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Biomedical subjects

J Giordano

Publications and source records attributed to J Giordano.

At least 19 recordsLinked to original sources

[Systematic infection consultation in the intensive care unit. Impact of short-term antibiotic use].

OBJECTIVES: Multiresistant bacteria are regularly isolated in nosocomial infections occurring in intensive care units due to wide use of antibiotics. We evaluated the impact of systematic infectiology consultations on the quality of antibiotic prescriptions in an intensive care unit. PATIENTS AND METHODS: Infectiology consultations (3 per week) were initiated mid February 1999. The infectiologist gave oral advice to be implemented (or not) by the intensive care unit according to ongoing therapeutic options. The hospital pharmacy recorded antibiotic use for March and April 1999 for comparison with use recorded in 1998 for a similar period. We retrospectively reviewed the files of patients hospitalized during these periods and who had received antibiotics to determine the modalities of antibiotic use. The 4 antibiotics used for the longest period for each patient were recorded. RESULTS: Thirty-one patients in 1999 and 30 in 1998 were given antibiotics. The SAPS score was similar for the two groups. Mean duration of antibiotic treatment was lower during the March-April 1999 period than during the corresponding period in 1998: 13 +/- 9 days/patient versus 23 +/- 21 days/patient respectively, p = 0.037. In 1998, there were 596 antibiotic-days and in 1999 there were 455 (-24%). The cost of antibiotic therapy in 1998 was 70,342 FrF compared with 56,804 FrF in 1999 (-19%). CONCLUSION: Infectiology consultation, in association with the opinion of the intensive care physician, is a simple way to limit antibiotic use.

Aged↗

p200 ARF-GEP1: a Golgi-localized guanine nucleotide exchange protein whose Sec7 domain is targeted by the drug brefeldin A.

The drug brefeldin A (BFA) disrupts protein traffic and Golgi morphology by blocking activation of ADP ribosylation factors (ARFs) through an unknown mechanism. Here, we investigated the cellular localization and BFA sensitivity of human p200 ARF-GEP1 (p200), a ubiquitously expressed guanine nucleotide exchange factor of the Sec7 domain family. Multiple tagged forms of the full-length polypeptide localized to tight ribbon-like perinuclear structures that overlapped with the Golgi marker mannosidase II and were distinct from the pattern observed with ERGIC53/58. Analysis of several truncated forms mapped the Golgi-localization signal to the N-terminal third of p200. BFA treatment of transiently or stably transfected cells resulted in the redistribution of Golgi markers and in loss of cell viability, thereby indicating that overproduction of p200 may not be sufficient to overcome the toxic effect. A 39-kDa fragment spanning the Sec7 domain catalyzed loading of guanosine 5'-[gamma-thio]triphosphate onto class I ARFs and displayed clear sensitivity to BFA. Kinetic analysis established that BFA did not compete with ARF for interaction with p200 but, rather, acted as an uncompetitive inhibitor that only targeted the p200-ARF complex with an inhibition constant of 7 microM. On the basis of these results, we propose that accumulation of an abortive p200-ARF complex in the presence of BFA likely leads to disruption of Golgi morphology. p200 mapped to chromosome 8q13, 3.56 centirays from WI-6151, and database searches revealed the presence of putative isoforms whose inhibition may account for the effects of BFA on various organelles.

Amino Acid Sequence↗

Synovial osteochondromatosis of the retrocalcaneal bursa: a case study.

A 42-year-old man presented with synovial osteochondromatosis (SO) of the retrocalcaneal bursa with intraosseous lesions in the calcaneum, leading to significant pain and consequent disability. Simple x-rays, computed tomography, and magnetic resonance imaging were performed preoperatively. The patient has remained asymptomatic, clinically and radiographically, without recurrent lesions for 18 months postoperatively.

Bursa, Synovial↗

Topical ondansetron attenuates nociceptive and inflammatory effects of intradermal capsaicin in humans.

Topical application of the 5-HT3 receptor antagonist ondansetron (50-250 microg) delivered in a pluronic lecithin organogel vehicle (PLO, 0.5 ml) produced dose-dependent attenuation of nociceptive and inflammatory effects of intradermally injected capsaicin (10 microg/10 microl) in humans. Significant, dose-dependent analgesic effects were produced by 100 microg and 250 microg doses of ondansetron; these doses also reduced mechanical hyperalgesia produced by capsaicin. However, only 250 microg dose of ondansetron diminished capsaicin-induced inflammatory flare.

Administration, Topical↗

Sub-anesthetic doses of bupivacaine or lidocaine increase peripheral ICS-205 930-induced analgesia against inflammatory pain in rats.

Intraplantar co-administration of sub-anesthetic doses of bupivacaine (2.5 microg) or lidocaine (7.5 microg) increased the dose- and time-dependent analgesic effects of the 5-HT3 receptor antagonist, 3-a-tropanyl-1-H-indole-3-carboxylic ester (ICS-205 930) (1-100 microg; 50 microl) against inflammatory pain induced by hindpaw inoculation with complete Freund's adjuvant. The effects of bupivacaine were greater than lidocaine at all doses of ICS-205 930 tested. These findings may reflect facilitation of ICS-205 930 effects through negative allosteric modulation by bupivacaine and lidocaine of peripheral 5-HT3 receptors involved in nociceptive processing.

Analgesia↗

Antinociceptive effects of intrathecally administered 2-methylserotonin in developing rats.

The present study examined developmental patterns of antinociception mediated by the spinal 5-HT3 receptor system in the neonatal rat. Intrathecally administered 2-methylserotonin (25-100 micrograms) first produced antinociception against formalin-induced acute inflammatory pain at 10 days postnatally, with effect only at the peak dose (100 micrograms). Intrathecal 2-methylserotonin produced dose-dependent antinociception at 14 and 28 days of age that was attenuated by i.t. pretreatment with the 5-HT3 receptor antagonist MDL-72222 (10 micrograms).

Animals↗

Experience with open-heeled Unna boot application technique.

One of the most common and effective treatments for venous stasis ulcers (VSUs) is the Unna boot dressing (UBD), first described by Unna in the 1890s. No one technique for UBD application has been documented by research to be the most effective for ulcer healing. This article discusses the open-heeled UBD application technique. Twelve patients with 17 VSUs that have been treated with the open-heeled UBD application technique are reviewed. The patients were primarily treated by the first author. Detailed patient education instructions are given. The open-heeled UBD is easier to apply patients are more comfortable and can fit into their normal shoewear condition of the heel can be monitored while the UBD is in place, and specially trained practitioners can apply UBDs with minimal to no compression on patients with concomitant venous arterial insufficiency. Ambulatory patients can also maintain greater ankle mobility during treatment. This may have important implications for activating the muscle pump under compression, which can facilitate blood return and reduce venous hypertension while the patient with venous stasis ulcer is ambulatory. The open-heel method may also allow greater mobility of the ankle that can help prevent "frozen" ankles associated with VSUs.

Adult↗

Serotonergic receptors as targets for pharmacotherapy.

Knowledge about neurotransmitters, their receptors and their physiological effects has exploded in the past 15-20 years. Serotonin exerts diverse effects as a neurotransmitter and in nonneural tissues. The molecular sites of serotonin binding, re-uptake and autoregulation have proven to be viable targets for pharmacological intervention in a variety of disorders.

Brain↗

A logistic regression model for the decision to perform access surgery.

Access surgery may be recommended to about 80% of patients who present with advanced forms of periodontal disease. In this report, a multivariate logistic regression analysis which incorporated several clinical parameters for each tooth examined, i.e., tooth type, furcation involvement, bleeding on probing, attachment level, probing depth, mobility and BANA test score, was conducted using generalized estimating equations (GEE). This approach identified parameters that were significantly associated at p < 0.05 level with the need for access surgery or extraction for periodontal purposes. The estimated probabilities derived from the GEE model were plotted over the complete spectrum of operating conditions to obtain a receiver-operator characteristic (ROC) curve. At a probability cutpoint of 0.8, the decision threshold for surgery/extraction at the pretreatment examination would have a sensitivity of 76.1% and a specificity of 75.3%. We have taken this 0.8 cut point to look at specific clinical decisions made by our examiners after the patients had received scaling and root planing plus 2 weeks unsupervised usage of systemic antimicrobials. The clinicians' decision was taken as the primary reference standard. The model's estimated decision agreed with the clinicians' decision in 226 of the 284 teeth, for an accuracy of 80%. The specificity was 90% and the sensitivity was 43%.

Algorithms↗

Nonsurgical treatment of patients with periodontal disease.

OBJECTIVE: To determine whether the short-term use of systemic antimicrobials (metronidazole or doxycycline) and locally delivered antimicrobials (metronidazole, chlorhexidine) in patients with advanced forms of periodontal disease could prevent the normally necessary access surgery. STUDY DESIGN: Ninety-four patients were randomly assigned with the use of a double-blind protocol. RESULTS: There was a 93% reduction in the need for periodontal surgery about individual teeth and an 81% reduction in the need for tooth extractions. Only 93 teeth of an initial total of 783 teeth actually needed surgery or extractions. Eighty-one percent of the patients entered into the maintenance phase of treatment without needing surgical treatments. CONCLUSION: These findings indicate that a treatment paradigm based on the diagnosis and treatment of anaerobic infections is likely to be successful in those patients for whom access surgery is recommended.

Administration, Oral↗

Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis.

We undertook this study to determine the incidence proportion of and risk factors for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia, central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis. A historical cohort of 487 consecutive inpatients with AIDS treated by San Francisco General Hospital inpatient and outpatient services entered the study. We abstracted all available records for demographic information, diagnoses, and dates of death and estimated the incidence proportion of AIDS patients diagnosed with major CNS complications using the Kaplan-Meier method. We used the Cox proportional hazards model to analyze the effect of demographic factors on the hazard (risk per unit time) of diagnosis with these CNS conditions. The estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18. Corresponding proportions were 0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal meningitis. Only HIV dementia was independently associated with increasing age at AIDS diagnosis (relative hazard [RH] of 2.75 for ages 41-50 [95% confidence interval, 1.08-6.98]; RH of 4.73 for ages > 50 [95% confidence interval, 1.41-15.87]) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19-3.47). HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about equally common complications in patients with AIDS, but only HIV dementia is associated with increasing age at AIDS diagnosis and injection drug use.

AIDS Dementia Complex↗

Monitoring the anticoagulant effects of a low molecular weight heparin preparation. Correlation of assays in orthopedic surgery patients receiving ardeparin sodium for prophylaxis of deep venous thrombosis.

This prospective, uncontrolled trial explored the relationship between varying dosages of a low molecular weight heparin (LMWH) preparation, ardeparin sodium (Normiflo, Wyeth-Ayerst, Philadelphia, PA), and anticoagulant effects, monitored by an amidolytic anticoagulation factor Xa (aXa) assay and by global coagulometric methods, including the activated partial thromboplastin time (APTT) and the Heptest (Haemachem, St. Louis, MO). Thirty-three patients undergoing elective unilateral total hip or knee replacement received subcutaneous ardeparin prophylaxis initiated 12 to 18 hours following surgery, administered at a fixed 40-mg dose twice daily, 50 aXa U/kg twice daily or 90 aXa U/kg once daily for up to 14 days. The target antithrombotic aXa levels, determined by amidolytic assay in plasma 6 hours after each ardeparin injection, were most optimally attained and maintained by twice-daily dosing based on body weight and correlated well with incremental increases in Heptest values measured chronometrically. The Heptest results at 12 hours after ardeparin administration indicated that the global anticoagulant effects produced by LMWH are sustained for many hours after subcutaneous dosing.

Anticoagulants↗

Takayasu arteritis.

OBJECTIVE: To evaluate prospectively the clinical features, angiographic findings, and response to treatment of patients with Takayasu arteritis. DESIGN: 60 patients with Takayasu arteritis were studied at the National Institute of Allergy and Infectious Diseases between 1970 and 1990 and were followed for 6 months to 20 years (median follow-up, 5.3 years). MEASUREMENTS: Data on clinical features, angiographic and laboratory findings, disease course, and response to therapy were all recorded and stored in a computer-based retrieval system. SETTING: The Warren Magnuson Clinical Center of the National Institutes of Health. RESULTS: In our series of patients, Takayasu arteritis was more common in Asian persons compared with persons from other racial groups. Females (97%) were most frequently affected. The median age at disease onset was 25 years. Juveniles had a delay in diagnosis that was about four times that of adults. The clinical presentation ranged from asymptomatic to catastrophic with stroke. The most common clinical finding was a bruit. Hypertension was most often associated with renal artery stenosis. Only 33% of all patients had systemic symptoms on presentation. Sixty-eight percent of patients had extensive vascular disease; stenotic lesions were 3.6-fold more common than were aneurysms (98% compared with 27%). The erythrocyte sedimentation rate was not a consistently reliable surrogate marker of disease activity. Surgical bypass biopsy specimens from clinically inactive patients showed histologically active disease in 44% of patients. Although clinically significant palliation usually occurred after angioplasty or bypass of severely stenotic vessels, restenosis was common. Medical therapy was required for 80% of patients, whereas 20% had monophasic self-limiting disease. Immunosuppressive treatment with glucocorticoids alone or in combination with a cytotoxic agent failed to induce remission in one fourth of patients; about half of those who achieved remission later relapsed. CONCLUSIONS: In North America, Takayasu arteritis is a rare disease. It is heterogeneous in presentation, progression, and response to therapy. Current laboratory markers of disease activity are insufficiently reliable to guide management. Most patients require repeated and, at times, prolonged courses of therapy. Although mortality was low, substantial morbidity occurred in most patients.

Adolescent↗

Metronidazole in periodontitis (IV). The effect of patient compliance on treatment parameters.

Patient compliance with the unsupervised usage of prescription medication can be poor. In the treatment of periodontal infections with systemic antimicrobial agents, in situations where the efficacy of the antimicrobial agent is being evaluated, non-compliance could underestimate the true efficacy of the agent. Metronidazole is an agent with reported success in the treatment of anaerobic periodontal infections. Metronidazole is particularly effective in vitro against spirochetes, and this efficacy was investigated as a means of measuring patient compliance with metronidazole usage. Patients who had high proportions of spirochetes, i.e., > 20%, in plaques removed from diseased periodontal sites, were given metronidazole (500 mg bid) under supervision. In all individuals who received the metronidazole, there was a significant and rapid decline and/or disappearance of spirochetes from the plaque during the time interval that metronidazole was detectable in the saliva. This observed decline in spirochetes was then used to determine which patients had been compliant in a double-blind clinical trial involving the unsupervised usage of metronidazole. Only 10 of 18 patients (56%) were considered compliant in their usage of metronidazole. These 10 patients experienced a significantly greater benefit from the metronidazole than did the 8 patients who were considered noncompliant, i.e., a reduction of surgical needs of 8.3 teeth per compliant patient versus 3.6 teeth per non-compliant patient. A test for the hydrolysis of the synthetic peptide (BANA) was also able to identify most non-compliant patients. Clinical trials involving the unsupervised usage of systemic medication need to take into account patient non-compliance.

Alveolar Bone Loss↗

Receptor mediation of 5-HT-induced inflammation and nociception in rats.

In light of evidence suggesting the proinflammatory and nociceptive action of peripheral serotonin (5-HT), the present study examined dose-dependent parameters of edema and algesia produced by intraplantar injections of 5-HT and the role of heterogeneous 5-HT receptors in these 5-HT-induced responses. Intraplantar 5-HT (0.05, 0.25, 0.5, or 1.0 mumols) produced paw edema at each 5-HT concentration and produced concentration-dependent increases in the nociceptive response as indexed by lifts of, and licks to the affected paw. Intraplantar pretreatment with the 5-HT1 receptor antagonist methysergide at concentrations greater than or equal to 3 nmol attenuated the 5-HT-induced (25 mumols) inflammatory and nociceptive responses. At concentrations greater than or equal to 300 nmol, both 5-HT2 receptor antagonist ketanserin and 5-HT3 receptor antagonist odansetron pretreatment blocked 5-HT-induced inflammatory and nociceptive responses. These results more completely define peripheral 5-HT-receptor-dependent systems of 5-HT-induced inflammation and nociception in rats.

Animals↗

Comparison of the benzoyl-DL-arginine-naphthylamide (BANA) test, DNA probes, and immunological reagents for ability to detect anaerobic periodontal infections due to Porphyromonas gingivalis, Treponema denticola, and Bacteroides forsythus.

Most forms of periodontal disease are associated with the presence or overgrowth of anaerobic species that could include Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus among others. These three organisms are among the few cultivable plaque species that can hydrolyze the synthetic trypsin substrate benzoyl-DL-arginine-naphthylamide (BANA). In turn, BANA hydrolysis by the plaque can be associated with periodontal morbidity and with the presence of these three BANA-positive organisms in the plaque. In this investigation, the results of the BANA test, which simultaneously detects one or more of these organisms, were compared with the detection of these organisms by (i) highly specific antibodies to P. gingivalis, T. denticola, and B. forsythus; (ii) whole genomic DNA probes to P. gingivalis and T. denticola; and (iii) culturing or microscopic procedures. The BANA test, the DNA probes, and an enzyme-linked immunosorbent assay or an indirect immunofluorescence assay procedure exhibited high sensitivities, i.e., 90 ot 96%, and high accuracies, i.e., 83 to 92%, in their ability to detect combinations of these organisms in over 200 subgingival plaque samples taken from the most periodontally diseased sites in 67 patients. This indicated that if P. gingivalis, T. denticola, and B. forsythus are appropriate marker organisms for an anaerobic periodontal infection, then the three detection methods are equally accurate in their ability to diagnose this infection. The same statement could not be made for the culturing approach, where accuracies of 50 to 62% were observed.

Bacteria, Anaerobic↗