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Biomedical subjects

J G Moore

Publications and source records attributed to J G Moore.

At least 73 records · Page 4Linked to original sources

Gas-chromatographic and mass-spectrometric analysis of the odor of human feces.

Gas-chromatographic and mass-spectrometric analysis of human fecal samples was performed to identify the volatile compounds responsible for fecal odor. The compounds identified with fecal odor were the methyl sulfides methanethiol, dimethyl disulfide, and dimethyl trisulfide. Skatole and indole, the benzopyrrole volatiles believed to be responsible for fecal odor, in fact elaborated a napthalenelike "mothball" odor in the crystalline state as well as after purging from feces. A small amount of hydrogen sulfide gas was also identified in fecal samples. The components responsible for fecal odor are complex and may be influenced by dietary and endogenous contributions. However, the major components are methyl sulfide compounds rather than skatole and indole as is currently believed.

Adult↗

Circadian variation in gastric emptying of meals in humans.

Circadian changes in drug absorption have been documented for several orally administered drugs in humans. To determine whether gastric emptying could account for these changes, morning (8 AM) and evening (8 PM) gastric emptying rates were measured in 16 healthy male subjects synchronized with diurnal activity and nocturnal rest. Gastric emptying half-times for the evening meal were significantly (p less than 0.001) longer for solids but not liquids when compared with morning emptying half-times. The increase in evening meal emptying time (53.6%) may account for the evening delay in reaching peak plasma concentrations documented for several drugs.

Adult↗

Circadian rhythm of gastric acid secretion in active duodenal ulcer: chronobiological statistical characteristics and comparison of acid secretory and plasma gastrin patterns with healthy subjects and postvagotomy and pyloroplasty patients.

Twenty-one male patients with active duodenal ulcer underwent hourly 24-hr gastric acid collections under controlled, calorically deprived conditions. The 24-hr hourly acid secretory output for the group displayed a statistically significant (p less than 0.001) rhythm, with peak rates occurring during the evening hours and low rates during the early morning hours, by population-mean cosinor statistical analysis. Population-mean cosinor analysis also verified the occurrence of a significant (p = 0.034) circadian rhythm in unstimulated acid secretion in a group (N = 14) of healthy male subjects similarly studied and reported previously. In contrast, population-mean cosinor analysis confirmed the absence of any detectable circadian rhythm in unstimulated acid secretion in a group (N = 17) of postvagotomy and pyloroplasty patients studied 2-11 years after surgery. Population-mean cosinor analysis of 4-hr plasma gastrin determinations, obtained in all groups during the 24-hr gastric acid collection, revealed an absence of any detectable circadian rhythm in plasma gastrin. This latter finding is compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, observed in the clinically healthy and active ulcer groups, is unrelated to changes in plasma gastrin levels. The employment of quantitative chronobiological inferential statistical techniques is important to the analysis of any time-dependent measurement in gastrointestinal function, of which gastric acidity is one example.

Adult↗

Day and night aspirin-induced gastric mucosal damage and protection by ranitidine in man.

The severity of gastric mucosal injury produced by aspirin (ASA) was endoscopically assessed during morning and evening studies in 10 healthy, male volunteers. In a randomized, double-blind design, subjects received either ASA (1300 mg) alone or ASA (1300 mg) plus Ranitidine (150 mg) or placebo tablets during morning and evening studies. Each subject had 3 morning and 3 evening studies. The severity of damage produced by ASA was assessed by counting the number of punctate mucosal hemorrhages observed in the gastric antrum and low-body. This study demonstrated (1) wide intersubject variability in the severity of damage produced by ASA (range of 47-1030 lesions/subject in morning studies), (2) significant protection against ASA-induced damage by Ranitidine and (3) significantly greater damage produced by ASA in the morning compared to the evening studies. Because evening acid secretory rates are higher and because ASA-induced damage is believed to be acid-dependent, this last observation was unexpected. It suggests mucosal resistance is higher in the evening and raises the possibility that there may be circadian variation in gastric mucosal resistance.

Adult↗

Hematologic effects of immunotherapy with lymphokine-activated killer cells and recombinant interleukin-2 in cancer patients.

Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells generated from autologous lymphocytes has produced significant tumor regressions in patients with advanced cancer. In the current study, we reviewed the hematologic effects associated with this therapy in our initial 42 patients. Eighty-eight percent of the treated patients developed anemia that required greater than or equal to 4 units of red cell transfusions, and 43% received at least 8 units. Only a blood loss of 2 to 3 units could be attributed to repeated phlebotomy, cytophereses, and hemodilution. IL-2 administration also resulted in thrombocytopenia as well as lymphopenia and eosinophilia. Forty-three percent of patients developed platelet counts of less than or equal to 50,000/microL, and 36% of the total group required platelet transfusions. Mild neutropenia and a rebound lymphocytosis followed discontinuation of IL-2 treatment. To explore the possible mechanisms for these hematologic effects, standard hematopoietic colony assays were conducted on serial blood samples from five patients. IL-2 produced a significant decline in circulating erythroid (BFU-E) and granulocytic/macrophage (CFU-C) progenitors, which rebounded after the discontinuation of IL-2 therapy. Infusion of IL-2 also resulted in measurable serum levels of gamma-interferon. Some of the hematologic effects of immunotherapy with LAK cells and IL-2 may be the result of IL-2-mediated suppression of hematopoiesis.

Adult↗

Variability of gastric emptying measurements in man employing standardized radiolabeled meals.

Radiolabeled liquid and solid portions of standardized 300-g meals were administered on four different study days to eight healthy subjects in an attempt to define the range of inter- and intrasubject variability in gastric emptying. Meal half emptying times, analysis of variance, and intraclass correlations were computed and compared within and between subjects. The mean solid half emptying time was 58 +/- 17 min (range 29-92), while the mean liquid half emptying time was 24 +/- 8 min (range 12-37). A nested random effects analysis of variance showed moderate intrasubject variability for solid emptying and high intrasubject variability for liquid emptying. The variability of solid and liquid emptying was comparable and relatively large when compared with other reports in the literature. The isotopic method for measuring gastric emptying is a valuable tool for investigating problems in gastric pathophysiology, particularly when differences between groups of subjects are sought. However, meal emptying time is a variable phenomenon in healthy subjects with significant inter- and intraindividual day-to-day differences. These day-to-day variations in gastric emptying must be considered in interpreting individual study results.

Adult↗

Circadian rhythm of gastric acid secretion in men with active duodenal ulcer.

Twenty-one men with active duodenal ulcer underwent hourly gastric acid and 4-hourly plasma collections under fasting conditions. A statistically significant circadian rhythm was demonstrated for the group by population-mean cosinor analysis, a statistical technique designed for time-dependent measurements, for the 24-hr acid secretory output but not for plasma gastrin concentration. These findings are compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, here observed in most patients of the active ulcer group and previously reported for a group of healthy subjects, does not depend critically upon a circadian-rhythm change in plasma gastrin. Chronobiologic statistical techniques add an important quantitative element to the time-dependent measurement of gastrointestinal function of which one example is gastric acidity, with high rates occurring during the evening and low ones in early morning.

Adult↗

Effect of synthetic prostaglandin E1 analog on gastric emptying of meals in man.

Forty-five subjects with healed duodenal ulcer were administered either a placebo or a low-dose or high-dose regimen of misoprostol, a synthetic PGE1 analog, in a double-blind, random, parallel-group design to assess the effect of this prostaglandin compound on the gastric emptying of liquid-solid meals. A dual-radionuclide technique to measure liquid- and solid-phase gastric emptying rates of physiological meals by external gamma camera imaging was used. All subjects had a pretreatment control (baseline) evaluation, followed one week later by a treatment-influenced emptying study. The results demonstrated that misoprostol did not significantly alter gastric emptying of either liquids or solids; however, these results cannot be extrapolated to other prostaglandin compounds because of the diverse and sometimes paradoxical effects of different prostaglandins on gastric motility.

Adult↗

Evidence for a midgastric transverse band in humans.

When the solid fraction of a standardized meal is labeled with technetium 99m-sulfur colloid-labeled chicken liver and fed to human subjects, linear regions of decreased radioactivity that have the appearance of a band are identified on the scintillation camera images of the stomach. The band is not a peristaltic contraction because it persists in individual subjects after 4 h of imaging. The band has also been identified in the dog, pig, and monkey. It is transverse and midgastric in location. William Beaumont noted a similar band in his observations on Alexis St. Martin in 1833, and a transverse band was noted in autopsy specimens of food-filled human stomachs in 1919. However, the finding has been ignored in current gastrointestinal or radiologic textbooks because the band cannot be identified with conventional barium sulfate meals. The anatomic basis for the band and its role in regulating gastric emptying remain unclear.

Adult↗

The effect of oral potassium chloride on upper gastrointestinal mucosa in healthy subjects: healing of lesions despite continuing treatment.

The effects of two dosage forms of wax-polymer matrix potassium chloride on the upper gastrointestinal mucosa were compared with placebo in 44 healthy volunteers. After 2 weeks of potassium chloride treatment, mucosal toxicity was observed. There was no correlation between the presence of lesions and symptoms. Six of seven volunteers with lesions healed spontaneously despite continuing treatment with potassium chloride.

Administration, Oral↗

Is the insulin resistance of patients with noninsulin-dependent diabetes mellitus secondary to insulin deficiency?

Defects in both insulin secretion and action have been documented in patients with noninsulin-dependent diabetes mellitus (NIDDM), leading to the suggestion that both fasting hyperglycemia and insulin resistance in NIDDM are secondary to insulin deficiency. In order to test this hypothesis, insulin secretion (plasma insulin response to oral glucose) and insulin action (insulin clamp) were determined in 25 patients with NIDDM. The results documented relationships between incremental plasma insulin response to glucose and degree of fasting hyperglycemia (r = -.045, P less than 0.05) and insulin-stimulated glucose utilization (r = 0.25, P = NS). These data indicate that differences in insulin secretory response accounted for only approximately 20% of the variance in fasting plasma glucose level and 6% of the variance in insulin resistance in NIDDM. Thus, differences in insulin-secretory response contribute modestly to magnitude of glycemia, and not at all to variations in insulin resistance in NIDDM, permitting rejection of the hypothesis that insulin resistance is secondary to insulin deficiency.

Age Factors↗

Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production.

Initial alterations in fetal hemoglobin (HbF) production among eight sickle cell anemia subjects treated with hydroxyurea (Hu) are summarized. Four of these subjects had been previously treated with 5-azacytidine (5-aza). All subjects treated with Hu (50 mg/kg/d for three to five days) had suppression of their total reticulocyte counts by seven days, whereas the four subjects previously treated with 5-aza (2 mg/kg/d for three to five days) had increased reticulocyte counts at day 7. The effect of Hu on increasing the number of HbF-containing reticulocytes (F reticulocytes) is extremely variable, ranging from ten-to less than onefold differences in maximal posttherapy v pretherapy levels. Recovery from marrow suppression did not result in greater than twofold increases in F reticulocyte counts. Mean day 7 F reticulocyte levels in the four subjects treated with both Hu and 5-aza were 4.1 X 10/microL and 15.4 X 10(4)/microL, respectively. Among Hu-treated subjects, increased F reticulocyte production was correlated with low serum creatinine levels and rapid removal of Hu from the plasma. Furthermore, suppression of CFU-E colony formation on day 2 of therapy with Hu was inversely correlated with maximal F reticulocyte response. We conclude that where Hu treatment results in marrow toxicity (decreased reticulocyte counts, decreased CFU-E colony formation) HbF production is less likely to increase. Those sickle cell anemia subjects with minimal renal dysfunction (serum creatinine level, greater than 1.0 mg/dL) exhibit the most cytotoxicity and least F reticulocyte response to Hu.

Anemia, Sickle Cell↗

Characterization of the hematopoietic defect in paroxysmal nocturnal hemoglobinuria.

We studied the relationship between paroxysmal nocturnal hemoglobinuria (PNH) and bone marrow failure using in vitro hematopoietic colony culture assays. Most of 17 patients with PNH showed decreased colony formation, by erythroid burst-forming cells (BFU-E) and granulocyte-macrophage colony-forming cells (CFU-C) in methylcellulose, disproportionate to their degree of bone marrow biopsy cellularity. Only a minority of the hematopoietic progenitors were sensitive to complement-mediated lysis in vitro. In contrast, normoblasts from maturing erythroid bursts removed from culture and exposed to acidified serum were sensitive to complement-mediated lysis. The size of bursts and the sensitivity of their progeny correlated strongly, suggesting that the PNH defect was acquired in culture as a function of the generational age of erythroid precursor cells. In addition, BFU-E of PNH patients were very sensitive to 3H-thymidine suicide, in comparison with normal individuals and patients with other hemolytic anemias, indicating that a large proportion of primitive erythroid progenitors in PNH bone marrow were in cell cycle. All of these results imply that acquisition of the PNH defect during erythropoiesis may lead to intramedullary destruction of developing erythroid cells. The increased demand that results on the progenitor pool may lead to stem cell depletion and bone marrow failure.

Adolescent↗

Gastric emptying studies in the morbidly obese before and after gastroplasty.

Dual isotope gastric emptying studies were performed on 16 morbidly obese patients before and after gastroplasty to determine the effect of this surgery on the rate of emptying. The solid and liquid phases of gastric emptying were compared with a normal control group. In the 900-g and 50-g meals there was a significant difference in the mean half emptying time between solid and liquid phases of emptying (p less than 0.05). Pre-operatively, the 900-g meal half emptying times of both solids and liquids and the 50-g liquid phase meal did not differ significantly between obese patients and the control group. However, in the solid phase of the 50-g meal obese patients differed significantly from a control group (p = 0.007). Three months after gastroplasty, gastric emptying of 50-g meals from the total stomach was not significantly changed from the pre-operative 50-g meal values in ten of 12 patients (p less than 0.05) and no change in total stomach emptying times were seen at 12 mo compared to the 3-mo study (p less than 0.05). Emptying of the pouch alone for both solids and liquids was significantly faster than the pre-operative and postoperative total stomach studies. Gastric emptying in the obese is normal with large meals, but is delayed in small meals. In most patients, gastroplasty does not result in slower emptying of meals.

Female↗

Successful management of post-cesarean-section acute pseudoobstruction of the colon (Ogilvie's syndrome) with colonoscopic decompression. A case report.

Although acute pseudoobstruction of the colon is a rare entity, a large percentage of the reported cases have occurred following obstetric and gynecologic surgical procedures. Early recognition is mandatory to avoid severe and potentially fatal complications and can allow successful decompression by means of colonoscopy, thus avoiding surgical intervention, as in the case reported on here.

Acute Disease↗

Decay-accelerating factor is present on paroxysmal nocturnal hemoglobinuria erythroid progenitors and lost during erythropoiesis in vitro.

A glycoprotein that regulates the deposition of C3b on the erythrocyte surface, called decay-accelerating factor or DAF, is absent from the red blood cells (RBC) of patients with paroxysmal nocturnal hemoglobinuria (PNH), explaining in part their abnormal sensitivity to complement. We used a specific antiserum to DAF, flow microfluorometry, and clonogenic assays for erythroid progenitor cells to study PNH erythropoiesis in vitro. By fluorescence-activated cell sorter analysis, all RBC from normal individuals are DAF+. In contrast, the RBC of six patients with PNH showed discrete populations of DAF- cells (10-44%; x +/- SEM = 31 +/- 6%). The DAF- RBC population was partly eliminated by prior acidified serum lysis. To determine whether erythropoietic progenitors expressed DAF, bone marrow cells were sorted by flow microfluorometry and the separated DAF+ and DAF- populations then cultured in vitro. In two normal individuals, but also in six patients with PNH, erythroid colonies formed only from cells in the DAF+ fraction. However, a variable proportion of the normoblast progeny of these DAF+ progenitor cells from patients with PNH was DAF-. Individual bursts removed from cultures of PNH bone marrow showed two discrete populations by fluorescence; the majority of normoblasts were DAF-, only 3 of 27 individual bursts had greater than 50% DAF+ cells, and in three patients, DAF- normoblasts averaged 79%. In contrast, the progeny of individual bursts from normal individuals comprised a unimodal DAF+ population. In each PNH patient, one normal burst (greater than 80% DAF+ normoblasts) was detected, possibly reflecting a normal residual population of erythroid progenitors. By the criterion of DAF expression, there was no evidence of separate populations of normal and PNH type progenitor cells. The phenotypically normal erythroid progenitors of PNH bone marrow acquire the PNH characteristics during differentiation in vitro.

Adult↗

Olfactory, gas chromatographic and mass-spectral analyses of fecal volatiles traced to ingested licorice and apple.

Volatile components of two foodstuffs with characteristic aromas, apple and licorice, and fecal samples obtained from subjects on high-apple and licorice diets, were analyzed by head-space gas chromatography and gas chromatography-mass spectrometer. The volatile compounds characteristic of the odors of apple and licorice were detected by "sniffing" the GC effluent. The aromatic component of licorice was identified by GC-MS as anethole [1-methoxy-4-(2-propenyl) benzene]. The aromatic component of apple could not be chemically characterized by our GC-MS system even though readily detected by the nose. Head-space, GC-MS analysis of fecal volatiles offers a means of tracing odorous and non-odorous components to ingested foodstuffs with potential applications to clinical and forensic medicine and anthropology.

Allylbenzene Derivatives↗