, the segregation and aggregation of Krebs cycle enzymes in the mitochondrial matrix, elucidated by Paul Srere, may be an example of a general pattern of enzyme organization pertaining to all metabolic pathways.


Orotidylate decarboxylase of yeast and man.

The mechanism for ODCase appears to involve the formation of a zwitterion of OMP and a ylid on decarboxylation. Thiamin pyrophosphate catalyzes various decarboxylation and transfer reactions involving ketone groups because the thiazolium ring with its positively charged N atom can, on the loss of a proton from the adjacent C-2, generate a ylid which adds to carbonyl groups to produce a substrate ylid. The unusual aspect, then, of the ODCase reaction is that the substrate itself becomes the ylid, presumably by gaining a proton from ODCase, which results in a positive charge on the N-1 atom of the pyrimidine ring. It is a zwitterion in the transition state which momentarily becomes a ylid on decarboxylation of OMP which then yields the product, UMP. There is no known cofactor for the ODCase reaction. It will be of interest to discover the groups on the enzyme that aid in formation of the zwitterion and the ylid. Further work on the crystal structure and on the production of altered enzymes (where specific amino acids suspected to be important for the reaction are changed) should reveal more details about this important and novel reaction.


Swallowing in torticollis before and after rhizotomy.

To determine risk factors for dysphagia after ventral rhizotomy, videofluoroscopic barium swallowing examinations were done on 41 spasmodic torticollis patients before and after surgery. Radiologic abnormalities were present in 68.3% of the patients before surgery, but these were only mildly abnormal in the majority. After surgery 95.1% showed radiologic abnormalities which were moderate or severe in one-third of the patients. Swallowing abnormalities correlated significantly with duration of torticollis and subjective complaints of swallowing difficulty both before and after surgery, but not with age, sex, or type of torticollis. The major acute postoperative finding was aggravation of preexisting pharyngeal dysfunction. Follow-up from about half of our original sample showed that gradual improvement occurred from 4 to 24 weeks after surgery by subjective report. We review the innervation of intrinsic and extrinsic pharyngeal musculature, and suggest that C1-3 rhizotomies and selective sectioning of the spinal accessory nerve are responsible for aggravation of pharyngeal swallowing dysfunction in the acute postsurgical period.


Periventricular white matter changes and oropharyngeal swallowing in normal individuals.

Cranial magnetic resonance imaging (MRI) has revealed patchy periventricular white matter lesions or "unidentified bright objects" (UBOs) in otherwise neurologically intact individuals. Quantitative videofluoroscopic swallowing evaluations and cranial MRI examinations were studied in 49 neurologically normal volunteers (ages 43 to 79 years). Total swallowing duration (TSD) and its subcomponents of oral transit duration (OTD), stage transition duration (STD), and pharyngeal response duration were measured for liquid and semisolid swallows. MRIs were graded from 0, or no UBOs, to 3, or multiple and confluent lesions. The effect of the presence of UBOs on swallowing durational measures and risk factors was analyzed with age differences accounted for statistically (ANCOVA). TSD and OTD for semisolids were significantly differentiated by MRI score (P less than 0.009 and P less than 0.047, respectively). That is, a demonstrable effect was found for an increased number of UBOs on duration of oropharyngeal swallowing in normal individuals.


Oral diseases in HIV-1 infection.

HIV-associated oral lesions have been reported since the beginning of the AIDS epidemic, be they fungal, viral, bacterial, neoplastic, or non-specific in origin. The most common lesions are oral candidiasis (OC; noted in several forms) and oral hairy leukoplakia (OHL). OC appears to be directly related to levels of immunosuppression while OHL, a newly described lesion, is associated with the Epstein-Barr virus. Although prevalence data for all types of oral lesions are scarce, this review identifies and describes those reported most often. Lesions associated with HIV may appear on most oral mucosal surfaces and may differ from those seen on other body areas. The role of saliva in reducing the potential for transmission of the HIV virus appears to be significant. Physicians and dentists should cooperate in the management of the HIV patient who has oral disease.


Novel primitive swallowing reflex: facial receptor distribution and stimulus characteristics.

We recently described a primitive swallowing reflex: swallowing as a response to a puff of air administered to the face. To identify the facial afferent distribution of this response, the necessary characteristics of the stimulus, and the role of the infant's antecedent behavior, we studied 13 infants who had demonstrated this reflex. We evaluated nine infants by clinically observing for swallowing in response to a total of 135 stimulus applications. All nine had consistently positive responses to the maxillary-ophthalmic area and to the maxillary-mandibular area. Two had consistent responses to stimulation of the mandibular area alone; these were positive. Six had consistent responses to stimulation of the ophthalmic area alone; these were negative. Four infants, evaluated by manometric documentation of swallowing (a total of 137 stimulus applications) demonstrated 47 of 79 (59%) positive responses to stimuli applied to facial areas including any parts of the lips, but only 7 of 28 (25%) positive responses to stimuli applied to facial areas excluding all parts of the lips (chi-square P = 0.002). Light touch to any facial area, including the cornea, failed to produce a swallow in any infant. Crying and sleep were incompatible with the reflex. This newly identified primitive swallow reflex seems to require diffuse stimulation, possibly thermal, to the perioral area of the face in an awake and noncrying infant.


Food intake by maneuver; an extreme compensation for impaired swallowing.

We report two young patients able to exist on exclusively oral intake despite an absent pharyngeal swallow response. Videofluoroscopic swallowing studies showed that both patients used a sequence of devised maneuvers rather than a coordinated pharyngeal swallow to move the bolus, protect the airway, and open the upper esophageal sphincter during bolus ingestion. We conclude that it is possible for young, highly motivated individuals to maintain oral intake despite ablation of neurologic elements crucial for the normal swallow response.


Sounds of swallowing following total laryngectomy.

Accelerometer transduced sounds of swallowing in total laryngectomees did not show acoustical differences for liquid vs paste swallows, as are found in normals. Compared with normal swallows, tongue propulsion of the bolus in laryngectomee swallows occurred closer in time to a distinctive spectral change associated with bolus flow into the esophagus. Interpretation stressed the lack of mechanical traction from laryngeal elevation contributing to pharyngoesophageal sphincter opening, and the increased role of tongue propulsion in laryngectomee swallows.


Achalasia evolving from segmental aperistalsis.

A 17-year-old woman was evaluated for dysphagia. Radiologic study revealed a rigid segment 10 cm long in the midesophagus, which was found to be aperistaltic on manometric evaluation. The rest of the esophagus and the lower esophageal sphincter were manometrically normal. Four years later the patient was seen for evaluation of severe dysphagia and symptoms of esophageal overflow. Characteristic radiologic and manometric findings of classic achalasia were noted. The case is discussed as an atypical form of achalasia evolving from a segmental esophageal aperistalsis.


Aspiration after stroke: lesion analysis by brain MRI.

Aspiration is a common problem following stroke, resulting in feeding difficulties and aspiration pneumonia. Despite past studies using clinical assessments and computed tomographic (CT) scans of the head, the correlation of stroke location with aspiration remains unclear. Since brain magnetic resonance imaging is more sensitive than CT for many stroke types, we have correlated MRI lesions with aspiration in patients who have sustained a stroke. We selected patients with acute stroke who underwent brain MRI and a swallowing evaluation. Aspiration was present in 21 of 38 patients (55%). Patients with just small vessel infarcts had a significantly lower occurrence of aspiration (3 of 14, 21%) compared to those with both large- and small-vessel infarcts (15 of 20, 75%, p = 0.002). Multivariate analysis of several specific brain areas failed to identify a significant association between stroke location and the occurrence of aspiration. These findings suggest that patients who have experienced stroke should be individually evaluated for swallowing dysfunction regardless of stroke location or size, since even small-vessel strokes can be associated with aspiration in greater than 20% of cases.


Risk factor patterns for coronary heart disease in China, Japan and Germany.

The risk factor patterns for coronary heart disease in China, Japan and Germany were studied. 6,025 Germans, 7,580 Japanese and 2,047 Chinese aged 30-59 were investigated following the protocol of the Göttingen Risk, Incidence, and Prevalence Study carried out in West Germany in 1982. It is concluded that in China, the risk factor intervention focuses mainly on smoking and hypertension; smoking also remains the most important risk factor in Japan; while in Germany the major targets are obesity and hyperlipidemia. However, about 38% of the participants from West Germany showed 3 or more risk factors accumulated per person. Thus the multifactorial risk factor reduction might be necessary in Germany.


Cardiovascular consequences of obesity.

Obesity is common in populations that are overnourished and can become a significant public health problem. Obesity predisposes to non-insulin dependent diabetes mellitus, hypertension, dyslipidemia, cholelithiasis, some malignancies and osteoarthritis. These consequences that most directly affect the cardiovascular system are dyslipidemia and hypertension. Nations in which obesity is rare should learn from the experience of the countries where it is prevalent, that prevention of obesity is a public health measure rather than weight reduction.


Trials in elderly patients with isolated systolic hypertension.

The hypothesis that antihypertensive drugs should be prescribed to elderly patients with isolated systolic hypertension is being addressed in at least 3 trials: the Systolic Hypertension in the Elderly Program (SHEP) in the United States, a trial in China, and the Syst-Eur study in Europe. The SHEP trial has recently reported its final morbidity and mortality results. This article summarizes the protocol of the European study. To be eligible for the Syst-Eur trial, patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized into active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/d), combined with enalapril (5-20 mg/d) and hydrochlorothiazide (12.5-25 mg/d), as necessary. The control group received matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the two treatment groups.


HDL and apolipoprotein A1 (apo A1). Their effects on retardation of lipid deposition in aortic intima.

The aim of this study is to clarify whether apo A1 displays a similar role as that of HDL in preventing the development of experimental atherosclerosis. Results were obtained from 4 groups of experiments. (1) Result from 4 successive experiments of tree shrews indicated that high serum HDL level is the main factor in preventing the development of experimental atherosclerosis; (2) Results from 4 successive experiments in rabbits showed that both HDL and apo A1 were able to decrease the extent of lipid deposition and atheromatous lesion developed in the aortic intima; (3) Apo A1 also inhibited the number of monocytes/macrophages infiltrated in aortic intima at the initial stage of fatty streak formation; (4) Similar as HDL, apo A1 phospholipid liposomes promoted markedly the clearance ability of smooth muscle cells on intracellular cholesterol. Conclusively, apo A1 is effective in preventing the development of experimental atherosclerosis. Further study, however, is required to detect an ideal combination of apo A1 with other component, e.g., phospholipid.


Recombinant tissue-plasminogen activator (rt-PA) in acute myocardial infarction in the Chinese in Hong Kong.

Eighty-nine consecutive Chinese patients (69 males, 20 females) with acute myocardial infarction treated by 100 mg recombinant tissue-plasminogen activator (rt-PA) (7 intracoronarily, 82 intravenously) at 3.7 +/- 1.0 hours after onset, and intravenous heparin or dipyridamole therapy started at 3 hours, were studied prospectively. Their mean age was 59.6 +/- 10.6 years. Forty-six patients (51.7%) had anterior and 39 patients (43.8%) had inferior infarcts. Clinical evidence of reperfusion was seen in 63 patients (72.8%), while new complications included hypotension (5.6%), heart failure (6.7%), cardiac arrhythmias (76.4%), hematoma around vascular access sites (23.6%), melena (2.2%) and cerebral infarction (2.2%). Maximal changes in coagulation profiles were seen at 3 hours, including a decrease in fibrinogen (by 64.2%), an increase in FDP by 11.7 times and D-dimers by 4.4 times. Nine patients (10.1%) had recurrence of angina and 6 patients (6.9%) died due to pump failure (5) and reinfarction (1). Angiogram at 14 days confirmed TIMI (2 or 3) patency of infarct related arteries in 62/81 (76.5%) patients, with a mean global ejection fraction of 52.5 +/- 12.4%. Nearly all survivors could maintain class I-II functional status after discharge. The safety and promises of rt-PA for acute myocardial infarction in the Chinese were confirmed.


Coronary atherectomy with the transluminal extraction endarterectomy catheter.

Percutaneous transluminal coronary atherectomy was attempted in 25 consecutive patients with the transluminal extraction-endarterectomy catheter. Successful revascularization with residual stenosis less than 50% in diameter was achieved in 23 patients (92%). There were 2 cases of major complications: one with distal embolization which subsided after rtPA infusion and the other with occlusion of RCA underwent bypass surgery. One patient who had restenosis 3 months after the procedure, was successfully treated with PTCA. The technical aspects, advantages and limitations of this method were discussed.


Quinaprilat increases total body vascular compliance in rats with myocardial infarction.

To test whether quinaprilat, a new angiotensin converting enzyme inhibitor, has any venous effect, its immediate effects were measured on mean circulatory filling pressure (MCFP), intravascular volume and total body vascular (i.e., venous) compliance in conscious rats with mild congestive heart failure induced by coronary artery ligation. MCFP was determined by inflating a right atrial balloon to arrest the circulation instantly and temporarily. Total body vascular compliance was derived from total circulatory pressure-volume relationships as determined by series measurements of MCFP with different intravascular volume status. In 8 rats with mean infarct size of 26 +/- 4%, 30-minute infusion of quinaprilat (0.1 mg/kg/min) decreased both mean arterial and central venous pressures by 8 mmHg and 0.7 mmHg, respectively (P less than 0.02); heart rate, MCFP, hematocrit and blood volume remained unchanged. Compared with control vehicle infusion, quinaprilat increased the total body vascular compliance (2.09 +/- 0.12 vs 2.69 +/- 0.23 ml/kg/mmHg; P less than 0.05) and decreased extrapolated unstressed circulating volume (34.96 +/- 1.10 vs 28.53 +/- 2.55 ml/kg; P less than 0.02). These data suggest that quinaprilat produces possible venodilation through immediately improved total body vascular compliance thereby reducing cardiac preload in this rat model of chronic heart failure.


Lessons in prevention of ischemic heart disease learned from pathological studies of coronary atherosclerosis.

The recent status of the extent and severity of atherosclerosis in Japanese children and young adults and its causative factor are presented. The material and data are collected from 2,856 autopsies, with the age range of 1 month to 39 years. Fibrinogen-fibrin metabolism in the arterial wall has a definite role in atherogenesis. The incidence of myocardial infarction in 539 consecutive autopsy cases over 40 years old at Kyushu University is 12.7%.


Etiological role of Alternaria alternata in human esophageal cancer.

In this paper, the mutagenicity and carcinogenicity of alternariol monomethyl ether (AME), alternariol (AOH), and their relevance to the etiology of human esophageal cancer were studied. These mycotoxins were produced by Alternaria alternata which was the main contaminating fungi isolated from the grain in Linxian County, an area with high incidence of esophageal cancer. This study demonstrated that: 1. AME and AOH might cause cell mutagenicity and transformation; 2. AME and AOH could combine with the DNA isolated from human fetal esophageal epithelium, activate the oncogens, c-H-ras and c-mys in it, and promote proliferation of human fetal esophageal epithelium in vitro; 3. squamous cell carcinoma of the fetal esophagus could be induced by AOH. According to the results of the studies of AME and AOH mentioned above, we consider that Alternaria alternata plays an important role in the etiology of human esophageal cancer.


Prevalence of growth hormone deficiency of children in Beijing.

103,753 (male 51,994, female 51,759) primary and middle school students aged 6-15 years in two districts in Beijing city were surveyed from October 1987 to April 1989. The heights of the students were measured. According to the height standard of northern cities in China, 202 students with heights below the 3rd percentile for age were requested for detailed history, physical examination, screening GH test bone age, T4, SGPT, chest X-ray, routine urine test and sex chromatin (in female). If GH less than 10 micrograms/L, two provocative tests (L-dopa or clonidine and insulin hypoglycaemia test) were done. Then the heights of the short students were observed for 1/2-2 years. GHD was diagnosed in 12 cases based on the GH peak levels less than 10 micrograms/L in two provocative tests, whose growth velocity was slower than that for students of the same age and sex. Of these subjects with GHD, total GHD (GH less than 5 micrograms/L) was present in 7 and partial GHD (GH = 5-9.9 micrograms/L) in 5. The 12 GHD students (male 9, female 3) aged 8.9-15.7 years accounted for 1/8,646 in the total surveyed students. The male and female GHD accounted for 1/5,777 and 1/17,253 in the total males and females respectively.


Treatment of severe Mooren's ulcer with cyclosporin A eyedrops.

Sixteen patients (21 eyes) with severe, progressive Mooren's ulcer, unresponsive to medical or surgical therapy, were treated with 0.5% cyclosporin A (CsA) eyedrops. Only 18 eyes were included in this study. Fifteen eyes showed marked effects within the first 12 days. Eleven eyes completely healed, on the average, in 1.3 months without side-effects. Follow-up for 24-31 months showed no recurrence. The whole-blood level of CsA determined randomly by high-pressure liquid chromatography in 7 patients was 28.95 micrograms/L on the average. It is concluded that autoimmunological mechanism plays an important part in pathogenesis of Mooren's ulcer, and the efficacy of topical CsA is attributable to its effect of local depression of ocular immunopathological reactions.


Nuclear morphometry and its prognostic significance in laryngeal squamous cell carcinomas.

The five parameters including nuclear area (NA), nuclear perimeter (NP), nuclear diameter (ND), axis ratio and nuclear roundness were evaluated with MIAS200 Image Analysis System (Sichuan University, Chengdu) in 45 patients with laryngeal primary squamous cell carcinoma, which were confirmed pathologically and operated on from January 1977 to October 1987. The results showed that NA, NP and ND are important prognostic indicators. The survival rate in patients with large nuclei (NA greater than 73 microns2, NP greater than 32.5 microns, ND greater than 12 microns) was significantly lower than that in those with small nuclei (NA less than 73 microns2, NP less than 32.5 microns, ND less than 12 microns) (P less than 0.0025). These findings strongly suggest that patients with laryngeal squamous cell carcinoma with large nuclei should be treated more aggressively.


An experimental study of pituitary transplantations in rabbits.

Experimental pituitary transplantations were carried out between the New Zealand white and American chinchilla rabbits. These two kinds of experimental rabbits were of different genotypes. The grafts were transplanted underneath the median eminences of the recipients after hypophysectomy. The rabbits with the transplants were treated with cyclosporine (CsA) and prednisone for the first month. Blood samples were taken at regular intervals for the determinations of serum thyroxine, prolactin and luteinizing hormone. The results suggested that neonatal grafts could survive and function almost normally with the aid of CsA and prednisone, but not without them. The results also disclosed that the interrelationship between the pituitary graft and the host's hypothalamus could be established. Pituitary transplantation from adult rabbit donors failed even though the recipients had been treated with CsA and prednisone in our experiment.


Purification of beta-lactamases and enzyme kinetic studies on aztreonam.

Standard beta-lactamases K1, P99, TEM-1, SHV-1 and beta-lactamase K-CAZ purified using FPLC through ion-exchange chromatography and filtration chromatography, were identified by determination of isoelectric points, molecular weights and substrate profiles. The results showed that the beta-lactamase stability of domestic aztreonam was very similar to that of cefotaxime, ceftazidime and much better than that of cefoperazone. Aztreonam showed a high affinity to chromosomal-mediated cephalosporinase P99, its Ki for inhibition of P99 with cephaloridine as substrate was 0.0159 microns. Aztreonam and the three third generation cephalosporins tested were not stable to beta-lactamase K-CAZ, which hydrolysed them in different degrees.


A new design of internal fixation for scoliosis and its preliminary clinical application.

A new scoliotone composed of screw, socket, distraction rod, lateral mass and compression rod can produce free movement in three different planes and fix the vertebral column in three-dimensions. The instrument has a strong force of fixation, distraction, compression and anti-rotation and it can be locked in any degree angle. Preliminary clinical application in 10 cases showed that when the spinal curvature (Cobb's angle) was less than 50, the average correction rate of scoliosis was 78.2% and that of the hump was 90%; when Cobb's angle was within 50-100 degrees, the average curve correction was 68.2%, and the hump correction 87.7%; when Cobb's angle was 100 degrees, the average curve correction was 63.3%, and the hump correction 82%. The vertebral column needed no external fixation after the operation. Biomechanical characteristics of the vertebral pedicle, and the technical features are discussed.


Rotationplasty in segmental resections of the femur.

The authors report 26 cases of high-grade malignant tumors of the distal femur (23 osteosarcomas, 3 Ewing's tumors) submitted to rotation-plasty. The five-years actuarial survival rate (in the 23 cases of osteosarcoma) was 69% and there was no incidence of local recurrence. The following complications were observed: wound dehiscence (6 cases), arterial thrombosis (in 2 patients submitted to resection and vascular termino-terminal suturing), paralysis of the sciatic nerve (2 cases), delay in consolidation (2 cases), traumatic fracture of the neo-femur (3 cases). All of the complications were resolved favorably, 5 of these requiring surgical treatment (33%). Satisfactory functional results were obtained in all of the cases, except in one patient who had limitation of the ankle joint subsequent to vascular compartmental syndrome. On the basis of the oncological, functional and biomechanical results reported in this study and in the literature, the authors discuss current indications for rotation-plasty.


The external fixator in the treatment of closed diaphyseal fractures of the lower limb during childhood. Indications and limits.

The authors successfully used an external fixator in 10 children affected by one of the following pathologies: fracture of the femur with poor consolidation and marked shortening of the limb; fracture in a hypoplastic segment; severe multiple trauma; delay in consolidation of pathologic bone; fracture in bone regeneration. On the basis of the results obtained, it is affirmed that the external fixator is the ideal means of osteosynthesis for use in any of the above-described situations.


Locked posterior dislocation of the shoulder.

What the authors mean by locked dislocation of the shoulder is an inveterate posterior dislocation of the humeral head which remains locked within the glenoid cavity as a result of anatomopathological lesion. Based on an analysis of four cases a diagnostic-therapeutic protocol is proposed in which the clinical and radiographic data obtained allows for a reliable diagnosis and suitable treatment.


The prognostic value of serum alkaline phosphatase in osteosarcoma of the limbs.

The values for serum alkaline phosphatase were evaluated in 340 patients affected with osteosarcoma of the limbs. The percentage of patients with high values for the enzyme at the onset of disease was significantly higher in the 69 cases who presented with metastases at the time of diagnosis, as compared to the 271 cases in which the neoplasm still appeared to be localized (81% vs 62%: p less than 0.001). In this last group of patients, treated with neoadjuvant chemotherapy, an evident relationship between values for alkaline phosphatase and prognosis was demonstrated. The percentage of patients who developed metastases was in fact 22% in the group with normal serum values for the enzyme at the onset of the disease and 40% for the patients with high values of the same (P less than 0.001). These data confirm the prognostic value for serum alkaline phosphatase in osteosarcoma, which should be taken into consideration when planning chemotherapy and in classifying patients for randomized therapeutic studies.


Post-chemonucleolysis computed tomographic findings.

The CT findings observed 6 months and 2 years after chemonucleolysis in 50 and 34 patients are reported. Emphasis is placed on the persistence of the hernia image in nearly 70% of the cases, together with an increase in degenerative intradiscal signs and degeneration of the facet joints; however, this did not lead to poor results 2 years after chemonucleolysis.


[Surgery of juvenile periodontitis].

The clinical efficiency of surgery for juvenile periodontitis (JP) followed-up for 13.5 (6-21) months was evaluated in this paper. A total of 102 teeth in 43 patients were included in the study, of them, three-wall infrabony pocket was in 74 teeth, two-wall infrabony pocket was in 21 teeth, one-wall infrabony pocket was in 7 teeth. After scaling, root planning and flap procedure, the rate of clinical efficiency was 74.51%, of which, three-wall infrabony pocket was 85.14%, two-wall infrabony pocket was 52.38%, one-wall infrabony pocket was 28.57%. The results show that if teeth with JP were effectively treated in time, better clinical efficiency can be obtained likewise, and if sectional osseous defects were properly treated, osseous restoration still is possible.


[Discussion of the effect of occlusal factor on bruxism].

Controversy has been existed on the effect of occlusal factor on bruxism. The purpose of this study is to evaluate the effect of occlusal factor on bruxism by clinical examination and photo-occlusion analysis. The patient group and control group are selected for this study. The results show that (1) the occlusal status in centric occlusion and eccentric articulation of the patient and control group has no significant difference; (2) the occlusal contact strength and distribution in centric occlusion of the patient and control group has no significant difference; (3) occlusal interferences are existed in different extent both in patient group and control group. This expresses that most of the subjects can compensate this kind of occlusal disorder without feeling any discomfort; (4) This can be concluded that occlusal factor is not an major causal factor on bruxism.


Intraoperative ultrasonography imaging in spinal surgery (technique and indications).

Intraoperative ultrasonography was conducted in 20 patients; the technique of intraoperative ultrasonography for use in spinal surgery is described. The authors emphasize that this non-invasive method obtains real time images of considerable diagnostic importance, allowing for a significantly minor use of image intensifier, with a consequent reduction in doses for both the patient and the staff.


The Gamma nail, sliding-compression plate. A comparison between the long-term results obtained in two similar series.

The authors report the results they obtained in a retrospective comparative study conducted on two systems of osteosynthesis used to treat trochanteric fractures: the sliding-compression screw-plate (CHS), and the Gamma nail. Two series were included in the study, each of which was made up of 50 cases; these were comparable in terms of fracture type, age of the patients, associated pathologies, and minimum follow-ups of 6 months. The parameters compared were: surgical trauma, average amount of time before a standing position could be resumed, resumption of motor activity previous to trauma, mechanical behavior of the instrumentation. The results show that both of the means of synthesis are capable of effectively stabilizing pertrochanteric fractures, avoiding the mechanical complications instead observed when more dated instrumentation, such as the screw-plate or nail-plate, are used, systems which are not characterized by a sliding cervico-cephalic screw. The amount of time before walking is resumed is quicker when the Gamma nail is used. There was no significant difference in terms of resumption of motor activity. Surgical trauma was the same in both series when the instrumentation was applied after reduction of the fracture in closed surgery, while blood loss was greater when fracture reduction required by application of the plate was performed in open surgery.


[Experimental canine maxillofacial arterial embolization with ethylcellulose microspheres].

External carotid artery tree embolization with ethylcellulose microspheres (EMS) was performed in ten mongrel dogs. Angiography, microangiography and pathological observations were carried out after embolization. In conclusion, EMS can permanently embolize the peripheral arterioles and histological changes of maxilla and mandible after embolization of internal maxillary artery are mainly nutrition defective and degeneration, such as microfracture of the bones, bony lacunae empty, disappearance of the intima of Haver's canals and pulpal degeneration. No evidence of whole or focal necrosis of the bones could be found from twelve hours to half a year after embolization.


Pure traumatic dislocation of the elbow.

A total of 89 patients with simple traumatic dislocation treated at the Rizzoli Orthopaedic Institute between 1975 and 1986 were reviewed. The authors considered trauma mechanism, treatment, and results. The evaluation showed that elbow dislocation without joint fracture has a favorable prognosis with return to complete functions. Frequently, para-articular calcifications do not negatively affect joint function. Immediate reduction and plaster immobilization for 2 to 3 weeks are required to obtain soft tissue repair, and in order to avoid functional restriction as a result of prolonged immobilization. After removal of plaster active mobilization is sufficient to obtain complete joint function.


[Study of dento-maxillo-facial growth and development on anterior deep bite with linguoversion of upper incisors during permanent dentition].

By means of computer-X-ray cephalometric system to study the dento-maxillo-facial growth and development was performed in 65 patients of anterior deep bite with lingoversion of upper incisors. The patients were divided into two groups: (1) 35 cases aged 12-16 years and (2) 30 cases aged 17-26 years. The same number of the subjects with normal occlusion were used as control group. The findings were as follows: 1. Besides the dento-maxillo-facial growth and development was abnormal vertically, the posterior anterior discrepancy of the growth trend is also one of the main problems in this kind of malocclusion. 2. The growth of the alveolar bone was inhibited anteriorly by the upper incisors; 3. The deformed mandible has the growth trend to rotate forward and upward in Counterclock wise direction so that it is wise to treat of early.


A case of membranous lipodystrophy with skeletal involvement.

It is the purpose of this study to describe the orthopaedic features of Nasu disease or membranous lipodystrophy based on the observation of a rare clinical case of the pathology and on a review of the international literature. The case described is probably the first to have been observed in Italy, and may be added to the 80 cases currently known to exist the world over. The disease affects young adults and involves pathologic fractures, as well as psychological and neurological disorders. It is currently of unknown etiology and its course is progressive until the death of the subject. The radiological aspect shows metaepiphyseal polycystic lesions of the long bones, with a tendency to expand, and involvement of the cortex. Causal treatment of the disease is currently not possible. The authors emphasize that differential diagnosis involving other diseases having a similar anatomopathological picture may be obtained, and they propose several suggestions for orthopaedic treatment based on their own experience.


[Central carcinoma of the jaws. A radiography and pathological analysis of 36 cases].

Records of 36 cases of central carcinoma of the jaws were collected, including 25 cases of squamous cell carcinoma; 9 cases of salivary gland carcinoma; one case of undifferentiated carcinoma and one case of basal cell carcinoma. The correlation between roentgenographic appearance and the histopathologic types are: (1) most lesions of osteolytic destruction are primary intraosseous carcinoma of the jaws (14/16); (2) most lesions of multilocular destruction are salivary gland carcinoma (8/11); (3) most lesions of unilocular destruction are malignant change of odontogenic cysts (7/9). Among 25 cases of squamous cell carcinoma, 7 cases are malignant change of typical keratocyst; 3 cases are similar to dentigerous cysts; 7 cases though show diffuse osseous destruction, they partly have characters of keratocyst in light microscope. So, the authors suggest that perhaps more central carcinomas of the jaws are arising from odontogenic keratocysts.


[Clinicopathological study of osteosarcoma of the jaw].

Eighty-five cases of osteosarcoma of the jaw were analyzed for clinical and histologic characters. According to the predominant histologic differentiation of the tumor, it was divided into osteoblastic, chondroblastic and fibroblastic type. Chondroblastic osteosarcoma was associated with the worst survival rate. The histologic grade was closely related to the prognosis of tumor.


[Immunohistochemical research for T cell subsets infiltrating in squamous cell carcinoma of oral cavity by monoclonal antibody].

Specimens from 25 patients with squamous cell carcinoma of the oral cavity were examined immunohistochemically, using Streptavidin-Biotin-Peroxidase Complex (ABC) with a series of monoclonal antibodies. Subsets of the infiltrating T lymphocytes in cancer tissues were identified and analysed. We found that, T cell infiltration was predominant. The degree of T cell infiltration was correlated well to the differentiation of cancer and a significant difference existed in OKT 3 + count between the better and the poorer differentiated tumors. Comparing with OKT4+, OKT8+ cells were predominant around cancer nest, the ratio is 1:2. Our results suggest that T cell subsets play a key role in immune response to tumor. Variable quantities and ratio of T subset might be associated with immune regulation imbalance, and reflected malignant grade of cancer and prognosis of the patients.


[Limulus lysate activity of some organisms resided in oral cavity].

Gram-positive and Gram-negative bacteria resided in oral cavity have been investigated using Limulus Lysate Assay. The study showed that both kinds of organisms have Limulus Lysate Activity (LLA). The data from the present study indicated that various species of Gram-positive and Gram-negative bacteria possess different degrees of LLA. There is no significant difference of LLA between Gram-positive and Gram-negative bacteria.


False aneurysms of the circumflex arteries of the femur as a complication of hip arthroplasty: description of one case.

The authors report one case of false aneurysms of the medial and lateral circumflex arteries of the femur in a patient submitted to cementless An.C.A. model hip arthroplasty. Clinical symptoms, characterized by fatigue, painful swelling in the proximal third of the thigh, in the anterolateral region, began three months after surgery. After an emergency arteriography was obtained, the presence of an aneurysm of the medial circumflex artery, and of the lateral circumflex artery one month later, was observed.


[The analysis of the maxillary complete denture and its underlying supporting tissues with three dimensional finite element method under the vertical occlusal force in centric occlusion].

A 3-dimensional finite element method was employed in this study to investigate the stress and displacement states of the maxillary complete denture and its underlying supporting tissues under the vertical occlusal force in centric occlusion. The calculation results show that the harmful transverse tension stresses within the base are concentrated on the maxillary incisor regions and its palatal area near the polishing surface. Pressure is exerted over most of the area of the jaw bone cortical surface and the compression stress is strongly concentrated over the alveolar ridge. The posterior palatal area of the denture base migrates away from the mucosa membrane and the other parts press the underlying tissues. These results indicate the biomechanical mechanism of the maxillary denture fracture and alveolar ridge resorption.


[Diagnosis of velopharyngeal incompetence after primary cleft palate repair].

Fifty four patients who had had primary cleft palate surgery and whose speech remained defective were examined by speech intelligibility test, lateral videofluoroscopy and flexible nasopharyngoscopy. We found that there are obvious individual differences in the velopharyngeal closure pattern of the patients with speech deficiency following primary surgery. The velopharyngeal closure patterns can be grouped into five categories according to the manner of the velum and lateral pharyngeal wall movements. The criteria of the classification and its significance are discussed in this paper.


[Arnold-Chiari malformation presenting in adult life].

Eleven patients of Arnold-Chiari malformation (ACM) in adults were reported. Nine of them associated with syringomyelia. The etiology, clinical features, diagnosis, differential diagnosis, the findings of SSEP, MEP, EMG, NCV, and the treatment of ACM in adults were discussed. Our observations lead us to consider that both clinical symptoms and examinations are crucial in the diagnosis. In addition, the delineation of ACM in adults with or without syringomyelia can be somewhat difficult by traditional radiological examinations, but can be readily demonstrated by MRI.


[Relationship among hyperglycemia growth hormone (CSF) and insulin in serum of cerebral hemorrhage].

40 patients of stroke were studied. The results showed that in Cerebral hemorrhage the correlation between ascending Growth hormone (GH) of CSF and insulin of serum was negative, but the positive correlation between ascending GH (CSF) and hyperglycemia. In patients of cerebral thrombosis the results of values above were no correlation. The pathological significance in such cases was discussed.


[A study of plasma von Willebrand factor concentration in patients with cerebrovascular disease].

The plasma vWF levels in patients with CVD were determined using ELISA technique with two monoclonal anti-human vWF antibodies. The results showed that the vWF values in the acute stage of CVD increased significantly. They gradually decreased third weeks after the onset of the CVD. The vWF in the chronic stage of CVD remained higher than normal, but lower than that in the acute stage. The plasma vWF values showed practically no difference in either cerebral infarction or hemorrhage. The average plasma vWF level in the patients with TIA was higher than that in the controls but lower than that in the patients with complete stroke. It was found that the plasma vWF correlated with platelet aggregation induced by ADP constantly, but not with other risk factors. It was considered that elevated vWF would rather be regarded in CVD as a relatively independent risk factor.


[A descriptive epidemiologic study of cerebrovascular disease (CVD) in the five provinces in northwest China].

In the five provinces of Northwest China. the population studied from random sampling was 693,190. The crude incidence rate of CVD was 88.2/100,000, the crude prevalence rate 195.6/100,000, and the crude mortality rate 74.4/100,000. The epidemic levels of CVD in Ning-Xia and Shan-Xi were the highest, Its epidemic levels in the urban areas were higher than those in the rural areas. The prevalence rate of CVD was highest in October. The epidemiologic study suggested that the epidemic levels of CVD in North west China was moderate only in comparison with similar studies carried out in some other parts of China.


[The endocrine abnormalities of depressive patients].

In the present study, the levels of the baseline cortisol, thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) and growth hormone (GH) were determined in 64 depressive patients, 17 patients with other depressive disorders and 19 normal controls. Meanwhile, dexamethasone suppression test (DST) and insulin tolerance test (ITT) were conducted. The baseline cortisol level at 23:00 in the depressive group (8.12 +/- 5.55 micrograms/dl) was significantly higher than that in the normal control group (4.80 +/- 2.10 micrograms/dl), and DST nonsuppression ratio in the depressive group (14.5%) was significantly higher than those in the other two groups (0%). There were not significantly differences in the levels of the baseline TSH, T3 and T4 between the three groups. There were not significantly differences in the baseline GH level between the three groups, but GH level in the depressive group at 90 min. after infusing insulin was significantly lower than that in the normal control group. The results showed the HPA axis hyperactivity, normal thyroid function and blunted GH response to insulin-induced hypoglycemia at 90 min. in ITT in the depressive patients.


[Plasma norepinephrine concentration and 24 hour urinary 3-methoxy-4-hydroxyphenylglycol sulfate excretion in endogenous depressed patients].

The plasma NE concentration was assayed with HPLC-ED and 24 hour urinary MHPG-SO4 excretion was determined in 23 endogenous depressed patients and 17 normal controls. In normal controls, plasma NE concentration was significantly correlated with age and was significantly higher in female than that in male. Plasma NE level in endogenous depressed patients was statistically higher than that in the age- and sex-matched controls (paired t test, P less than 0.05). The causes of the result difference among the past plasma NE studies was discussed and the necessity to design the age- and sex-matched controls in the future plasma NE study was suggested.


[Clinical practice of the diagnostic criteria of schizophrenia of Chinese classification of mental diseases II (CCMD-2) in 1,394 inpatients].

Re-diagnosed according to diagnostic criteria of schizophrenia of CCMD-2 was applied to 1,394 inpatients, who were diagnosed as schizophrenia when stayed the hospital in 1990. As a result, 98.5% of the cases conformed with four items diagnostic criteria of schizophrenia of CCMD-2; 98.7% of the cases conformed with the criteria of symptomatology; 99.4% of the cases conformed with the criteria for the course of illness; 99.8% of the cases conformed with the for the degree of seriousness; 100% of the cases conformed with the criteria of exclusion. Concordant rate in subtype: catatonic type 96.7%, hebephrenic type 92.2%, regressive type 90.9%, paranoid type 90.6%, residual type 50%, atypical type 50%. The must common symptoms were affective disorder (91%), disturbance of association (83.5%), delusion (62.2%). Frequency of other individual symptom were obviously difference, from 76.8% to 2.9%. We consider that diagnostic criteria of the schizophrenia of CCMD-2 is a appropriate for application in both clinical diagnosis and research work.


[Iatrogenic addiction of pethidine: clinical feature and experience of detoxification].

Narcotic analgesic pethidine is widely applied in clinical practice to relieve pain caused by cancer or severe surgical conditions. Iatrogenic addiction following long term medication of narcotic analgesics have been noticed but rarely documented. In this presentation, the authors studied the clinical feature of pethidine dependency as well as experiences of residential detoxification in analysing 34 cases collected in the National Drug Dependence Treatment Center in previous two years. Manifestation of pethidine addiction are much alike to heroin and all abstinent syndromes can be relieved either by methadone or clonidine within 3 weeks except psychological craving throughout the detoxification period. In conclusion, the authors hold that iatrogenic narcotic addiction of this kind is curable as long as the addicts are highly and conscientiously motivated together with rehabilitation measures after detoxification.


[Epilepsy and hypohaptoglobinemia].

The serum haptoglobin (Hp) of 24 patients with familial epilepsy and 21 relatives of them, as well as 21 patients with secondary epilepsy was determined by the method of linear concentration gradient (4-22%) polyacrylamide gel electrophoresis. The mean value of their serum Hp was significantly reduced to 54.83% (P less than 0.001), 76.48% (P less than 0.01) and 74.91% (P less than 0.01) of that of the control (109.63 mgHb/dl, n = 201) respectively. The possible pathophysiological mechanism of the epileptic seizures and reduced serum Hp level was discussed briefly.


[A neuropsychologic study in migraine patients].

A neuropsychologic test battery (nine kinds, eighteen items) was administered to 16 patients with classic migraine and 32 with common migraine in between attacks, 20 patients with functional headache and 20 physically and mentally healthy volunteers were sustained the test battery as control. The results suggested that the patients of both migraine groups had higher nervous dysfunction in motor, perception, memory, abstract thought, attention and information processing, statistic analysis showed significant difference between both migraine groups and normal control group. The higher nervous dysfunction became worse with the prolongation of course of migraine.


[Transcranial magnetic motor evoked potentials (MEP) and somatic sensory evoked potentials (SEP) in the management of cervical spondylitic myelopathy (CSM)].

Fourteen CSM patients with clinical findings of myelopathy had their diagnoses proved with MRI imaging and at operation. There were a control group of 28 normal subjects for MEP and another control group of 32 for SEP. The results of the study showed that 72.7% had MEP abnormality with prolongation of the central motor conduction time (CMCT) in 7 cases and absence of motor action potentials after C7 stimulation in one of the 11 patients. In 2 patients with prolongation of CMCT, normal SEPs were found in the same arm while 1 patient showed directly a reversal of the results. The short-term follow-up study in 10 patients showed normalization of the prolonged CMCT in one and reappearance of motor action potentials with C7 stimulation in another. The authors considered that the non-invasive and painless, transcranial magnetic stimulation of the motor pathways might be useful in the assessment and management of CSM patients and better than the electrical stimulation.


[Diagnosis of anterior cruciate ligament injury of the knee joint].

From January, 1979 to May, 1989, 107 patients with problems related to anterior cruciate ligament (ACL) were treated in our hospital. 100 of the patients had anterior cruciate ligament injury confirmed by arthrotomy or arthroscopy. The remaining 7 patients were found to be normal either by arthroscopy or arthrotomy. 29 patients had fresh ACL injury and 71 old. All the patients had history of trauma of the knee joint. Swelling and pain in the affected knee joint took place in fresh cases and few of them complained of instability or deformity of the knee. On examination, floating patella test was positive in the majority of the fresh cases. It was shown that accurate diagnosis could be made by Lachman test rather than by conventional anterior drawer test in dealing with fresh injury, but with old ones, Lachman test didn't show the advantages. Examination under anesthesia or arthroscopy helped a lot in diagnosing fresh ACL injury. Anterior drawer test (ADT) was significant in determining the existence of ACL injury. When ADT was positive, ACL injury was found in the majority of the cases, however, injured ACL couldn't be ruled out by negative ADT only. Positive valgus stress test on 0 degrees position suggests possibility of ACL injury, even ADT was negative. Despite the negative anterior drawer test positive posterior drawer test on three directions indicated the injury of the posterior cruciate ligament and the anterior cruciate ligament. The positive rate of ADT was higher than that of pivot shift test in dealing with anterior cruciate ligament injury. Positive pivot shift test suggests ACL injury.


[Interposition arthroplasty with pedicled island fascia flap. Experimental study and clinical application].

Interposition arthroplasty of knee joint, using island fascia flap, was performed on 90 rabbits. The fascia flap was vessel pedicled in 54 rabbits and not vessel pedicled in 36 for control. Results of the vessel pedicled island fascia flaps showed that clinically, the range of joint motion was 142.5 degrees on the average. Histologically, the transplanted fascia showed good vascularity and elasticity. There were no signs of adhesion or degeneration. Analogous cartilage appeared in 12 to 15 months. In the control group, the average joint motion was 83.61 degrees and the transplanted fascia showed degeneration of varying degree in each cases. On the basis of these experimental findings, we performed interposition arthroplasty with vessel-pedicled island fascia flap on 20 patients suffering from different joint diseases. The joints were 14 hips, 3 knees, and 3 elbows. Follow-up for 9 to 48 months after arthroplasty revealed clear-up of previous troubles with satisfactory function.


[Relation of ultrastructural changes of articular cartilage and the arthroscopic classification in osteoarthritic knee].

This paper reported the ultrastructural changes found in the diseased articular cartilages of 43 osteoarthritic knee joints, which were assessed according to the "Arthroscopic classification of the articular cartilage". The electron microscopic findings and the arthroscopic classification of the articular lesions were correlated. The lesioned articular cartilage revealed two categories of pathological changes. 1. The changes on the part of the articular chondrocytes comprised (1) The nucleus showed pyknosis and karyorrhexis. (2) The cytoplasm exhibited fat droplets, glycogen granules, and/or microfilaments. Lysosomes also emerged frequently. The mitochondria swelled and the rough-surfaced endoplasmic reticulum dilated and became vesiculated. At the same time there was detachment of cell processes or of the cytoplasmic membrane. The chondrocyte underwent necrosis, contracted and eventually disintegrated into lipid debris. These changes increased in extent and degree with the lesion and the severity went parallel with the sequence of the "Arthroscopic stage classification". 2. The changes on the part of the matrix included appearance of electron-dense lipid debris and numerous, coarse and banded collagen fibrils. They resided both in the pericellular matrix and in the general matrix. Sometimes fibroblast-like cells made their appearance in the matrix. These cells also revealed degenerative changes. All these changes went parallel with the sequence of the "Arthroscopic grade classification".


[Allotransplantation of meniscus in dog's knee. An experimental study].

This experimental study was to show the difference and outcome of allotransplantation and autotransplantation of meniscus in dogs. In the experimental group (9 dogs), the lateral meniscus was removed and replaced by one preserved for 2 weeks in tissue culture. In the control group (9 dogs), the lateral meniscus was excised but was sutured back to the place immediately. The specimens in each group were taken at 3, 6, 12, and 24 weeks after operation, and were examined microangiographically and histologically under light microscope and electron microscope. The results in both groups showed that the meniscus united to the capsule, chondrocytes in the menisci were intact and the collagen fiber orientation was regular. The articular cartilage of the uncovered area of the tibial plateaus showed normal appearance, and vascular neogenesis in the meniscal periphery was found 12 weeks after operation. These observations suggest that allogenic meniscus maintains its original histologic pattern and functional behavior after its transplantation. It makes possible to protect the knee joint from osteoarthritis.


[Risk factors of acute pancreatitis].

A total of 689 operative cases of acute necrotic pancreatitis (ANP) were collected from 42 hospitals all over the country by the ANP Cooperative Study Group in the years of 1987 to 1989. General data, laboratory findings, pathology of the pancreas and the type of surgical treatment were analysed according to the outcome of the patient. The results showed that 37% of the cases were related to cholelithiasis, the highest incidence was in age above 60, and female patients were predominant and with higher mortality. Laboratory findings at admission, WBC greater than 20,000/mm3, Hb greater than 15 g%, blood sugar greater than 200 mg%, serum bilirubin greater than 5 mg%, BUN greater than 20 mg%, and serum calcium less than 7 mg% were related to the markedly elevated mortality rate. Operative findings noted in patients with bloody or cloudy peritoneal fluid, necrotic changes up to 75% of the pancreas, more than 2 areas of extrapancreatic involvements and resection of a large portion of the pancreas was found to be necessary were all related to a higher mortality. And emergency operations performed within 24 hours after the onset of the disease was also related with a highest mortality rate.


[Diagnosis and treatment of closed complete rupture of patellar tendon. Analysis of 11 cases].

Eleven cases of closed complete rupture of patellar tendon (4 neglected ruptures and 7 fresh ruptures) were treated. Seven of them were treated in extension for 6-8 weeks after operation, 1 was immobilized with patellar traction in the early stage on bed, and 3 were mobilized and assisted with movable brace standing and walking through the body weigh on the knee in the early stage after operation. The aim was to promote the functional recovery of the knee joint. The mechanism of injury, clinical diagnosis, treatment and rehabilitation of closed rupture of patellar tendon were discussed in combination with clinical experience. And the suggestion of movement and active recovery in the early stage after patellar tendon surgery was put forward.


[Prognostic significance of cellular DNA ploidy level of the breast cancer].

This paper reports that cellular DNA ploidy level of paraffin-embedded histological material from 47 patients with stage II breast cancer was measured by flow cytometry. Meanwhile, the influence of cellular DNA level on disease-free survival (DFS) of postoperative patients for the breast cancer was analyzed. The results showed eighteen (38.3%) of tumors examined were DNA diploid, and the remainder were DNA aneuploid. Patients with diploid cancer had a significantly better disease-free survival compared with the patients with aneuploid cancer (P less than 0.02). Our results suggested that cellular DNA ploidy level is a good prognostic factor and of important significance in predicting prognosis of patients with the breast cancer.


[Low dose heparin in the treatment of deep vein thrombosis].

From 1988 to 1990, 45 cases of lower extremity deep vein thrombosis (DVT) was confirmed by 99mTc radionuclide venography (RNV) at PUMC hospital. Each case was treated by subcutaneous injection of low dose heparin. 21 cases of the 45 cases had post-therapeutic RNV. The results were excellent in 19 cases (complete improvement: swelling, discolouration and pain disappeared), good in 18 cases (marked improvement) and poor in 8 cases (incomplete improvement). Low dose heparin subcutaneous injection can relieve symptoms of DVT and avoid bleeding complication.


[Experience in surgical treatment of tetralogy of Fallot].

Corrective Surgery was done in 122 patients with tetralogy of Fallot between May 1981 and Oct. 1989. The surgical mortality was 7.4% (9 patients) and no late death were noted. Multiple stenoses of the RV out-flow tract were observed in 84 patients (69%). The rate of patching of RV out-flow tract was 85.2%. The operation was performed without preoperative cardiac catheterization or angiocardiography in 24 patients (19.6%). Selection of cases without angiocardiography, operative techniques, and management of anomalous coronary vessels were discussed.


[Long-term effect of one-stage urethroplasty with perineoscrotal insular skin tube in the treatment of complex posterior urethral stricture].

Thirty-one cases with complex stricture of posterior urethra were treated with one stage urethroplasty adopted perineoscrotal insular skin tube. The results of follow-up for 1 to 6 years were as follows: All cases urinated normally; The cystourethrography in 21 cases showed that urethrae were unobstructed; The urinary flow studies were carried out in 16 cases and the results showed that urinary flow rate curves were normal and that the maximum flow rate, the mean flow rate and the voiding time were all beyond normal values; The urethroscopy in 8 cases revealed that the surfaces of skin tubes remained smooth and without growth of hair stem. The facts stated as above indicated that this procedure was an ideal method for the treatment of long posterior urethral stricture.


[Large dose of penicillin misinjected into the spinal subarachnoid space].

Large dose of penicillin was misinjected into the spinal subarachnoid space of 3 patients. Dangerous symptoms such as epileptic status, difficult respiration and severe cerebral edema occurred. Fortunately, the patients were treated promptly without sequelae.


[Complications of hump nose after transplantation of tissue ersatz materials. Analysis of 349 cases].

Since 1986, 349 cases of postoperative complications of hump nose were treated (local high lension in 155, shape nonsatisfaction 104, red twelling and distortion 64, transplant exposure 13, and rejection and/or infection 13) and satisfactory results were obtained. The causes of these postoperative complications, remedial methods, and relation of ersatz materials to the complications were analyzed.


[Role of neutrophil and hydroxyl radical in shock-induced gut origin infection].

The relative roles of hydroxyl radical and neutrophils in the pathogenesis of shock-induced mucosal injury and gut origin infection (GOI) were determined. The incidence of GOI was higher in the shocked rats (30 mmHg for 30 min) than the sham-shock controls (87% vs 12.5%; P less than 0.01). Administration of the hydroxyl radical scavenger, dimethyl sulfoxide (DMSO) or iron chelator and deferoxamine reduced the incidence of GOI from 87% to 20% and 40% respectively (P less than 0.05). DMSO and deferoxamine appeared to prevent shock-induced GOI by blunting the magnitude of shock-induced mucosal injury. In contrast, neutrophil depletion did not prevent GOI or protect the intestinal mucosal in the shocked rats. Instead, the incidence of systemic spread of bacteria past the mesenteric lymph nodes to the livers and spleens of the shocked rats was higher in the neutrophil depleted rats (56%) than any other group (7%) (P less than 0.01). Thus, shock-induced GOI and intestinal injury appears to be mediated by xanthine oxidase generated oxidants such as hydroxyl radical rather than neutrophil-generated factors. In addition, neutrophil depletion may be clinically deleterious, since it promotes systemic sepsis rather than preventing shock-induced GOI.


[Early arthroscopy in diagnosis and treatment of acute injury of the knee].

Twelve patients with swelling and functional embarrassment of the knee joint caused by a traffic accident were radiographically found to have tibial plateau fractures (7 patients), posterior dislocation (1), fracture of anterior tibial spine (1), single fracture of the posterior tibial spine (1), anterior dislocation (1), and negative findings (1). Arthroscopy was performed 2 to 10 days after trauma, revealed associated injuries not shown on X-ray films in every knee including rupture of cruciate ligaments (ACL 8, PCL 1), tear of menisci (lateral one 8; medial one 2), and disruption of collateral ligaments (medial one 3; lateral 1). These injuries were promptly treated accordingly either through the scope or by open operation. Beside, inadequately reduced bone fragments, viewed through the scope, were further corrected incidentally and conveniently. We believe that early arthroscopy for acute knee injury is a real necessity in perfecting diagnosis and improving treatment.


[Clinical analysis of Vogt-Koyanagi-Harada's disease and its association with HLA].

Clinical analysis of 34 patients with Vogt-Koyanagi-Harada's disease in Hunan Province showed that most patients had good visual prognosis following intensive corticosteroid therapy. A multivariate stepwise regression analysis indicated that visual acuity at the first visit, elapse of time before treatment began, duration of papilledema, and presence of ocular complications were significant factors for eventual visual acuity. HLA typing on 25 patients and 65 normal controls suggested that HLA-DR4 and DRW53 might be an immunogenetic background for the high incidence of the disease in oriental populations.


[Development of the lens and zonulae in the human embryo].

The embryonic development and ultrastructures of the lens and zonulae in 212 eyes of 131 human embryos were studied by light and electronic microscopy, with the finding that the capsule and zonulae appeared earlier than previously reported. The laminate structure of the capsule was observed in the 7 week embryo, and the early structures of zonulae were discernible in the 10th week on the basement membrane of the non-pigmental epithelium of the ciliary body and on the capsule, indicating that the capsule was specialized basement membrane of the lenticular epithelial cells, and the zonulae originated from the non-pigmental epithelium of the ciliary body and the capsule of lens.


[Experimental autoimmune uveitis--a clinical and pathological study].

Experimental autoimmune uveitis (EAU) was induced in 95% of guinea pigs after immunization by a single intradermal injection of homologous retinal tissue in Freund's complete adjuvant and subcutaneous injection of dead pertussis bacilli. The clinical features were circumcorneal injection, cells and flare in the anterior chamber, vasodilation in the iris, and marked cellular exudate in the vitreous. The pathological changes were characterized by diffuse proliferative granulomatous panuveitis, consisting of lymphocytes, macrophages, and epithelioid cells. The outer layers of the retina were disrupted or missing in areas where the pigment epithelium was damaged.


[Establishment and computer drawings of a dynamic mathematical eyeball model].

A dynamic mathematic model of the eyeball is established with the computer on the basis of ocular anatomical data and equations of the axial length as the variable in relation to other parameters. With an automatic plotter, the model is transformed into 4 geometric diagrams of the frontal and lateral views, and the meridian and coronary sections. Meanwhile, a set of pictures for intraocular foreign body localization is developed.


Immunonutrition and enteral hyperalimentation of critically ill patients.

Physicians need to be maximally aggressive in their use of total enteral nutrition (TEN) in the critically ill patient, due to its lower cost, better physiology, and lower complication rate when compared to parenteral therapy. Various components in TEN such as glutamine, arginine, RNA nucleotides, omega-3 fish oils, and fiber, may have important roles in immunonutrition by maintaining gut integrity, stimulating the immune system, and preventing bacterial translocation from the gut. For each patient, the physician must choose the optimal enteral formula for that particular disease or organ failure state to maximize nutrient substrate assimilation and tolerance. Total parenteral nutrition (TPN) should be used only when a true contraindication to enteral feedings exists or as adjunctive therapy when full nutritional requirements cannot be met by TEN alone.


Alterations in protein kinase C system of colonic epithelium during fasting-refeeding. Evidence for protein kinase C independent pathway of enhanced proliferative activity.

In the present study, we compared (1) incorporation of [3H]dThd into DNA, (2) total protein kinase C (PKC) activity, (3) the subcellular distribution of PKC, and (4) PKC isozyme (alpha, beta and gamma) mass in colonic mucosal scrapings and isolated superficial and proliferative colonic epithelial cells from 48-hr fasted, 48-hr fasted-refed, and ad libitum-fed rats. Total colonic mucosal PKC activity and PKC alpha mass were higher and the in vivo rate of [3H]dThd incorporation into mucosal DNA was markedly depressed in 48-hr fasted rats compared to ad libitum-fed or fasted-refed rats. These alterations were localized predominantly to the proliferative pool of colonic epithelial cells. Despite an 11-fold increase in mucosal DNA synthesis, no alterations in total mucosal PKC activity were detected in fasted-refed rats compared to rats fed ad libitum. Moreover, no differences in the subcellular distribution of PKC were noted among any of the dietary groups. Intrarectal instillation of deoxycholate activated PKC and increased DNA synthesis 1.5- to 2-fold. Deoxycholate-induced increases in DNA synthesis, but not those induced by refeeding, were inhibited by treatment of rats with the PKC inhibitors H-7, sphingosine, or staurospaurine. The results do not support a role for PKC in the mediation of increased proliferative activity of colonic mucosa induced by refeeding.


Cytokine effects in a human colonic goblet cell line. Cellular damage and its partial prevention by 5 aminosalicylic acid.

The aim of the present study was to investigate the effects of cytokines on intestinal goblet cells in vitro. For this purpose, we examined the effects of recombinant interferon gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on the human colonic goblet cell line Cl.16E by morphological and kinetic studies, and by the assessment of mucus production during IFN-gamma/TNF-alpha treatment. Control cultures of Cl.16E cells grown on nitrocellulose filters formed monolayers of polarized goblet cells, which had kinetic characteristics similar to those of a differentiated epithelium in steady state. The combined action of IFN-gamma and TNF-alpha caused a dose-related cellular exfoliation, leading to the formation of a mucoid cap made of mucus and cellular debris. The remaining viable cells underlying the mucoid cap were cuboidal and devoid of mucus granules. A dose-related increase in cellular incorporation of [3H]thymidine was reactive to the cytokine-induced cell loss. The synergistic effects of IFN-gamm and TNF-alpha were found to be reversible when the cells were reincubated in a culture medium without cytokines. Furthermore, 5-aminosalicylic acid partially protected Cl.16E cells against cellular injury caused by IFN-gamma and TNF-alpha. On the whole, these morphological and kinetic findings argue that the changes induced in Cl.16E cells by IFN-gamma and TNF-alpha closely parallel those observed during the acute phase of ulcerative colitis, and show that these cytokines can regulate intestinal mucus production by modulating cellular exfoliation, thus leading probably to a reinforced protection of the damaged mucosa.


Risk factors for small bowel cancer in Crohn's disease.

Suspected risk factors for adenocarcinoma of the small bowel in Crohn's disease include surgically excluded small bowel loops, chronic fistulous disease, and male sex. Review of all seven University of Chicago cases failed to confirm any suspected risk factor. A case-control study was performed to identify possible alternatives. Each case was matched to four randomly selected controls from an inflammatory bowel disease registry matched for year of birth, sex, and confirmed small bowel Crohn's disease. Three factors were significantly associated with the development of cancer: (1) Four cancers developed in the jejunum, and jejunal Crohn's disease was associated with the development of cancer [odds ratio (OR) 8.0, 95% confidence interval (CI) 1.6-39.3]. (2) There was an association between the development of cancer and occupations known to be associated with an increased colorectal cancer risk (OR 20.3, CI 2.7-150.5). Three cases (a chemist with exposure to halogenated aromatic compounds and aliphatic amines, a pipefitter with exposure to asbestos, and a machinist with exposures to cutting oils, solvents, and abrasives) and one of 28 controls (a fireman with multiple hazardous exposures) had an occupational risk factor. (3) Among medications taken for at least six months, only 6-mercaptopurine use was associated with cancer (OR 10.8, CI 1.1-108.7). In conclusion, proximal small bowel disease, 6-mercaptopurine use, and hazardous occupations are associated with cancer of the small bowel in patients with Crohn's disease and can be added to the list of suspected risk factors.


Gastroesophageal pH step-up inaccurately locates proximal border of lower esophageal sphincter.

Limiting the widespread use of 24-hr pH monitoring is the necessity of manometrically placing the pH probe 5 cm above the proximal lower esophageal sphincter (LES) border. Therefore, we prospectively compared LES localization by gastroesophageal pH step-up with manometry in 71 patients and 14 asymptomatic volunteers. The gastroesophageal pH step-up significantly correlated with the proximal LES border in patients (r = 0.53, P less than 0.0001) and volunteers (r = 0.91, P less than 0.0001). Based on previously published criteria, the pH step-up value was considered acceptably accurate if it was within +/- 3 cm (6 cm total span) of the manometrically determined proximal LES border. In 58% of patients and 29% of volunteers the pH step-up occurred outside this accuracy range. Esophagitis (P = 0.015) and abnormal reflux parameters (P = 0.002) were variables contributing to this error. Subsequent analysis found that the pH step-up overestimated the proximal LES border and occurred at the midportion of the sphincter. The pH step-up still inaccurately located the mid LES in 34% of patients. Therefore, manometry should remain the standard for accurate LES localization prior to placing the pH probe.


Interaction of gastroesophageal reflux and esophageal motility. Evaluation by ambulatory 24-hour manometry and pH-metry.

The present study addresses the question of whether esophageal motility shortly before, during, and after gastroesophageal reflux (GER) is different in patients with GER disease and healthy controls. Twenty-four-hour continuous recordings of intraesophageal pressures and pH were performed in 12 unselected patients with clinically proven GER disease and in 11 volunteers using a new ambulatory and digital recording device. All GER episodes in each studied subject were classified according to their associated motility pattern shortly before (induction period) and during (response period) GER. More GER episodes were analyzed in patients than in volunteers (median: 41 vs 26, P less than 0.05), and a total of 917 GER episodes (593 in patients, 324 in volunteers) was recorded. During the induction period patients more often had irregular esophageal contractions (median: 23% vs 13%, P less than 0.05) and less often had a peristaltic sequence (median: 6% vs 21%) than normals. No difference between patients and controls existed when comparing the frequency of negative pressure peaks or common cavity phenomena shortly before GER. During the response period peristaltic motility in patients was decreased (median: 10% vs 47%, P less than 0.05). We conclude that: (1) GER events in GER patients are more often associated with irregular esophageal contractions than in healthy controls; (2) GER patients present with a diminished, if any, esophageal peristalsis during GER; and (3) combined ambulatory manometry and pH-metry provides clinically useful information on the individual pathogenesis of GER disease, which is superior to the information retrieved by pH-metry alone.


Effect of cold stress on postprandial lower esophageal sphincter competence and gastroesophageal reflux in healthy subjects.

The effect of cold stress on postprandial lower esophageal sphincter competence and gastroesophageal reflux was investigated in nine healthy subjects. All subjects were studied twice in a randomized order according to a common protocol: 30 min after completion of a 700-kcal meal they put their nondominant hand in water either at 37 degrees C (control stimulus) or at 4 degrees C (stressful stimulus) cyclically for 20 min. Pulse rate and blood pressure rose significantly (P less than 0.01) during the stressful stimulus, but remained unaffected by the control stimulus. Rate of transient lower esophageal sphincter relaxations/30 min [median (interquartile range)] was similar before and during control stimulus, 4 (2.7-5.0) and 3 (2.0-4.5), respectively, whereas it was markedly inhibited during the stressful stimulus [from 5 (3.7-6.0) to 2 (1.0-2.0); P less than 0.05 vs control stimulus]. Rate of reflux episodes/30 min was also similar before and during control stimulus, 1 (0-1.2) and 1 (1.0-2.2), but fell consistently during the stressful stimulus [from 2 (0-3.2) to 1 (0-2.0); P less than 0.05 vs control stimulus]. Percentage of transient lower esophageal sphincter relaxations accompanied by a reflux episode was unaffected by stress as was basal lower esophageal sphincter pressure. It is concluded that cold stress decreases the postprandial rate of transient lower esophageal sphincter relaxations and reflux episodes in healthy humans.


Continuous versus intermittent acid exposure in production of esophagitis in feline model.

Our morphometric feline model of acid-induced esophageal damage histologically resembles human reflux esophagitis. The histologic scoring system includes intensity and linear extent of basal cell hyperplasia, intraepithelial and subepithelial segmented leukocytes, and ulcers. Each of these four categories is scored from 0 to 4, for a potential total score of 16. Some reports have indicated that the long-duration acid exposure episodes during recumbent nighttime reflux are apt to be associated with greater injury than shorter episodes during daytime upright exposure. We tested the hypothesis that longer single exposures to acid would incite greater morphologic damage in the cat than would multiple, shorter acid exposures. To study the influence of continuous versus intermittent hydrochloric acid exposure, groups of six cats each were infused continuously (single infusion) for 15, 20, or 30 min, and compared with cats infused for 2-min acid infusion times. Our studies indicate that total acid exposure and mucosal damage are more likely to be greater after multiple episodes of the same total duration with adequate clearing (ie, awake upright reflux) than after single long episodes of acid exposure that are poorly cleared (ie, sleeping).


Acid perfusion and edrophonium provocation tests in patients with chest pain of undetermined etiology.

During the last five years, 672 patients were referred to our esophageal investigation unit; 110 patients (16.3%) of these presented with chest pain of undetermined etiology (CPUE) alone. Since the nature of this pain is intermittent and rarely present during the diagnostic study, acid perfusion and intravenous edrophonium tests were added as provocative tests after baseline esophageal manometry. Following completion of the motility studies, 24-hr pH study was performed to detect gastroesophageal reflux (GER). Twenty-nine patients (26.4%) had positive acid perfusion (APT) test whereas 26 patients (23.6%) had positive edrophonium test (ET). In the group of patients with positive acid perfusion test, 12/29 (41.3%) had GER, 8/29 (27.5%) had both motility disorder and GER, 2/29 (6.8%) had motility disorder, and 7/29 (24.1%) had normal esophageal motility and 24-hr pH studies. In the other group, 13/26 (50%) had motility disorder and 13/26 (50%) had both motility disorder and GER. There were no significant differences between the two tests as far as reproducibility of symptoms was concerned. We conclude that ATP and ET showed the esophageal origin of CPUE in half of our patients and therefore in a substantial percentage of patients the esophageal origin of chest pain will remain very difficult to prove.


Effect of indomethacin and misoprostol on fasted gallbladder volume and meal-induced gallbladder contractility in humans.

Impaired gallbladder contractility is a prerequisite for gallstone formation in animal models. Prostaglandins are important mediators of gallstone formation and may affect gallbladder contractility in animals. The aim of this study was to evaluate the effect of indomethacin, an inhibitor of prostaglandin synthesis, and misoprostol, a synthetic prostaglandin, on gallbladder contractility in man. Seven male volunteers (18-33 years old, mean age 23 years) were studied under blinded conditions after an overnight fast, during control periods and following ingestion of indomethacin 125 mg (75 mg at 10 PM, 50 mg at 6:30 AM) or misoprostol 800 micrograms (400 micrograms at 10 PM, 400 micrograms at 6:30 AM) orally. Gallbladder residual volume was determined by real-time ultrasonography before and 10, 20, 30, 40, and 50 min after ingestion of a standard liquid fatty meal stimulus. Fasting gallbladder volume (milliliters) was similar in all three periods [control 20.8 (1.6); indomethacin 20.8 (2.9); misoprostol 18.3 (1.6)]. The fatty meal stimulus caused prompt contraction, resulting in minimum residual volume of 7.5 (1.4) ml in the control period. Pretreatment with misoprostol or indomethacin did not affect the minimum volume obtained compared with control period [misoprostol: 5.8 (1.4) ml; indomethacin 5.9 (1.3) ml)]. Thus administration of indomethacin and misoprostol had no effect on fasting gallbladder volume or gallbladder contractility in humans as assessed by ultrasonography.


Effect of cholecystectomy on gallbladder bile composition.

Human bile samples are commonly used in biliary research; however, the optimal sampling technique is not known. The current study examines whether bile obtained prior to operative manipulation of the gallbladder differs in composition from samples obtained after cholecystectomy. Gallbladder bile samples were obtained from 26 patients undergoing cholecystectomy. An initial sample was obtained prior to manipulation or devascularization of the gallbladder, and a second sample was obtained after the removal of the gallbladder from the operative field. Gallbladder bile pH and total protein were significantly increased in the postcholecystectomy samples. Bile obtained after cholecystectomy also contained significantly less phospholipid. Gallbladder bile cholesterol, total bile acids, bilirubin, ionized and total calcium, cholesterol saturation index, and total lipids were similar between techniques. These results indicate that manipulation of the gallbladder during cholecystectomy produces alterations in gallbladder bile composition. These results also emphasize the need for consistent sampling technique when obtaining samples for biliary research.