MD-directed critical pathways: it's time.
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Medical Staff, Hospital↗
Biomedical subjects
R Hart
Publications and source records attributed to R Hart.
Ethanol inhibits interferon-gamma secretion by human peripheral lymphocytes.
Clinical and epidemiological evidence exists that subjects who chronically abuse alcohol are disposed to infections and certain types of cancer. In vitro inhibition of mitogen-induced lymphocyte proliferation has been shown suggesting a direct immunosuppressive effect of ethanol. Using human peripheral blood mononuclear cells we could demonstrate in vitro for the first time that even low ethanol concentrations of 6 and 12.5 mM significantly inhibit spontaneous and mitogen-induced secretion of interferon-gamma. This effect was more pronounced with lower mitogen stimulation and it increased in a dose dependent manner when higher ethanol concentrations were used. Inhibition of cell proliferation as measured by 3H-thymidine incorporation did not parallel the inhibition of interferon-gamma secretion. As this lymphokine exerts a great number of immunostimulating effects, diminished secretion might well contribute to the immune defect observed in alcoholics.
Alcohol Drinking↗
Nonspecific immunostimulation with low doses of cyclophosphamide (LDCY), thymostimulin, and Echinacea purpurea extracts (echinacin) in patients with far advanced colorectal cancers: preliminary results.
Outpatients (n = 15) with metastasizing far advanced colorectal cancers received immunotherapy consisting of low-dose cyclophosphamide (LDCY) 300 mg/m2 every 28 days i.v., thymostimulin 30 mg/m2, days 3-10 after low-dose cyclophosphamide i.m. once daily, then twice a week, and echinacin 60 mg/m2 together with thymostimulin i.m. All patients had had previous surgery and/or chemotherapy and had progressive disease upon entering the study. Two months after onset of therapy a partial tumor regression was documented in one and a stable disease in 6 other patients by abdominal ultrasonography, decrease of the tumor markers carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, and/or chest roentgenography, which may also be attributed to the natural course of disease. Mean survival time was 4 months, 2 patients survived for more than 8 months. Immunotherapy was well tolerated by all patients without side effects.
Adjuvants, Immunologic↗
The laboratory and clinical safety evaluation of a dentifrice containing hydrogen peroxide and baking soda.
This study reports the laboratory, clinical, and microbiological finding of the safety testing and daily use of a dentifrice delivering 0.75% hydrogen peroxide and 5% baking soda. Laboratory studies using Ca45 labeled teeth and biologically stained teeth confirmed that the dentifrice did not decalcify enamel or bleach teeth. Over the course of a six-month period, 62 subjects using a hydrogen peroxide-baking soda dentifrice and 21 subjects using a control dentifrice were examined for oral soft tissue change and hard tissue alterations. No soft tissue changes attributable to the use of either dentifrice were noted. Experienced clinicians using Trubyte shade guide teeth observed no significant changes to the subjects' anterior teeth following 6 months use of the test dentifrice. Paired discrimination tests revealed that the examiners could distinguish color differences in the shade guide teeth at 0.7%. Microbiological monitoring of the subjects for six months use of their assigned dentifrice and for the following months on the control dentifrice, revealed neither an increased incidence of candida nor increased candida counts.
Adult↗
Glucose malabsorption associated with rapid intestinal transit.
Twenty-five patients with chronic diarrhea were studied with a combined glucose-hydrogen breath test (GHBT) and nuclear transit scan to elucidate the role of abnormal transit in the pathogenesis of diarrhea. Eight of the 25 patients demonstrated both a rapid orocecal transit time by nuclear scan (less than 30 min) and a positive hydrogen breath test (greater than 20 ppm increase in H2 after a 50-g glucose challenge). Because these individuals had no anatomic abnormalities predisposing to small bowel bacterial overgrowth, it is probable that they demonstrated colonic bacterial metabolism of carbohydrate secondary to glucose malabsorption associated with rapid small bowel transit. The eight patients exhibited some form of autonomic dysfunction generally related to systemic disease. Thus, there may be a subset of patients with chronic diarrhea related to rapid intestinal transit. A combined GHBT-nuclear transit scan permits accurate identification of such individuals and improves the accuracy of hydrogen breath tests in the diagnosis of bacterial overgrowth.
Adult↗
Effects of aging and dietary restriction on DNA polymerase expression in mice.
DNA polymerase alpha was isolated from livers of 6-month-, 16-month-, or 26-month-old mice fed ad libitum, or calorically restricted. The enzymes differed in chromatographic characteristics, binding affinity for DNA, and activity, with both total activity and specific activity of DNA polymerase alpha decreasing as a function of age. A positive correlation was observed between polymerase alpha specific activity and the affinity of enzyme binding to activated DNA template-primer. The age-associated decline in enzyme activity was modified by dietary restriction, with measurably higher activity seen for polymerases from dietary restricted animals compared with ad libitum animals of all ages. The data suggest that dietary restriction could act to delay the age-associated decrease in cellular capacity for DNA synthesis, which may play a significant role in prolonging the onset of age-related diseases in which decreased DNA synthesis is a potential component.
Aging↗
Isolation, localization, and physical mapping of a highly polymorphic locus on human chromosome 11q13.
A highly polymorphic repetitive sequence, D11S533, was isolated by oligonucleotide hybridization from an arrayed chromosome 11q-specific cosmid library. The DNA sequence of this element was determined and found to consist of a repetitive degenerate hexanucleotide sequence [T(Pu)T(Pu)T(Pu)]n extending over 438 bp. Southern blot analysis demonstrated that this element is relatively unique in the human genome. This sequence can be detected by amplification using the polymerase chain reaction (PCR) with oligonucleotide primers complementary to unique sequences flanking the repetitive element. This sequence displays a high degree of polymorphism, and analysis of 15 individuals demonstrated at least 10 alleles ranging in size from 300 to 900 bp. Fluorescence in situ hybridization was used to localize this sequence to 11q13 (FLpter 0.60 +/- 0.02). Pulsed-field gel electrophoresis and the isolation of yeast artificial chromosomes established the long-range physical map surrounding the locus. Because various alleles of this polymorphic sequence can be easily detected by PCR amplification, this probe has potential usefulness in genetic linkage mapping as well as identity testing.
Base Sequence↗
[Endoscopic hemostasis of the upper digestive tract].
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Electrocoagulation↗
[Immunomodulation with gastrointestinal neuropeptides].
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Adjuvants, Immunologic↗
Effect of thyrotropin-releasing hormone on immune functions of peripheral blood mononuclear cells.
The tripeptide thyrotropin-releasing hormone (TRH) works as a hypothalamic hormone, but is found also outside the brain in intrinsic nerve fibers of the gastrointestinal tract. There is evidence that TRH modulates the activity of immunocompetent cells, although there are only very few data on TRH-mediated immune effector functions. Since we could recently show that TRH inhibits monocyte activities we were also interested in other possible TRH modulated immune functions. Peripheral blood mononuclear cells (PBMC) from ten healthy subjects were cultured for 7 days and pulsed with 0.125 and 0.250 microgram/ml Pokeweed mitogen (PWM). 10(-12) to 10(-6) M TRH was added simultaneously with PWM. Lymphocyte proliferation [(3H]thymidine incorporation), interferon-gamma (IFN-gamma) activity (RIA) and immunoglobulin activities (IgG, IgM, IgA; ELISA) were determined in the supernatants. We could demonstrate a TRH-dependent decrease in PWM-pulsed IgG activity with significant (alpha = 0.05) values at 10(-8) and 10(-10) M (-29 +/- 6%/-16 +/- 3% for PWM 0.125 microgram/ml and -17 +/- 9%/-11 +/- 9% for PWM 0.250 microgram/ml). This inhibitory effect could be abolished by an anti-TRH antiserum. There was no TRH effect on IgM and IgA activities, IFN-gamma activity and lymphocyte proliferation compared with the PWM stimulated values alone. The described TRH effect on the polyclonal IgG response by PBMC gives further evidence for a functional link between the immune system and the endocrine system, although its underlying mechanism is not yet clear.
Enzyme-Linked Immunosorbent Assay↗
Mitogen-activation of spleen cells in aged animals is potentiated by dietary restriction: a preliminary report.
Dietary restriction has been reported to be associated with increased life span and increased DNA repair capacity in both male and female rats and mice. We examined dietary restriction effects on immune system function and prolongation of life span in specific pathogen free rats and mice. In this preliminary report the authors show that dietary restriction is correlated with a dramatic increase in the lifespan of both male and female rats and mice in a pathogen free environment, and in the capacity of cultured splenocytes from those animals to initiate blastogenesis in response to antigenic stimulation.
Aging↗
Effect of substance P on immunoglobulin and interferon-gamma secretion by cultured human duodenal mucosa.
Recently, we have demonstrated a substance P (SP)-dependent modulation of in vitro IgM and interferon-gamma (IFN-gamma) secretion by human peripheral blood mononuclear cells, as well as lymphokine activities in supernatants of cultured duodenal mucosa. Therefore we investigated other local immunoregulatory effects of SP. Duodenal biopsies of 7 healthy subjects were cultured with Pokeweed mitogen (PWM, 1 microgram/ml) for 4 days at 37 degrees C in 1 ml medium each. SP was added in concentrations ranging from 10(-12)M to 10(-6)M on day 1. Fresh media with fresh PWM were added every day. IgG, IgM, IgA (ELISA) and IFN-gamma (RIA) were determined in the culture supernatants. Values were referred to 5 mg biopsy weight and expressed as % change in basal PWM pulsed secretion, or as units/ml. 10(-6) M and 10(-12) M SP increased secretion of all immunoglobulin isotypes. Compared to controls, 10(-6) M and 10(-12) M SP led to an increase in IgM secretion of up to 73 +/- 23% and 41 +/- 32% and to an increase in IgA secretion up to 96 +/- 35% and 25 +/- 33%, respectively (alpha = 0.02 for both isotypes at 10(-6) M). 10(-12) M to 10(-6) M SP led to a significant dose-dependent increase in IFN-gamma secretion from 7.08 +/- 1.65 up to 21.8 +/- 12.6 units/ml/5 mg. The maximum effect could be seen on culture days 3 and 4. We were able to demonstrate for the first time that SP stimulates PWM pulsed immunoglobulin and IFN-gamma secretion by human duodenal immunocompetent cells. These results support the hypothesis of local neuropeptidergic-immune interactions.
Adult↗
Complications of diagnostic gastrointestinal endoscopy.
Undesired side effects and complications of gastrointestinal endoscopy and premedication are rare events. However, this is true only of endoscopic units with experienced investigators, modern equipment and monitoring. The complication rate of upper gastrointestinal endoscopy is about 0.1% with cardiopulmonary events predominating. The typical complication of colonoscopy is perforation, seen in 0.2%. The relevant ERCP specific complication is acute pancreatitis in about 1%, followed by acute cholangitis. The most serious complications of laparoscopy are hemorrhage from the liver biopsy site, bleeding from abdominal wall varices, and perforation of the colon. The cardiopulmonary mortality is low for upper gastrointestinal endoscopy as well as for colonoscopy (1 death/20,000 procedures). Premedication, chronic obstructive pulmonary disease, coronary heart disease, valvular heart disease and, last but not least, advanced age, must be considered risk factors for the development of complications of gastrointestinal endoscopy. Balanced indication, particularly in the elderly patient, should be the consequence. If possible, endoscopy should be performed without sedatives. If premedication is necessary, it should be used sparingly. Not only patients at high risk for the development of cardiopulmonary complications, but all patients undergoing endoscopy must be carefully monitored after premedication, during and after endoscopy. The non-invasive procedure of pulse-oximetry is appropriate for continuous monitoring of arterial oxygen saturation in patients with cardiopulmonary diseases, irrespective of their premedication status. Antibiotic prophylaxis is recommended in patients with valvular heart disease or prosthetic valves. Standardized cleaning and disinfection of the instruments is of great importance to avoid hepatitis B or HIV transfer.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholangiopancreatography, Endoscopic Retrograde↗
Evaluation of inter- and intramolecular primary structure homologies of interferons by a Monte Carlo method.
Using Sellers TT algorithm, primary structure repeats have been described for interferon (IFN)-alpha, -beta 1, and gamma. To reevaluate these results and to extend them to IFN-beta 2 (interleukin-6), a modified algorithm was developed that uses a metric to define the "best" partial homology of two peptide sequences and to compare it to those detected in random permutations of the peptide. Using this approach, the known structural homologies of IFN-alpha with IFN-beta 1 and of human (Hu) IFN-gamma with murine (Mu) IFN-gamma were identified correctly. However, the primary structure repeats in the amino acid sequences of IFN-alpha, -beta 1, and -gamma turned out to be no better than those detectable in random permutations of these sequences. These results were confirmed using a different, nonlinear metric. A previously used approach to demonstrate significance was shown to produce false-positive results. No significant primary structure homologies were detected among IFN-beta 1, -beta 2, and -gamma. In contrast to the amino acid sequence analysis, the DNA sequence of HuIFN-beta 1 contained a significant repeat that had no significant counterpart in MuIFN-beta or in IFN-alpha. In conclusion, some previously reported results obtained with Sellers TT algorithm on amino acid sequences are easily explained as random similarities, and it is therefore strongly recommended that a method like ours should be used to control significance.
Algorithms↗
Soluble interleukin-2 receptor and soluble CD8 in liver cirrhosis and obstructive jaundice.
Activated lymphocytes secrete soluble interleukin-2 receptor (sIL-2R); CD8-positive lymphocytes secrete soluble CD8 (sCD8). Liver dysfunction in cirrhosis and obstructive jaundice is known to result in depressed cellular immunity. To evaluate whether this is due to real inactivation of the immune system, we measured sIL-2R and sCD8 in the serum of 46 patients with liver cirrhosis, 25 patients with obstructive jaundice, 32 patients with alcoholic liver disease without evidence of cirrhosis, 23 healthy persons and 43 patients with unrelated disease. sIL-2R in patients with cirrhosis (mean +/- s.e.m. 1499 +/- 140 U/ml) and obstructive jaundice (1517 +/- 204) was significantly increased compared with healthy subjects (363 +/- 29) and patients with unrelated diseases (685 +/- 92); sCD8 was significantly increased in patients with cirrhosis (737 +/- 63) but not in patients with obstructive jaundice (419 +/- 32) compared with healthy subjects (322 +/- 23) and patients with unrelated diseases (375 +/- 22). No difference was found between patients with cirrhosis due to alcohol abuse (n = 15) and chronic hepatitis B (n = 6). The Child-Pugh score had no significant influence on the sIL-2R or sCD8 value. In obstructive jaundice, sIL-2R correlated with alkaline phosphatase as marker of cholestasis (r = 0.43). These data show that in spite of the apparent depressed cellular immune defense both in liver cirrhosis and obstructive jaundice there is a general activation of the immune system but the CD8+ cell compartment is only activated in liver cirrhosis. The great changes of sIL-2R and sCD8 in liver dysfunction are important for the interpretation of studies using these serum proteins as markers for immune activation.
Adult↗
Stimulation of the immune response in outpatients with hepatocellular carcinomas by low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (Echinacin) and thymostimulin.
Outpatients with inoperable far advanced hepato-cellular carcinomas (n = 5) were treated with LDCY--300 mg/m2 i.v. every 28 days-, echinacin--60 mg/m2 i.m.--and thymostimulin--30 mg/m2 i.m., day 3-10 after LDCY, then twice a week. Therapy was well tolerated by all patients. Their Karnofsky' index increased for 10% in the mean. A stable disease for more than 8 weeks was documented by abdominal ultrasonography in one patient. Serum levels of Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) did not increase in 2 patients. Median survival time was 2.5 months. One patient is still alive after 8 months. Absolute numbers of CD8+ cells significantly (p less than 0.02) decreased for 7% 1 day after LDCY, whereas CD4+ cells increased (p less than 0.02) from day 1-7. Numbers of natural killer (NK-) cells increased for 17% (p less than 0.05), their activity for 90% (p less than 0.05). Activities of peripheral polymorphs (p less than 0.05) increased for 27% and of Lymphokine Activated Killer (LAK-) cells for 180% (p less than 0.05).
Adjuvants, Immunologic↗
Interleukin 4 inhibits the interleukin 2-induced production of its functional antagonist, interferon gamma.
Interferon gamma (IFN gamma) inhibits many effects of interleukin (IL)-4. Its production largely parallels cell proliferation but is regulated independently. As IL-4 inhibits several IL-2-induced effects including proliferation of human peripheral blood mononuclear cells, we investigated its influence on the IL-2-induced IFN gamma production. We found that both absolute IFN gamma production and IFN gamma production per proliferation unit (1000 cpm) in response to IL-2 were inhibited by IL-4. IL-2-induced interferon production was inhibited by IL-4 in both sheep red blood cell rosetting and non-rosetting cells. In bidirectional mixed lymphocyte culture, IL-4 alone enhanced proliferation but suppressed IFN gamma production. As 48% of IFN gamma-producing cells are known to show T cell phenotype, the nearly total inhibition of IFN gamma production is evidence for suppression of T cell response to IL-2. Additionally, we found that the inhibition of IL-2-induced proliferation by IL-4 was significantly more pronounced at low cell densities. Basal proliferation was only inhibited in serum-containing media. These data stress the importance of other lymphokines or accessory cells in the regulation of early lymphocyte activation.
Cells, Cultured↗
Complications and protocol considerations in carbon monoxide-poisoned patients who require hyperbaric oxygen therapy: report from a ten-year experience.
We conducted a study to determine the type, incidence, and timing of complications that occur in patients who have a carbon monoxide (CO) exposure serious enough to require hyperbaric oxygen therapy (HBOT). Complication data were retrospectively collected from a ten-year period for 297 consecutive CO-poisoned emergency department patients who received HBOT. HBOT was indicated for 41% of the patients because of an elevated carboxyhemoglobin (COHb) level alone. Central nervous system dysfunction, including loss of consciousness, and/or cardiovascular dysfunction, was the criteria for HBOT in 59% of patients, regardless of their COHb level. The mean peak COHb level was 38 mg%, with 88% of patients having a peak COHb level greater than 25 mg%. The mortality rate was 6% in this case series. Cardiac arrest occurred in 8% of patients; all experienced their first arrest prior to HBOT. The 3% of patients who sustained an isolated respiratory arrest and those who had a myocardial infarction did so prior to HBOT. Several complications, however, occurred for the first time or as a recurrent event during HBOT. These included emesis (6%), seizures (5%), agitation requiring restraints or sedation (2%), cardiac dysrhythmias or arrests (2%), and arterial hypotension (2%). No patient's level of consciousness deteriorated subsequent to the initial resuscitation except for those who later had a generalized seizure. The most significant complication attributable to HBOT was tension pneumothorax, noted in three patients (1%).(ABSTRACT TRUNCATED AT 250 WORDS)
Carbon Monoxide Poisoning↗