[Alfred Th. Leber (1881-1954): a pioneer in tropical ophthalmology. Missing in the South Seas--rediscovered in India]. In spite of the brief duration of German colonial rule during that period tropical medicine enjoyed a remarkable growth and development. This is the first account of the career of the pioneer of tropical ophthalmology, Alfred Theodor Leber (1881-1954); medical history had previously reported him missing in Java after the 1st world war. His career was greatly influenced by his uncle, Theodor Leber (1840-1917), the founder of experimental ophthalmology. Alfred Leber was the one who combined teaching and research in the subjects of ophthalmology and tropical medicine. During his first expedition as a private lecturer together with von Prowazek in Samoa (1910-1911), he discovered the involvement of the eye in filarial infections with Wuchereria bancrofti (Lebers fundus). In consideration of his extraordinary work he was appointed professor at the young age of 33. After his training at the eye clinic at Berlin University under von Michel he worked as senior physician with von Hippel in Göttingen. Both Ludwig Külz and the famous painter Emil Nolde joined him on his second expedition, to New Guinea, in 1913. During his expedition in summer 1914 World War I broke out. Leber could not return to Germany. He stayed in the neutral Dutch East Indies during these years. Favoured by the ravages of war, British and Australian authorities (Military Intelligence, War Office, Defence) succeeded in seizing some of Leber's research reports and kept them under lock and key. The "Leber-Külz medical demographic New Guinea expedition on behalf of the Reich's Colonial Office" was therefore known to the public only as "Emil Nolde's travels in the South Seas".(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical and histopathological observations of retinal sutures. Preliminary report]. One of the therapeutical methods in the great hole and ora serrata retinal detachment are the retino-scleral sutures. The study evaluates the tolerance of this type of stitches. Experimental investigations have been performed in rabbits with sutures of Ethilon 8-0 or chromic collagen 8-0 put through the sclera. Both segments--the anterior and posterior one have been taken under consideration. The eye have been enucleated on the 1st, 2d, 7th, 14th and 60th day after surgery and evaluated macroscopically. The specimen from the spot of stitching have been executed after fixation in formaline. Clinical observations, macroscopic evaluation of the enucleated eyes and results of the histopathological examination showed good tolerance of the retinal stitches through the tissue of the rabbits eye and indicate the possibility of a clinical utilization of this method.


[Detection of early cataract changes in the crystalline lens by using in vivo spectrophotometry of the eye]. The aim of the paper was to study with the use of in vivo spectrophotometry of the eye the threshold values of the registered light above which one can observe clinically visible opacities of the lens. The performed experiments did not however show any major differences in the values of the registered light between persons with early cataract and control group because of considerable scattering of the results in both these groups. In order to explain the prognostic value of the in vivo spectrophotometry of the eye it is necessary to perform long-term observations of the further fate of persons with high values of the registered light.


[Effect of cataract extraction on the results of in vivo spectrophotometry of the eye]. The authors compared the results of in vivo spectrophotometry of the eye in persons with a normal lens, in patients with aphakia and after an operation of intraocular lens implantation. The results received show that in the range of 400-500 microns half of the light registered by the spectrophotometer is connected with the lens in the eye. This speaks for the assumption that in vivo spectrophotometry in this range of the wave length may be one more method enabling an objective evaluation of the transparency of the lens. In the case of patients after operation of implantation of an intraocular lens the quantity of of the light reaching the retina is only slightly larger than in persons with a normal lens.


[The SRK formula for calculating the power of intraocular anterior-chamber lenses]. Presented is the evaluation of the usefulness of the SRK formula for the calculation of the power of the intraocular anterior chamber lens of Pannu type. This accuracy is characterised by the value of the postoperative deviation of refraction of the operated eye. It has been noticed that the value of this deviation is fluctuating in the early postoperative period. Its stabilization comes out not before the 6th-9th month after surgery. This points out to the necessity of calculating the correcting coefficient A for the SRK formula into the late postoperative period.


[Organization and the results of surgical treatment of cataract with implantation of artificial lenses in ambulatory conditions]. Forty one patients aged 29 to 82 years were subjected to cataract extraction in ambulatory conditions. Fifty eyes were operated, among them 33 with implantation of a posterior chamber artificial lens. In cases of a lack of opacities in the cortex layers their structure was loosened before the operation by a YAG laser. The lens was extracted mainly by phacoemulsification. The ambulatory procedure did not result in any undesirable consequences. The profits of operation performed in such a way were stressed. Attention was called to the fact that by prudent qualification of patients and a careful selection of surgical methods the risk of this kind of treatment is not greater than in stationary conditions.


[Cyclosporine in the treatment of uveitis]. The study presents several years of observations concerning the application of cyclosporin in 2 cases of a very severe recurrent uveitis. The treatment by cyclosporin enabled to control the situation. In 1 case a cataract extraction was performed without complications. Both patients remain in observation of the out-patients department. The treatment with cyclosporin requires observation of some precautions (control of function of the liver, kidneys etc.). No complications after cyclosporin therapy were seen.


[Oral acyclovir treatment of viral eye infections]. Forty four patients with virus conjunctivitis, keratitis, uveitis and retinitis were treated by acyclovir in tablets--5 times a day 400 mg.; the results were satisfactory. The drug was well tolerated and it could be used also in patients who showed hypersensitivity for acyclovir after ++intra-conjunctival application in the form of ointment.


[Preliminary report on using therapeutic ozone in infectious conjunctivitis and keratitis and in corneal degeneration]. The preliminary report presents the results of application of ozone preparation in form of ophthalmic drops in 89 patients (134 eyes). This preparation has been used in virus conjunctival and corneal diseases as well as in corneal degenerations after inflammatory conditions and chemical burns. One observed as acceleration of the regeneration processes in active inflammatory conditions of the anterior eye segment; instead the cases of leucoma and corneal opacities did not show any clinical effect.


[Preliminary report on using general ozone therapy in diseases of the posterior segment of the eye]. Autotransfusion of ozone venous blood was performed in 174 patients, in 32 patients ozone was given intraarterially. General ++ozone therapy was used for the first time in Poland in the following ophthalmological conditions: retinal pigment dystrophy, glaucomatous optic atrophy, in optic neuritis, after injuries and in cases of unknown aetiology; in degenerative-atrophic changes of the choroid, in high myopia, in post-inflammatory cases, in other degenerative diseases and in bacterial corneal ulcerations. Ozone therapy in these conditions seems to be favourable especially when the pathological process is not extensive. One could observe an improvement of the visual acuity and of the visual field.


[Personal experiences with transplantation of antigenically compatible cornea. Preliminary report]. Ten corneae from donors selected in respect of partial compatibility of the HLA antigens were transplanted in the period October 1988--October 1989. The grafting was performed in 10 patients with leukomas included in the group of maximal risk (5+). In 9 patients the leukomas were due to ocular burns (chemical in 8 patients and thermal in 1 patient). In 1 patient, a 74 years old man the grafting was performed in the single eye with Salzman's corneal dystrophy with a simultaneous cataract extraction. During observation, which lasted 2 to 12 months 6 grafts remained transparent, 1--partly opacified. Not any transplant did totally opacify.


[Transplantation of the cornea from the donor selected on the basis of HLA compatibility in high risk leukoma]. Fifteen corneal grafts were performed in 15 men with high risk leukoma (5+) in the period October 1988--November 1990. The age of the patients oscillated between 11 and 76 years. In 5 patients the grafting was done in only eye. The period of observation after surgery amounted 4-29 months. The favourable results (transparent and ++semi-transparent grafts) were obtained in 9 eyes (60 p.c.) and partly opacified grafts in 6 (40 p.c.). Neither of the grafts opacified. In the preceding years--without taking into account the antigenic selection of the donor--favourable results in similar leukoma cases were achieved in ca. 42 p.c. of cases.


[Preliminary results of laser coagulation of the retina in the treatment of diabetic retinopathy in pregnant women]. The authors observed a group of 16 pregnant women aged 22-38 years with insulin-dependent diabetes of D, R, RF class (accor. to White). All the patients were treated by conventional insulin therapy. The fundus in 8 of them (16 eyes--group 1) was normal, in following 8 the fundus showed changes of the type of simple retinopathy (13 eyes--group 2) and proliferative retinopathy (3 eyes--group 3). Laser photocoagulation of the fundus changes was executed in 9 eyes. In the final period of gravidity the group 1 and 2 did not exhibit any new changes or intensification of the already existing; this could be connected with application of an intensive conventional insulin therapy. All the eyes (group 1 and 2) except one showed stabilization of the retinal changes after laser treatment.


[Laser photocoagulation as a completion of the surgical treatment of retinal detachment]. Among 600 operated retinal detachments in the last 5 years (1985-1989) there was no tight closure of the retinal hole after operation in 78. The causes were: the implant situated paracentrally to the hole, lack of contact between the implant and the hole, an insufficient scar, additional hole. Various types of the performed surgery were analyzed: the meridional or parallel implant, the balloon and endotamponade with the SF6 gas, executed with and without drainage of the subretinal fluid. In cases in which in the postoperative course was detected a lack of tightness of the hole the laser photocoagulation was performed in the area of the flat retinal detachment on the implant in a couple of stages. A favourable result of photocoagulation was attained in 75 patients (96.2 p.c.); in the remaining 3 patients (3.8 p.c.) a second surgical procedure was performed.


[Hereditary macular degeneration in 3 generations]. The family was described, where the vitelliruptive macular degeneration with various morphological picture was diagnosed in four persons (two males and two females) on the basis of ophthalmoscopic examination as well as fluorescein angiography. Morphologic variability of this dystrophy may lead to diagnostic difficulties, what previously caused unnecessary treatment of two examined men as cases of "central choroiditis".


[6 cases of bilateral melanoma of the uvea]. Six patients with bilateral ocular melanoma were treated in the period 1967-1989. In one case both eyes were enucleated, in 4 one eye only, the other eye was treated. In all enucleated eyes the clinical diagnosis of melanoma was confirmed histopathologically. Two patients died because of metastases to the lungs and liver, one is alive and remains in a periodical control; there are no informations on the remaining 3 patients.


[Familial occurrence of congenital aniridia]. Aniridia and coloboma iridis are congenital defects which are inherited in common as an autosomal dominant trait. The study presents an analysis of 15 pedigrees of 15 patients from 3 families; it confirms the hereditary character of aniridia and iris coloboma and indicates the variability of the genetic expression.


Regulation of neurite outgrowth through protein kinase C and protease nexin-1 in neuroblastoma cell. Accumulating evidence has demonstrated that protein kinase C (PKC) and protease nexin-1 (PN-1) may be involved in neuronal differentiation including migration, neurite outgrowth, target recognition, and synaptogenesis. We investigated the potential roles of PKC and PN-1 in neurite outgrowth of human neuroblastoma cell line, GOTO. Upon withdrawal of serum GOTO cells extended neurite processes within 3 h and formed fine network of neurites after 24 h. This morphological change was completely inhibited by thrombin and phorbol-12-myristate-13-acetate (PMA). Withdrawal of serum increased the neurofilament (NF)-L and -M mRNA levels and thrombin did not inhibit the effect of withdrawal of serum. A potent PKC inhibitor, H-7 induced neurite outgrowth in the presence of serum, however, it did not increase the NF mRNA levels. Actinomycin D and cycloheximide did not inhibit the initial neurite outgrowth induced by withdrawal of serum, while these inhibited the increase in the NF mRNA levels. Thrombin retracted the serum depletion-induced neurites but did not retract the neurites induced by H-7. The specific activity and subcellular localization of PKC did not differ between GOTO cells cultured in serum-containing and -free media for 12 h. The serine protease inhibitory activity was undetectable in the serum-free conditioned medium of GOTO cells but the PN-1 mRNA was clearly detected by Northern blot analysis to a less extent than glial cells. Withdrawal of serum or treatment with H-7 did not increase the PN-1 mRNA level in GOTO cells, but thrombin increased its level about 7 folds in serum-free condition. These results indicate that the initial neurite outgrowth requires neither new RNA nor protein synthesis, and that PKC negatively regulates neurite outgrowth and thrombin blocks neurite outgrowth through PKC-dependent pathways.


Genetic changes in multi-step development of colorectal cancer. We studied activated mutations of K-ras gene in three forms of colorectal tumors, i.e., 45 specimens of colorectal adenoma (CA), 10 of 'cancer in adenoma' (CIA), and 24 of colorectal cancer (CC), and in 15 of gastric cancer (GC) as controls. Chromosome aberrations were also examined in 7 specimens of CA, 3 of CIA, 8 of CC, and 7 of GC. Mutation of K-ras Codon 12 was observed in 12 (26.7%) of the 45 specimens of CA, 6 (60.0%) of the 10 specimens of CIA, 6 (25.0%) of the 24 specimens of CC, and 1 (6.7%) of the 15 specimens of GC. In CA, its frequency increased with the degree of histological atypism. In CA and CIA, its frequency increased with the increase in short diameter. The most frequent chromosome aberration was the numerical excess of chromosome 7. Numerical deficiencies of chromosomes 17 and 18 or structural abnormalities of 17p+ and 18q+ were noted in 1 specimen each of CA and CIA, and 2 of CC. Thus, aberrations of these two chromosomes were concurrent. 5q--was observed in 1 specimen each of CA and CC. These findings were not contradictory to the multi-step carcinogenesis model of the colorectum based on the hypothesis that carcinogenesis requires activation of an oncogene by mutation accompanied by defects of several genes that might normally inhibit tumorigenesis.


[Evaluation of pupillary reaction to light flash in patients with retinitis pigmentosa]. Twenty four patients with retinal pigment dystrophy were subjected to examination of pupillary reaction. Evaluated was the amplitude of pupillary reaction on a standard light flash. The results received were compared with the field changes. It was noted that the amplitude is diminished depending on the changes in the visual field.


Phosphorylation of CRE-BP1, a cyclic AMP response element binding protein, by protein kinase C and cyclic AMP-dependent protein kinase. CRE-BP1 is a transcriptional activator binding to the cyclic AMP response element, which has a putative metal finger structure and the leucine zipper motif linked to a cluster of basic amino acids in the amino and carboxyl-terminal regions, respectively. The activities of a number of transcription factors are known to be controlled through phosphorylation and dephosphorylation. At the first step for understanding of the regulation of CRE-BP1, phosphorylation of CRE-BP1 was studied in vitro. The human recombinant CRE-BP1 was phosphorylated by protein kinase C and cyclic AMP-dependent protein kinase. These two protein kinases recognized distinct seryl residues of CRE-BP1. Amino acid sequence analysis after phosphopeptide map indicated that two seryl residues, Ser-340 and Ser-367, located in the basic region of CRE-BP1 were identified as the major protein kinase C phosphorylation sites, whereas Ser-62 downstream of the metal finger structure was determined as the phosphorylation site by cyclic AMP-dependent protein kinase. The phosphorylation of CRE-BP1 by these two protein kinases may regulate the function of this transcriptional activator protein.


Multiple hormone secretion and gene expression in clones isolated from rat insulinoma cell lines. Current evidence suggests that a multipotential endodermal cell may give rise to all islet cell phenotypes. Five (N1-N5) and twenty-one (m1-m21) pluripotent rat islet cell clones were isolated from two hormone-producing cell line (RIN-r, RINm5F) derived from a radiation-induced islet tumor. To investigate the characteristics of these clones, we analyzed the hormone expression and secretion by Northern blot, immunocytochemistry, and radioimmunoassay. Increased expression and secretion of insulin and glucagon were observed in these clones. The present examination might also be proof of the secretion of both insulin and glucagon in the single cell of the m21 clone isolated from RINm5F. These cell lines also overexpress the Ha-ras proto-oncogene. In order to determine whether or not the overexpression was caused by gene translocation, the insulin and Ha-ras gene loci in N3 isolated from RIN-r were assigned by in situ hybridization. Both of the genes were located on the long arm of chromosome 1, but no gene translocation was observed. These findings suggest that the expression of insulin and Ha-ras is not affected by chromosomal translocation, but it may be functionally linked in these clones. Overexpression of these three genes may indicate that these clones have the same characteristics as the embryonic immature islet cell.


[Internal ophthalmoplegia as a direct consequence of head injury. Report on 2 cases]. The authors describe two cases admitted following head injury and presenting with a dilated, stiff pupil. CT scan of the head revealed no intracranial mass lesion. The symptoms persisted over a year in one case, whereas in the other one they faded away within a few weeks. The symptoms are believed to arise due to a downward shift of the brainstem which is known to occur at the moment of head injury. The oculomotor nerve is ++over-stretched and is supposed to be partially damaged at the posterior petroclinoid ligament. The roots of the pupillomotor fibers may also be supposedly torn at the site where they leave the brainstem.


[Temporal arteritis].

[Temporal arteritis]. Presented is a case of a 74 years old patient whose ailment was diagnosed as Horton's disease (temporal arteritis) on the basis of general clinical symptoms (constant headache, sclerosis of the temporal artery, anorexia and sleeplessness) and ocular signs (poor visual acuity and pale papilloedema).


[Transplantation of the retina--the near or distant future?]. In the review the results of the recently published experimental papers concerning transplantations of embryonic retina, retinal pigment epithelium and photoreceptors are discussed. The results of these studies indicate that in humans transplantation of the whole retina is the matter of the distant future but in the near future one can expect transplantation of the isolated retinal layers namely pigment epithelium and photoreceptors.


Evaluation of the viability and energy metabolism of ischemically damaged canine pancreas during preservation by the two-layer (University of Wisconsin solution/perfluorochemical) cold storage method. We evaluated the viability and energy metabolism of ischemically damaged pancreas during preservation by the two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) cold storage method. The pancreas grafts subjected to 60-120 min warm ischemia were preserved by the two-layer (UW/PFC) cold storage method for 24 hours (group 3), a simple cold storage in UW for 24 hours (group 2) or without preservation (control) (group 1). The tissue concentration of adenine nucleotides (ANs) were determined using high performance liquid chromatography (HPLC) and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. The functional success rates of pancreas grafts of groups 1, 2 and 3 after 60 min of warm ischemia were 5/5 (100%), 4/5 (80%) and 5/5 (100%). After 90 min warm ischemia, the success rates of groups 1, 2 and 3 were 0/5 (0%), 0/5 (0%) and 5/5 (100%) respectively. Only the two-layer method (group 3) was effective for functional recovery of the pancreas suffered 90 min warm ischemia. However, after more than 105 min, the result was 0/5 (0%) in group 3. In groups 1 and 2, there was no correlation between the posttransplant viability and tissue concentration of ANs and energy charge potential (ECP) at the end of preservation. However, in group 3, there was an excellent correlation between the posttransplant viability and tissue concentration of adenosine triphosphate (ATP) and total adenine nucleotides (TAN) at the end of preservation. We conclude that tissue concentration of ATP and TAN at the end of 24 hour preservation by the two-layer (UW/PFC) method will predict the posttransplant outcome of pancreas graft subjected to significant warm ischemia.


Attitudes, perceptions, and risk-taking behaviors of smokers, ex-smokers, and nonsmokers. A sample of American adults completed questionnaires relevant to cigarette smoking. The questions were related to three areas: risk, perceptions of their or others' smoking, and satisfaction with life and health. The results revealed that smokers were greater risk-takers, that they perceived their smoking to be due to both physical and psychological addictions, and that they expressed less satisfaction and control. Results also indicated that smokers who saw their smoking as being addictive tended to be less satisfied with their health and felt less control over their lives. On the other hand, those smokers who were more likely to deny the health risks did not differ from either non- or ex-smokers on any of the satisfaction or control questions.


Neuroticism and intensity of religious attitudes among clergy in England. Ninety-two male and 20 female clergy completed the short-form Revised Eysenck Personality Questionnaire (Eysenck, Eysenck, & Barrett, 1985) and the Francis Scale of Attitude Towards Christianity (Francis & Stubbs, 1987). The findings support Eysenck's central theory regarding an inverse relationship between psychoticism scores and religious attitudes, and they confirm the view that neuroticism scores are also implicated in predicting the intensity of religious attitudes among the religiously committed.


The effect of hypnotically elicited testimony on jurors' judgments of guilt and innocence. Survey data from several countries indicate that many people believe that hypnosis may increase the accuracy of an eyewitness's memory; most experimental research, however, suggests that this belief is inaccurate. This study examined whether the belief could influence judgments of guilt and innocence in a simulated criminal trial. The results indicated that British undergraduates were more likely to find a male defendant guilty when told that the testimony against him had been elicited under hypnosis. Results concerning a nonhypnotic memory facilitation technique were found to be inconclusive, and the salience of hypnotically elicited testimony was ruled out as a contributory element.


Love attitudes of white South African and British university students. The Munro-Adams Love Attitude Scale was administered to 133 randomly chosen final-year undergraduate White South African and British university students in this examination of their attitudes toward love, courtship, and marriage in relation to the observation that, although South African tertiary educational institutions exist within the authoritarian and restrictive culture of apartheid, they nevertheless are modeled on the British educational system, which has its roots deeply embedded within a politically democratic context. Results indicated that the South African sample's endorsement of the love attitude items was weaker, except for those pertaining to the power of love, than that of their British counterparts. In addition, the South African scores were lower than those previously reported in other similar cross-cultural research, and there was a differential ranking of the three love styles by the male and female subjects.


Social perceptions of male and female extreme mesomorphs. In this study, male and female university students in the United States were exposed to mesomorphic or nonmesomorphic stimuli as reflected by photographs of either male body builders and non-body builders or female body builders and non-body builders. Then they were asked to attribute various personality traits and sex-role behaviors to them. Subjects, irrespective of their sex, perceived male and female body builders as possessing more traditionally masculine and less traditionally feminine personality characteristics than male and female non-body builders. Also, male and female body builders were seen as possessing less socially desirable traits than non-body builders. As predicted, female body builders were perceived generally as being more likely to engage in traditionally masculine sex-role behaviors in their dating and marriage relationships than female non-body builders. Contrary to expectation, however, male body builders were not perceived as more likely to engage in higher levels of masculine sex-role behaviors than male non-body builders.


Optimal selection of metabolic fluxes for in vivo measurement. I. Development of mathematical methods. The measurement of uptake and secretion rates is often not sufficient to allow the calculation of all internal metabolic fluxes. Measurements of internal fluxes are needed and these additional measurements are used in conjunction with mass-balance equations to calculate the complete metabolic flux map. A method is presented that identifies the fluxes that should be selected for experimental measurement, and the fluxes that can be computed using the mass-balance equations. The criterion for selecting internal metabolic fluxes for measurement is that the values of the computed fluxes should have low sensitivity to experimental error in the measured fluxes. A condition number indicating the upper bound on this sensitivity, is calculated based on stoichiometry alone. The actual sensitivity is dependent on both the flux measurements and the error in flux measurements, as well as the stoichiometry. If approximate physiologic ranges of fluxes are known a realistic sensitivity can be computed. The exact sensitivity cannot be calculated since the experimental error is usually unknown. The most probable value of the actual sensitivity for a given selection of measured fluxes is estimated by selecting a large number of representative error vectors and calculating the actual sensitivity for each of these. A frequency distribution of actual sensitivities is thus obtained giving a representative range of actual sensitivities for a particular experimental situation.


Optimal selection of metabolic fluxes for in vivo measurement. II. Application to Escherichia coli and hybridoma cell metabolism. A method of analysis was presented in part I of this series for determining the fluxes in a biochemical network that are the optimal choices for experimental measurement. This algorithm is applied to two important biological models: Escherichia coli and a hybridoma cell line (167.4G5.3). Our results show that potentially poor choices for in vivo measurement of metabolic fluxes exist for both model systems. For the subset of reactions in E. coli that was studied, the condition number of the augmented stoichiometric matrix reveals that a 60-fold amplification of experimental error during computations is possible. The biochemical network of the hybridoma cell is more complex than the E. coli system, and thus results in much larger possible error amplification--up to 100,000-fold. The physiological situations appear to have sensitivities that are less than 1/4 to 1/10 of those estimated by the condition number, and the maximum sensitivities are proportional to the condition number. These maximum sensitivities calculated using estimates of the fluxes and the worst possible error vector are upper bounds on the system's actual sensitivity. By examining the effect of measurement error on the sensitivity, the most probable sensitivity is calculated. These results indicate that an approximate two-fold increase in sensitivity of the E. coli system is likely when the worst set of fluxes are measured rather than the best set. The most likely sensitivity of the hybridoma system can range three orders of magnitude, depending on the set of fluxes that are measured. The propagation of experimental error during computations can be diminished for both systems by increasing the number of flux measurements over and above the minimum number of experimental measurements. The findings from these two model systems indicate that the calculation of the condition number can be a useful method for efficient experimental design, and that the usefulness of this method increases as the order of the system increases.


The eukaryotic CCAAT and TATA boxes, DNA spacer flexibility and looping. Regulation of RNA transcription in eukaryotic polymerase II promoters involves a complex assembly of protein factors. Some of the factors bind to their cognate DNA-sequence elements while others mediate between the DNA bound ones. In order to enable protein-protein interaction, their spatial positioning with respect to each other is critical. Here two DNA-sequence-elements are investigated, the CCAAT and the TATA boxes and their spacers. Whereas the position of the TATA is fixed at about -30, that of the CCAAT can vary substantially from -50 to -200. Despite the variable loop sizes, the CTF (CCAAT-binding) protein interacts--either directly or indirectly via a co-activator--with the general basal TATA-binding transcription factors. Sequence analysis of the spacers, as a function of their sizes, reveals that in the upstream regions of the spacers RR and YY are abundant. In the downstream, 3' region of the spacers RY and YR are very frequent. The DNA sequence elements and their intervening spacers are analyzed in terms of their geometry, anisotropic flexibility and local superhelical density. Our results indicate that the CCAAT and its vicinity is rigid, whereas the TATA and its surroundings is flexible. It is the large flexibility of this region in twist and in roll which allows DNA looping. General mechanistic implications for pol II promoters are discussed.


The pharmacology of extinction.

The pharmacology of extinction. It is impossible to predict what compounds of pharmacological interest may be present in an unexamined species. The extinction of such species may result, therefore, in the loss of therapeutically significant compounds. The fact that science will never know what has been lost does not lessen the significance of the loss. A number of species are discussed to exemplify the potential loss. Ginkgo biloba is an ancient plant, apparently saved from a natural extinction by human intervention. From this tree, the ginkgolides have been isolated. These are potent inhibitors of platelet activating factor and hold promise in the treatment of cerebral ischemia and brain edema. Two species, the tree Taxus brevifolia and the leech Hirudo medicinalis, are threatened as a result of human activity. Both have recently yielded complex compounds of therapeutic importance. The antitumor agent, taxol, is obtained from T. brevifolia and the thrombin inhibitor, hirudin, is found in H. medicinalis. Catharanthus roseus, source of the anticancer agents vincristine and vinblastine, although not threatened, derives from a largely unexamined but severely stressed ecosystem of some 5000 plant species. In other examples, ethnobotanical knowledge of certain plants may be lost while the species survive, as exemplified by the suppression of the Aztec ethnobotany of Mesoamerica by the invading Spanish. Finally, the fallacy of the 'snail darter syndrome', where species may be viewed as too insignificant to worry about, is exposed by consideration of the pharmacological activities of a sea hare (a shell-less marine mollusc) and various leeches.


Kava: an overview.

Kava: an overview. Since the first significant contact with Europeans in the 18th century, the Oceanic plant, Piper methysticum Forst. (Piperaceae) and the beverage prepared from it, both of which are called kava, have become familiar to much of the outside world through both the written and visual media. The ceremonial preparation and consumption of the beverage are probably its most conspicuous and spectacular features. Kava continues to occupy a central place in everyday life in the islands concerned, although its role has been somewhat diminished by time and outside influences. Despite the large body of literature on kava--about 800 entries are listed in a recent bibliography by Singh (1986)--there has been no comprehensive review on the subject. Earlier contributions by Keller and Klohs (1963) and Shulgin (1973) were selective in treatment and dealt primarily with chemical and pharmacological aspects. The monograph by Steinmetz (1960) remains a standard reference but understandably some of the information in it has become dated. The attention of the reader is also drawn to two excellent additions to the recent kava literature, by Lebot and Cabalion (1988) and Brunton (1989), which are, although somewhat restricted in focus, are very significant contributions to the subject. The present review paper provides an updated and a multidisciplinary overview of the subject. It was prepared on the basis of the author's personal experience--he is a native of Fiji and lived in that country for about 30 years--as well as the relevant literature listed in the Singh (1986) bibliography and some more recent publications.


Inventory of plants used in traditional medicine in Somalia. II. Plants of the families Combretaceae to Labiatae. Fifty-nine plants are listed, which are used by traditional healers in the central and southern parts of Somalia. For each species are listed: the botanical name with synonyms, collection number, vernacular name, medicinal use, preparation of remedy and dosage. Results of a literature survey are also reported including medicinal use, substances isolated and pharmacological effects.


Preliminary pharmacologic evaluation of crude whole plant extracts of Elephantopus scaber. Part I: In vivo studies. Elephantopus scaber has been used in Brazil as a traditional remedy to cause diuresis, antipyresis and to eliminate bladder stones. In the current study, aqueous and hydroalcoholic extracts of whole plants were tested for acute toxicity, analgesic, antipyretic, antiinflammatory, cardiovascular, diuretic and constipating activities. Both extracts (0.3-6 g/kg i.p.) induced writhing, loss of muscle tone, ataxia, prostration and death in mice. No analgesic effects of these extracts were detected using mouse hot-plate and acetic acid-induced writhing tests. Both extracts failed to modify diuresis or carrageenan-induced rat paw edema. In contrast, given intraperitoneally, both reduced brewer's yeast-induced hyperthermia in rats, but when given orally did not affect it. Moreover, the aqueous extract decreased the intestinal transit time in mice while the hydroalcoholic extract increased it. Finally, these extracts, given intravenously, reduced blood pressure and heart rate in rats; these effects could be blocked by atropine but not by co-administration of pyrilamine and cimetidine.


Maternity and medicinal plants in Vanuatu. I. The cycle of reproduction. Ethnobotanical data collection to select pharmacologically active species was carried out within a clearly defined therapeutic context: those plants used during the course of a woman's reproductive life. Extensive bibliographical and field data collection and cross-examination of the information thus gathered have provided us with a clearer picture of the effectiveness of these plant species. Various concepts, behaviours and practices relating to menstruation, pregnancy, birth and birth control were examined in detail from an ethnopharmacological point of view. A list of selected species of particular interest is proposed for further study.


The tradition of medicinal plants in Zagori, Epirus (northwestern Greece). Traditional herbal medicine in the Zagori region of Greece was studied by obtaining information from users and collecting herbs. In addition, traditional remedies found in old manuscripts and books were compared with those currently used in modern literature. The 36 medicinal plants used today are listed, including their common and scientific names, indications (some new) and recipes for preparations.


Ethnobotanical study in River Tenes valley (Catalonia, Iberian Peninsula). An ethnobotanical survey was carried out in the River Tenes valley, in an area of 260 km2 not far from the city of Barcelona. Although this setting might suggest that the area was unsuitable for research of this kind, the variety of microclimates--which implies a rich flora--and the existence of small villages and isolated houses made it possible to obtain valuable information. We obtained data on 209 species belonging to 60 families and here we present our findings on the properties, preparations and uses.


Antibiotic screening of medicinal plants of the British Columbian native peoples. One hundred methanolic plant extracts, 96 of which had documented medicinal uses by British Columbian native peoples, were screened for antibiotic activity against 11 bacterial strains. Eighty-five percent were found to have significant antibiotic activity against at least two of the bacteria tested. Ninety-five percent of the plants categorized as potential antibiotics based on their ethnobotanical usage were found to exhibit significant antibiotic activity. Seventy-five were found to be active against methicillin-resistant Staphylococcus aureus, 46 were active against an antibiotic supersusceptible strain of Pseudomonas aeruginosa and 18 of these were also active against a wild type strain. The extracts with the broadest spectra of activity were prepared from: Alnus rubra bark and catkins, Fragaria chiloensis leaves, Moneses uniflora aerial parts, and Rhus glabra branches.


Thrombolysis and postinfarction ventricular septal rupture. We studied all patients with postinfarction ventricular septal rupture referred to the Oxford Heart Centre for operation over a 4 1/2-year period. Twenty one women and 8 men were admitted to the Centre, 13 of whom had received streptokinase and 16 of whom had not. The median interval between symptomatic onset of myocardial infarction and the development of septal rupture was 24 hours for those treated by early thrombolysis (all streptokinase) and six days for those who were not. Of the 26 patients who underwent surgical repair, three were operated on less than 36 hours after streptokinase infusion, in one case within 12 hours of thrombolytic treatment. Macroscopic observation of the disintegrating myocardium showed muscle bundles dissected by blood rendered incoagulable by thrombolytic treatment, together with the histologic features of reperfusion injury. The overall surgical mortality rate for the streptokinase group was 33% and for the others 21%. The patient operated on within 12 hours of thrombolytic treatment recovered uneventfully. Six of seven surgical deaths were caused by left ventricular or biventricular failure and one by gastrointestinal hemorrhage. All survivors were in New York Heart Association classes II or III between 2 weeks and 4 1/2 years after operation. We conclude that thrombolysis leads to early breakdown of the interventricular septum after acute myocardial infarction but does not preclude early repair.


Differential effects of advanced age on neurologic and cardiac risks of coronary artery operations. Two thousand patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were prospectively studied to compare the influence of age on the incidence of neurologic, cardiac, and other complications. Postoperative neurologic events were found in 56 (2.8%) patients, with an incidence in patients > or = 75 years (8.9%) more than twice that of patients 65 to 74 (3.6%) and nine times larger than in patients < 65 (0.9%). Cardiac complications did not differ between age groups except for low cardiac output state, which occurred 1.7 times more frequently in patients > or = 75 years compared with those < 65. Patients with postoperative neurologic events had a ninefold increase in mortality--35.7% versus 4.0%. Logistic regression analysis demonstrate the most important predictors of a postoperative neurologic event to be age, preoperative neurologic abnormality, recent myocardial infarction, and duration of cardiopulmonary bypass. The risk of neurologic complications increases disproportionately to the risk of cardiac complications in the elderly undergoing coronary artery bypass grafting with cardiopulmonary bypass. Despite neurologic improvement (32 of 56 patients), a postoperative neurologic event was second only to low cardiac output state as the postoperative complication most highly associated with in-hospital death. These results are important for decisions regarding selection of candidates for coronary artery bypass grafting and for prediction of surgical outcome.


Risk factors for stroke after coronary artery bypass. To determine the prevalence of stroke after coronary artery bypass grafting and to evaluate risk factors, we reviewed the records of 1000 patients undergoing coronary bypass within a 1-year time period. Demographic and perioperative data were evaluated by chi 2 analysis. A history of diabetes, evidence of mural thrombus, positive oculopneumoplethysmography findings, increased age, aortic calcification, and postoperative arrhythmias all correlated with increased risk of permanent neurologic deficit for the patient undergoing coronary bypass. Risk factors were analyzed with stepwise logistic regression. A history of diabetes, presence of mural thrombi, and aortic calcification carried a higher probability that the patient would have a permanent neurologic deficit.


On-line intraoperative quantitation of regional myocardial perfusion during coronary artery bypass graft operations with myocardial contrast two-dimensional echocardiography. We hypothesized that the success of coronary artery bypass graft operations could be assessed by means of on-line quantitative myocardial contrast echocardiography. Accordingly, myocardial contrast echocardiography was performed at baseline and after each placement of venous graft in 21 patients undergoing coronary artery bypass graft operations. Time-intensity plots were generated on-line with the use of a dedicated computer system, and areas under the curve were assessed for each injection. Successful on-line quantitation of myocardial contrast echocardiography data was performed in 17 patients; this allowed comparison before and after coronary artery bypass graft operations for 21 grafts, with agreement between expert visual analysis and quantitative data in 91% of these cases. Three distinct perfusion patterns were noted on myocardial contrast echocardiography: (1) reduced contrast effect before coronary artery bypass graft operations with improvement after coronary artery bypass graft operations (n = 11); (2) adequate contrast effect before coronary artery bypass graft operations with no change after coronary artery bypass graft operations (n = 9) (for patients in group 2, the mean percentage of coronary stenosis was less than the mean for patients in group 1-67% +/- 25% vs. 88% +/- 20%, p = 0.05); and (3) no contrast effect either before or after coronary artery bypass graft operations in one patient with previous infarction. One third of the time (34 of 95 injections), on-line quantitation was unsuccessful. Failure was related three times more often to problems associated with myocardial contrast echocardiography, such as attenuation and inadequate quality of bubbles, than to computer failure. Despite its limitations, on-line quantitative myocardial contrast echocardiography is feasible in patients undergoing coronary artery bypass graft operations and provides important objective information regarding the success of revascularization.


A quantitative study of postoperative luminal narrowing of the internal thoracic artery graft in coronary artery bypass surgery. We used quantitative angiography to determine the postoperative diameter of the internal thoracic artery graft at the point close to the anastomosed site in 147 patients who received the graft for the left anterior descending coronary artery. We performed generalized multiple linear regression analysis (Type I quantification method) to assess the effects of the following factors on the internal thoracic artery graft diameter: age, gender, time of angiography, laterality of the internal thoracic artery used, presence of an undivided major side branch of the internal thoracic artery, presence of a saphenous vein graft having blood flow competition with an internal thoracic artery graft, presence of distal stenosis of the recipient left anterior descending coronary artery, severity of postoperative left anterior descending coronary artery stenosis, and presence of coronary risk factors. The standardized category scores for 25% left anterior descending coronary artery stenosis, 50% left anterior descending coronary artery stenosis, and presence of a saphenous vein graft having blood flow competition with an internal thoracic artery graft were -1.418, -0.767 and -0.622, respectively. Thus, the internal thoracic artery diameter was smaller in patients with well-preserved flow of the recipient coronary artery. The internal thoracic artery diameter had a particularly strong correlation with the degree of left anterior descending coronary artery stenosis (partial correlation coefficient: 0.670). The other factors seemed to have little or no correlation with the postoperative internal thoracic artery diameter. With the criterion that the internal thoracic artery diameter below 1.0 mm represents the "string sign" of internal thoracic artery graft, this phenomenon was observed in nine patients (6.1%). In all of these patients, left anterior descending coronary artery flow was well-preserved, and no ischemia was disclosed in the left anterior descending coronary artery-perfused area. These results indicate that internal thoracic artery grafts have flow adaptability responding to the flow demand of the recipient coronary artery and that the string sign of internal thoracic artery grafts is mainly an outcome of its physiologic characteristics.


Use of internal mammary artery in myocardial revascularization after mediastinal irradiation. Ten patients with radiation-associated proximal coronary artery disease underwent myocardial revascularization. In seven patients (group A) the internal mammary artery was used and in the other three (group B) only venous conduits were used. Except for mild adhesions between the pericardium and the epicardium, no unusual technical problems were encountered. In all patients in group A the internal mammary artery exhibited excellent flow, and histologic examination in two patients revealed a normal intima and media with only slight fibrosis of the adventitia. In two patients in group B, fibrosis of the internal mammary artery precluded its use, whereas the third patient had contraindications prohibiting use of the internal mammary artery. Long-term follow-up (range 6 to 72 months) revealed that one patient in group A died late of metastatic disease, and of the remainder (nine patients), seven were in New York Heart Association class I and two were in class II. Preoperative assessment of the internal mammary artery by angiography or, alternatively, B-mode imaging with Doppler spectrum analysis is recommended in patients with radiation-induced coronary artery disease who are scheduled to undergo myocardial revascularization with intended use of the internal mammary artery. In our experience, despite previous exposure to irradiation, the internal mammary artery should still be considered as a viable conduit for myocardial revascularization when preoperative assessment shows patency.


Direct imaging of the tricuspid valve annular motions by fiberoptic cardioscopy in dogs. I. Does De Vega's annuloplasty preserve the annular motions? Applying the technology of direct imaging by fiberoptic cardioscopy, physiologic and pathophysiologic motions of the tricuspid valve anulus were studied in 10 anesthetized normal dogs (control group) and in 9 dogs that had chronic tricuspid regurgitation (TR group). The heart was perfused with transparent modified Tyrode's solution by working heart method, and the anuli, outlined by sutured beads, were observed and recorded on a high-speed video system in real time. Tricuspid valve annular area was calculated at 14 points during the cardiac cycle. The control group was studied in the normal condition, and the tricuspid regurgitation group was studied during four interventions: nontricuspid annuloplasty group and three tricuspid annuloplasty groups with reducing tricuspid valve annular area to 80%, 65%, and 50% of that of the non-tricuspid annuloplasty group by De Vega's procedure. Tricuspid valve annular area in the control group increased by 7% during atrial systole and was reduced by 34% mainly during ventricular systole, in which the free wall annular area and the septal annular area narrowed by an equal 34%. Chronic tricuspid regurgitation lessened tricuspid valve annular area narrowing to 20% in percent reduction (p < 0.01). In the TR group the decrease in tricuspid valve annular area narrowing was attributed mainly to lessened narrowing of the free wall anulus (percent reduction of tricuspid valve annular area, 19%; p < 0.01). The amplitudes in tricuspid valve annular area narrowing were unchanged in the tricuspid annuloplasty groups even when tricuspid valve annular area, was reduced to 50% by De Vega's tricuspid annuloplasty (percent reduction of tricuspid valve annular area, 16%; not significant). These findings suggest that De Vega's tricuspid annuloplasty is a reasonable method that does preserve the physiologic annular motions in the opening and closing mechanism of the tricuspid valve.


Direct imaging of the tricuspid valve annular motions by fiberoptic cardioscopy in dogs with tricuspid regurgitation. II. Does flexible ring annuloplasty preserve the annular motions? Applying the technology of direct imaging by fiberoptic cardioscopy in a working-heart condition, we studied the tricuspid valve annular motions with flexible rings in nine dogs with chronic tricuspid regurgitation. Three annuloplasty studies with a totally flexible polytetrafluoroethylene ring, an elastic silicone ring, and a rigid metal ring were compared with a nonannuloplasty study. The annuloplasty was performed by reducing tricuspid valve annular area to 65% of that of nonannuloplasty condition. The anuli were observed and recorded on a videotape in real time. The three rings effectively reduced and remodeled the dilated anuli and improved the valve coaptation. The patterns of annular motions with the polytetrafluoroethylene and silicone ring were similar to that of normal anulus; the free wall anulus contracted centripetally, and the septal anulus moved toward the free wall side during systole. Pliability of both the anteroseptal and posteroseptal commissures with the flexible rings made these motions possible. The polytetrafluoroethylene ring followed a natural undulation of the anulus, whereas the silicone and rigid metal rings forced the annular planes to horizontal ones. Percent reductions of tricuspid valve annular area were 25%, 21%, and 23% in the nonannuloplasty, polytetrafluoroethylene, and silicone ring studies, respectively, without significant differences in annular contraction. In contrast, rigid metal rings completely disturbed the annular motions. These findings indicated that the two flexible rings did preserve the physiologic annular motions to the degree that the anuli had in the chronic tricuspid regurgitation condition. Especially, the totally flexible polytetrafluoroethylene ring preserved not only the annular motions but also the natural undulation, which resulted in reinforcing the valve coaptation. We believe that the flexible ring, especially a totally flexible one, is superior to the rigid ring in the aspect of reinforcing the valve coaptation to prevent further regurgitation.


Excellent durability of the Hancock porcine bioprosthesis in the tricuspid position. A sixteen-year follow-up study. From February 1975 to August 1981, 23 consecutive patients underwent tricuspid valve replacement, which was either isolated (six patients) or combined with the replacement of other valves (17) by means of a standard, glutaraldehyde-preserved Hancock porcine bioprostheses. Patients' ages ranged from 9 to 53 (mean 36.2) years. The follow-up period ranged from 0.2 to 16.5 years (mean 9.1) and was complete in 100% of all cases. Structural valve failure of the tricuspid Hancock valve was noticed in two patients, a 9-year-old boy and a 13-year-old girl 3.4 and 16.5 years after implantation, respectively. The actuarial freedom rate from structural valve failure at 10 years was 94 +/- 6%. There were six tricuspid prosthesis-related events: structural valve failure in two and valve thrombosis, anticoagulant-related bleeding, prosthetic valve endocarditis, and periprosthetic leak in one each, respectively. The actuarial freedom from these events at 10 years was 78 +/- 10%. Five pairs of aortic/mitral-tricuspid Hancock valves were explanted simultaneously from the same patients after 8.1 to 13.9 (mean 11.4) years postoperatively. A gross examination showed no valve dysfunction in the explants from the tricuspid position, but degenerative changes with valve dysfunction in those from the mitral and aortic position were observed (none of five versus five of seven; p < 0.03). We concluded that the selection of a Hancock bioprosthesis in the tricuspid position is acceptable because of the low incidence of prosthesis-related complications and the excellent durability of more than 10 years.


Collins' solution for cold storage of the heart for transplantation must be reversed with cardioplegic solution before reperfusion. A functional and metabolic study in the rat heart. The following hypotheses were tested using an isolated perfused working rat heart model: (1) Collins' solution for cold storage of the heart is harmful for the heart during reperfusion; (2) a "reverse" of the intracellular-type Collins' solution with an extracellular-type cardioplegic solution before reperfusion is able to prevent this disadvantage of Collins' solution. The following two major groups (I and II) and five subgroups (-a to -e) in each group were prepared. In group I (reversed group); the hearts were initially stored in Collins' solution but were reversed by a 1-minute flush with cardioplegic solution followed by storage in cardioplegic solution for the last 1 to 180 minutes of the total 3-hour storage, that is, groups I-a (reversed for 1 minute), I-b (10 minutes), I-c (30 minutes), I-d (90 minutes), and I-e (180 minutes). In group II (nonreversed control group); the hearts were stored in Collins' solution throughout 3 hours and were also divided into five subgroups of groups II-a, II-b, II-c, II-d, and II-e in which only a 1-minute flush with Collins' solution was performed at the point corresponding to group I. The coronary flow in any of group II showed a marked decrease during the early reperfusion period. In group I, however, the coronary flow increased significantly in proportion to the duration of the reversing phase. The recovery of the aortic flow and the cardiac output in group I showed a bell-shaped pattern in relation to the duration of the reversing phase, reaching their peak values when reversed for 30 minutes (group I-c). The prolonged reverse (180 minutes) resulted in a deterioration of functional recovery associated with a poorer preservation of high-energy phosphates and a larger enzyme leakage. These results suggest that the beneficial effects of intracellular-type Collins' solution for cold storage of the heart were further improved by reversing Collins' solution with the extracellular-type cardioplegic solution for the last 30 minutes of the 3-hour cold storage because the disadvantageous vasoconstriction due to Collins' solution during reperfusion was successfully prevented by the replacement of intravascular and extravascular Collins' solution with cardioplegic solution before the reperfusion.


Polyethylene glycol-conjugated superoxide dismutase attenuates reperfusion injury when administered twenty-four hours before ischemia. Covalent linkage of polyethylene glycol to superoxide dismutase prolongs the serum half-life of the enzyme and may facilitate intracellular access. We tested the myocardial protective effect of polyethylene glycol superoxide dismutase administered once, 24 hours before ischemia. Because hearts were studied ex vivo in a crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of polyethylene glycol alone, without conjugation to superoxide dismutase (n = 8); (3) PEG-SOD 10,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4) PEG-SOD 30,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG-control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of polyethylene glycol superoxide dismutase significantly reduce reperfusion injury when administered 24 hours before initiation of global ischemia. Moreover, since the perfusate was superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating superoxide dismutase.


Nucleoside transport inhibition mediates lidoflazine-induced cardioprotection during intermittent aortic crossclamping. The effects of pretreatment with the nucleoside transport inhibitor lidoflazine on repeated ischemia-reperfusion injury induced by normothermic intermittent aortic crossclamping were studied in canine hearts. Eighteen mongrel dogs were allocated to three groups: placebo (n = 6), lidoflazine (1 mg/kg) (n = 6), and lidoflazine (1 mg/kg) plus the adenosine receptor blocker aminophylline (7 mg/kg) (n = 6). Pretreatment was performed intravenously during 15 minutes before extracorporeal circulation. All hearts were subjected to four intervals of 15 minutes of global ischemia each followed by 10 minutes of reperfusion. After weaning from extracorporeal circulation, functional recovery was followed for 1 hour. In the lidoflazine group, myocardial adenosine content (0.25 +/- 0.06 mumol/gm dry weight) was 3.5 times higher than that in the control group (0.07 +/- 0.03 mumol/gm dry weight; p < 0.05) at the end of the last aortic crossclamping. The release of adenosine from the myocardium during each reperfusion period was significantly higher than that in the control group (p < 0.05). Myocardial extraction of lactate was normalized at every reperfusion interval in the lidoflazine group but not in the control group (p < 0.05). In the lidoflazine group functional recovery was significantly better than that in the control group. Positive rate of rise of pressure, negative rate of rise of pressure, and cardiac output recovered to, respectively, 150% +/- 19%, 82% +/- 8%, and 131% +/- 15% in the lidoflazine group versus, respectively, 37% +/- 9%, 23% +/- 7%, and 29% +/- 8% in the control group (p < 0.001) at 1 hour after extracorporeal circulation. When the adenosine receptor blocker aminophylline was administered in association with lidoflazine, protection dropped significantly: positive and negative rate of rise of pressure and cardiac output were, respectively, 58% +/- 8%, 46% +/- 9%, and 67% +/- 16% at 1 hour after extracorporeal circulation (p < 0.05 versus lidoflazine alone). These results suggest that the cardioprotective effects of lidoflazine are at least in part mediated by adenosine receptor stimulation via nucleoside transport inhibition-induced accumulation of endogenous adenosine in the myocardium.


Effects of nucleoside transport inhibition on long-term ex vivo preservation of canine hearts. The effect of nucleoside transport inhibition on 24-hour preservation of canine hearts was studied in 36 hearts arrested either with a cold hyperkalemic cardioplegic solution without (group I) or with supplementation of a specific nucleoside transport inhibitor (R75231, 1 mg/L) (groups II and III). The hearts were excised and stored for 24 hours at 0.5 degrees C. Then they were reperfused for 3 hours with use of a closed perfusion system primed with normal blood (groups I and II) or with blood supplemented with the same nucleoside transport inhibitor (0.32 mg/L) (group III). Serial biopsy specimens for determination of myocardial purines were taken. Creatine kinase and heat-stable lactate dehydrogenase release from the myocardium were examined during reperfusion. Recovery of function was studied during reperfusion by measurement of isometric contraction in a fluid-filled intraventricular balloon. After 24 hours of preservation, without the use of the drug, myocardial inosine and hypoxanthine accumulated to, respectively, 4.05 +/- 1.18 and 0.28 +/- 0.08 mumol/gm dry weight. In the drug-treated groups (II and III pooled), significantly less inosine and hypoxanthine accumulated (1.68 +/- 0.33 and 0.05 +/- 0.02 mumol/gm dry weight, respectively) (p < 0.05 versus group I). Upon reperfusion, intramyocardial adenosine was lost in the control hearts and maintained in the drug-treated hearts. Hypoxanthine accumulated significantly (p < 0.05) during reperfusion in group I (1.08 +/- 0.43 versus 0.16 +/- 0.13 in group II and 0.03 +/- 0.03 mumol/gm dry weight in group III). The rate of creatine kinase and heat-stable lactate dehydrogenase release was significantly lower (p < 0.05) in group III (that is, pretreatment and posttreatment with the drug) than in the control group. Functional recovery of hearts in group III was superior to that in group II (p < 0.05), while hearts in group I showed no recovery at all. We conclude that nucleoside transport inhibition improves long-term preservation of the heart and that the mechanism of this protection may be related to an increase in endogenous adenosine and reduction of myocardial hypoxanthine content.


Endothelial dysfunction caused by University of Wisconsin preservation solution in the rat heart. The importance of temperature. The superiority of the University of Wisconsin solution over routinely used crystalloid cardioplegic solutions for myocardial preservation has been demonstrated in animal studies. We have investigated the effect of the University of Wisconsin solution at different temperatures on endothelial function by examining its influence on 5-hydroxytryptamine- and nitroglycerin-induced increase in coronary flow in the isolated rat heart. Thirty-eight rat hearts were perfused on a modified Langendorff preparation. In the control experiments, there was no significant difference in the percentage increase in coronary flow induced by 5-hydroxytryptamine and nitroglycerin after 30 minutes of perfusion with Krebs-Henseleit buffer (n = 6). Continuous infusion of the University of Wisconsin solution for 30 minutes at 4 degrees C or at 10 degrees C did not alter the 5-hydroxytryptamine or nitroglycerin response. However, infusion at 15 degrees C reduced the 5-hydroxytryptamine-induced vasodilation, while at 20 degrees C the 5-hydroxytryptamine response was converted to vasoconstriction without a significant change in nitroglycerin effect (15 degrees C, 5-hydroxytryptamine, before: 30.2% +/- 1.5%, after: 6.0% +/- 1.0%, nitroglycerin, before: 28.8% +/- 1.3%, after: 31.2% +/- 1.8%; 20 degrees C, 5-hydroxytryptamine, before: 32.2% +/- 2.5%, after: -23.8% +/- 3.6%, nitroglycerin, before: 30.3% +/- 1.9%, after: 33.5% +/- 1.7%). Coronary vascular resistance in the control experiments rose from 55.0 +/- 2.5 cm H2O/ml/gm/min to 58.4 +/- 2.3 cm H2O/ml/gm/min (p = not significant). The increase after University of Wisconsin solution infusion at 4 degrees C and at 10 degrees C was similarly not significant. Coronary vascular resistance increased significantly following infusion of University of Wisconsin solution at 15 degrees C (p < 0.001) or at 20 degrees C (p < 0.01). We conclude that University of Wisconsin solution produces temperature-dependent endothelial dysfunction in the isolated rat heart.


Renal function in patients undergoing cardiopulmonary bypass operations. We evaluate short- and long-term effects on renal functional reserve of cardiopulmonary bypass in 11 patients. A selected group (persistence of renal functional reserve before operation) of 11 adult patients undergoing cardiopulmonary bypass for aorta-coronary bypass were studied. Renal functional reserve tests were performed in all patients before the operation, at postoperative day 9, and at 6 months after operation. Basal glomerular filtration rate did not show significant changes at 9 days and at 6 months after operation. On the contrary, renal functional reserve was absent at 9 days, but it was restored to preoperative levels at 6 months after operation. In conclusion, our data indicate that cardiopulmonary bypass probably causes renal damage that is not sufficient to influence routine renal function parameters.


Does flow character of cardiopulmonary bypass make a difference? The influence of pulsatile bypass flow on the performance of the cardiovascular system, fluids and blood balance, acid-base equilibrium, and splanchnic function was investigated. One hundred patients scheduled for elective coronary artery bypass grafting were randomly divided into a group of standard perfusion (NP) and a group of pulsatile perfusion (PP). At the end of the operation, similar cardiac performance developed in both groups that was higher than before bypass: left ventricular stroke work index after bypass, 56.8 +/- 2.7 gm/beat per square meter in the NP group and 56.7 +/- 2.6 gm/beat per square meter in the PP group (not significant). Further determinations did not differ among the groups. After discontinuation of cardiopulmonary bypass, bypass grafts flow measured using an electromagnetic probe did not differ among the groups. During the postbypass period, mean arterial pressure and systemic vascular resistance were similar (mean arterial pressure 86.8 +/- 1.6 mm Hg in the NP group and 88.5 +/- 1.7 in the PP group; systemic vascular resistance 817 +/- 33 dyne.sec/cm5 in the NP group and 881 +/- 34.5 in the PP group), as were further determinations. However, severe hypotension requiring the administration of vasoconstrictors was observed more frequently in PP group of patients (20 versus 6%; p < 0.05). Fluid balance determined at the second postoperative day was similar among the groups (+1307 +/- 239 ml in the NP group and +1535 +/- 266 ml in the PP group). Blood loss was 1122 +/- 120 ml in the NP group and 1263 +/- 119 ml in the PP group during the first postoperative day (p = 0.407). Urine output during bypass was lower in the PP group (261 +/- 25 versus 341 +/- 26 ml/hr; p = 0.028). The creatinine clearance was 96.4 +/- 10.3 ml/min in the NP group and 92.6 +/- 7.0 ml/min in the PP group (not significant); amylase and lipase clearance did not differ among the groups. Finally, no significant difference was detected in arterial lactic acid determinations and acid-base balance assessment between the groups postoperatively. Thus equivalent cardiovascular hemodynamics, a good control of fluids and blood balance, acid-base equilibrium, and a satisfactory protection of the function of kidneys and pancreas were obtained with both types of perfusion.


The acoustic filter: an ultrasonic blood filter for the heart-lung machine. Cardiopulmonary bypass-associated encephalopathy is thought to be due in part to continuous microembolization of the brain with gas microbubbles more than 40 microns in diameter during bypass. Current barrier filter technology cannot effectively remove such small microbubbles in fragile fluids such as blood. The design concepts for a new nonbarrier ultrasound-based fluid filtration system (an "acoustic filter") capable of filtering small microbubbles from blood are presented. The acoustic filter uses a field of high-intensity ultrasound to push microbubbles down an acoustic gradient, where they can be collected and removed. To test the filtration efficiency of the system, a Doppler ultrasound bubble detector was built. By monitoring the prefilter and postfilter Doppler signal an assessment of filtration efficiency was made. A suspension of stable albumin-encapsulated microbubbles (4 to 32 microns) were used as a model of the microbubble contaminants that might be found in the arterial return line of the heart-lung machine. Inactivated, the acoustic filter neither removed nor added microbubbles to the fluid. Activated, the acoustic filter provided total or near-total clearing of microbubbles. We conclude that the acoustic filter can remove microbubbles from a cardiopulmonary bypass-like apparatus.


Intraaortic balloon pumping in patients requiring cardiac operations. Risk analysis and long-term follow-up. The intraaortic balloon pump is usually the first mechanical device inserted for perioperative cardiac failure; however, little current information is available regarding short- and long-term effectiveness. From January 1983 through November 1990, 6856 adult patients underwent cardiac surgical procedures, 580 of whom (8.5%) had an intraaortic balloon inserted preoperatively (107 patients), intraoperatively (419 patients), or postoperatively (54 patients). There were 374 men and 206 women with a mean age of 63.9 years (range 19 to 88). Operations included 376 coronary artery bypass grafts, 100 mitral valve replacements (with or without bypass grafting), 70 aortic valve replacements (with or without bypass grafting), 15 double valve replacements (with or without bypass grafting), and 32 other procedures. There were 72 (12.4%) complications related to the balloon pump, of which 42 necessitated surgical intervention including thrombectomy (21), vascular repair (13), fasciotomy (2), aortic repair (1), and amputation (4). Operative mortality for patients supported by the balloon pump was 44%. Multivariate stepwise analysis of 27 parameters revealed six independent predictors of mortality: preoperative New York Heart Association class, transthoracic intraaortic balloon insertion (both p < 0.0001), preoperative administration of intravenous nitroglycerin, age, female gender, and preoperative balloon insertion (p < 0.001). Balloon-related complications were not predictive of death. Of the 326 hospital survivors, only 34 were lost to follow-up. There were 75 late deaths, the cause of which was cardiac in 41 (55%), noncardiac in 20 (27%), and unknown in 14 (19%). Actuarial survivals at 1, 5, and 9 years are 51%, 42%, and 33%. Of the 217 hospital survivors still alive and contacted, 81% were in class I (114) or II (60). These data demonstrate (1) operative mortality for patients requiring an intraaortic balloon in the perioperative period remains high, (2) perioperative risk factors can be identified, (3) complications related to the balloon pump do not affect survival, (4) operative survivors can achieve prolonged survival with excellent functional results, and (5) consideration for alternative methods of circulatory support is justified.


Dynamic cardiomyoplasty acutely impairs left ventricular diastolic function. In patients with congestive heart failure, medical treatment has a high rate of mortality and morbidity, and transplantation is limited by the availability of donor hearts. Dynamic cardiomyoplasty is being investigated as surgical therapy to improve left ventricular function in these patients. To evaluate the early postoperative effects of this procedure on left ventricular diastolic function, we studied seven dogs through the use of sonomicrometry and micromanometry in a canine model of dynamic cardiomyoplasty. Left ventricular diastolic parameters were determined before wrapping the latissimus dorsi muscle (baseline), after latissimus dorsi muscle wrap but without stimulation, and with synchronous left ventricular contraction-latissimus dorsi muscle stimulation. End-diastolic pressure was increased in both conditions after latissimus dorsi muscle wrap (without stimulation, 5 +/- 1; with stimulation, 6 +/- 2 mm Hg; p < 0.05) compared with baseline (3 +/- 2 mm Hg). The peak rate of diastolic pressure decay was greater at baseline (1560 +/- 370 mm Hg/sec) than after latissimus dorsi muscle wrap, both without (1260 +/- 330 mm Hg/sec, p < 0.01) and with (1120 +/- 420 mm Hg/sec, p < 0.01) stimulation. The constant of pressure decay was prolonged both without (53 +/- 10 seconds, p < 0.05) and with (62 +/- 11 seconds, p < 0.01) latissimus dorsi muscle stimulation compared with the baseline (38 +/- 5 seconds). Compared with baseline (0.2 +/- 0.2 cm-2), the constant of passive chamber stiffness increased after the latissimus dorsi muscle was wrapped around the heart (1.6 +/- 0.7 cm-2, p < 0.05) and with stimulation (2.1 +/- 1.0 cm-2, p < 0.01). The maximal diastolic filling rate (baseline, 18.1 +/- 6.7; without stimulation, 16.6 +/- 8.9; with stimulation, 16.6 +/- 4.1 cm2/sec, not significant) and end-diastolic short-axis area (baseline, 7.3 +/- 2.3; without stimulation, 7.4 +/- 2.1; with stimulation, 7.5 +/- 2.3 cm2, not significant) were similar among the three conditions. The latissimus dorsi muscle wrap prolonged relaxation and increased left ventricular passive stiffness. Synchronous latissimus dorsi muscle stimulation with left ventricular contraction did not improve diastolic function in this model. The results suggest that in the early postoperative period, dynamic cardiomyoplasty impairs diastolic function.


High-dose intravenous beta 1-blockade in patients early after cardiac operations. Negative inotropism versus myocardial oxygen economy. A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. Negative inotropic effects may outweigh the expected benefit, however. Against this background hemodynamic and metabolic effects of early postoperative infusion with the beta 1-selective agent metoprolol were studied in 22 patients after coronary operations. During basal postoperative conditions, intravenous metoprolol reduced cardiac index and stroke volume index compared with control patients, while other variables were unaffected. During the higher adrenergic level of a dopamine infusion (7 micrograms/kg per minute), the heart rate, rate pressure product, and myocardial oxygen uptake were attenuated in proportion to the plasma level of metoprolol. Intravenous beta 1-blockade did not affect the cardiac output or stroke volume responses to dopamine (the cardiac output was still, however, 19% lower than in control patients). A release of myocardial creatinine kinase isoenzyme myocardial band was observed during dopamine infusion, suggesting that myocardial ischemia was induced. The release was not influenced by metoprolol, but it correlated with heart rate (r = 0.60; p < 0.01). It is concluded that infusion of metoprolol early after coronary operations depresses myocardial contractility with some 19%, which was without clinical significance in straightforward patients; the increased myocardial metabolic demand during a period of increased adrenergic stress was attenuated by metoprolol. This may be of importance for myocardial recovery.


Video-assisted thoracic surgical resection of malignant lung tumors. Forty patients with malignant pulmonary disease underwent evaluation, staging, and a biopsy or resection by means of video-assisted thoracic surgery. There were 20 men and 20 women whose ages ranged from 27 to 82 years. Eight patients had a wedge resection for metastatic carcinoma, three a lobectomy for primary carcinoma, six exploration of the thorax, five biopsy of the aortopulmonary window, and eighteen a sublobar resection for primary carcinoma of the lung. There was no mortality. Three patients had air leaks that lasted an average of 8 days. Video-assisted thoracic surgery seems to be useful for more precise staging of carcinoma of the lung, and, in some patients, resectional operations can be performed.


The role of mediastinoscopic biopsy in preoperative assessment of lung cancer. Between 1970 and 1989, mediastinoscopy and thoracotomy were performed on 619 patients admitted to our clinic with lung cancer. When mediastinoscopy was analyzed by lymph node location, the highest sensitivity (95.7%) was for the left paratracheal nodes and the lowest (64.0%) was for nodes at the bifurcation (p < 0.01). The 5-year survivals according to the results of mediastinoscopy were 47% for negative results, 14% for false-negative results, and 6% for positive results. The 5-year survival rate however, was significantly higher (28%) in patients (n = 13) with positive mediastinoscopic findings who underwent complete resection of the primary tumor and all involved nodes than in patients (n = 78) who underwent incomplete resection (p < 0.01). These data support our opinion that patients with positive mediastinoscopic results should not always be excluded from treatment by thoracotomy. The role of mediastinoscopy is not to select patients for thoracotomy but to evaluate lung cancer at the pretreatment stage.


Endothelin-1 mediates regional blood flow during and after pulmonary operations. To investigate the role of endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells, in the physiologic response to surgical stress, we measured plasma endothelin-1 concentrations by a sandwich-enzyme immunoassay in patients with lung cancer undergoing pulmonary operations (n = 12). In the first group (n = 6), we measured plasma endothelin-1 concentrations at multiple sampling sites (median cubital vein, pulmonary artery, and left atrium). Plasma endothelin-1 levels were significantly increased at all sampling sites at the end of the operation. Although there was no difference between the increased plasma levels of endothelin-1 in the pulmonary artery and in the left atrium, the increased level in the median cubital vein (peripheral venous blood) was significantly higher than that in the pulmonary artery (mixed venous blood). This result suggests that the production of endothelin-1 might differ between various organs under surgical stress. In the second group (n = 6), we measured plasma endothelin-1 concentrations both in the median cubital vein and in the ipsilateral radial artery, and also measured cardiac output and forearm blood flow. The increase in endothelin-1 levels in the median cubital vein was significantly higher than that in the radial artery after the operation. The endothelin-1 output from the forearm, calculated by the forearm blood flow and the arteriovenous difference of endothelin-1 concentrations, significantly increased after the operation. Although the cardiac output significantly increased after the operation, the forearm blood flow significantly decreased. The present findings provide a novel hypothesis that the preferential release of endothelin-1 from the peripheral vasculature of the forearm may partly contribute to a compensatory response to surgical stress, for example, the reduction of local blood flow in nonvital organs so as to increase the blood flow in vital organs.


Quantification of flow through an interatrial communication. Application to the partial Fontan procedure. The partial Fontan procedure has become an accepted alternative for the high-risk candidate. Creation of a small right-to-left shunt will lower the systemic venous pressure and improve systemic cardiac output while maintaining an acceptable systemic arterial saturation. However, because of variations in patient size and postoperative transpulmonary gradient, proper sizing of the residual defect is difficult. We have therefore conducted a series of experiments on a model that simulates the blood flow across interatrial defects of varying sizes at several pressure gradients. We used porcine blood to develop guidelines for the sizing of the residual defect. Our results demonstrate a linear relationship between flow and pressure gradient across all hole sizes tested. In addition, there was a linear relationship between atrial septal defect size and flow at each pressure gradient. Our data show that the Gorlin formula predictions overestimated flow by 10% to 40%. It is evident from these data that relatively small changes in the size of the atrial septal defect or in the pressure gradient result in significant changes in flow. Therefore we advocate the use of an adjustable interatrial communication such as the snare-controlled adjustable atrial septal defect for patients undergoing partial Fontan procedures.


Balloon dilation of stenotic aortic valve in children. An intraoperative study. Ten children in the age range of 3 to 17 years with moderate to severe aortic valve stenosis (gradients of 55 to 109 mm Hg) underwent cardiac operations. At the time of the operation, during bypass, balloon dilation of the stenotic valve was performed and the results were visually assessed by the surgeon. Of the 10 consecutive cases, only three showed dilation results that were comparable to what seems optimal from a surgical point of view. The adverse effects in the remaining seven patients and the corrective measures taken were as follows: (1) too extensive a rupture requiring stabilizing sutures in one patient; (2) too short a rupture, requiring additional commissurotomy in three patients; (3) rupture into the valve leaflet, requiring valve suture and corrective comissurotomy in another three patients. This last, rather serious complication occurred in patients having functionally bicuspid valves with slightly thickened free valve edges, whereas valves with severely thickened edges ruptured in the commissure line but often to an insufficient degree. Because of the high incidence of suboptimal separation of the stenotic aortic valves with balloon dilation, we recommend that further evaluation of long-term results and identification of unsuitable cases should precede widespread use of the technique.


Long-term results of survivors of surgical valvotomy for severe aortic stenosis in early infancy. Long-term morbidity and mortality were evaluated in the 21 survivors of a cohort of 51 consecutive infants with severe aortic valve stenosis who underwent surgical treatment in the first 3 months of life during the period from 1958 to 1988. The 21 early survivors have been followed up from 3 to 27 years (median 7.5 years). There have been two late deaths: one at age 13 year from bacterial endocarditis and the other at age 14 years after dislodgment of a prosthetic valve. The calculated 10-year actuarial survival for this group is 100%, with a 15-year actuarial survival of 75% (standard error 15%). Seven repeat operations have been performed in six patients: Three had persistent stenosis and a repeat valvotomy was performed in two of them, aged 2 years and 15 years. The other underwent placement of a conduit from the left ventricle to the descending aorta at 2 years of age. Replacement of the aortic valve has been performed in four patients because of severe valvular insufficiency 13 to 27 years after the initial operation. One of these had required a repeat valvotomy at the age of 15 years. The calculated actuarial freedom from reoperation at 10 years is 90% (standard error 6%) and at 15 years, 67% (standard error 15%). Aortic insufficiency was progressive throughout the period of follow-up. No patient had more than moderate aortic insufficiency 3 to 5 years after the initial valvotomy, whereas aortic insufficiency was severe in five of the eight patients followed up for 11 or more years. Progression of aortic insufficiency and the need for reoperation were not related to the age at initial valvotomy. Survivors of surgical aortic valvotomy in early infancy have a relatively good long-term prognosis and a high freedom from reoperation in the period leading to adolescence. Aortic insufficiency in these patients is progressive, and valve replacement eventually may be required.


The role of coronary artery abnormalities in the prognosis of truncus arteriosus. A high incidence of coronary ostial and arterial abnormalities was found in a study of 30 pathologic specimens of classic truncus arteriosus at Children's Hospital of Pittsburgh. The following were of special note: (1) left coronary ostium in a posterior and high position; (2) close relation of the left coronary ostium to the pulmonary artery segment in three-leaflet truncal valves; (3) stenosis of the coronary ostium caused by small size, slitlike shape, or the location of the ostium above or in a commissure; (4) the acute angle takeoff of the coronary artery; (5) the position of the left anterior descending artery as it courses posteriorly and close to the truncal wall, and then to the left of the interventricular septum; (6) the size and course of the conal and diagonal arteries from the right coronary artery across the right ventricular outflow area; (7) other coronary abnormalities, including a single coronary artery or ostium with branches crossing the right ventricle below the truncus, the circumflex arising from the right coronary artery and coursing behind the truncus, and the right coronary artery originating from the left anterior descending artery and vice versa. Eight heart specimens with conduit repair were reviewed, and all had injury to coronary arteries, possibly responsible for or contributing to the deaths of six of the eight patients. Coronary abnormalities, often several occurring in combination, may contribute to high operative mortality rate and may be a cause of late sudden death in truncus arteriosus. Surgical procedures should be planned with a view to protecting coronary arteries in the region of the right ventricular outflow tract below the truncus. Coronary artery obstruction (ostial or luminal) can occur and may need to be addressed as a separate issue during surgical procedures.


Clinical and experimental studies on tong yu ling in the treatment of diabetic hyperlipemia. 72 diabetes mellitus patients (70 cases non-insulin-dependent) were treated routinely with D860. After one month, cases with persisting hyperglycemia and hyperlipemia were randomly divided into Group A to be treated with D860 plus Tong Yu Ling (TYL), and Group B to continue treatment with D860 alone, while Group C, comprising cases with persisting hyperlipemia only, were treated with TYL alone. Therapeutic results showed that of the total 50 cases of Group A and C, 26 were markedly improved, 14 improved, and 10 cases ineffective. The antihyperlipemic effect was pronounced in Group A, where the blood cholesterol, beta-lipoprotein and triglyceride showed remarkable decline, less pronounced in Group C, and insignificant in Group B. Experiments in rat models of non-insulin-dependent diabetes demonstrated that TYL was markedly effective in treating hyperlipemia.


Obstinate cases of stromal keratitis treated by combined traditional Chinese and Western medicine. Twenty-two cases 23 eyes with obstinate stromal keratitis treated by combination of traditional Chinese and Western medicines are reported in this paper. According to clinical manifestations, they are consistent with the clinical diagnosis of stromal herpes simplex keratitis. Since no specific Western medicine is known to be effective in treating this disorder, it is proposed to apply systemic and topical TCM and, if necessary, add beta-ray irradiation to shorten the clinical course of disease, decrease or prevent recurrence and maintain useful visual acuity, avoiding frequent relapses leading to blindness.


Treatment of tonic headache with acupuncture. Headache is a common symptom of complicated etiology; treatment is often ineffective when the intrinsic cause of the manifestation is not identified. The author found that tonic headache was very common in Germany, where few patients were helped in spite of various modalities of treatment. Since acupuncture proved useful to many cases it is the author's wish to add this ancient practice to the armory of the medical profession.


The effect of radix Salviae miltiorrhizae on the changes of ultrastructure in rat brain after cerebral ischemia. The effect of RSM on ultrastructural alterations of the cortical, hippocampal and caudate neucleus areas brought about by forebrain ischemia in rats were studied. In both RSM-treated and saline-treated groups the ischemic damage was detected in nearly all animals three hours after bilateral common carotid artery ligation, while it was much more mild in RSM-treated animals. The ultrastructural changes consisted of swollen mitochondria, partial loss of cristae, dilatation of rough endoplasmic reticulum and Golgi's complex. In addition, some dark neurons were present, capillary endothelial cells and processes of astrocytes were swollen and active pinocytosis appeared in the endothelial cells. Their presence was most severe in the hippocampus region and the least in the caudate nuclear area. No ultrastructural changes exhibited in the sham-operated animals. The findings of the present experiment demonstrate that RSM can reduce ultrastructural abnormalities of cerebral ischemia and are also direct evidence of the protective effect of RSM on cerebral ischemia.


Experimental studies on the inhibition effects of 1000 Chinese medicinal herbs on the surface antigen of hepatitis B virus. The reverse passive hemagglutination inhibition test was used in the screening of 1000 Chinese materia medica for inhibitors of hepatitis B virus surface antigen. The herbal drugs were commercially available and the surface antigen was from sera of hepatitis B patients. 127 effective drugs were obtained from the survey of which 28 were highly inhibitory (8:1), 35 were moderately effective (4:1), and 64 mildly effective (2:1). Further experiments with varying dosages of the drug, dosages of HBsAg and duration of contact showed 10 drugs to be of optimal effect.


Present status of research abroad concerning the effect of acupuncture and moxibustion on immunologic functions. Japan is one of the countries that have done extensive research on the effect of acupuncture and moxibustion on the immunologic functions. With China first, Japan ranks second among the countries in this study. Concerning research in this field concerned the level abroad can scarcely reach that in China. Scholars abroad fail to base their research on TCM theory. In addition not only the type of diseases studied, and the indexes observed are far less than those in China, but also the scope of their research is far narrower. However, certain diseases under study (for instance, AIDS) and certain indexes under observation (for instance, analysis of changes in T subsets of lymphocytes with monoclonal antibodies), as well as certain aspects of their investigation are worthy of consideration by scholars in China.


Combined therapy with all-trans-retinoic acid and high-dose chemotherapy in patients with hyperleukocytic acute promyelocytic leukemia and severe visceral hemorrhage. Acute promyelocytic leukemia (APL) is associated with a high incidence of disseminated intravascular coagulation (DIC) and early hemorrhagic death. The risk of early fatal hemorrhage is increased when high peripheral-blood blast count and severe DIC accompanied by visceral hemorrhage are present at diagnosis. Progressive cytolysis induced by daily increased doses of chemotherapy, or differentiation all-trans-retinoic acid (ATRA) therapy have been proposed for initial control of DIC, but both are dangerous in hyperleukocytic APL patients. We report our results obtained in three high-risk APL patients treated with a combination of conventional chemotherapy and ATRA. All patients had documented hyperleukocytic APL [M3 or M3-variant subtype, (15, 17) translocation] with DIC, and all had critical clinical course before treatment. Patient 1 presented with cerebral hemorrhage, patients 2 and 3 had acute respiratory failure probably due to pulmonary leukemic infiltration and pulmonary hemorrhage. In order to minimize the severity of DIC during chemotherapy-induced acute cytolysis, ATRA (45 mg/m2 per day) was started on the first or second day of chemotherapy and withdrawn when complete remission (CR) was achieved. Despite adverse clinical features, CR was obtained in these three high-risk patients. Patient 1 showed no increase of cerebral bleeding during therapy. Patients 2 and 3 required transient intensive care, with mechanical ventilation from day 4 to day 11 for one of them. Differentiating granular cells were present in peripheral blood of all patients from the day 5, 12 and 8 of cytotoxic therapy. For the three patients, the number of days with white blood cell count < 1 x 10(9)/l was only 2, 7 and 11 days respectively. These results suggest that differentiation therapy with ATRA may be useful even in hyperleukocytic APL patients, when ATRA is used in combination with chemotherapy. The mechanisms of this putative beneficial effect are discussed.


Clinical significance of monoclonal proteins in chronic lymphocytic leukemia. Serum monoclonal proteins were found in 36 of 111 (32%) chronic lymphocytic leukemia (CLL) patients studied using high-resolution agarose gel electrophoresis combined with immunofixation. In contrast, using immunoelectrophoresis (IEP) and serum protein electrophoresis (SPEP), monoclonal proteins were found in 20 and 4% of CLL patients, respectively. The presence of a monoclonal protein was associated with a median survival of 63 months compared to 103 months for individuals without a monoclonal spike (p < 0.012). This was independent of clinical stage. The data also suggests that the presence of a monoclonal protein may define a group of patients at greater risk for disease progression in the low and intermediate risk groups. (Rai stages, 0, I, II). Further follow-up will be required to determine if this is statistically significant.


The detection of Philadelphia chromosome negative metaphases in long-term bone marrow cultures of the peripheral blood from patients with chronic myeloid leukemia predicts response to interferon-alpha 2a. The cytogenetic response of 10 patients with chronic myeloid leukaemia (CML) to human recombinant interferon-alpha 2a (rhIFN alpha 2a) was compared to the Philadelphia chromosome (Ph) status of the pre-treatment peripheral blood cells after in vitro culture under long-term bone marrow culture (LTBMC) conditions. Pre-treatment light density peripheral blood cells were cultured in LTBMC on sex-mismatched irradiated allogeneic stromal layers with weekly cytogenic examination of metaphases in the non-adherent cell fraction. This was correlated with the patients' response to rhIFN alpha. Two groups of patients, five showing a cytogenetic response (responsive) and five who failed to achieve a cytogenetic response (nonresponsive) were studied. At the initiation of the LTBMCs the Ph' was found to be present in 100% of the cells analysed for nine patients and 97% for one patient. Pretreatment peripheral blood from four responsive patients demonstrated a decline in the proportion of Ph'-positive cells (Ph+) after 1 to 2 weeks in LTBMC. In contrast, peripheral blood from all the non-responsive subjects showed persistence of the Ph+ clone in 100% of the cells analysed out to a maximum of 3 to 5 weeks in LTBMC. A significant difference was observed (Fisher exact test, p = 0.023) between the two patient groups in respect to the appearance of normal clones in the nonadherent population. The presence of Ph- metaphases in LTBMC of peripheral blood cells of CML patients may predict their cytogenetic response to rhIFN alpha 2a.