A universal data acquisition program for use with anesthetic monitors and Windows 3.0. A method is described whereby a single program can acquire data from any patient monitor which has a data output facility. No changes are necessary to the program for different monitors. It provides a method of standardizing data transfer between computers and monitors. The program runs in the Microsoft Windows 3.0 operating system. It utilizes Dynamic Link Libraries (DLL) which enable the operating system to communicate with monitors. Each kind of monitor will use a unique DLL in order to provide a standard interface to the Windows 3.0 operating system.


Transputer-based parallel system for acquisition and on-line analysis of single-fiber electromyographic signals. We describe a transputer-based system suitable for accurate measurements of single-fiber electromyographic jitter. It consists of a conventional electromyograph, a home-made interface and a commercially available transputer-based board installed within a PC/AT compatible. Taking advantage of the concurrent operation of two transputer modules, the system features simultaneous data acquisition and statistical signal processing: while data are acquired and analyzed, a real-time visualization of the signal latency and its variability is provided. In the present configuration, the system can acquire and analyze up to 40,000 consecutive action potentials, which can be grouped into up to eight sets at different stimulation rates programmable up to 16 Hz. Since the determination of the electromyographic signal latency relies on least-squares smoothing and interpolation of the acquired data rather than on amplitude-threshold triggering, a low value (0.7 microsecond) of so called technical jitter is achieved. Computing power and memory can be easily extended by addition of transputer-based modules. Typical results of data acquisition and on-line analysis are reported.


Relationships between the thyroid and somatotropic axes in steers. I: Effects of propylthiouracil-induced hypothyroidism on growth hormone, thyroid stimulating hormone and insulin-like growth factor I. The effects of propylthiouracil (PTU)-induced thyroid hormone imbalance on GH, TSH and IGF-I status in cattle were examined. In the first study, four crossbred steers (avg wt 350 kg) were fed a diet dressed with PTU (0, 1, 2 or 4 mg/kg/d BW) in a Latin square design with four 35-d periods. On day 29 in each period, steers were challenged with an intrajugular bolus of thyrotropin releasing hormone (TRH, 1.0 microgram/kg). Blood samples were obtained to assess the change in plasma GH and TSH as affected by PTU. Plasma IGF-I was measured from blood samples obtained before and after (every 6 hr for 24 hr) intramuscular injection of bovine GH (0.1 mg/kg, day 31). Doses of 1 and 2 mg/kg PTU increased plasma T4 (P < .01). At 4 mg/kg, PTU depressed T4 concentrations to 30% of control (P < .01). Plasma T3 linearly decreased with increasing doses of PTU (P < .01). Plasma TSH increased when PTU was fed at 4 mg/kg (P < .05) while the TSH response to TRH declined with increasing PTU (P < .02). Neither basal nor TRH-stimulated plasma concentration of GH was affected by PTU; the IGF-I response to GH tended to increase at the 1 and 2 mg/kg PTU (P < .01). In a second study 24 crossbred steers were fed PTU (1.5 mg/kg) for 119 d in a 2 x 2 factorial design with implantation of the steroid growth effector, Synovex-S (200 mg progesterone + 20 mg estradiol), as the other main effect. Basal plasma GH and IGF-I were not affected by PTU treatment. Synovex increased plasma concentration (P < .01) of IGF-I without an effect on plasma GH. The data suggest that mild changes in thyroid status associated with PTU affects regulation of T3, T4 and TSH more than GH or IGF-I in steers.


Partial prostaglandin-mediated mechanism controlling the release of cortisol in plasma after intravenous administration of endotoxins. In a first series of experiments we studied the influence of E. coli endotoxins or lipopolysaccharides (LPS) administered either intravenously (i.v.) or intramammarily (i.mam.) to lactating goats on plasma cortisol and rectal temperature (RT). Differences in the magnitude of the cortisol release and shape of the fever curve were observed. In both models maximal pyrexia and fever index (FI) were comparable. In a second series of experiments the influence of LPS on the plasma cortisol and RT was studied after i.v. injection of increasing doses of LPS:low (25 ng/kg), moderate (200 ng/kg) and relatively high (500 ng/kg). Although the cortisol response was dose dependent, the effect was not correlated with FI. The administration of flurbiprofen, a non steroidal antiinflammatory drug (NSAID), resulted in a complete inhibition of fever at all LPS doses and the cortisol release after administration of low doses LPS. This indicates a prostaglandin mediation. With moderate and high doses LPS the cortisol release was only partially inhibited and delayed suggesting a non prostaglandin mediated mechanism. In a third series of experiments the influence of flurbiprofen on fever and cortisol release was studied after i.mam. LPS administration. The observed increase of plasma cortisol and RT were completely abolished after flurbiprofen treatment. It is concluded that: 1) the increase of plasma cortisol after LPS administration in lactating goats is not related to hyperthermia per se, 2) the control of fever and cortisol release may, to some extent, differ according to the LPS dose and method of administration, 3) the cortisol release observed after moderate and high doses of LPS is probably controlled by two phenomena. The first being induced by cyclo-oxygenase metabolites, the second by intermediary mediators other than prostaglandins or by LPS itself. 4) Although an eight-fold higher dose of LPS was given i.mam., a cortisol release comparable to the lowest dose of LPS (25 ng/kg) was observed. These differences in cortisol release can be ascribed to 1) a detoxification of LPS at the level of the mammary gland or 2) a slower resorption of LPS from the mammary gland.


Effect of ovarian regression and molt on plasma concentrations of thymosin beta 4 in domestic hens (Gallus domesticus). Molt induced by infusion of a gonadotropin-releasing hormone agonist (GnRH-A, ([D-leu6,Pro9]-GnRH N-ethylamide]) or feed withdrawal (FW) has been used as a model to study interactions between ovarian activity and thymosin beta 4 during molting in domestic hens. Thirty-three laying hens were divided into three groups: 1, controls, 2, GnRH-A infusion induced molt (GnRH-A), or 3, FW induced molt. All groups had reduced daylength. Blood was sampled weekly and assayed for concentrations of thymosin beta 4 and progesterone (P4). Plasma P4 concentrations were significantly depressed in both treatment groups compared to controls, indicating ovarian regression. Plasma P4 concentrations had returned to control values in the GnRH-A group by 28 d after the start of treatment, while P4 was still depressed in the FW group at day 42 when the experiment ended. Plasma concentrations of thymosin beta 4 were elevated relative to controls from day 7 through day 14 in the GnRH-A group and from day 7 until day 28 in the FW group. It is concluded that plasma concentrations of thymosin beta 4 are elevated during molting in domestic hens, but the elevation is not attributable to depressed P4 concentrations.


Effects of body condition and estradiol on luteinizing hormone secretion in post-partum beef cows. An experiment was conducted to test the hypothesis that the effect of body fatness on LH pulsatility in post-partum cows is entirely independent of the negative feedback effects of ovarian steroids. Forty beef cows were fed in the last 100 d of gestation so that they achieved either a thin (mean score 1.97) or fat (mean score 2.79) body condition (0 to 5 scale) at calving and were fed after calving to maintain live weight and body condition. At 15 (sd 3.7) d post partum all cows were ovariectomised and half from each body condition score treatment group received a subcutaneous estradiol implant (+EST) while the remainder received no implant (-EST). At weeks 5 and 9 post-partum blood samples were collected via jugular catheter every 20 minutes for 10 hr on two consecutive d and on the third d cows were injected via the jugular vein with 2.5 micrograms GnRH. Blood samples were collected every 15 minutes for 1 hr before and 2 hr after GnRH injection. At 5 and 9 weeks the fatter cows had significantly higher mean LH concentrations, baseline LH concentrations, LH pulse amplitudes and pulse frequencies (P < 0.01). Implantation with estradiol in both fat and thin cows reduced mean LH concentrations, baseline LH concentrations, LH pulse amplitudes and pulse frequencies (P < 0.001). The lack of interaction between body condition and the presence or absence of estradiol implies that the effect of body condition on LH release is independent of ovarian steroid feedback mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of a nonsteroidal aromatase inhibitor on in vitro and in vivo secretion of estradiol and on the estrous cycle in ewes. Three experiments were performed to study effects of decreased concentrations of estradiol-17 beta (E2) on lifespan and function of ensuing ovine corpora lutea (CL). In experiment 1, 52 follicles were collected from 10 ewes and placed into individual culture with 0 or .01 microCi 3H-androstenedione (10 ng; 3H-A) and 0, 10(-11), 10(-9), 10(-7), or 10(-5) M of a nonsteroidal aromatase inhibitor, CGS16949A (CGS). Concentrations of E2 secreted into the medium, and synthesis of estrogens as estimated by formation of 3H-water from 3H-A were decreased by 10(-5) and 10(-7) (P < .01), but not 10(-9) or 10(-11) M CGS. In experiment 2, luteolysis was induced in 24 ewes by injection of PGF2 alpha on days 5 to 10 of the estrous cycle (0 hr). Ewes received 0, 0.5, 1.0, 2.0 or 4.0 mg CGS per kg BW i.v. at -12, 0, 12 and 24 hr, and an ovulatory dose of hCG at 36 hr. Jugular (P < .001) and vena caval (P < .001) concentrations of E2 were decreased by CGS at all doses tested for 8 to 10 hr, but had returned to levels similar to control ewes by the time of the next injection. Concentrations of E2 around the time of the LH surge were similar in control and treated ewes. During the subsequent luteal phase, concentrations of progesterone (P4) were similar in control and treated ewes. Thus, transient decreases in E2 during the follicular phase were not deleterious to the subsequent luteal phase. In experiment 3, luteolysis was induced in 18 ewes by injection of PGF2 alpha on days 6 or 7 (0 hr) of the estrous cycle. Ewes received 0 or 1 mg CGS per kg BW i.v. every 8 hr from 0 to 40 hr. Ovulation was induced with hCG at 36 hr. CGS reduced jugular (P < .001) and vena caval (P < .001) concentrations of E2, prevented an endogenous surge of LH (P < .05) and increased (P < .001) concentrations of FSH. All ewes had ovulated a marked follicle by 72 hr, but onset of the luteal phase, as assessed by concentrations of P4, was delayed (P < .01) in ewes receiving CGS. Delayed luteal phases were not solely attributable to the presence of new CL or to luteinization of follicular cysts. When data were aligned according to the day ewes were observed in estrus, profiles of P4 did not differ with treatment.(ABSTRACT TRUNCATED AT 400 WORDS)


Guide to identification of origins of DNA replication in eukaryotic cell chromosomes. Several experimental approaches for identification of origins of DNA replication have been developed recently that allow, for the first time, unique initiation sites in mammalian chromosomes to be mapped at single-copy loci. A brief description of the rationale, advantages, and limitations has been provided for each approach, as well as information that can help the reader choose the method(s) most suitable for a particular system. The various methods are divided into three groups: (1) analysis of nascent DNA strands, (2) analysis of DNA structures, and (3) analysis of origin activity (i.e., ability to support autonomous replication). It is hoped that this information will serve as a practical guide for identifying new origins of replication.


Biochemistry of methanogenesis.

Biochemistry of methanogenesis. Methane is a product of the energy-yielding pathways of the largest and most phylogenetically diverse group in the Archaea. These organisms have evolved three pathways that entail a novel and remarkable biochemistry. All of the pathways have in common a reduction of the methyl group of methyl-coenzyme M (CH3-S-CoM) to CH4. Seminal studies on the CO2-reduction pathway have revealed new cofactors and enzymes that catalyze the reduction of CO2 to the methyl level (CH3-S-CoM) with electrons from H2 or formate. Most of the methane produced in nature originates from the methyl group of acetate. CO dehydrogenase is a key enzyme catalyzing the decarbonylation of acetyl-CoA; the resulting methyl group is transferred to CH3-S-CoM, followed by reduction to methane using electrons derived from oxidation of the carbonyl group to CO2 by the CO dehydrogenase. Some organisms transfer the methyl group of methanol and methylamines to CH3-S-CoM; electrons for reduction of CH3-S-CoM to CH4 are provided by the oxidation of methyl groups to CO2.


In vitro stimulation of peripheral blood mononuclear cells by phytohaemagglutinin A induces CD45RA expression on monocytes. Following phytohaemagglutinin A stimulation, CD45RA positive monocytes increased from 12.2 +/- 8.9% to 63.5 +/- 8.8% (p < 0.001), without a significant change in cell surface antigen density. In contrast, HLA-DQ antigen, also expressed in 76.8 +/- 10.5% of the monocytes after PHA stimulation for 48 h, revealed a marked enhancement in fluorescence intensity (p < 0.001). This up-regulation is already evident in unstimulated cultures. The percentages of CD45RA and HLA-DQ positive monocytes were correlated (r = 0.80, p < 0.001), substantiating a previous clinical observation. CD45RA expression may probe activated mono/macrophages.


Monoclonal antibodies against Nereis virens brain homogenates as probes for isolation and in situ detection of new neurosecretions. The brain of Nereis contains 26 ganglionic nuclei which produce numerous neurosecretions. Only a few of them have been characterized. The production of monoclonal antibodies was adopted as an approach to discover unknown neurosecretions. Monoclonal antibodies produced against Nereis virens brain homogenates were selected using stepwise ELISA tests first with brain homogenates, then with brain neurosecretions. Eight antibodies specific for Nereis neurosecretions were selected. The results are illustrated with one of these monoclonal antibodies which was directed against a major peak after HPLC purification of brain neurosecretions. This antibody was subsequently used for the in situ detection of recognized epitope(s) in the brain and ventral nerve cord cells.


Influence of prolactin on ultrastructure of pinealocyte in sexually immature female pigs: a quantitative study. The effects of long-term prolactin administration on the ultrastructure of pinealocytes in young female pigs were studied by means of morphometric analysis. Prolactin administration for 26 consecutive days resulted in an increase in the cytoplasmic dense bodies type MBB-1 and some differences in their structure. There were no significant changes in the other cytoplasmic structures. Prolactin appeared to stimulate the process of formation of dense bodies.


Cytotoxic effects of Sumicidin, a type II synthetic pyrethroid, on mice in vivo at 6, 12 and 24 h after exposure. The ability of Sumicidin, a synthetic pyrethroid, to induce cytotoxicity in Swiss albino mice was evaluated before completion of the first cell division following oral exposure. Mice were administered orally different concentrations (32.50, 75 and 150 mg/kg body wt) of Sumicidin in a single dose. Mitotic index and chromosomal aberrations were screened after 6, 12 and 24 h following exposure. The frequency of dividing cells decreased significantly, indicating mitostatic action. The frequency of chromosomal aberrations was directly related to the concentrations used and the duration after exposure, and was significant at all concentrations. The highest frequency of aberrations was observed 24 h after exposure.


Pharmacokinetics of cefodizime in patients with liver cirrhosis and ascites. The pharmacokinetics of cefodizime were studied in 6 healthy male volunteers (group A) and 6 patients with liver cirrhosis and ascites (group B) receiving 1 g of the drug as an i.v. bolus. Cefodizime was assayed in serum and ascitic fluid (AF) samples by a microbiological assay. The serum concentration-time curve fitted a two-compartment open model in group A and a three-compartment open model in group B. Initially, the serum level of cefodizime in group A exceeded that in group B for about 10 h; thereafter the reverse occurred until 24 h post-dosing. Cefodizime penetrated rapidly into the AF, reaching a peak at 6 h, and its AF level was still above the MIC90 for Enterobacteriaceae in most patients at 24 h post-dosing. The half-life of distribution did not differ significantly between the two groups, while the elimination half-life was prolonged significantly (p < 0.001) from 2.7 +/- 0.2 h in group A to 5.4 +/- 0.8 h in group B. The central volume of distribution (Vc) did not differ significantly in the two groups, while the terminal volume of distribution (Vp) was significantly smaller (p < 0.01) in group A (0.172 +/- 0.30 l/kg) than in group B (0.55 +/- 0.20 l/kg). The area under the serum concentration-time curve (AUC0-infinity serum) was significantly larger (p < 0.001) in group A [322 +/- 34 (micrograms/ml).h than in group B (180 +/- 34 (micrograms/ml).h]. The area under the AF concentration-time curve (AUC0-infinity ascites) in group B was 141 +/- 37 (micrograms/ml).h.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro susceptibility of methicillin-resistant Staphylococcus aureus and slime-producing and non-slime-producing coagulase-negative staphylococci to fusidic acid. The in vitro susceptibility of 100 oxacillin-resistant Staphylococcus aureus and 100 oxacillin-resistant coagulase-negative staphylococci (CNS; 50 slime-negative and 50 slime-positive strains) was determined by agar dilution technique, with and without the addition of 50% human serum. All strains tested were highly sensitive to fusidic acid. S. aureus and CNS showed MIC50 values of 0.125 and 0.25 mg/l, respectively. MICs of all strains increased significantly in the presence of 50% human serum. Only minor differences were noted between the MICs of slime-producing and slime-deficient CNS.


Influence of exogenous factors and antibiotics on the cytoplasmic membrane proteins of Staphylococcus aureus. The influence of various nutrient media, growth temperature, phase of growth and subinhibitory concentrations of antibiotics from various groups on the cytoplasmic membrane proteins was studied in 6 clinical S. aureus isolates; further study included the comparison of the cytoplasmic membrane proteins in antibiotic-sensitive wild-type (parent) strains with their resistant counterparts. Resistant clones could be selected with a frequency ranging from 10(-7) to 10(-8) from the parent strain at twice the MIC. The following was observed from the study of six clinical isolates: (a) there was no uniform pattern of cytoplasmic membrane proteins among the isolates; (b) during the phase of growth, the number of high-molecular-weight proteins showed a decrease according to the duration of growth; (c) the addition of 1% w/v glucose to the growth medium resulted in the loss of an approximately 75 kD protein in five of the six strains; (d) subinhibitory concentrations of various antibiotics (1/4 of the MIC) resulted in major changes of cytoplasmic membrane proteins, when the strains were exposed to oxacillin, whereas this was not the case for erythromycin, rifampicin, gentamicin, trimethoprim, fleroxacin and vancomycin; (e) the resistant clones differed from their sensitive parent strains in their cytoplasmic membrane protein patterns. The alterations were not characteristic either for the strain or for the antibiotic considered, thus suggesting an 'unspecific' defense mechanism characterized by individual changes of the cytoplasmic membrane proteins.


Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity. The affinity of meropenem for various known types of beta-lactamases and its stability to them were tested in comparison with other beta-lactams, including imipenem. Meropenem exhibited a marked stability to all beta-lactamases tested and was only hydrolyzed by Xanthomonas maltophilia beta-lactamase, as were other beta-lactams. This was responsible for the potent antibacterial activities of meropenem against beta-lactamase-producing strains. Meropenem and imipenem had almost the same, relatively high affinity for beta-lactamases; however, they had a lower affinity than clavulanic acid for penicillin beta-lactamases and cefoxitin for cephalosporin beta-lactamases. Meropenem also had higher beta-lactamase inhibitory activity than imipenem. Meropenem inhibited type III (TEM-1), Ia Citrobacter freundii and Ic Proteus vulgaris beta-lactamases in a progressive manner. Meropenem was thought to be a potent inhibitor of various beta-lactamase because of its ability to form stable enzyme-meropenem acyl-complexes. Meropenem generally exhibited a lower induction potential than imipenem against five clinical isolates of C. freundii, Enterobacter cloacae and Pseudomonas aeruginosa, but its induction potential was higher than that of ceftazidime. Meropenem induced beta-lactamases at concentrations above the MIC.


Comparative in vitro activity of cefepime and four extended-spectrum beta-lactams on 1,251 aminoglycoside-resistant gram-negative hospital strains. Cefepime was the most active compound on the Enterobacteriaceae with a MIC90 of 0.26 microgram/ml and a resistance rate of 0.1%. Ceftazidime was the most active drug on the non-fermenting bacilli (MIC90 9.65 micrograms/ml; resistance rate 3%). Amikacin- and gentamicin-resistant strains showed a decreased susceptibility to the beta-lactams, though the Enterobacteriaceae and the non-fermenters remained fairly sensitive to cefepime and ceftazidime, respectively. Aminoglycoside-3-N-acetyltransferase was the most prevalent enzyme and was often associated with intermediate resistance or resistance to beta-lactams. Non-fermenters showing aminoglycoside impermeability were very often intermediately resistant or resistant to beta-lactams.


In vitro antimicrobial activity of amiloride analogs against Pseudomonas. The effects of specific amiloride analogs on Na+ channel and Na+/H+ antiport function in eukaryotic cells have been well studied, but the effect of these agents on Pseudomonas is unknown. The antimicrobial activity of benzamil HCl, 5-(N-N-dimethyl)amiloride HCl (DMA), 5-(N,N-hexamethylene)amiloride HCl (HMA), and 5-(N-methyl-N-isobutyl)amiloride HCl (MIA) on 30 Pseudomonas strains (20 P. aeruginosa and 10 P. cepacia) were compared to amiloride HCl after a 24-hour incubation in Mueller-Hinton broth at 35 degrees C. At pH 7.3 the MIC range and MIC50 (in mg/l; MIC50 in parentheses) for amiloride HCl, benzamil HCl, DMA, HMA and MIA were 400 to > 800 (> 800), 200 to 800 (400), 200 to > 800 (400), 100 to 400 (200), and 100 to 400 (200), respectively, for P. aeruginosa and > 800 (> 800), 400 to > 800 (800), 400 to > 800 (800), 200 to 800 (200), and 200 to 800 (200), respectively, for P. cepacia. Alteration of pH from 5.5 to 8.5 had a slight effect on potency. We conclude that all the analogs studied were more potent antipseudomonal agents in vitro than amiloride, with the more lipophilic compounds HMA and MIA, having the most profound activity.


Synergistic effect of romurtide with ampicillin against pneumococcal pneumonia in mice. The anti-infective activity of romurtide, a synthetic muramyl dipeptide (MDP) derivative, was evaluated in experimental pneumococcal pneumonia in mice deficient in the third component of complement (C3). The compound was found to be effective against the pneumonia in combination with subcutaneous ampicillin (ABPC). This synergistic effect of romurtide with ABPC was most pronounced when the compound was administered subcutaneously 1 day before infection. Romurtide alone, however, was not effective, irrespective of its treatment timing. Similarly, consecutive treatment with ABPC alone failed to kill pneumococci in the lungs completely, and resultant regrowth of the organisms provoked purulent pneumonia. In contrast, the combination treatment of romurtide with ABPC successfully prevented most of the mice from the purulent pneumonia: the initial infiltration of resident alveolar macrophages and subsequent accumulation of macrophages were observed in the pneumonic foci. In accordance with the occurrence of these cellular responses in the lungs, pneumococci were successfully eliminated from the lungs in mice treated with romurtide in combination with ABPC. Thus, romurtide was suggested to promote recovery of the mice with pneumococcal pneumonia by activating resident and accumulated macrophages in the pneumonic foci to eliminate pneumococci from the lung.


Experimental animal model for the evaluation of chemotherapeutical effects on osteosarcoma. In previous studies radiation-induced osteosarcoma transplanted onto nude rats has been shown to have an extraordinary similarity to human osteosarcoma. In this report the effects of a standard chemotherapeutic regimen on this experimental bone tumor are described. Examination of the histology and of the water content of the tumor confirmed that a high-dose cyclophosphamide monotherapy can cause severe necrosis in the tumor and its seeded lung metastases. A significant decrease in tumor volume of 50% (p < or = 0.01) was provoked and increased the mean survival rate of the treated rats (untreated rats: mean = 39.3 days) significantly to 53.6 days after transplantation of tumor fragments (p < or = 0.01).


Influence of enoxacin sub-MICs on the adherence of Staphylococcus aureus and Escherichia coli to human buccal and urinary epithelial cells. Bacterial adhesion is the first step in the sequence of events leading to infection. It has been observed that subinhibitory concentrations of antibiotics can interfere with the mechanism of bacterial adhesion. The purpose of the present study was to investigate the capacity of sub-MICs of enoxacin, a new 4-quinolone with 6-fluoro and 7-piperazino substituents, to interfere with the adhesiveness of Staphylococcus aureus and Escherichia coli to human buccal cells and of E. coli to urinary epithelial cells. A significant decrease was observed with 1/2-1/64 the MIC for the adhesion of S. aureus to buccal cells. Inhibition of adhesion was also observed for E. coli strains, but in this case a marked decrease was observed across the range from 1/2 to 1/128 the MIC for urinary cells, and from 1/2 to 1/256 the MIC for buccal cells. Enoxacin also caused elongation of E. coli.


Peripheral blood cell repopulation following high-dose cyclophosphamide. High-dose cyclophosphamide can be used to obtain haematological stem cells from the peripheral blood. In this paper we analyse the dynamics of appearance of cells with these characteristics, together with the impact of this drug on the immunological system. Cyclophosphamide seems to possess immunomodulating effects even at high doses.


Ciprofloxacin plus vancomycin versus ceftazidime plus gentamicin in the treatment of pneumonia in granulocytopenic patients with or without venous catheters. Short communication. 58 granulocytopenic patients with confirmed bronchopneumonia were divided retrospectively into two groups for this pilot study: group 1 included neutropenic patients with venous catheters who were treated with ciprofloxacin (CIP; 200-300 mg, i.v. b.i.d.) + vancomycin (VAN; 0.5-1 g, i.v. b.i.d.), and group 2, which included patients without venous catheters treated with ceftazidime (2 g, i.v. t.i.d.) + gentamicin (1 mg/kg, i.v. t.i.d.). Pneumonia was diagnosed clinically and radiologically in all patients; 92.3% in group 1 and 46.8% in group 2 were also microbially confirmed. Mixed infections were present in most patients. 3 of 26 patients (11.5%) in group 1 and 9 of 32 (20.1%) in group 2 did not recover while 88.5% in group 1 and 71.9% in group 2 recovered. CIP + VAN seems to be more effective in treating pneumonia in neutropenic patients, with only 1 patient in the group suffering an adverse effect compared with 5 in group 2.


Bacterial flora in mal perforant and antimicrobial treatment with ceftriaxone. The objectives of this pilot study were to identify the bacterial flora of neurotrophic ulcers, and to determine whether treatment with ceftriaxone improves the clinical picture. Twenty-five patients (15 male, 10 female, mean age 70 +/- 11 years) with mal perforant were treated with 2 g ceftriaxone once daily until the ulcer was healed, or for a period of 6 weeks. Biopsies were taken from the ulcer floor before and after therapy. Initially, the following bacteria were found, in order of frequency: Staphylococcus aureus, enterobacteria, coagulase-negative staphylococci, enterococci and streptococci as well as Pseudomonas aeruginosa. Under therapy with ceftriaxone, the lesions of 11 patients were healed; in 5 patients improvement > 50% was observed and in 4 patients improvement was < 50%. In 3 patients there was no change in the condition. Two patients had to stop treatment due to diarrhea. Asepsis was achieved in 5 patients despite persistence of the ulcer. The control group (25 patients without antibiotic therapy) showed the following results: healing in 6, improvement > 50% in 5, improvement < 50% in 10, and no change in 4. The results for the treatment group have to be compared with a historical control group since, for ethical reasons, the implementation of a double-blind study would not be feasible.


Detection of Listeria monocytogenes by non-radioactive RNA probe and polymerase chain reaction. A HindIII fragment, 651-base-pair, from the listeriolysin 0 gene of Listeria monocytogenes was cloned into pGEM4Z. Radioactive 32P labeled and non-radioactive digoxigenin labeled RNA probes were made by in vitro transcriptions. These probes hybridized only to L. monocytogenes strains. Polymerase chain reaction was performed by using a 22-mer and a 23-mer oligonucleotide primer, and segment of about 700-base-pair was amplified only in L. monocytogenes strains and this band was visualized by hybridization with the non-radioactive probe.


[Modified selective medium for isolation of Helicobacter pylori]. To improve the detection rate of Helicobacter pylori, many kinds of media were tried and other antibiotics were incorporated according to the antimicrobial susceptibility patterns of clinical isolates in our hospital. We found that brain heart infusion agar supplemented with 1% IsoVitaleX and 5% sheep blood, containing nalidixic acid 10 micrograms/ml, vancomycin 6 micrograms/ml, amphotericin B 2 micrograms/ml and polymixin B 16 micrograms/ml (BNVP) or colistin 5 micrograms/ml (BNVC) inhibited the growth of contaminants without significant influence on the growth of H. pylori. However, colonies of primary isolates of H. pylori on BNVP media were larger than those on BNVC media, and easier to detect, Both BNVP and BNVC media yielded the same isolation rate. The organism was isolated from 67 of 91 endoscopic biopsy specimens (73.6%) obtained from the area of peptic ulcers, and from 37 of 125 specimens obtained from the area without lesion. The data were much superior to those in the early day, when the organism was only isolated from 6 of the 27 specimens (22%) obtained from patients with peptic ulcer disease. Because the contaminants and their antimicrobial susceptibility patterns may be varied in different hospitals, it is mandatory to modify selective media suitable for recovering H. pylori.


[Identification and typing of Pseudomonas pickettii during an episode of nosocomial outbreak]. From January to April 1989, Pseudomonas pickettii was isolated from clinical specimens of 24 hospitalized patients at the National Taiwan University Hospital in Taipei. The source of the organism was the 0.9% NaCl solution prepared by the hospital pharmacy. A total of 39 isolates of P. pickettii were collected, including 28 from clinical specimens and 11 from 0.9% saline and distilled water during the outbreak. These microorganisms were studied by using four methods, namely, conventional biochemical method, Vitek Auto-Microbic System (Vitek AMS), gas-liquid chromatographic analysis of cellular fatty acids composition and determination of the minimum inhibitory concentrations of 10 different antimicrobial agents. By conventional biochemical method, 16 isolates were typed as biovar 1 and 23 strains were biovar 3. Strains of both biovars were recovered from clinical specimens and 0.9% saline. Vitek AMS was able to identify P. pickettii correctly, but the result of biotyping was not satisfactory. Analysis of cellular fatty acids could rapidly identify P. pickettii to the species level, but could not distinguish the different biovars. By determination of the MICs, the antibiogram could be classified into 9 patterns. Of 16 isolates of P. pickettii biovar 1, 7 (44%) belonged to pattern I, and 9 (56%) pattern II. Strains of both patterns were found in cultures of clinical specimens and 0.9% saline. Of 23 isolates of P. pickettii biovar 3, 11 (48%) belonged to pattern III, 4 (17%) pattern IV and 8 (35%) pattern V to IX. Pattern III and pattern IV were seen in isolates from clinical specimens and 0.9% saline, while pattern V to IX were only seen in isolates from clinical specimens.(ABSTRACT TRUNCATED AT 250 WORDS)


Absence of genomes of DNA tumor viruses and expression of oncogenes and growth factors in two esophageal carcinoma cell lines of Chinese origin. To study the oncogenesis of human esophageal carcinoma, the presence of DNA sequences homologous to several DNA tumor viruses and the expression of oncogenes and growth factor genes were examined in two esophageal carcinoma cell lines of Chinese origin, CE48T/VGH and CE81T/VGH. Southern blot analyses failed to detect sequences homologous to hepatitis B virus (HBV), Epstein-Barr virus (EBV), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV) or human papilloma virus (HPV) genomes. Northern blot analyses revealed that c-myc, c-src, c-H-ras, c-abl, c-sis, and p53 genes were expressed. In addition, transcripts of transforming growth factor alpha (TGF alpha), TGF beta, and platelet derived growth factor A (PDGF A) genes were detected. These studies suggest that DNA tumor viruses may not be involved in the carcinogenesis of esophageal carcinoma. However, cooperation among different oncogenes and the production of growth factors may play an important role in that carcinogenesis.


Immunochemical characterization and therapeutic effect of house dust extract in bronchial asthma. The immunochemical characteristics of house dust extract used in hyposensitization were studied by SDS-polyacrylamide gel, isoelectrofocusing, counterimmunoelectrophoresis and Western blot. The gel electrophoregram and isoelectrofocusing plate demonstrated a complex mixture of acid proteins with molecular weights ranging from 56 to 12 KD and isoelectric point distributing from 4.6 to 5.6. The counterimmunoelectrophoresis revealed as many as five precipitating bands in sera from 60% asthmatic patients after hyposensitization. The Western blot showed heterogeneous IgE reaction bands varied from 45 to 22 KD, including a strong 27 KD reaction band found in 40% of the asthmatic patients not receiving hyposensitization. The efficacy of house dust extract hyposensitization was evaluated in 102 asthmatic patients, followed up at the Allergic Clinic since 1980. There were 42 malea and 60 females with a mean age of 30.8 (16 to 60), and the total follow-up patient-year was 512.6 with a mean of 5.0 year per patient (1 to 11). Complete remission of asthmatic symptoms and medication was found in 5% patients, and 12% patients had little or no improvement. The majority of patients (83%) had improvement in asthmatic symptoms and medication dosage. The average serum IgE levels and total eosinophil count dropped significantly after hyposensitization (p < 0.001). In conclusion, the immunochemical characteristics of house dust extract were analyzed and mite allergens, especially Group I antigens, may be the important constituents. Good therapeutic effect, both clinically and with laboratory evaluation, was obtained with more than 80% of the asthmatic patients achieving improvement under house dust hyposensitization.


The effects of asthmatic mononuclear cell cultured supernatant on human eosinophils-chemiluminescence response, complement receptor expression and cellular density alteration. We investigated the contributing effect of mononuclear cell (MNC) on granulocyte function in asthmatics. MNC, obtained from either normal subjects or asthmatics, were cultured with or without phytohaemagglutinin. The supernatants were tested on granulocyte luminol-dependent chemiluminescence (CL) response. The optimal incubation time was 30 min for neutrophils and 90 min for eosinophils. There was a dose-dependent enhancement of CL response by MNC supernatant on both neutrophils and eosinophils. When comparing the activities of MNC supernatants between asthmatics and normal, there was a significant enhancement of eosinophil CL response by MNC supernatants of asthmatics (70 +/- 24% from 29 +/- 28%, P = 0.0043). However, the degree of enhancement in neutrophil CL response was similar between the MNC supernatants of asthmatics and normal subjects. MNC supernatant not only enhanced eosinophil CL response, but also induced eosinophil hypodensity change (12 +/- 4% in RPMI, 26 +/- 10% in MNC supernatant), and enhanced complement receptor CR3 expression (102.4 +/- 25.5 in PRMI, 111.7 +/- 17.7 in MNC supernatant). These results provide evidence that MNC activation might contribute to the eosinophil activation in asthmatics.


[Morphologic and biochemical characteristics of viridans streptococci isolated from dental plaque]. The purposes of this study were to give the characteristics of viridans streptococci isolated from dental plaque, and the relationships with dental caries. We stained 69 patients' teeth on supragingival plaques (Plaque Index = 1) with the Pfiffer's reagent or FD&C RED#28 dye, then isolated 80 strains of oral streptococci from 69 patients. Cultures were grown in TSB, MS, and MSB media. A total of 80 fresh-isolated plaque streptococci, including strains of S. salivarius, S. sanguis, S. mitis, and S. mutans were identified on the basis of morphologic, dark field, SEM, and biochemical characteristics. All of the oral plaque streptococci were to be found in significant percentages in dental plaque. Patients who had caries harboured S. mutans more often (37/40) than patients without caries (7/29). S. mutans comprised the greatest percentage (37/69) of microorganisms encountered in caries' plaque, and there was an association between high counts of S. mutans and the presence of dental caries. Cultural and biochemical methods were used for the isolation and identification of the different species of S. mutans. The result indicated that biotype I were the most predominant species (50%) in dental plaque. Thus, it is possible to isolate, screen and identify unknown strains through the morphologic, darkfield, SEM, and biochemical characteristics of viridans streptococci isolated from human dental plaque. By means of the present methods for identification, we hold considerable promises for contributing to the prevention and diagnosis of dental diseases.


[Improvement in the resection of intestinal Peutz-Jeghers polyps]. Polyps in patients with Peutz-Jeghers syndrome (PJS) are found in the large and small bowels. In the past, intestinal polyps were treated mainly by multiple abdominal operations. The authors reported resecting 259 polyps in 13 patients with PJS by laparotomy plus colonoscopy via small bowel incision for small intestines, and/or plus colonoscopy via the anus for ileum and large bowel polyps at a time combined with periodic colonoscopy via the anus for colorectal polyps. The largest polyp resected in this way was 10 x 9 x 8 cm. As many as 46 polyps were resected by snare polypectomy at a single colonoscopic attempt. Using the above-mentioned methods, multiple intestinal polyps can be resected more thoroughly, and postoperative recurrence and complication became less frequent.


[Temporary distal arteriovenous fistula in the treatment of post-thrombotic iliofemoral occlusion]. Post-thrombotic iliofemoral occlusion, not rarely encountered, causes significant long-term disability of the patients. Satisfactory method of treatment is not available. Temporary distal arteriovenous fistula was made in 9 patients (10 legs) with iliofemoral occlusion with excellent results which were confirmed by average follow-up of 2 years. The mechanism is thought to be that after surgery the arteriovenous fistula may open and dilate the pelvic venous collaterals to relieve the venous hypertension of the diseased limbs.


[Determination and treatment of human body total potassium capacity]. The system of determination and treatment of human body total potassium capacity (HBTPC) were based on curves: the values of serum potassium concentration, arterial blood pH and variation of HBTPC. We compared the values of 40 health persons and those of 350 patients who received abdominal operation. The patients with abnormal HBTPC were treated successfully. We consider that this system is better than traditional method.


[Autotransfusion in hemothorax patients]. From Nov. 1978 to Dec. 1988, autotransfusion was done in 25 patients, of which 23 suffered from traumatic hemothorax and 2 from spontaneous hemothorax. The amount of blood autotransfused was 500-2300ml (average 950ml). The time elapsed from accident was 5-44 hours (average 21 hours). Two patients had febrile reaction for a short period of time after operation. The rest recovered uneventfully. Hematological examination revealed that the quality of the blood collected from hemothorax was similar to that of the systemic blood of the patients and was superior to the stored blood. Free hemoglobin determination showed that 40% was in normal value (average 18.9%), and hemolysis was less serious than that of the blood after CPB. The results of aerobic and anaerobic cultures were negative. We believe that the quality of the blood collected from traumatic hemothorax was quite acceptable, and autotransfusion with such blood was adequate not only for war casualties but also for everyday emergency patients.


[Surgical treatment of obstructed superior vena cava]. From 1979 to 1989, 17 patients with obstructive superior vena cava resulted from different causes underwent various operations: azygos vein-right atrium bypass with an artificial vein (1 patient), external jugular vein-right atrium bypass (3 patients), innominate vein-right atrium bypass with the artificial veins made of autofascia (2 patients), and great saphenous veni-external jugular vein version (9 patients). Follow-up showed that version method is better than others because of good circulation and less thrombus formation.


[Anterior approach micro-decompression for cervical spondylotic myelopathy. Report of 74 cases]. From Oct. 1986 to Dec. 1990, 74 patients with cervical spondylotic myelopathy were treated by anterior micro-decompression. According to the Guidetti's classification of spine cord dysfunction, minor paralysis was detected in 18 patients, moderate in 49, and severe in 7. Thirty-five patients with monointervertebral space compression were operated on at the involved space only, and 39 patients with poly-level masses, two or three intervertebral spaces were operated. The results of the patients after microsurgery were good in 55 patients (74.3%), improved in 16 (21.6%), unchanged in 3 (4.1%). None worsened after operation. The total effective rate was 95.9%. We emphasize that the bony compressive mass should be resolved completely and the same time spine cord involvement must be avoided.


[Transplantation of fetal adrenal medullary to the brain in Parkinson's disease]. The adrenal medullary tissue removed from the fetus donor aborted at the age of 24 weeks was cultured for one week. Approximately 200-300 mg tissue was placed at the head of bilateral caudate in 17 severe patients with PD. Follow-up lasted for 3 to 18 months. Improvement was observed in all patients 3 months after grafting. Clinical analysis showed that the efficacy was significant and that one of the 17 patients relapsed. The response rate of 6 to 12 months was 87.5%. Immediately after operation, the drug was withheld or decreased in dosage. The low density areas in the head of caudate nucleus was found by CT within 1 to 10 days, and disappeared one month after operation. We conclude that the human fetal adrenal medullary tissue can survive in the human brain and is associated with functional effect. Transplantation of the brain tissue is useful in the treatment of PD.


[Neurosurgical problems in craniofacial surgery for maxillofacial and ENT diseases]. From June 1978 to June 1990, 48 patients (34 patients with skull base tumors and 14 with congenital hyperterolism) were treated by combined craniofacial surgery. Cranial approaches were performed through the anterior fossa in 7 patients, middle fossa in 19, posterior fossa in 1, both anterior and middle fossa in 6, middle and posterior fossae in 1 and bilateral anterior fossae in 14. Neurosurgical problems were discussed.


[Trephine craniotomy in neurosurgery].

[Trephine craniotomy in neurosurgery]. For three years, we have performed craniotomy with a 5 cm diameter trephine through a linear incision. 53 craniotomies were done in 49 patients. This simple and time-saving method produced little bleeding and slight injury to the brain. The technique allowed the surgeon to spend most of his time at the management of lesion. Healing of wound was rapid and brain edema was minimal.


[The clinical features and surgical treatment of intracranial cavernous angioma]. 18 histologically verified cases of intracranial cavernous angioma were reviewed in terms of clinical features, radiological and histopathological findings. The cases were divided into 3, groups: seizures (5), subarachnoid hemorrhage (6), and intracranial space occupied lesions (7). CT scan was done for surgical planning. Tumors were successfully removed in 17 cases except one died from edema after operation. The relations between radiological and pathologic features of intracranial cavernous angioma were discussed.


[Difficulties in surgical management of lung carcinoma with cardiovascular involvement]. 15 patients with lung carcinoma associated with cardiovascular involvement were treated surgically. Of these patients, 2 had involvement of the heart, 3 the superior vena cava, and 10 the pulmonary artery. Patient selection, operation forms, techniques, complications, and operation-made metastasis were discussed.


[Diagnosis and treatment of pheochromocytoma. Report of 48 cases]. A total of 48 patients with pheochromocytoma were treated during 1965-1989. The incidence of pheochromocytoma was about 2% in hypertensive patients at same period. In this series, 31 (64.6%) had adrenal pheochromocytoma and 17 (35.4%) extra-adrenal pheochromocytoma. More than 50% of the patients showed such symptoms as hypertension, headache, sweating and palpitation. Urinary catecholamine level was significantly elevated in 97.6% of the patients. In tumor localization, CT showed an accurate diagnostic rate of 95.5% and ultrasonography 85.7%. The fluctuation of blood pressure and the amount of fluid requirement during operation in phenoxybenzamine-treated patients were lower than those in non-phenoxybenzamine-treated patients, but there was no statistically significant difference between < 14 days of treatment group and > 14 days of treatment group in phenoxybenzamine-treated patients. 47 patients underwent complete excision of tumor, except 1 patient with a gigantic tumor from the organs of Zuckerkandl. One patient died after operation.


[One-stage operation for treatment of transposition of penis and scrotum complicated by hypospadia]. Transposition of penis and scrotum is often complicated by hypospadia and used to be corrected by staged operation. Since 1984 a new procedure has been developed in which the transposition of penis and scrotum and clubbed penis were corrected, and urethroplasty was performed at same time. Six children received this operation uneventfully. Postoperative follow-up revealed that normal penis position, erection and urination were achieved in these patients. This operation is applicable to patients with transposition of penis and scrotum complicated by various hypospadia. The operative method and key to ensure success are described in this article.


[Male pseudohermaphroditism. Testicular feminization syndrome]. Male pseudohermaphroditism--testicular feminization syndrome is a rare genetic entity with considerably familial predisposition. Of the 9 cases, 7 except 2 children were confirmed surgically. Clinical manifestations of the disorder were primary amenorrhea, infertility and a mass in groin. We suggested that orchiectomy is necessary after puberty. The genetic pattern, clinical characteristics, diagnosis and treatment of the condition were briefly discussed with a review of the literature.


[Efficacy of succinylcholine under hyperventilation]. To evaluate hypocapnic effect on muscle relaxant, we investigated succinylcholine under normal condition (PetCO2 5-5.5kPa) and hyperventilation (PetCO2 3-3.5kPa), with the patients as the self control. Fifteen patients undergoing selective surgery were divided randomly into two groups. The hypocapnic effect on single intubational dose course as well as sustaining two hours was observed with the neuromuscular blockade traced by accelograph. The results showed that the speed of onset, recovery time and duration of succinylcholine after 1 mg/kg i.v. have no significant difference between normal condition and hyperventilation. It is indicated that in good risk adult patients, ventilatory hypocapnia for two hours causes no significant change in succinylcholine relaxation.


[Oxygen-lactated Ringer's solution for surgical patients]. The effects of intravenous infusion of the lactated Ringer's solution inflated with oxygen (Oxygen-LR) and lactated Ringer's solution (LR) on oxygenation of blood were studied in 23 patients undergoing abdominal surgery under epidural anesthesia. LR 1000 ml was infused with inflated oxygen at 1L/min in 30 minutes in the oxygen-LR group (n = 12). The partial pressure of oxygen-LR was increased to 600.45 +/- 78.78 from 129.4 +/- 9.69 mmHg. LR 1000 ml was infused in 30 minutes in the control group (n = 11). There was no significant difference in PaO2, PaCO2, SatO2, A-aDO2 during and 30 minutes after infusion between the oxygen-LR and control groups. We believe that oxygen-LR is of no clinical value because of its low ability is of no carrying oxygen.


[Hemodynamic changes in normovolemic and hypovolemic canines during epidural block]. Hemodynamic changes were studied in normovolemic and hypovolemic canines during epidural block. In normovolemic canines after epidural block, stroke volume (SV) increased, heart rate (HR) slowed down and total peripheral resistance (TPR) and mean arterial pressure (MAP) decreased. In addition, hepatic vascular resistance (HVR) and renal vascular resistance (RVR) decreased but quantity of hepatic artery per beat (QHR/HR), quantity of hepatic artery per beat (QPV/HR) and quantity of renal artery per beat (QRA/HR) increased significantly. In hypovolemic canines, the hemodynamic changes after epidural block were similar in normovolemic ones but more abrupt. The increase of QHA/HR, QPV/HR and QRA/HR was not statistically significant, but minute hepatic blood volume quantity of hepatic artery (QHA), quantity of portal vein (QPV) and hepatic blood flow (HBF) decreased significantly. In hypovolemic canines during epidural block, ischemic injury of the liver should be alerted and abrupt hemodynamic changes should be well controlled.


[Free radical damage to chondrocytes and protection by selenium, tocopherol and ascorbic acid using serum-free medium method]. Free radical derived from xanthine oxidase damage to rabbit articular chondrocytes cultured in serum-free medium and antioxidant defense factors protecting chondrocytes from free radical were studied. The results showed that free radical mediated an inhibition of DNA as well as proteoglycan synthesis in cultured chondrocytes and selenium, a-tocopherol and L-ascorbic acid failed to protect chondrocytes from free radicals.


[The therapeutic effect of pulsed electric field on experimental spinal cord injury]. Pulsed electric field was used on 22 dogs with incomplete spinal cord injury for 8-10 weeks. Nerve cells, nerve fibres and astrocytes were identified by monoclonal antibody to neurofilament or glial fibrillary acidic protein. Morphometric analysis was used for axon counting and GFAP area ratio calculation. The result indicated that there were more axons in the treated group than in the control group at the distal part of injured site. The cellular distribution and patterns of the active and stable phases may be a pathological recovering mark of the injured spinal cord. We conclude that the pulsed electric field may promote sprouting and elongating of the regenerative nerve fibres and may also have some modulating effects on the interaction of growth cones and astrocytes. The pulsed electric field may be superior to the direct current field in some aspects.


[Anatomic study of longitudinal cutting of the right hepatic duct]. 6 fresh liver from adult human specimen to casting model by perfusing with A. B. S. acetone solution and 42 formalin-fixated livers (adult 32 and children 10) were used in present study. The whole length and inner-diameter of the right hepatic duct as well as the angle between right and common hepatic duct were measured. The right hepatic duct were cut open longitudinally and their relations were classified. The relationship among the right hepatic duct and the right hepatic artery, the right trunk of portal vein and its branches, as well as gallbladder bed were observed. The method and the cautions in the operation of Longitudinal cutting of the right hepatic duct were described.


[Posterior spinal rami in localization of low back pain]. Objective findings even after standard evaluations could hardly be obtained in some low back pain (LBP). Neurolocalization of LBP is dependent on the relationship between the complaint site of pain and the distribution of the posterior branch of the spinal nerves to search for the source and to localize the level of injury. The primary sites of LBP we suggested are higher than the complaint site. In 1263 cases of LBP, the results of contrast test with procaine injection at both sites have shown that nearly all the complaint sites are secondary. According to the theory as mentioned, satisfactory effects of 1108(87.73%) of 1263 treated by freezing the posterior spinal rami at the primary site have been obtained.


[Corrective surgery for tetralogy of Fallot. Analysis of 156 cases]. 156 consecutive patients with tetralogy of Fallot underwent corrective surgery between Sept. 1987 and Mar. 1991 at Fuwai hospital in Beijing. The patients consisted of 96 males and 60 females. Their age ranged from 3 to 32 years (average 12 +/- 6 years). 141 patients (91%) had cyanosis at rest and 135 patients had clubbed fingers and toes. Hemoglobin level ranged from 130 to 265 g/L (average 192 +/- 38 g/L), and more than 18 g/L in 84 patients. All the patients were confirmed by UCG and ventricular cinecardiogram. The operation was performed under CPB and hypothermia. Typical pathological changes were found in all the patients. Severe hypoplasia of infundibular and pulmonary trunk or stenosis at pulmonary annulus valves was noted in 60 patients, absence of pulmonary valve syndrome in 2, absence of left pulmonary artery in 2, abnormality of coronary artery in 3, pulmonary atresia in 1, ASD in 15, and foramen ovale in 23. All the patients recovered uneventfully except one who died from acute renal failure in the fifth day after operation. The criteria for size were suggested for the reconstruction of the right ventricular outflow tract and pulmonary trunk.


[Open mitral valvuloplasty in 40 cases]. From Dec. 1987 to June 1991, open mitral valvuloplasty was done in 40 patients. Among them rheumatic valve disease was observed in 35 cases. The early postoperative result was excellent. We consider that the requisites for this operation are noncalcification of anterior mitral leaflet with sufficient size and flexibility, without significant fusion and shortening of subvalvar structures, and readiness of valve replacement in case of its failure.


[Delayed hemothorax after chest injuries. Report of 31 cases]. Thirty-one patients with delayed hemothorax were treated. The time from trauma to hemothorax formation ranged from 2 to 30 days. The patients with chest injuries accompanied by multiple rib fracture, potential vascular injuries and foreign body retention the thoracic cavity were observed closely. The diagnosis, pathogenesis and treatment were discussed.


[Total esophagectomy and colon transplantation in treatment of upper neck esophageal carcinoma. Report of 16 cases]. Sixteen patients with carcinoma of the upper neck esophagus were treated by total esophagectomy and replacement with transverse colon in this hospital from 1982 to 1989. The operative morbidity rate was 18.7% and no death occurred. There were 8 patients with lesion longer than 5 cm, 3 less than 3 cm, and 5 between 3 cm and 5 cm. The length between the tumor and the proximal margin of resection was less than 2 cm in 5 patients, between 2 and 4 cm in 8, and more than 4 cm in 3. No residual tumor was found pathologically at stumps. Follow-up study showed that 5 patients survived more than 5 years, 5 patients 3 to 5 years, 6 patients less than 3 years. The maneuver and advantages of the operation were introduced and the problems concerning the prevention of operative complication were investigated.


[Surgical management of complicated pulmonary hydatidosis]. 1954-1988, 680 patients with pulmonary hydatid cysts were operated upon at our hospital. 320 of the patients were classified as having complicated pulmonary hydatidosis (CPH). The criteria for CPH are as follows: (1) huge in size, occupied 2/3 or one side of the chest; (2) ruptured hydatid cyst or cysts, with or without secondary infection; (3) multiple lesions involving both lungs, sometimes combined with liver involvement; (4) the presence of hepato-pleural and/or hepato-bronchial fistulae. We advocated intact endocystectomy and saucerization of the residual actocystic pit for individual lesion. The diagnosis and management of different CPH, especially those with hepato-pleural or hepato-bronchial fistulae were discussed in detail. There were 2 operative deaths. The mortality rate of the whole series was 0.29%, and of those with CPH was 0.6%.


[Surgical treatment of superior vena cava syndrome]. Thirty-seven patients with superior vena cava (SVC) syndrome were admitted to our hospital during the recent six years. Among them, 23 were treated surgically. The approaches we used included SVC-atrial shunt plus lesion resection (1), innominate-atrial shunt without (2) or with membranotomy (1), jugular-atrial shunt (1), azygous-atrial shunt plus meso-atrial shunt (1), jugular-saphenous shunt (8), omental neck transplantation substernally (4) including one with omental-cervical vein anastomosis, and so on. Follow-up for an average of 40 months, showed marked effect in 55% of the surgical cases, improvement in 30%, and death in 10%. It is suggested to select intrathoracic operations for young, good risk, and surgically resectable patients and saphenous transplantation for elder, high risk and unresectable patients.


[Surgical correction of 34 patients with hypertelorism]. In 34 patients with hypertelorism aged on the average 12.6 years, 24 underwent intracranial surgery (combined intra- and extracranial approach), 2 (moderate) U-osteotomy (subcranial approach), and 8 (mild) canthoplasties. Improved results were obtained in the patients with various types of hypertelorism. The complications were reviewed. Of the 24 patients undergone intracranial surgery, one died, 4 had cerebrospinal fluid leakage, and 4 had keratitis. No seizure, cerebral edema, meningitis, blindness, and ptosis were observed in these patients. Average blood loss was 72% of blood volume. Average duration of surgery was 7.5 hours. The causes of hypertelorism such as craniofacial cleft, craniosynostosis, frontoethmoidal meningoencephalocele, frontonasal fibrous dysplasia, and trauma were also discussed. Satisfactory appearance was seen in most of the patients.


[Percutaneous nephrostomy as a pretreatment in extracorporeal shockwave lithotripsy]. ESWL was performed in 572 patients with renal and ureteral stones between Dec. 1988 and Dec. 1990. All the patients recovered uneventfully without any serious complications. In 6 of these patients with bilateral urinary stones complicated by bilateral hydronephrosis or azotemia, unilateral percutaneous nephrostomy was done before ESWL. We conclude that in such cases a unilateral percutaneous nephrostomy before ESWL is helpful in reducing renal pelvic pressure, improving renal function, decreasing complication and shortening the period of treatment.


[Adrenal medullary phaeochromocytoma and adrenal medullary hyperplasia]. From 1979 to 1989, 8 cases of adrenal medullary phaeochromocytoma (AMP) and 6 cases of adrenal medullary hyperplasia (AMH) were treated surgically. We reviewed the two groups of patients, and the results suggested that though the patients of AMP are similar to those of AMH in clinical symptoms and signs, AMP and AMH are virtually two different diseases of the adrenal medulla. CT and echography are helpful in distinguishing AMP from AMH, but the determination of the two diseases depends on the histological findings. The diagnostic criterion of pathology for AMP and AMH, as well as the treatment of the two diseases are discussed.


[Ileocecum with appendix in reconstruction of bladder and urethra]. New bladder and urethra were reconstructed by transplanting the ileocecum with appendix and part of the ascending colon. Ileocecal valve was used to prevent urine reflux into the ureters. The appendix and its seromuscular layer were used as "sphincter muscle" to prevent overflow of urine in the cecum. From March, 1988, to October, 1991, 38 cases of carcinoma of bladder were treated by this way. Follow-up for 0.5 to 3.5 years showed that the reconstructed bladder had large capacity, good urination function, no electrolyte disorder, urine reflux and infection of renal pelvis.


[Surgical treatment of myasthenia gravis and its evaluation]. 30 cases of myasthenia gravis (MG) were treated with thymectomy. Before and after operation, peripheral blood lymphocyte subpopulation was determined in 10 cases and acetylcholine receptor antibody titer was determined in 6. The results confirmed the efficacy of thymectomy in treating MG. We suggest that application of hormone for regulating immune function of the body and/or plasma exchange for alleviating symptoms in patients with generalized MG before and after the operation. The results of treatment did not correlate with age, sex, length, and course of the disease. Radical operation, proper anaesthesia and appropriate antibiotics may ensure a smooth operation and high curative effect.


[Clinical study of prophylactic use of gentamicin and metronidazole in the surgery of colorectal carcinoma]. From Oct. 1989 to Apr. 1990, 16 patients with colorectal carcinoma undergoing elective radical resection were randomly divided into two groups to receive oral and combined (oral + i.v.) antimicrobials respectively. Patients in the oral group received preoperative oral gentamicin and metronidazole for two days, in the combined group oral medication was followed by the same antimicrobials intravenously during perioperative period. Quantitative bacterial cultures were performed before and after the regimen. Results showed that the preoperative prophylaxis with oral antimicrobial resulted in a significant reduction in the bacterial counts of the rectum contents in all the patients (P < 0.001). The NICs of gentamicin and metronidazole for E. coli and B. fragilis were found to be 2.31 micrograms/ml and 0.66 micrograms/ml respectively. The perioperative blood samples and the intraoperative tissue specimens were taken for gentamicin and metronidazole determination. In the oral group, effective concentration of metronidazole were found in serum and tissues but gentamicin was undetected. In the combined group, effective concentrations of both gentamicin and metronidazole were detected. According to our results, the short-term preoperative oral medications combined with perioperative intravenous gentamicin and metronidazole prophylaxis appears to rational.


[Air pressure vascular clamp. Experimental study and clinical application]. An air pressure vascular clamp was designed for vascular surgery. On femoral arteries of 90 rats, vascular injury and anastomosis experiments were made to compare this clamp with 2 other vascular clamps commonly used, and the pressure on blood vessels from different clamps was determined. Examination with operating, light and electron microscopes showed that the number of vascular injuries and their degree were the least after use of this clamp, the pressure of which could be adjusted just to block blood flow, suitable for blood vessels of different calibers. Satisfactory results have been obtained through its clinical application in 43 patients having 119 vascular anastomoses. It is thought that the unobstructed rate of vascular anastomosis can be raised by the application of this vascular clamp, especially for vessels of small caliber and long period of compression.


[Protective effect of antiserum to Re-LPS on experimental multiple organ failure]. We determined the possible beneficial effect of administering antiserum against Re-LPS(F515) on experimental multiple system organ failure (MSOF) in rabbits. The results showed that there were a more significant decrease of the plasma LPS level and a shorter period to recovery than in the control group after receiving antiserum to Re-LPS. Pretreatment with antiserum can remarkably improve the function of liver, lung, kidney, blood and gastrointestinal tract. The incidence of MSOF in rabbits receiving immune sera was only 11.2% and the survival rate was increased by 40.0%. The results suggest that early passive immunotherapy may neutralize gut-derived endotoxin, inhibit endotoxin-induced mediator release and prevent development of severe complication due to sepsis. Prophylactic application of antiserum to LPS core region may provide protective effect on experimental MSOF.


Computed tomography in the initial management of acute left-sided diverticulitis. Computed tomography (CT) was used in place of contrast enemas as the initial imaging study to evaluate patients with the clinical diagnosis of acute sigmoid diverticulitis. This report attempts to clarify the role of CT in the management of acute sigmoid diverticulitis by reviewing its usefulness in the diagnosis and treatment of 59 patients. CT established that three patients (5 percent) were hospitalized with an incorrect clinical diagnosis. Thirty-seven patients (62.7 percent) were identified as having uncomplicated acute diverticulitis. These patients were all treated successfully with nonsurgical therapies and were discharged in an average of 6.8 days. In the remaining 19 patients (32.2 percent), CT revealed complicated acute diverticulitis by identifying abscess, fistula, peritonitis, or obstruction. Eleven of these 19 patients required urgent surgery or CT-guided percutaneous drainage of an abscess. The four patients whose abscesses were drained percutaneously responded favorably and underwent an elective single-stage resection. The average hospital stay for patients with complicated diverticulitis was 13.6 days. Computed tomography is a useful aid in the initial management of patients with acute diverticulitis. It is a noninvasive test that recognizes and stratifies patients according to the severity of their disease. It has the further advantage of providing information about extracolonic pathology and anatomic variation useful for surgical planning. Additionally, early CT-guided needle drainage allowed downstaging of complicated diverticulitis, avoided emergent surgery, and permitted single-stage elective surgical resection.


DNA index as a significant indicator of lymph node metastasis and local recurrence of rectal cancer. To confirm the prognostic significance of the DNA index (DI) in cases of rectal cancer, the nuclear DNA content of tumor cells was examined in 184 cases of rectal cancer treated with curative surgery, and the incidence of lymph node metastasis and recurrence of the cancer was analyzed. The incidence of lymph node metastasis was 43.9 percent in cases with aneuploidy (DI above 1.5), being statistically different from the 18.0 percent incidence in cases with diploidy (P < 0.001). Although the extent of lymph node metastasis was limited to adjacent lymph nodes in cases with diploidy, distant lymph node metastases were frequent in cases with aneuploidy, especially in those with a DI above 1.5. Furthermore, the incidence of recurrence of cancer, and especially of local recurrence, was significantly higher (P < 0.001) in cases with aneuploidy (DI above 1.5) than in cases with diploidy and aneuploidy (DI below 1.4). These findings indicate the significant value of the DNA index for the prediction of lymph node metastasis and local recurrence in patients with rectal cancer.


Ogilvie's syndrome: colonoscopic decompression and analysis of predisposing factors. Forty-eight cases of Ogilvie's syndrome, colonic pseudo-obstruction, presenting between 1983 and 1989 were retrospectively reviewed to assess the results of colonoscopic decompression and to identify potential etiologic factors. Three patients had spontaneous resolution with medical treatment. Forty-five patients required 60 colonoscopic decompressions: 38 (84 percent) were successfully treated using colonoscopy; five (11 percent) required an operation; and two died within 48 hours of colonoscopy from medical causes. No complications or deaths were the result of colonoscopy. Twenty-nine patients (64 percent) were successfully treated with a single colonoscopy. One-third of patients required serial decompressions. Average cecal diameter in patients with successful colonoscopic decompression was 12.4 cm but was larger for patients requiring more than one colonoscopy (13.3 cm) and for those who failed colonoscopic therapy (13.4 cm). The spine or retroperitoneum had been traumatized or manipulated in 52 percent of patients. Patients with Ogilvie's syndrome were being treated with narcotics (56 percent), H-2 blockers (52 percent), phenothiazines (42 percent), calcium-channel blockers (27 percent), steroids (23 percent), tricyclic antidepressants (15 percent), and epidural analgesics (6 percent) at diagnosis. Electrolyte abnormalities included hypocalcemia (63 percent), hyponatremia (38 percent), hypokalemia (29 percent), hypomagnesemia (21 percent), and hypophosphatemia (19 percent). Colonoscopic decompression in Ogilvie's syndrome is safe and effective management. Multiple pharmacologic and metabolic factors, as well as spinal and retroperitoneal trauma, appear to alter autonomic regulation of colonic function, resulting in colonic pseudo-obstruction.


Morbidity and mortality of wide pelvic lymphadenectomy for rectal adenocarcinoma. This retrospective study was aimed at defining the morbidity and mortality of a radical resection for adenocarcinoma of the rectum complemented by a wide pelvic lymphadenectomy. Twenty-seven consecutive patients with rectal carcinoma who underwent a surgical resection with conventional (Group I) or wide (Group II) pelvic lymphadenectomy were analyzed. Group I consisted of 10 patients (three women and seven men; mean age, 71 years) with tumors between 6 and 14 cm (mean, 10.6 cm) from the anal verge. Group II consisted of 17 patients (eight women and nine men; mean age, 67 years) with tumors between 3 and 14 cm (mean, 9 cm) from the anal verge. The choice of lymphadenectomy in association with colorectal resection was left at the discretion of the surgeon. There were no deaths within 60 days of operation. Mean intraoperative blood loss was the same in the two groups, although three patients (18 percent) required blood transfusions of over two liters during the performance of a wide pelvic lymphadenectomy in comparison with only one (10 percent) during conventional pelvic lymphadenectomy. The rate of early postoperative complications and the average length of postoperative hospital study were each similar between the two groups. After a wide pelvic lymphadenectomy, three (18 percent) patients developed a neurogenic bladder, requiring intermittent self-catheterization, and they all recovered within one, four, and eight months, respectively. Of the 16 males, three from Group I and four from Group II were sexually active and potent before surgical treatment; after recovering from surgery, only two patients from Group I regained their sexual potency. We conclude that the performance of a wide pelvic lymphadenectomy did not increase the intraoperative or early postoperative complication rate, the mean intraoperative blood loss, or the length of postoperative hospital stay. Technical refinements are currently under study to obviate the neurologic long-term complications.


Villous component as a marker for synchronous and metachronous colorectal adenomas. To determine whether patients with colorectal adenomas containing a villous component (+vc group) have a higher incidence of synchronous or metachronous colorectal adenomas, 527 consecutive cases of completely removed colorectal adenoma were used. Synchronous adenomas were detected in 22.6 percent and 19.0 percent of the patients in the +vc and -vc groups, respectively. In the analysis of metachronous adenomas, 164 patients who had been followed for 1 to 11 years (mean, 3.31 years) were included. The cumulative adenoma-free rate according to Kaplan-Meier tended to be lower in the +vc group, the difference being statistically significant 1.0 to 1.2 years after treatment of the initial adenoma and the two curves being different based on the generalized Wilcoxon test. The numbers of newly detected adenomas annually were 1.76 and 0.86, and their annual incidences were 1.09 and 0.59 times, in the +vc and -vc groups, respectively. These results suggest the importance of the villous component as a predictor of metachronous colorectal adenomas.


Management of acute incarcerated rectal prolapse. Perineal excision was used to treat eight elderly patients with acute incarcerated prolapse: four showed signs of strangulation with areas of gangrene, six made an uneventful recovery without colostomy, and two developed anastomotic leak, needing diverting colostomy with a complete recovery. There were no mortalities. There were no recurrences of rectal prolapse.


Abdominopelvic omentopexy: preparatory procedure for radiotherapy in rectal cancer. Adjuvant radiotherapy (RT) in adenocarcinoma of the rectum requires the application of between 5,500 and 6,600 cGy, while the small bowel does not tolerate doses beyond 4,200 cGy without developing enteritis, often followed by stenosis, fistulas, or perforation. This has spurred several attempts to form an artificial diaphragm between the abdominal cavity and the true pelvis, but they were all burdened with various sequelae. Thus, we developed a simple technique to retain the small bowel out of the RT target volume. From the greater omentum we form a bag, which houses the intestinal loops. The lower margin of the omentum is attached to the parietal peritoneum of the posterior abdominal wall beyond the promontorium. The lateral edges are sutured to the ascending and descending colon. RT starts immediately after the laparotomy wound has healed. With the help of this abdominopelvic omentopexy, we have performed high-dose RT following tumor resection in 43 patients. RT was free of complications in all of them as far as the small bowel is concerned. Proctitis and/or cystitis occurred in 14 patients.


Normal variation in anorectal manometry. A study was performed to define the normal range of values for anorectal manometry. Normal volunteers were divided according to gender and parity. There were 20 males, 21 nulliparous females, and 18 multiparous females among the 59 subjects. Anorectal manometry using a radial eight-port catheter was performed during resting and squeezing maneuvers of the anal sphincter. Computerized data analysis and three-dimensional imaging were used to calculate sphincter length at rest and squeeze, mean maximum resting and squeeze pressures, and vector symmetry index. The sphincter length at rest and with squeezing in males was significantly greater compared with the two female groups (P < 0.007). Mean maximum squeeze pressures were also significantly elevated in the male group compared with the female groups (P = 0). Mean maximum resting pressures were significantly higher in nulliparous women than in multiparous women (P = 0.04). However, no difference in resting pressures was found between males and nulliparous females. A comparison of the symmetry of the anal canal revealed no differences among the three groups. Ranges for normal anorectal manometry are definable. Normal ranges are distinct for subgroups of patients, particularly with regard to gender and parity. Patients must be compared with their normal subgroups to correctly identify manometric abnormalities.


Prospective, randomized trial comparing pain and clinical function after conventional scissors excision/ligation vs. diathermy excision without ligation for symptomatic prolapsed hemorrhoids. Forty-nine consecutive patients with symptomatic prolapsed hemorrhoids were prospectively randomized for conventional scissors excision with ligation (Group A; n = 16) or diathermy excision without ligation (Group B; n = 33). The median time taken to complete the procedure was 20 minutes (range, 10-40 minutes) and 10 minutes (range, 5-35 minutes) in Groups A and B, respectively (P < 0.05). Length of hospital stay was similar in both groups, with a median of three days and a range of two to five days. The median length of follow-up was 35 weeks (range, 20-50 weeks) and 35 weeks (range, 20-51 weeks) for Groups A and B, respectively. There was no statistical difference in the severity of postoperative pain between the two groups. The use of postoperative oral analgesics was significantly lower in Group B (P < 0.02), but there was no significant difference in the demand for intramuscular or topical analgesics. Diathermy excision of hemorrhoids is significantly faster than scissors excision, there is less bleeding, the vascular pedicles need not be ligated, and there is significant reduction in the requirement for oral analgesics postoperatively without any increase in early or late postoperative complications.


Proctitis cystica profunda in paraplegics. Report of three cases. Proctitis cystica profunda is a benign disease of the rectal mucosa that can be mistaken for rectal carcinoma both grossly and microscopically. Symptoms may consist of blood or mucus in the stool, diarrhea, tenesmus, or rectal pain. The disease has never been reported in a paraplegic population before, but the proposed etiology makes this group seem to be at high risk. We report three cases in our paraplegic population and discuss the nature of the disease as well as its treatment.


Technique for nipple valve fixation to prevent valve slippage in continent ileostomy. There have been several developments in the evolutionary process associated with continent ileostomy. Despite a progressive decline of the early and late complications associated with this procedure, nipple valve slippage remains a common complication. A technique that provides additional stability to the nipple valve is described here. This procedure involves stapled anchorage of the nipple valve to the anterior pouch wall.


Arterial vasopressin for control of bleeding from a stapled intestinal anastomosis. Report of two cases. Postoperative bleeding from a stapled intestinal anastomosis is a rare complication. In previously reported cases, the bleeding either ceased spontaneously or required reoperation for direct control. We report two cases in which the bleeding was controlled using an intra-arterial vasopressin infusion. To our knowledge, this technique has not been previously reported for management of this problem. We had initial concerns about creating ischemia at the anastomosis, which could lead to disruption. Neither patient demonstrated subsequent problems with the anastomosis. Intra-arterial vasopressin infusion appears to be an effective method for controlling bleeding from a stapled intestinal anastomosis and can avert the need for reoperation.


Transanal endoscopic microsurgery.

Transanal endoscopic microsurgery. Transanal endoscopic microsurgery (TEM) has emerged as a minimally invasive means of resecting rectal tumors. Developed in Germany and now being used with increasing frequency in the United States, TEM utilizes a 40-mm operating rectoscope, which is sealed with an airtight facepiece. Carbon dioxide is constantly infused, thereby distending the rectum and maintaining visibility. A variety of instruments, such as tissue graspers, a high-frequency knife, suction, and needle holders, are inserted through the facepiece. Adenomas that are small, large, or even circumferential, as well as selected carcinomas up to 24 cm, can be removed with TEM instrumentation. The optics provide sixfold magnification, and this, combined with the constantly distended operative field, allows for a precise excision of the tumor as well as closure of the wound. For lesions in the mid and upper rectum, TEM is an alternative to a transsacral or transabdominal approach, with subsequently shorter hospital stay and fewer complications.


Indications for 24-hour gastric pH monitoring with single and multiple probes in clinical research and practice. The methodology of prolonged gastric pH monitoring has not yet been standardized with regard to the number and position of pH probes. Twenty-seven healthy volunteers and 11 patients affected by nonulcer dyspepsia have been submitted to 24-hr ambulatory simultaneous pH monitoring of the distal esophagus, fundus, and antrum. Fundic and antral pH profiles have been compared and causes of pH variations (pH > 4) identified. Both in healthy volunteers and dyspeptic patients, percentile curves of fundic and antral pH were statistically different in more than one of the daily periods considered (24-hr, postprandial, interdigestive, nocturnal). Percent time of duodenogastric reflux is significantly higher in the antrum than in the fundus in both groups. Modalities of gastric alkalinization secondary to food or duodenogastric reflux were different for the fundus and for the antrum both in healthy and dyspeptic subjects and between the two groups. These differences suggest that single and multiple pH monitoring of the stomach have different indications, and the position of the probes should vary according to the purpose of the test.


Twenty-four-hour intragastric pH patterns in ICU patients on ranitidine. Thirty critically ill patients with mixed diagnoses underwent continuous intragastric pH monitoring for 72 hr while confined to a shock/trauma intensive care unit. The first 24 hr were monitored under no specific acid-suppressing therapy (placebo control). During the second and third consecutive 24-hr periods, patients received continuous infusion of intravenous ranitidine in the dose of 6.25 mg/hr and 12.5 mg/hr, respectively. Results of the placebo-control 24-hr study revealed that one third (N = 10) of the patients were gastric acid hyposecretors (24-hr median intragastric pH values above pH 4.0). In the normosecreting group (N = 20), both ranitidine schedules significantly elevated 24-hr median pH values, when compared to placebo (placebo 24-hr median intragastric pH 1.75; ranitidine 6.25 mg/hr 24-hr median intragastric pH 4.625, P < 0.0001; ranitidine 12.5 mg/hr 24-hr median intragastric pH 6.29, P = 0.0099). Five patients (18%) failed to adequately respond to the ranitidine 12.5 mg/hr dose (24-hr median intragastric pH < 4.0). These findings suggest that a significant percentage of intensive care unit patients are not in need of acid-suppressing therapy as prophylaxis against stress-induced ulceration. Conversely, other patients may require more intensive acid-suppressing regimens because of failure to respond to high dose H2-antagonist therapy.


Comparison of low-dose antacids, cimetidine, and placebo on 24-hour intragastric acidity in healthy volunteers. Low-dose aluminium (Al) antacids are effective in promoting ulcer healing and symptomatic relief in peptic ulcer patients, although the effect on intragastric acidity is very weak. In this randomized, double-blind study, 24-hr intragastric acidity was compared in 11 healthy volunteers, treated with a low-dose Al antacid regimen (1 tablet four times a day), cimetidine (800 mg at bedtime) and placebo, using the double-dummy technique. Standardized meals were given at 8 AM, noon, and 5 PM. Medication was given 1 hr after meals and at bedtime. Intragastric acidity was recorded with a nasogastric monocrystant antimony pH catheter, connected to an ambulatory digital data recorder. No significant difference in intragastric acidity was observed between antacid and placebo treatment. Treatment with cimetidine reduced circadian and nocturnal (but not diurnal) intragastric acidity significantly, as compared to both placebo and antacid treatment. The results support the hypothesis that Al antacids promote peptic ulcer healing by other mechanisms than acid neutralization.


Inhibition and stimulation of prolactin release. Delayed response in duodenal ulcer patients. Prolactin inhibitory tests (bromocriptine in a single dose 2.5 mg orally) as well as stimulatory tests (metoclopramide in a single dose of 10 mg intravenously) were performed in 33 patients with endoscopically proven duodenal ulcer and in 32 healthy volunteers. Delayed response in inhibition of prolactin release as well as in stimulation of prolactin release was observed in duodenal ulcer patients compared to healthy volunteers (P < 0.01). The results implicate the role of the dopamine-prolactin axis in the pathogenesis of duodenal ulcer disease.


Treatment of nonsteroidal antiinflammatory drug-induced gastric ulcers with misoprostol. A double-blind multicenter study. One hundred sixty-two patients chronically ingesting ibuprofen, piroxicam, or naproxen for osteoarthritis, who had abdominal pain and an endoscopically proven gastric ulcer were evaluated for eight weeks in a randomized, double-blind trial comparing misoprostol (200 micrograms four times daily with meals and at bedtime) (N = 77) with placebo (N = 85). Patients discontinued their usual daily dose of antiarthritic medication throughout the study period, and an endoscopy was performed at four weeks and eight weeks (if necessary) to assess ulcer healing. Gastric ulcers were defined as circumscribed breaks in the gastric mucosa of 0.3 cm in diameter or greater. Misoprostol therapy significantly accelerated the rate of gastric ulcer healing compared to placebo (P = 0.033). The cumulative percent healed after four and eight weeks of therapy for misoprostol versus placebo were: 83% vs 61% at four weeks and 96% vs 90% at eight weeks (P = 0.0028 and P = 0.0977, respectively by lifetable analysis). Relief of abdominal pain did not differ significantly between the treatment groups. Misoprostol significantly accelerates the healing of ibuprofen-, piroxicam-, or naproxen-induced gastric ulcers.


Placebo-controlled comparison of piroxicam-beta-cyclodextrin, piroxicam, and indomethacin on gastric potential difference and mucosal injury in humans. The acute gastroduodenal mucosa injury and gastric potential difference (GPD) drops provoked by 14-day administration of 20 mg/day of a new piroxicam formulation (piroxicam-beta-cyclodextrin), 20 mg/day standard piroxicam and 100 mg/day indomethacin were evaluated and compared in a randomized, double-blind, placebo-controlled study carried out on 64 volunteers. Endoscopic examinations, performed after 14-day treatment, demonstrated that piroxicam-beta-cyclodextrin was less gastrolesive (mean endoscopic score +/- SE = 0.56 +/- 0.2) than either piroxicam (2.06 +/- 0.5) or indomethacin (2.25 +/- 0.5) (p < 0.01). The drop in GPD after a single dose of the assigned drug was considerably greater for piroxicam and indomethacin than for piroxicam-beta-cyclodextrin (p < 0.01), which registered similar values to placebo. Since GPD is an expression of the anatomo-functional integrity of the gastric barrier, the results indicate that piroxicam-beta-cyclodextrin exerts less direct acute damage on the gastric mucosa. Therefore, when administered short-term, piroxicam-beta-cyclodextrin appears to be less gastrolesive than either indomethacin or the standard piroxicam formulation.


Effect of difluoromethylornithine (DFMO) on NSAID-induced intestinal injury in rats. Combination therapy with difluoromethylornithine (DFMO) and a nonsteroidal antiinflammatory drug (NSAID) has been proposed for the chemoprevention of colonic neoplasia. The purpose of this study was to examine whether DFMO would affect NSAID-mediated intestinal injury. Male Sprague-Dawley rats were gavaged with 20 mg/kg of indomethacin, after seven days of exposure to drinking water with or without 2% DFMO. The rats were killed 24 or 48 hr later, and the small intestine removed for macroscopic and microscopic quantitation of intestinal injury by computerized image analysis. Seven days of DFMO alone had no effect on overall mucosal thickness, but did increase the depth of proximal intestinal crypts. Forty-eight hours after indomethacin, DFMO treatment decreased the number of indomethacin-induced ulcers and percent of the surface area ulcerated. However, DFMO also decreased the mucosal thickness, villus height, and crypt depth in indomethacin-treated rats. Thus although DFMO decreases macroscopic intestinal ulceration by indomethacin, the reduction in villus and crypt height suggests that it also impairs the mucosa's ability to recover from microscopic indomethacin-induced damage. This study shows DFMO does impact NSAID-mediated intestinal injury and therefore human trials with combinations of DFMO and NSAIDs should include monitoring for small intestinal injury.


Antiinflammatory and gastrointestinal effects of nabumetone or its active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). Comparative studies with indomethacin. 6MNA, the active metabolite of the nonacidic antiinflammatory drug nabumetone, was investigated using intravenous administration for effects on (1) carrageenan paw edema and gastric irritancy compared with either oral nabumetone or both oral and intravenous indomethacin when given acutely and (2) gastrointestinal irritancy when given in repeat dosing studies. Oral doses of nabumetone or intravenous 6MNA produced effective antiinflammatory activity together with significant inhibition of paw exudate PGE2. Antiinflammatory oral doses of nabumetone or intravenous 6MNA produced minimal effects on gastric 6-keto PGF1 alpha production with an absence of gastric damage, in contrast with indomethacin. In repeat dose studies, 6MNA failed to induce gastrointestinal damage even at doses where general toxicity was evident. These results show that in the rat, 6MNA is an effective antiinflammatory drug but even in very high intravenous doses does not have the propensity to induce gastrointestinal damage.


Effect of sucralfate on components of mucosal barrier produced by cultured canine epithelial cells in vitro. The mucous gel maintains a neutral microclimate at the epithelial cell surface, which may play a role in both the prevention of gastroduodenal injury and the provision of an environment essential for epithelial restitution and regeneration after injury. Enhancement of the components of the mucous barrier by sucralfate may explain its therapeutic efficacy for upper gastrointestinal tract protection, repair, and healing. We studied the effect of sucralfate and its major soluble component, sucrose octasulfate (SOS), on the synthesis and release of gastric mucin and surface active phospholipid, utilizing an isolated canine gastric mucous cells in culture. We correlated these results with the effect of the agents on mucin synthesis and secretion utilizing explants of canine fundus in vitro. Sucralfate and SOS significantly stimulated phospholipid secretion by isolated canine mucous cells in culture (123% and 112% of control, respectively). Indomethacin pretreatment significantly inhibited the effect of sucralfate, but not SOS, on the stimulation of phospholipid release. Administration of either sucralfate or SOS to the isolated canine mucous cells had no effect upon mucin synthesis or secretion using a sensitive immunoassay. Sucralfate and SOS did not stimulate mucin release in the canine explants; sucralfate significantly stimulated the synthesis of mucin, but only to 108% of that observed in untreated explants. No increase in PGE2 release was observed after sucralfate or SOS exposure to the isolated canine mucous cells. Our results suggest sucralfate affects the mucous barrier largely in a qualitative manner. No increase in mucin secretion or major effect on synthesis was noted, although a significant increase in surface active phospholipid release was observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of intragastric and intravenous glucose on restraint model of stress ulceration. Intragastric glucose prevents acute stress-induced gastric mucosal injury in the restrained rat. Because increased gastric contractions contribute to mucosal injury in this model and because parenteral glucose infusions have been shown to suppress gastric contractility, we hypothesized that centrally mediated responses to hyperglycemia might contribute to the cytoprotective effect of intragastric glucose. We compared intragastric and intravenous 25% glucose with saline infusions during cold restraint and measured their impact on gastric lesions, serum glucose levels, gastric residual volume (an indirect indicator of net gastric contractility), acidity, and mucin concentration. We found that both intravenous and intragastric glucose infusions increased serum glucose to over 500 mg/dl after 4 hr of stress. Intragastric glucose increased residual volume and gastric pH, as well as decreased gastric mucosal injury, but intravenous glucose had no effects on gastric function. We found that none of the potentially protective effects of intragastric glucose are mediated by central responses to hyperglycemia, and likewise that intravenous glucose has no effect on gastric mucosal injury.


Hormonal and pharmacologic regulation of sodium absorption in rabbit cecum in vitro. The rabbit cecum is a moderately tight epithelium with amiloride-resistant but phenamil-sensitive electrogenic Na absorption. We performed flux and electrical studies under short-circuit conditions in vitro to further characterize the mechanisms of ion transport in cecum in normal and animals pretreated with methylprednisolone (MP) and deoxycorticosterone acetate (DOCA). MP treatment increased Na absorption and decreased tissue conductance. In contrast, DOCA increased Isc but did not significantly alter Na or Cl fluxes. Amiloride analogs with primary specificity for Na channel and Na/H exchanger both inhibited Isc and Na absorption. Ethacrynic acid, but not bumetanide, inhibited Isc. Nystatin and amphotericin B increased Isc. We conclude that: (1) Steroids have a differential effect on cecal ion transport; methylprednisolone increases Na absorption, but DOCA does not. (2) The response to amiloride analogs is different from other electrogenic transport systems, suggesting a distinct mechanism of Na transport in cecum. (3) The effect of ethacrynic acid was unexpected, suggesting an inhibitory response on an alternate transport system. (4) The effects of polyene antibiotics are similar to those found in other tight epithelia. Electrogenic Na absorption in rabbit cecum represents a distinct transport system, significantly different from Na absorptive mechanisms in other segments of the gut.


Spread and distribution of 5-ASA colonic foam and 5-ASA enema in patients with ulcerative colitis. Rectal treatment with enemas, foams, and suppositories is the most efficient method of delivering an adequate quantity of locally active drugs to the distal colon. In a pilot study carried out by colonoscopy in four patients, it was observed that 4 g 5-ASA in 20 ml foam spread up or beyond the splenic flexure and more extensively than 2 g 5-ASA in 10 ml foam. Therefore we have undertaken a study in order to compare by scintigraphy the colonic distribution of 4 g 5-ASA foam versus 4 g 5-ASA in 100 ml liquid enemas in 10 patients with ulcerative colitis using a crossover randomized design. Both preparations were labeled with 100 MBq [99mTc]sulfur colloid before administration. Anterior scans were taken at intervals for 4 hr. Activity, expressed as a percentage of total radioactivity, was measured in the rectum, sigmoid, descending, transverse, and ascending colon. Six patients had the same extent of spread with the two formulations; in three patients with foam and in one patient with enema a greater spread was observed. The foam reached the upper limit of disease in all cases, while enema failed in two cases. The maximum spread with foam was observed within 30 min in nine of 10 patients compared with seven of 10 after enema. Compared to enema, foam distributes more uniformly and seems to persist longer in the descending and sigmoid colon. The 5-ASA colonic foam shows some more favorable characteristics than enema for the local treatment of left-sided ulcerative colitis.