ABSTRACT
BACKGROUND: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres. METHODS: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables. RESULTS: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI. CONCLUSIONS: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI.
Subject(s)
Arthroplasty, Replacement, Hip , Prosthesis-Related Infections , Staphylococcal Infections , Humans , Staphylococcus aureus , Incidence , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/etiology , Retrospective Studies , Arthroplasty, Replacement, Hip/adverse effects , Staphylococcal Infections/epidemiology , Hospitals , Patient Acceptance of Health Care , Cost of IllnessABSTRACT
INTRODUCTION: Ultrasound imaging has many clinical applications, but there is a lack of data about its use by infectiologists. The aim of this study was to describe ultrasound performed routinely by infectiologists and to assess the diagnostic performance of ultrasound with aspirate and fluid analysis in prosthetic joint infections. METHODS: Retrospective study between 1st June 2019 and 1st June 2020 in an infectious and tropical diseases unit in a tertiary University Hospital. RESULTS: One hundred and thirty-one ultrasounds were performed on 127 patients by the infectious diseases team. These included 64 musculoskeletal ultrasounds (31 in native joints and 33 in prosthetic joints including 15 knees, 13 hips and 5 spacers) and 33 led to a fluid aspirate. Fourteen lung ultrasounds were done, 11 confirmed pneumopathy and 7 resulted in pleural puncture. Twenty-three vascular ultrasounds were done, 17 to insert a catheter, and four to perform a blood test. Five ultrasounds explored adenopathy, of which one node tuberculosis and one Bartonella infection were diagnosed. In prosthetic joint infections, sensitivity and specificity of ultrasound with fluid aspirate and analysis were respectively 100% and 100% for the knee and 40% and 100% for the hip. CONCLUSION: Ultrasound performed by infectiologists is useful and contributes to a faster diagnosis. Furthermore, the specificity of ultrasound with aspirate and fluid analysis is very high in prosthetic joint infection. Ultrasound training courses should be considered for infectiologists including residents.
Subject(s)
Arthritis, Infectious , Prosthesis-Related Infections , Humans , Prosthesis-Related Infections/diagnostic imaging , Retrospective Studies , Synovial Fluid , UltrasonographySubject(s)
Arthritis, Infectious/etiology , BCG Vaccine/adverse effects , Mycobacterium Infections/etiology , Mycobacterium bovis/isolation & purification , Urinary Bladder Neoplasms/drug therapy , Aged , Aged, 80 and over , Antitubercular Agents/therapeutic use , Arthritis, Infectious/diagnosis , Arthritis, Infectious/drug therapy , Arthritis, Infectious/microbiology , BCG Vaccine/therapeutic use , Ethambutol/therapeutic use , Fatal Outcome , Humans , Isoniazid/therapeutic use , Male , Mycobacterium Infections/diagnosis , Mycobacterium Infections/drug therapy , Rifampin/therapeutic use , Treatment OutcomeABSTRACT
INTRODUCTION: The management of prosthetic joint infection requires a complex treatment procedure and can be associated with complications. However, the occurrence of severe adverse events during this intervention has been poorly evaluated. PATIENTS AND METHODS: A 5-year multicentric retrospective study including patients from 3 hospitals in the South-Western France referral center for complex bone and joint infections (Crioac GSO) and treated for hip or knee prosthetic joint infection with 1 or 2-stage implant exchanges. The objective was to describe grade≥3 adverse events, according to the CTCAE classification, occurring within 6 weeks after surgery and to identify their associated factors. RESULTS: One hundred and eighteen patients were identified. We observed 71 severe events in 50 patients (42.3%; 95% confidence interval [CI95%]: 33.8-51.4%). Sixteen severe events were an evolution of the infection. The remaining 55 others (47 grade 3 and 8 grade 4) occurred in 41 patients (34.7%; CI95%: 26.8-43.7%). They were distributed as follows: 27 (49.1%) medical complications, 21 (38.2%) surgical complications and 7 (12.7%) antibiotic-related complications. The main identified risk factor was a two-stage prosthetic exchange with OR=3.6 (CI95% [1.11-11.94], P=0.032). Obesity was limit of significance with OR=3.3 (CI95% [0.9-12.51], P=0.071). Infection with coagulase negative Staphylococcus was a protective factor with OR=0.3 (CI95% [0.12-0.99], P=0.047). CONCLUSION: Severe adverse events are frequent following prosthetic exchange for PJI (34.7%) and are related to the high frequency of comorbidities in this population and to the complex surgical procedures required. The risk factor significantly associated with these events was a two-stage exchange.
Subject(s)
Hip Prosthesis/adverse effects , Joint Diseases/epidemiology , Knee Prosthesis/adverse effects , Prosthesis-Related Infections/epidemiology , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Comorbidity , Female , France/epidemiology , Hip Joint/surgery , Humans , Joint Diseases/microbiology , Knee Joint/surgery , Male , Middle Aged , Obesity/epidemiology , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/microbiology , Reoperation/statistics & numerical data , Retrospective Studies , Risk FactorsABSTRACT
INTRODUCTION: Periprosthetic knee infection is a severe complication. Confirmed criteria are lacking to choose between one-stage or two-stage prosthesis replacement to treat the infection. The one-stage replacement could lead to a satisfactory control of the infection and to better functional results. METHOD: Retrospective study conducted between January 1, 2009 and December 31, 2014. The objectives of this study were to compare the infection outcome and functional results between the one-stage and two-stage replacement procedures. Functional results were evaluated using the IKS score, KOOS score, and SF-12 quality of life score. RESULTS: Forty-one patients underwent a two-stage replacement procedure and 21 patients a one-stage replacement. The average follow-up was 22 months after surgery. The infection was cured in 78% of patients who underwent a two-stage replacement and 90% of patients who underwent a one-stage replacement (P=0.3). The flexion range of motion was significantly better in the one-stage group than in the two-stage group (P=0.04). Results of the IKS score and of the KOOS score were better in the one-stage group. No difference was observed for the SF-12 score. CONCLUSION: The one-stage replacement procedure for periprosthetic knee infection was associated with a similar healing frequency as the two-stage replacement procedure, and with better knee function.
Subject(s)
Arthroplasty, Replacement, Knee/methods , Knee Prosthesis/adverse effects , Prosthesis-Related Infections/etiology , Prosthesis-Related Infections/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Reoperation , Retrospective StudiesABSTRACT
BACKGROUND: During prosthetic joint infection (PJI), surgical management is sometimes impossible and indefinite chronic oral antimicrobial suppression (ICOAS) may be the only option. The outcomes of elderly patients who benefited from ICOAS with strictly palliative intent were evaluated. METHODS: A national retrospective cohort study was performed in France, involving patients aged >75 years with a PJI who were managed with planned life-long ICOAS from 2009 to 2014. Patients who experienced an event were compared to those who did not. An event was defined as a composite outcome in patients undergoing ICOAS, including local or systemic progression of the infection, death, or discontinuation of antimicrobial therapy because of an adverse drug reaction. RESULTS: Twenty-one patients were included, with a median age of 85 years (interquartile range 81-88 years). Eight of the 21 patients experienced an event: one had an adverse drug reaction, three had systemic progression of sepsis, and two had local progression. Two of the 21 patients died. No death was related to ICOAS or infection. There was no significant difference between the population with an event and the population free of an event with regard to demographic, clinical, and microbiological characteristics (p>0.05). CONCLUSIONS: ICOAS appeared to be an effective and safe option in this cohort.
Subject(s)
Anti-Infective Agents/administration & dosage , Palliative Care/standards , Prosthesis-Related Infections/drug therapy , Administration, Oral , Aged , Aged, 80 and over , Anti-Infective Agents/therapeutic use , Cohort Studies , Communicable Diseases/drug therapy , Female , Follow-Up Studies , France , Humans , Male , Palliative Care/methods , Prosthesis-Related Infections/microbiology , Retrospective StudiesABSTRACT
During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI. We performed a national cross-sectional cohort study of patients >75 years old and treated with PSAT for PJI. We evaluated the occurrence of events, which were defined as: (i) local or systemic progression of the infection (failure), (ii) death and (iii) discontinuation or switch of PSAT. A total of 136 patients were included, with a median age of 83 years [interquartile range (IQR) 81-88]. The predominant pathogen involved was Staphylococcus (62.1%) (Staphylococcus aureus in 41.7%). A single antimicrobial drug was prescribed in 96 cases (70.6%). There were 46 (33.8%) patients with an event: 25 (18%) with an adverse drug reaction leading to definitive discontinuation or switch of PSAT, 8 (5.9%) with progression of sepsis and 13 died (9.6%). Among patients under follow-up, the survival rate without an event at 2 years was 61% [95% confidence interval (CI): 51;74]. In the multivariate Cox analysis, patients with higher World Health Organization (WHO) score had an increased risk of an event [hazard ratio (HR) = 1.5, p = 0.014], whereas patients treated with beta-lactams are associated with less risk of events occurring (HR = 0.5, p = 0.048). In our cohort, PSAT could be an effective and safe option for PJI in the elderly.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/drug therapy , Arthritis, Infectious/epidemiology , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/epidemiology , Age Factors , Aged, 80 and over , Arthritis, Infectious/microbiology , Arthritis, Infectious/mortality , Female , Humans , Male , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/mortality , Time Factors , Treatment OutcomeABSTRACT
Relapse after treatment of a spinal infection is infrequent and difficult to diagnose. The aim of this study was to assess the diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this setting. Thirty patients (21 men, nine women; median age 61.2 years) with a suspected spinal infection relapse were prospectively included between March 2010 and June 2013. The initial diagnosis of spinal infection was confirmed by positive bacterial cultures. The patients underwent [(18)F]FDG PET/CT and magnetic resonance imaging (MRI) 1 month after antibiotic treatment interruption. PET/CT data were interpreted both visually and semi-quantitatively (SUVmax). The patients were followed for ≥12 months and the final diagnosis of relapse was based on new microbiological cultures. Seven patients relapsed during follow up. Sensitivity, specificity, positive predictive value and negative predictive value were 66.6%, 61.9%, 33.3% and 86.6%, respectively for MRI and 85.7, 82.6, 60.0 and 95.0 for PET/CT. Although these values were higher for PET/CT than for MRI, the difference was not statistically significant (p=0.3). [(18)F]FDG PET/CT may be useful for diagnosing a relapse of spinal infections, in particular if metallic implants limit the performance of MRI.
Subject(s)
Fluorodeoxyglucose F18/administration & dosage , Meningitis/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Spinal Diseases/diagnostic imaging , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Recurrence , Sensitivity and SpecificitySubject(s)
Breast Diseases/diagnosis , Mycobacterium tuberculosis/isolation & purification , Skin Ulcer/diagnosis , Tuberculosis, Cutaneous/diagnosis , Adolescent , Breast Diseases/drug therapy , Breast Diseases/microbiology , Breast Diseases/pathology , Colony Count, Microbial , Diagnosis, Differential , Female , Humans , Skin Ulcer/drug therapy , Skin Ulcer/microbiology , Skin Ulcer/pathology , Tuberculosis, Cutaneous/drug therapy , Tuberculosis, Cutaneous/microbiology , Tuberculosis, Cutaneous/pathologyABSTRACT
BACKGROUND AND PURPOSE: There is little published data on the diagnostic and therapeutic management of lower-limb stump infections (excluding toe and forefoot amputations). PATIENTS AND METHODS: We made a retrospective observational study of 72 patients having undergone a major lower-limb amputation for a vascular or traumatic reason, complicated by post-surgical stump infection, between January 1, 2000 and December 31, 2009. RESULTS: Stump infection was diagnosed more than 6weeks after amputation in half of the patients. Staphylococcus was the most frequently isolated bacterium. Ultrasonography and CT scan combined with fistulography were useful to confirm the diagnosis and to determine the extension of infection. Thirty-two patients (44%) needed surgical revision in addition to antibiotic treatment. Patients diagnosed with bone infection more frequently required complementary surgery than those with soft tissue infection (P<0.001). CONCLUSION: The optimal management of this type of infection requires obtaining reliable bacteriological documentation (abscess aspiration in case of soft tissue infection or bone biopsy in case of osteomyelitis) to adapt to the antibiotic treatment. The management should be multidisciplinary (orthopedic or vascular surgeons, rehabilitation specialists, and infectious diseases physicians). Most patients may use prosthesis once the infection is treated.
Subject(s)
Amputation Stumps , Amputation, Surgical , Leg/surgery , Surgical Wound Infection/epidemiology , Abscess/epidemiology , Abscess/microbiology , Abscess/therapy , Adult , Aged , Aged, 80 and over , Algorithms , Amputation, Surgical/rehabilitation , Amputation Stumps/diagnostic imaging , Amputation Stumps/microbiology , Amputation Stumps/surgery , Artificial Limbs , Coinfection , Combined Modality Therapy , Cutaneous Fistula/diagnosis , Cutaneous Fistula/epidemiology , Cutaneous Fistula/microbiology , Cutaneous Fistula/therapy , Debridement , Female , France/epidemiology , Humans , Leg Ulcer/epidemiology , Leg Ulcer/microbiology , Leg Ulcer/therapy , Male , Middle Aged , Osteomyelitis/diagnosis , Osteomyelitis/drug therapy , Osteomyelitis/epidemiology , Osteomyelitis/microbiology , Osteomyelitis/surgery , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/therapy , Radiography , Recurrence , Retrospective Studies , Soft Tissue Infections/diagnosis , Soft Tissue Infections/epidemiology , Soft Tissue Infections/microbiology , Soft Tissue Infections/therapy , Staphylococcal Infections/diagnosis , Staphylococcal Infections/epidemiology , Staphylococcal Infections/therapy , Surgical Wound Infection/diagnosis , Surgical Wound Infection/microbiology , Surgical Wound Infection/therapy , UltrasonographySubject(s)
Anti-Bacterial Agents/pharmacology , Arthritis, Infectious/microbiology , Staphylococcal Infections/microbiology , Staphylococcus/drug effects , Acetamides/pharmacology , Bone and Bones/microbiology , Daptomycin/pharmacology , Drug Synergism , Humans , Joints/microbiology , Linezolid , Microbial Sensitivity Tests , Minocycline/analogs & derivatives , Minocycline/pharmacology , Oxazolidinones/pharmacology , TigecyclineABSTRACT
UNLABELLED: Management of febrile neutropenic patients is described in guidelines. Each cancer center can adapt these according to its local bacterial ecology. We present a retrospective study made in a cancer center from 2001 to 2003. METHOD: Three hundred and fifteen febrile neutropenic episodes after chemotherapy (66% for solid tumor) were analysed. RESULTS: For 279 episodes, no antibiotic therapy was given before admission. Clinical or radiological manifestations occurred in 46%; microbiologically documented infections by hemocultures in 28% (Gram positive: 42%; Gram negative: 51%) and by puncture in 14% (Gram negative: 58%). The length of pyrexia was inferior to 7 days in 88% and neutropenia inferior 7 days in 80.8%. 79.7% of episodes were treated with one of the three antibiotic therapy recommended by the center (ceftriaxone+tobramycin; ceftriaxone+ciprofloxacin; ceftriaxone+ofloxacin); 13.3% were treated with an other therapy; 7% received no antibiotic therapy. 68.5% of patients treated with one of the three antibiotic therapies, became afebrile without changing the antibiotic protocol. CONCLUSION: In our study, there were a majority of Gram negative bacteria except for Pseudomonas aeruginosa. The three antibiotic therapy recommended by the center (third generation cephalosporin+aminoglycosides or fluoroquinolones) were effective and glycopeptide was not necessary in first intention treatment.
Subject(s)
Fever/epidemiology , Neoplasms/complications , Neutropenia/epidemiology , Anti-Bacterial Agents/therapeutic use , Antineoplastic Agents/adverse effects , Drug Therapy, Combination , Fever/drug therapy , Fever/etiology , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/epidemiology , Humans , Neoplasms/drug therapy , Neutropenia/drug therapy , Neutropenia/etiology , Retrospective StudiesABSTRACT
The aim of this 4-year, observational, single-center study was to identify prognostic factors and evaluate the need for intensive care in cases of bacterial meningitis. During the study period, 60 cases of adult bacterial meningitis were identified. Fifty-one patients were transferred to the intensive care unit at various times during their hospital stay. In the multivariate analysis, factors significantly associated with the need for mechanical ventilation and/or vasopressive drugs included comorbidity and a Glasgow coma score of less than 12 at hour 6 following presentation. The results indicate patients with a decreased level of consciousness, neurological deficit or comorbidity should be admitted to the intensive care unit at an early stage of illness. When patients lack these criteria 6 h following presentation, admission to the medical ward is reasonable.
Subject(s)
Community-Acquired Infections/microbiology , Meningitis, Bacterial/diagnosis , Neisseria meningitidis/isolation & purification , Streptococcus pneumoniae/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Community-Acquired Infections/diagnosis , Female , Humans , Intensive Care Units , Male , Meningitis, Bacterial/blood , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/mortality , Middle Aged , Penicillin Resistance , Prognosis , Retrospective Studies , Risk Factors , Sensitivity and SpecificityABSTRACT
PURPOSE: To present a comprehensive description of the clinical features of patients with renal manifestations during lymphoma. METHODS: Retrospective review of medical records from all patients diagnosed with lymphoma associated with kidney involvement in our hospital between 1996 to 2004. Four cases were identified and analysed. RESULTS: Four patients presented a non-Hodgkin's lymphoma. One patient showed intravascular large B-cell lymphoma, revealed by proteinuria. Another patient had a nephrotic syndrome, and two had a renal mass. Renal histology allowed diagnosis of lymphoma in 3 cases. CONCLUSION: The diagnosis of lymphoma associated with renal involvement is rather difficult, and more specifically in case of intravascular large B-cell lymphoma, or even primary renal lymphoma. We present here a comprehensive review of the literature and we discuss pathogenesis of these conditions.
Subject(s)
Kidney Neoplasms/pathology , Kidney/pathology , Lymphoma, Non-Hodgkin/pathology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy, Needle , Fatal Outcome , Female , Humans , Kidney Neoplasms/diagnosis , Kidney Neoplasms/therapy , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/therapy , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Nephrectomy , Nephrotic Syndrome/etiology , Retrospective Studies , Treatment Outcome , Vascular Neoplasms/diagnosis , Vascular Neoplasms/therapyABSTRACT
INTRODUCTION: Mantle cell lymphoma reached rarely ophtalmic sphere and salivary glands. CAS REPORT: We reported a dry syndrome seen in a 67 year-old patient. The first patological analysis of accessory salivary glands evoked a primary Gougerot-Sjögren syndrome. Secondary, he presented a mantle cell lymphoma. DISCUSSION: The pathological lack of specifity and the discovery of atypical Gougerot-Sjögren syndrome must encourage complementary immunohistochemical study of salivary glands biopsy.
Subject(s)
Exophthalmos/etiology , Lymphoma, Mantle-Cell/diagnosis , Sjogren's Syndrome/diagnosis , Aged , Humans , Immunohistochemistry , Keratoconjunctivitis Sicca/diagnosis , Magnetic Resonance Imaging , MaleABSTRACT
UNLABELLED: Fascioliasis is a parasitic infection caused by the ingestion of food contaminated with Fasciola hepatica. OBJECTIVE AND DESIGN: We report an epidemic of eight cases of fascioliasis in southern France, and describe the clinical features, and the diagnostic and therapeutic tools. RESULTS: Our series includes almost every clinical form described, apart from the pseudotumoral form. Early diagnosis relied mainly on serum assays. Among these, counter-electrophoresis was the first to be positive and therefore appears to be the most useful test, including cases where patients are asymptomatic or mildly ill. Patients were treated with the usual dose of triclabendazole, but six of them required a double dose to recover. CONCLUSION: The use of 20 mg/kg triclabendazole is safe and efficient for patients with acute fascioliasis when a single dose has failed to cure them.
Subject(s)
Disease Outbreaks , Fascioliasis/epidemiology , Adult , Animals , Anthelmintics/therapeutic use , Antibodies, Protozoan/blood , Benzimidazoles/therapeutic use , Counterimmunoelectrophoresis , Duodenum/parasitology , Dyspnea/etiology , Enzyme-Linked Immunosorbent Assay , Fasciola hepatica/immunology , Fasciola hepatica/isolation & purification , Fascioliasis/diagnosis , Fascioliasis/drug therapy , Fascioliasis/parasitology , Female , Fever/etiology , Food Parasitology , France/epidemiology , Humans , Middle Aged , Nasturtium/parasitology , Pain/etiology , TriclabendazoleABSTRACT
The prevalence of urinary tract infection is high in patients with diabetes mellitus. The presence of gas in the bladder lumen or wall constitute emphysematous cystitis. This disease is usually observed in diabetic patients. Early diagnosis and treatment are important factors for the outcome and absence of after-effects. We report the case of a 85 Year old women who was admitted to the hospital because of a gastrointestinal bleeding and subsequently developed an emphysematous cystitis. We present a comprehensive review of the literature and discuss pathogenesis, diagnosis and treatment of this condition.
Subject(s)
Cystitis/etiology , Diabetes Mellitus, Type 2/diagnosis , Emphysema/etiology , Gastrointestinal Hemorrhage/diagnosis , Aged , Aged, 80 and over , Cystitis/diagnostic imaging , Emphysema/diagnostic imaging , Female , Gastrointestinal Hemorrhage/etiology , Humans , RadiographyABSTRACT
Parasympathetic hyperactivity is found in some infants presenting faint episodes and could be responsible of certain Sudden Infant Death Syndrome cases. Therefore it was interesting to look for a noninvasive biochemical indicator of parasympathetic activity. A parasympaticomimetic syndrome associated with muscarinic receptor stimulation, which has been followed during 48 h, was obtained in the awake rat by reserpine injection (6.25 mg/kg at T0 and T24h), and a model of prolonged parasympatholytic syndrome, by administration of diphemanil-methylsulfate (DPMS), a muscarinic receptor inhibitor, in drinking water (mean daily dosis: 150 mg/kg). Significant bradycardia and tachycardia were respectively observed. In the reserpine-treated rats we found significantly increased cyclic guanosylmonophosphate (cGMP) urinary excretion between T24h and T48h, when compared with vehicle-treated controls (+87% in one experiment, +135% in the other, when expressed in pmol/microg creatinine); norepinephrine urinary excretion between T24h and T48h was decreased (-44%); the increase in cGMP urinary excretion was not significantly modified by the NO-synthase inhibitor, L-nitroarginine-methyl-ester. In the DPMS-treated rats, we observed a significantly decreased cGMP (-20%) and increased norepinephrine urinary excretion (+61%). Thus cGMP excretion varied in opposite directions in the reserpine- and DPMS-treated rats. The link between these modifications in cGMP excretion and muscarinic receptor stimulation or blockade has still to be fully demonstrated. Urinary cGMP excretion could be tested as screening parameter in infants at risk of faint episodes associated with bradycardia.
Subject(s)
Autonomic Nervous System Diseases/urine , Cyclic GMP/urine , Parasympathetic Nervous System/physiopathology , Parasympatholytics/pharmacology , Piperidines/pharmacology , Reserpine/pharmacology , Animals , Autonomic Nervous System Diseases/chemically induced , Autonomic Nervous System Diseases/physiopathology , Dose-Response Relationship, Drug , Heart Rate/drug effects , Hemodynamics/drug effects , Male , Muscarinic Agonists/administration & dosage , Muscarinic Agonists/pharmacology , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/physiology , Nitric Oxide Synthase/antagonists & inhibitors , Norepinephrine/urine , Parasympathetic Nervous System/drug effects , Parasympatholytics/administration & dosage , Piperidines/administration & dosage , Rats , Rats, Sprague-Dawley , Reserpine/administration & dosage , SyndromeABSTRACT
OBJECTIVE: The aim of this study was to look for a relationship between autonomic dysfunction and alterations in glucose- induced thermogenesis (GIT) and lipid oxidation rate in obese non-diabetic women. SUBJECTS: 37 obese women, 20 with impaired cardiac autonomic function tests (group 1) were matched with 17 women with normal tests (group 2) according to age, weight, body mass index (BMI), waist-to-hip ratio (WHR), fat mass (FM) and fat free mass (FFM). MEASUREMENTS: A series of five standardized tests was carried out, three of which were based mainly on cardiac parasympathetic control (heart rate response to Valsalva, deep breathing and lying-to-standing) and two on cardiovascular sympathetic function (blood pressure response to standing and to handgrip). Energy expenditure (EE), lipid and glucose oxidation rate were determined by indirect calorimetry at fasting and after an oral glucose load (75 g). Blood glucose, insulin and catecholamines responses to glucose were examined. RESULTS: There was no significant difference in plasma glucose, insulin, catecholamines, metabolic rate, glucose and lipid oxidation rate at fasting and plasma glucose, insulin and catecholamine responses to glucose. GIT was slightly but not significantly lower in group 1 (24.7+/-10.4 kJ) than in group 2 (46.8+/-9.0 kJ). The cumulative glucose oxidation rate did not differ significantly in the two groups. The cumulative lipid oxidation rate was significantly lower in group 1 than in group 2 (-49.4+/-4.1 vs -30.8+/-8.0, respectively, P = 0.033). It correlated negatively with the area under the curve of insulin response (r=-0.37, P=0.04). In the multivariate analysis, both autonomic dysfunction and the area under the curve of insulin response correlated significantly with the cumulative lipid oxidation rate. CONCLUSION: This study suggests that 1) the glucose-induced inhibition of the lipid oxidation rate in obese women is greater in the patients with autonomic dysfunction; 2) a decrease in sympathetic activity is likely to be involved in this phenomenon.