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Biomedical subjects

R P Smith

Publications and source records attributed to R P Smith.

At least 19 recordsLinked to original sources
PubMed1995

Gallbladder disease and the gynecologist.

Gallbladder disease continues to be a common problem for women. Diagnostic tools such as ultrasonography have allowed earlier and more accurate diagnoses to be made. Therapies have changed significantly in the past few years, and the new treatments are associated with lower morbidity than is the classic cholecystectomy. The gynecologist should be aware of evolving technologies to assist his or her patient in choosing the safest and most cost-effective therapies.

Adult↗
PubMed1995

Inhibitory and bactericidal activities of levofloxacin, ofloxacin, erythromycin, and rifampin used singly and in combination against Legionella pneumophila.

The susceptibilities of 56 Legionella pneumophila isolates (43 clinical and 15 environmental isolates) to levofloxacin, ofloxacin, erythromycin, and rifampin were studied with buffered charcoal yeast extract (BCYE) agar (inoculum, 10(4) CFU per spot), and the susceptibilities of five isolates were studied with buffered yeast extract (BYE) broth (inoculum, 10(5) CFU/ml). The MICs inhibiting 90% of strains tested on BCYE agar were 0.125, 0.25, 1.0, and < or = 0.004 micrograms/ml for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MICs by the BYE broth dilution method were 1 to 3, 2, 1 to 2, and 1 tube lower than those by the agar dilution method for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MBCs were 1 to 2 tubes higher than the broth dilution MICs for levofloxacin, 1 to 3 tubes higher than the broth dilution MICs for ofloxacin, 1 to 3 tubes higher than the broth dilution MICs for erythromycin, and the same as the broth dilution MICs for rifampin. In kinetic time-kill curve studies, at drug concentrations of 1.0 and 2.0 times the MIC, the most active drugs were levofloxacin and rifampin. At 72 h, concentrations of levofloxacin and rifampin of 2.0 times the MIC demonstrated a bactericidal effect against L. pneumophila. In contrast, at concentrations of 1.0 and 2.0 times the MICs regrowth was observed with ofloxacin and only a gradual decrease in the numbers of CFU per milliliter was observed with erythromycin. Only a minor inhibitory effect was observed with 0.25 or 0.5 time the MICs of all drugs at 24 to 48 h, with regrowth occurring at 72 h. In contrast to erythromycin or ofloxacin plus rifampin at 0.25 time the MICs, only levofloxacin plus rifampin demonstrated synergy. Thus, levofloxacin demonstrated the best inhibitory and bactericidal effects against L. pneumophila when it was studied alone or in a combination with rifampin.

Anti-Bacterial Agents↗
PubMed1995

C-reactive protein in simple community-acquired pneumonia.

STUDY OBJECTIVE: To assess whether C-reactive protein (CRP) is a sensitive marker of pneumonia and to evaluate whether it may be used as an index of treatment response. DESIGN: A retrospective casenote review was carried out on 40 patients admitted with simple community acquired pneumonia and 20 patients admitted with purulent bronchitis (infective exacerbations of chronic obstructive airways disease). Serum CRP levels, in addition to other traditional markers of infection, were measured in all patients on the first day. In 21 cases of pneumonia, a second CRP measurement was available after 3 to 7 days of antibiotic therapy. RESULTS: Temperature and WBC count showed considerable overlap between the pneumonia and bronchitic groups, whereas there was no overlap in serum levels of CRP. C-reactive protein levels were above 100 mg/L in all but two cases. In the bronchitic group only 7 out of 20 had levels above the normal range (< 10 mg/L). Mean +/- Standard Error of the Mean and lower/upper quartiles for CRP (mg/L) were as follows: pneumonia 217 +/- 16 mg/L, 130/275; purulent bronchitis, 18 +/- 3 mg/L, 10/18; [95% confidence interval (CI) for difference 153, 244 mg/L]. A CRP above 70 mg/L in pneumonia on day 1 occurred in association with a WBC count < 12 x 10(9)/L in 45% of cases and with a temperature < 37.0 degrees C in 32%. CRP levels fell to < 100 mg/L in all cases of pneumonia after antibiotic treatment: pretreatment 213 +/- 21 mg/L +/- 2, 138/270; posttreatment 31 +/- 5 mg/L, 14/47; [95% CI for difference 141, 221 mg/L]. CONCLUSION: Serum CRP may be a useful adjunctive test in pneumonia, both in terms of distinguishing parenchymal from endobronchial infection, as well as being a marker of treatment response.

Biomarkers↗
PubMed1995

C-reactive protein. A clinical marker in community-acquired pneumonia.

STUDY OBJECTIVE: To assess the range of plasma C-reactive protein (CRP) in patients presenting with community-acquired pneumonia and to compare the serial changes of this acute-phase protein with clinical outcome. DESIGN: Prospective hospital-based study, including separate retrospective case series. PATIENTS: Twenty-eight consecutive patients (mean age, 60 years) admitted to our hospital with community-acquired pneumonia were studied. Serial daily plasma samples were taken and assayed for CRP, tumor necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6). Clinical parameters, laboratory data, and response to treatment were recorded. Four other patients considered to be antibiotic failures (three empyemas, one death) were studied separately. RESULTS: Two patients died. Of those who survived, mean (+/- SD) CRP values for days 1,2,3,4, and 5 were as follows: 136 +/- 43, 96 +/- 44, 53 +/- 36, 54 +/- 43, and 44 +/- 31 mg/L. CRP levels on day 1 in patients who had received antibiotics prior to hospital admission were significantly lower than those who had not, 107 +/- 42 and 152 +/- 44 mg/L (p < 0.05). CRP levels did not correlate with other laboratory parameters or with recognized predictors of mortality. A CRP value that continued to rise despite antibiotic treatment was associated with infective complications or death. Only 52% of patients had detectable TNF-alpha and 24% detectable IL-6 at some point during their hospital stay. CONCLUSIONS: CRP is a sensitive marker of pneumonia. A persistently high or rising CRP level suggests antibiotic treatment failure or the development of an infective complication. These results suggest that CRP, rather than TNF-alpha or IL-6, may have a role as a clinical marker in pneumonia.

Adult↗
PubMed1995

Interactions between hydroxocobalamin and nitric oxide (NO): evidence for a redox reaction between NO and reduced cobalamin and reversible NO binding to oxidized cobalamin.

Interactions of nitric oxide (NO) with various cobalamin species have been examined, apparently for the first time, with both absorption and electron paramagnetic resonance spectroscopy. Only slight shifts in the absorption spectrum of hydroxocobalamin, B12a [Cb(III)], were produced by NO, but dramatic changes in the spectrum of B12r [Cb(III)] were found on addition of NO. The addition of NO shifted the spectrum of Cb(II) to one very similar to that of Cb(III), indicating the oxidation of Cb(II). The addition of NO to Cb(III) resulted in a novel, weak and previously undescribed electron paramagnetic resonance signal. Although it has not been fully characterized, this appears to represent a reversible complex in which NO is liganded to the Cb(III). When NO was added to Cb(II), its strong electron paramagnetic resonance spectrum was replaced by that of this novel species, consistent with oxidation of Cb(II) by NO and then binding of additional NO by the resulting Cb(III). Porcine, aortic endothelial cells were able to partially reduce Cb(III), and release to the supernatant a previously characterized superoxide cobalt(III) complex, but some Cb(II) remained with the cell fraction. These reactions of Cb species could play a role in altering intracellular and intratissue levels of NO.

Animals↗
PubMed1994

Comparative capacity of four antifungal agents to stimulate murine macrophages to produce tumour necrosis factor alpha: an effect that is attenuated by pentoxifylline, liposomal vesicles, and dexamethasone.

The efficacy and toxicity of certain antifungal agents may be related to their ability to induce the production of cytokines by mononuclear phagocytes. The capacity of incremental concentrations of fluconazole, 5-fluorocytosine (5-FC), amphotericin B (AmB), and liposomal AmB (LAB) to stimulate murine peritoneal and RAW 264.7 macrophages to secrete tumour necrosis factor alpha (TNF alpha) after 3, 6 and 24 h incubation was assessed by L929 cytotoxic bioassay. Fluconazole (2.5-40 mg/L) and 5-FC (25-100 mg/L) did not have a stimulatory effect. However, AmB (0.25-10 mg/L) elicited TNF alpha production by macrophages. This response was concentration-dependent, and peak TNF alpha levels were detected between 3 and 6 h. This effect was attenuated by incorporation of AmB into liposomal vesicles and by pretreating macrophages with pentoxifylline or dexamethasone. AmB I mg/L in combination with 1 x 10(6) cfu of Candida albicans stimulated peritoneal macrophages to produce similar quantities of TNF alpha as AmB alone, and two- to four-fold more TNF alpha than C. albicans alone. Thus, this study suggests that: (1) the immunomodulatory activity and toxicities of AmB, in part, may be attributed to the capacity of this drug to stimulate macrophages to secrete TNF alpha, (2) the TNF alpha that is produced by macrophages in response to AmB may have clinical relevance even in the face of C. albicans infection, and (3) the failure of fluconazole, 5-FC, and LAB to elicit a TNF alpha response may explain their improved side-effect profiles.

Amphotericin B↗
PubMed1993

Identification of increased nitric oxide biosynthesis during pregnancy in rats.

We reported previously that plasma levels, urinary excretion, and metabolic production of cyclic guanosine 3',5'-monophosphate (cGMP) are increased in gravid rats, and postulated that endogenous nitric oxide (NO), a potent vasodilator and immune modulator, may mediate this change. Four lines of evidence are now presented demonstrating increased biosynthesis of NO during pregnancy in rats: 1) Urinary excretion and plasma levels of the stable NO metabolite, nitrate, are elevated in pregnant rats; urinary excretion of nitrate is increased in pseudopregnant rats. 2) The urinary excretion of cGMP also increases during pregnancy and pseudopregnancy, paralleling the rise in urinary nitrate excretion. 3) Chronic treatment with the NO synthase inhibitor, NG-nitroarginine methyl ester (NAME), inhibits the increase in urinary nitrate excretion. 4) Nitric oxide hemoglobin is detected by electron paramagnetic resonance spectroscopy in the blood of pregnant, but not in nonpregnant, rats. The results show endogenous NO production is increased in gravid rats. This finding raises the possibility that NO may contribute to maternal vasodilation and uterine immune suppression of normal pregnancy.

Amino Acid Oxidoreductases↗
PubMed1992

Characterization of platelet-releasable forms of beta-amyloid precursor proteins: the effect of thrombin.

Activated platelets release a potent inhibitor of factor XIa previously identified as a Kunitz proteinase inhibitor domain-containing form of the beta-amyloid precursor proteins (beta APP). Two carboxy-terminal truncated forms of the beta APP, beta APP-751 and beta APP-770, are shown to be the predominant isoforms secreted by platelets. The release of beta APP from platelets is responsible for the higher concentration of beta APP in serum compared with plasma, and thrombin dose-response data show that release of beta APP is most consistent with alpha granule localization within the platelet. Thrombin induces a limited and specific proteolysis of platelet-secreted beta APP, resulting in loss of a carboxy-terminal fragment. This phenomena is dependent on both thrombin concentration and duration of incubation and is inhibited by the thrombin-specific inhibitor hirudin, characteristics that can be duplicated in a mixture of purified recombinant beta APP-751 and thrombin. A similar effect of thrombin on full-length transmembrane forms of beta APP would result in a membrane-bound remnant containing the intact beta-amyloid protein.

Alternative Splicing↗
PubMed1992

Formation of nitric oxide hemoglobin in erythrocytes co-cultured with alveolar macrophages taken from bleomycin treated rats.

Alveolar macrophages, taken from rats treated with a single intratracheal dose of bleomycin, release reactive nitrogen intermediates in the form of nitric oxide which are cytostatic to murine leukemia L1210 cells. When cultured in the presence of erythrocytes the cytostatic activity of alveolar macrophages was inhibited which corresponded with an increase in nitrosylated hemoglobin content when compared with erythrocytes cultured alone. These results suggest that erythrocytes inhibit alveolar macrophage cytostatic activity by preventing reactive nitrogen intermediates from reaching target cells because the hemoglobin serves as a sink for reactive nitrogen intermediates in the form of nitric oxide.

Animals↗
PubMed1992

Unrecognized association of sleep disorders and depression with chronic pelvic pain.

Assessment of cases of chronic pelvic pain presents a challenging problem, and many physicians overlook the association of sleep disorders and depression with such pain. We examined these linkages in our chronic pelvic pain clinic, using a questionnaire that assists in diagnosis and management of these cases. To date, the cases of 72 patients (both physician- and self-referred) with pelvic pain have been evaluated. Of these patients, 51 of 71 (72%) reported sleep disorders, and 37 of 72 (51%) had clinical depression, as determined by the Beck Depression Inventory. After adjustment for a sleep-related item on the Beck scale, these two measures showed a positive correlation of .355 (P < .01). The scores of pain patients differed significantly from those of a control group of asymptomatic patients on the depression and sleep disorder measures. By being aware and using a simple questionnaire, the clinician may readily identify overlooked factors, such as sleep disorders and depression, when assessing cases of chronic pelvic pain.

Adult↗
PubMed1992

Ventilatory and hematopoietic responses to chronic hypoxia in two rat strains.

Hilltop (H) and Madison (M) strains of Sprague-Dawley rats exhibit strikingly different susceptibilities to the effects of chronic altitude exposure. The H rats develop greater polycythemia, hypoxemia, and pulmonary hypertension. We studied ventilation, pulmonary gas exchange, tissue oxygenation, and hematologic adaptations in the two rat strains during a 50-day exposure to a simulated altitude (HA) of 5,500 m (18,000 ft). There were no strain differences among the variables we studied under sea level (SL) conditions. Within the first 14 days of hypoxic exposure, the only significant strain differences were that erythropoietin (EPO) rose much higher and erythroid activity was greater in the H rats, even though arterial Po2 and PCo2 (Pao2 and PaCo2, respectively), renal venous PO2 (Prvo2), and ventilation (VE) were equivalent in the two strains during this time. By day 14 at HA, the H rats had significantly higher erythroid activity, hematocrit (Hct), and EPO levels, significantly lower PaO2 and PrvO2, but equivalent VE and PaCO2. These changes persisted for the remainder of the exposure, except that the Hct continued to rise and the increase was greater in H rats. Despite the greater O2-carrying capacity of H rats in the later stages of hypoxic exposure, PaO2 and PrvO2 were significantly lower in H rats. There were no strain differences at either SL or HA in ventilatory responses to hypercapnia or hypoxia, in blood O2 affinity or 2,3-diphosphoglycerate, in extrarenal production of EPO, or in EPO clearance. We conclude that early in the hypoxic exposure the H rats produce more EPO at apparently equivalent levels of hypoxia, and this is the first step in the pathogenesis of the maladaptation to HA manifest by H rats. We find no consistent evidence that differences in VE contribute to the variable susceptibility to hypoxia in the two rat strains.

Altitude Sickness↗
PubMed1992

Diversity of tick species biting humans in an emerging area for Lyme disease.

BACKGROUND: Although most tick bites in humans in areas of the northeastern United States in which Lyme disease is highly endemic are due to Ixodes dammini, no study documents the frequency of I. dammini bites in low-prevalence or emerging areas for Lyme disease. Data on the proportion of tick bites in humans that are due to I. dammini in a region may have implications for public health policy and clinical management. METHODS: A statewide survey of the tick species that parasitized humans in Maine was conducted during 1989 and 1990. Tick submissions from throughout the state were elicited through media announcements. All ticks that had been removed from humans were identified, and data were collected that included bite seasonality and geography and demographics of tick bite victims. RESULTS: Of 709 ticks submitted, only 17% were I. dammini. Ixodes cookei, a vector for Powassan encephalitis, accounted for 34% of bites, and Dermacentor variabilis accounted for 45%. Other tick species were occasionally implicated. CONCLUSIONS: The likelihood that a tick bite was due to I. dammini was lower in Maine than in areas in the northeastern United States in which Lyme disease is highly endemic. Other tick vectors, associated with diseases other than Lyme disease, were more frequently implicated. Regional tick bite surveys may prove useful in assessing the risk of Lyme disease following a tick bite.

Adolescent↗
PubMed1992

Recreational propane inhalation in an adolescent male.

Propane inhalation may be widespread, yet only a few cases have been reported. The victims were usually found dead, and only one other report describes firsthand the sought-after effects. We report on a 17 year-old male with a six month history of repeated inhalation. The patient manifested no pathophysiologic signs, but the ready availability of propane may result in an increase in its abuse. This activity carries considerable risk for trauma and/or sudden death. Our patient was able to recruit others to the practice by finding ways to avoid some of the unique, inherent deterrents.

Adolescent↗
PubMed1992

Nitric oxide hemoglobin in patients receiving nitroglycerin as detected by electron paramagnetic resonance spectroscopy.

Blood specimens were obtained from 30 adult patients admitted to a coronary care unit after the decision to use nitroglycerin had been made by their physicians. The samples were drawn before nitroglycerin administration, within 1 hour after starting nitroglycerin, after several hours of therapy, and more than 4 hours after discontinuing therapy. One patient was admitted twice, accounting for 31 sets of blood specimens. A positive identification of nitric oxide-hemoglobin (NOHb), with electron paramagnetic resonance (EPR) spectroscopy could be made in the blood of 10 of the subjects after they had been receiving nitroglycerin for several hours (third blood sample). In seven subjects this third blood sample was not drawn, and they were dropped from the study. A final positive finding of NOHb was made in 10 of 24 patients. NOHb has not been identified previously in human subjects given nitroglycerin, and a significant dose-response relationship was observed between nitroglycerin and NOHb. We ascribe our inability to detect NOHb in all subjects before nitroglycerin (basal levels) and after nitroglycerin in 14 subjects to concentrations that were below the limits of detection of the technique as used. Subtraction of the EPR signal for plasma ceruloplasmin was necessary to detect the NOHb EPR signals. Thus we have shown EPR spectroscopy to be a highly specific and sensitive method for detecting and quantifying NOHb in human subjects. Further refinements in the technique to improve sensitivity are possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Acute neurotoxicity of sodium azide and nitric oxide.

Sodium azide is a chemical of rapidly growing commercial importance with a high acute toxicity and an unknown mechanism of action. Although it has some chemical properties and biological effects in common with cyanide, its lethality does not appear to be due to inhibition of cytochrome oxidase. Unlike cyanide it is a potent vasodilator and inhibitor of platelet aggregation presumably by virtue of its conversion to nitric oxide in vivo and in isolated preparations of blood vessels and thrombocytes. It is not clear whether the high toxicity of azide is due to nitric oxide or to the parent anion. Of a number of possible azide antagonists tested in intact mice only phenobarbital in both anesthetic and subanesthetic doses afforded statistically significant protection against death. Diazepam, phenytoin, and an anesthetic dose of a ketamine/xylazine combination had no effect. Major motor seizures are sometimes seen in human azide poisoning, and these are a regular feature of azide poisoning in laboratory rodents. Solutions of nitric oxide given systemically to mice produced no signs of toxicity, but doses 1,000-fold lower placed in the cerebroventricular system of rats produced brief but violent tonic convulsive episodes. A dose of 0.61 mmol/kg azide as given systemically regularly produced convulsions whereas a dose of 6 mumol/kg given icv produced seizures in rats. The icv convulsive dose of azide was 50-fold larger than the icv dose of nitric oxide. These results suggest that azide lethality is due to enhanced excitatory transmission in the central nervous system perhaps after its conversion to nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Antimicrobial effect of clindamycin in combination with aztreonam or aminoglycosides against Klebsiella spp.

The antimicrobial effect of clindamycin combined with aztreonam or an aminoglycoside (gentamicin, tobramycin or amikacin) was studied against 84 strains of Klebsiella pneumoniae and 18 strains of K. oxytoca with an agar dilution technique. Clindamycin concentrations of 1-20 mg/l and an inoculum of 10(4) cuf/spot were used. Anaerobic incubation of agar plates was associated with an increase in the MIC of aminoglycosides and no change or a decrease in the MIC of aztreonam. Lower concentrations of clindamycin (1-2 mg/l) were associated with a decrease in the MIC of aztreonam for 18% and an increase in the MIC of aminoglycosides for between 7% and 44% of the strains, depending upon the precise concentration used. However, higher concentrations of clindamycin (10-20 mg/l) were associated with a decrease in the MIC of aztreonam for between 36 and 87% and an increase in the MIC of aminoglycosides for between 13 and 64% of the isolates. These observations could be important when treatment plans for mixed aerobic/anaerobic infections including mixed Klebsiella spp. are considered.

Aminoglycosides↗