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The thyrotropin-releasing hormone and dexamethasone suppression tests in the familial classification of depression.

Eighty-eight depressed patients who had received a dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) test were divided into four subgroups based on family history of psychiatric illness. Nonsuppression on the DST was found in 46% of familial pure depressive disease (FPDD) patients, 38% of sporadic depressive disease (SDD) patients, 38% of depressive spectrum disease (DSD) patients, and 50% of mixed depressive disease patients (patients with both a first degree relative with alcoholism and one with depression). A blunted thyroid-stimulating hormone response to TRH was found in 50% of FPDD patients, 56% of SDD patients, 47% of DSD patients, and 56% of mixed depressive disease patients. Neither the DST nor TRH test was found to distinguish significantly among the four familial subgroups of depression.

Adult↗

Modifications of [3H]imipramine binding sites in platelets of chronic pain patients treated with mianserin.

Tritiated imipramine binding to whole platelets was measured in 16 chronic pain patients who were free from major depression, and in a control group. The maximum binding was significantly lower in chronic pain patients than in the control group, whereas the binding affinity was not significantly different. Twelve patients were treated with mianserin for 21 days; this produced a significant improvement in the mean scores for pain (evaluated with the McGill Questionnaire) and depressive symptoms (assessed with the Zung Self-Rating Scale). The improvement in both types of symptom was accompanied by a significant mean increase in the density of the [3H]imipramine binding sites without modifications in the values of the constant of affinity. All the patients who responded well to treatment (N = 8) had a family history of depressive spectrum disorders (DSD), while none of those who failed to respond had a first degree relative with DSD.

Binding Sites↗

Differential upregulation of extracellular matrix molecules associated with the appearance of granule cell dispersion and mossy fiber sprouting during epileptogenesis in a murine model of temporal lobe epilepsy.

We have investigated changes in the extracellular matrix of the hippocampus associated with the early progression of epileptogenesis in a murine model of temporal lobe epilepsy using immunohistochemistry. In the first week following intrahippocampal injection of the glutamate agonist, domoate, there is a latent period at the end of which begins a sequential upregulation of extracellular matrix (ECM) molecules in the granule cell layer of the dentate gyrus, beginning with neurocan and tenascin-C. This expression precedes the characteristic dispersion of the granule cell layer which is evident at 14 days post-injection when the first recurrent seizures can be recorded. At this stage, an upregulation of the chondroitin sulfate proteoglycan, phosphacan, the DSD-1 chondroitin sulfate motif, and the HNK-1 oligosaccharide are also observed. The expression of these molecules is localized differentially in the epileptogenic dentate gyrus, especially in the sprouting molecular layer, where a strong upregulation of phosphacan, tenascin-C, and HNK-1 is observed but there is no expression of the proteoglycan, neurocan, nor of the DSD-1 chondroitin sulfate motif. Hence, it appears that granule cell layer dispersion is accompanied by a general increase in the ECM, while mossy fiber sprouting in the molecular layer is associated with a more restricted repertoire. In contrast to these changes, the expression of the ECM glycoproteins, laminin and fibronectin, both of which are frequently implicated in tissue remodelling events, showed no changes associated with either granule cell dispersion or mossy fiber sprouting, indicating that the epileptogenic plasticity of the hippocampus is accompanied by ECM interactions that are characteristic of the CNS.

Animals↗

Glucose metabolism in the amygdala in depression: relationship to diagnostic subtype and plasma cortisol levels.

In a previous positron emission tomography (PET) study of major depression, we demonstrated that cerebral blood flow was increased in the left amygdala in unipolar depressives with familial pure depressive disease (FPDD) relative to healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained from relatively low-resolution PET images using a stereotaxic method based upon skull X-ray landmarks. The current experiments aimed to replicate and extend these results using higher-resolution glucose metabolism images and magnetic resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this finding to FPDD was also investigated by assessing depressed samples with bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship between amygdala metabolism and plasma cortisol levels obtained during the scanning procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose (18FDG) in healthy control (n=12), FPDD (n=12), DSD (n=9) and BD-D (n=7) samples in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed across groups (P<.001), being increased in both the FPDD and BD-D groups relative to the control group. The left amygdala metabolism was positively correlated with stressed plasma cortisol levels in both the unipolar (r=.69; P<.005) and the bipolar depressives (r=0.68;.1<P<.05). In contrast, neither significant main effects of diagnosis nor significant relationships with plasma cortisol were evident in post hoc analyses of metabolism in the right amygdala or the hippocampus. Preliminary assessment of BD subjects imaged during remission suggested that amygdala metabolism is also elevated in remitted subjects who are not taking mood-stabilizing drugs, but within the normal range in subjects taking mood stabilizers. These data confirm our previous finding that neurophysiological activity is abnormally increased in FPDD, and extend it to BD-D. These abnormalities were not accounted for by spilling in of radioactivity from the adjacent hippocampus. The correlation between left amygdala metabolism and stressed plasma cortisol levels may conceivably reflect either the effect of amygdala activity on corticotropin-releasing hormone (CRH) secretion or the effect of cortisol on amygdala function.

Adolescent↗

Regulation of RPTPbeta/phosphacan expression and glycosaminoglycan epitopes in injured brain and cytokine-treated glia.

Several chondroitin sulfate proteoglycans (CSPGs) are upregulated after CNS injury and are thought to limit axonal regeneration in the adult mammalian CNS. Therefore, we examined the expression of the CSPG, receptor protein tyrosine phosphatase beta (RPTPbeta)/phosphacan, after a knife lesion to the cerebral cortex and after treatment of glial cultures with regulatory factors. The three splice variants of this CSPG gene, the secreted isoform, phosphacan, and the two transmembrane isoforms, the long and short RPTPbeta, were examined. Western blot and immunostaining analysis of injured and uninjured tissue revealed a transient decrease of phosphacan protein levels, but not of short RPTPbeta, in the injured tissue from 1 to 7 days postlesion (dpl). By real time RT-PCR, we show that phosphacan and long RPTPbeta mRNA levels are transiently down-regulated at 2 dpl, unlike those of short RPTPbeta which increased after 4 dpl. In contrast to the core glycoprotein, the phosphacan chondroitin sulfate (CS) glycosaminoglycan epitope DSD-1 was up-regulated after 7 dpl. Phosphacan was expressed by cultivated astrocytes and oligodendrocyte precursors but was more glycanated in oligodendrocyte precursors, which produce more of DSD-1 epitope than astrocytes. Epidermal growth factor/transforming growth factor alpha strongly increased the astrocytic expression of long RPTPbeta and phosphacan and slightly the short RPTPbeta protein levels, while interferon gamma and tumor necrosis factor alpha reduced astrocytic levels of phosphacan, but not of the receptor forms. Examining the effects of phosphacan on axon growth from rat E17 cortical neurons, we found that phosphacan stimulates outgrowth in a largely CS dependent manner, while it blocks the outgrowth-promoting effects of laminin through an interaction that is not affected by removal of the CS chains. These results demonstrate complex injury-induced modifications in phosphacan expression and glycanation that may well influence axonal regeneration and repair processes in the damaged CNS.

Animals↗

Stereochemistry and size of sugar head groups determine structure and phase behavior of glycolipid membranes: densitometric, calorimetric, and X-ray studies.

The role carbohydrate moieties play in determining the structure and energetics of glycolipid model membranes has been investigated by small- and wide-angle X-ray scattering, differential scanning densitometry (DSD), and differential scanning microcalorimetry (DSC). The dependence of a variety of thermodynamic and structural parameters on the stereochemistry of the OH groups in the pyranose ring and on the size of the sugar head group has been studied by using an homologous series of synthetic stereochemically uniform glyceroglycolipids having glucose, galactose, mannose, maltose, or trimaltose head groups and saturated ether-linked alkyl chains with 10, 12, 14, 16, or 18 carbon atoms per chain. The combined structural and thermodynamic data indicate that stereochemical changes of a single OH group in the pyranose ring can cause dramatic alterations in the stability and in the nature of the phase transitions of the membranes. The second equally important determinant of lipid interactions in the membrane is the size of the head group. A comparison of lipids with glucose, maltose, or trimaltose head groups and identical hydrophobic moieties has shown that increasing the size of the neutral carbohydrate head group strongly favors the bilayer-forming tendency of the glycolipids. These experimental results provide a verification of the geometric model advanced by Israelachvili et al. (1980) [Israelachvili, J. N., Marcelja, S., & Horn, R. G. (1980) Q. Rev. Biophys. 13, 121-200] to explain the preferences lipids exhibit for certain structures. Generally galactose head groups confer highest stability on the multilamellar model membranes as judged on the basis of the chain-melting transition. This is an interesting aspect in view of the fact that galactose moieties are frequently observed in membranes of thermophilic organisms. Glucose head groups provide lower stability but increase the number of stable intermediate structures that the corresponding lipids can adopt. Galactolipids do not even assume a stable intermediate L alpha phase for lipids with short chain length but perform only Lc----HII transitions in the first heating. The C2 isomer, mannose, modifies the phase preference in such a manner that only L beta----HII changes can occur. Maltose and trimaltose head groups prevent the adoption of the HII phase and permit only L beta----L alpha phase changes. The DSD studies resulted in a quantitative estimate for the volume change associated with the L alpha----HII transition of 14-Glc. The value of delta v = 0.005 mL/g supports the view that the volume difference between L alpha and HII is minute.(ABSTRACT TRUNCATED AT 400 WORDS)

Calorimetry, Differential Scanning↗

Three-Dimensional Hückel Theory for closo-Carboranes.

We have recently developed a 3-dimensional Hückel method for cluster compounds. The method uses a set of approximations for Coulomb, resonance, and overlap integrals very similar to those employed in the familiar 2-dimensional Hückel theory for the pi electrons of planar conjugated hydrocarbons. The method can be adapted to heteroatomic clusters by introducing heteroatomic Coulomb integrals, alpha(Y) = alpha(X) + hbeta, whereh is a parameter for heteroatom Y. In this paper, we use the 3-dimensional Hückel method to study the properties of the closo-carboranes, C(2)B(n)()(-)(2)H(n)(). We calibrate the method by choosing a value of the heteroatomic parameter h that distinguishes positional isomers by energy and gives them relative energies in rough agreement with those established by observation and ab initio calculations. We obtain modest improvement in matching ab initio relative energies of isomers by means of a three-parameter, first-order perturbation treatment. We use the calibrated method to evaluate various mechanisms proposed for the isomerizations of C(2)B(4)H(6), C(2)B(5)H(7), and C(2)B(6)H(8), all of which have been observed to undergo intramolecular isomerizations. Rearrangements of C(2)B(6)H(8) have been satisfactorily explained by a single-DSD (diamond-square-diamond) process. Those for C(2)B(5)H(7) require at least two DSD processes, concerted, consecutive, or overlapping. Several different mechanisms have been proposed for the rearrangement of C(2)B(4)H(6). In evaluating intermediate and transition state structures, the 3-dimensional Hückel method gives higher energies to those structures with a larger number of nontriangular faces, a plausible conclusion except that occasionally it is wrong. In comparison with ab initio results, the 3-dimensional Hückel method fails to give low energies for classical structures.

Journal Article↗

Urodynamic findings in primary progressive multiple sclerosis are associated with increased volumes of plaques and atrophy in the central nervous system.

OBJECTIVE: Voiding dysfunction is more frequent in primary progressive multiple sclerosis (PPMS) than in other subtypes of MS. We investigated whether lower urinary tract disorders are reflected in the extent of changes in brain and spinal cord detected by magnetic resonance imaging (MRI). METHODS: Micturition symptoms and specific urodynamic findings in 24 patients with PPMS were related to MRI abnormalities as analysed by segmentation and volumetric analysis. RESULTS: Urgency and urge incontinence were the most frequent urinary symptoms (83 and 75 %), while detrusor sphincter dyssynergia (DSD) (71%), detrusor hyperreflexia (58%) and obstruction (58%) were the most common micturition dysfunctions. Comparison between patients with detrusor hyperreflexia and those with normal bladder function revealed higher volumes of T2-weighted plaques in the brains of former (P = 0.01). In patients with hypotonic bladder the total brain volume was smaller (P = 0.02) and the number of thoracic plaques in T2-weighted images higher (P = 0.02) compared to patients with normal bladder function. Furthermore, DSD was associated with a higher volume of T2-weighted plaques in the brain (P = 0.02). CONCLUSIONS: Voiding dysfunction in PPMS is associated with increasing brain and spinal cord abnormalities. Urodynamic investigation is, however, needed for specific definition of micturition disturbances and should be made before therapeutic decisions.

Atrophy↗

Long term urinary prognosis of cervical cord injury patients.

We made a retrospective comparative study of 88 cervical cord injury patients concerning their long term urological prognosis. In all, 129 urinary complications have occurred in 54 cases (61.4%). The incidence of urinary complications was high in those with higher levels of injury (except C integral of 4 lesions), a complete injury, a younger age of onset and a longer period after injury. Patients who had an indwelling catheter and a suprapubic cystostomy showed a higher rate of urinary complications. Urodynamically, there was no significant difference between the presence and absence of detrusor hyperreflexia. Those with detrusor-sphincter dyssynergia (DSD) also showed no difference compared to those without DSD. For the prevention of urinary complications in cervical cord injury patients, proper urinary management with clean intermittent catheterisation (CIC), or low pressure voiding is necessary in the early period after the onset of the injury.

Adult↗

Neuromodulation through sacral nerve roots 2 to 4 with a Finetech-Brindley sacral posterior and anterior root stimulator.

STUDY DESIGN: Investigation of five patients receiving an implant, using laboratory cystometry and self-catheterisation at home. OBJECTIVES: To use the established Finetech-Brindley sacral root stimulator to increase bladder capacity by neuromodulation, eliminating the need for posterior rhizotomy, as well as achieving bladder emptying by neurostimulation. SETTING: Spinal Injuries Unit, Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK. METHODS: Five patients underwent implantation of a Finetech-Brindley stimulator without rhizotomy of the posterior roots. This was either a two channel extradural device (four cases) or a three channel intrathecal device (one case). In each patient, the implant was configured as a Sacral Posterior and Anterior Root Stimulator (SPARS). Postoperatively, repeated provocations using rapid instillation of 60 ml saline were used to determine the relative thresholds for neuromodulation using each channel. The effect of continuous neuromodulation was examined in the laboratory using slow fill cystometrograms, and conditional stimulation was also studied (neuromodulation for 1 min to suppress hyperreflexic contractions as they occurred). In one patient, neuromodulation was applied continuously at home, and volumes at self catheterisation recorded in a diary. RESULTS: Reflex erections were preserved in each patient. In three patients, detrusor hyperreflexia persisted postoperatively and neuromodulation via the implant was studied. In these three patients, the configuration was: S2 mixed roots bilaterally (channel B), and S34 bilaterally (channel A). Both channels could be used to suppress provoked hyperreflexic contractions, with the S2 channel effective at a shorter pulse width than S34 in a majority of cases. Continuous stimulation more than doubled bladder capacity in two out of three patients during slow fill cystometry. Conditional stimulation was highly effective. In the one patient who used continuous stimulation at home, bladder capacity was more than doubled and the effect was comparable with anticholinergic medication. Bladder pressures >70 cm water could be achieved with intense stimulation in three patients, but detrusor-external urethral sphincter dyssynergia (DSD) prevented complete emptying. CONCLUSIONS: Neuromodulation via a SPARS was effective and may replace the need for posterior rhizotomy. However, persisting DSD may prevent complete bladder emptying and warrants further investigation.

Adult↗

Long-term follow-up study of intraurethral stents in spinal cord injured patients with detrusor-sphincter dyssynergia.

STUDY DESIGN: Retrospective study. OBJECTIVES: To assess in the long-term clinical and urodynamic results of intraurethral stents in a group of patients with spinal cord injury. SETTING: Spinal Cord Injury Unit, Juan Canalejo Hospital, A Coruña, Spain. METHODS: Forty-seven consecutive male patients were studied from 1993 to 2002. All of them suffered from hyperreflexia with detrusor-sphincter dyssynergia (DSD) owing to spinal cord injury, and were treated by means of the placement of an intraurethral stent at the external sphincter. RESULTS: After surgery, significant decreases in all the parameters studied were observed. The number of patients with symptoms of urinary tract infection decreased by 25% (P<0.031). Post-void residual urine volume experienced an average decrease of 224.3 cm(3) (P=0.001). Episodes of dysreflexia decreased from 35.1 to 16.2% (P=0.039). The urodynamic study showed an average reduction of 44.36 cm H(2)O in the maximum detrusor pressure (P<0.0001). Complications in the upper urinary tract descended from 46.8 to 23.4% after placing the stent (P=0.013). The most frequent stent complication was displacement, followed by stenosis, lithiasis and intraprosthetic calcification. In all, 8.5% required the stent removal. CONCLUSIONS: Intraurethral stent is a good choice for the long-term management of DSD in spinal cord-injured patients, even in those who had been previously submitted to prior sphincterotomy. It has the advantage of being a potentially reversible procedure, so patients prefer it to more invasive therapies such as sphincterotomy.

Adult↗

Dressing size and pain: a prospective trial.

BACKGROUND: Pain is a personal, subjective experience. In the postoperative period, pain may be influenced by patient, pharmacological and environmental factors. In surgery the aim is to reduce pain in this period by educating patients and using adequate analgesia. The aim of the present study was to assess the effect of perceived wound size on pain, as indicated by wound dressing, in the immediate postoperative period. METHODS: Patients undergoing appendicectomy were randomized into a group having a dressing the same size (SSD) as the surgical wound or double the size (DSD) of the wound. Patients' pain perception and analgesic requirements were then recorded and analysed to compare the two groups. RESULTS: Both groups had similar results when comparing pain perception. The median total pain score for the SSD and DSD groups at 12 and 24 h postoperatively revealed no statistically significant difference (P > 0.05). CONCLUSION: The data do not support the hypothesis that postoperative pain may be altered by perceived wound dressing size. Dressing size does not appear to be a variable that could easily be altered to reduce postoperative pain in surgical patients.

Adolescent↗

The influence of colonic enema irrigation on urodynamic findings in patients with neurogenic bladder dysfunction.

OBJECTIVE: To evaluate whether colonic enema irrigation influences the urodynamic characteristics of patients with spina bifida, an overactive bladder and detrusor sphincter dyssynergia (DSD). PATIENTS AND METHODS: Since 1991, 83 patients with spina bifida at our institution have treated their bowel dysfunction by colonic irrigation every 24-48 h. In 12 patients (seven boys and five girls, mean age 7.7 years, range 0.7-13.8) with an overactive bladder and DSD, urodynamic studies of the bladder before and after enema treatment were available with no intercurrent changes in urological therapy. RESULTS: There were no significant changes overall in bladder capacity, leak-point pressure, bladder compliance and bladder instability in the selected group of children. CONCLUSION: Although enema therapy for bowel treatment in patients with spina bifida gave good results for faecal incontinence, with good patient compliance, no favourable effect on bladder function should be expected in most patients with a high-risk urinary tract dysfunction. Further study is needed to determine factors in patients who will benefit urologically from enema treatment.

Child↗

Developmental system drift and flexibility in evolutionary trajectories.

The comparative analysis of homologous characters is a staple of evolutionary developmental biology and often involves extrapolating from experimental data in model organisms to infer developmental events in non-model organisms. In order to determine the general importance of data obtained in model organisms, it is critical to know how often and to what degree similar phenotypes expressed in different taxa are formed by divergent developmental processes. Both comparative studies of distantly related species and genetic analysis of closely related species indicate that many characters known to be homologous between taxa have diverged in their morphogenetic or gene regulatory underpinnings. This process, which we call "developmental system drift" (DSD), is apparently ubiquitous and has significant implications for the flexibility of developmental evolution of both conserved and evolving characters. Current data on the population genetics and molecular mechanisms of DSD illustrate how the details of developmental processes are constantly changing within evolutionary lineages, indicating that developmental systems may possess a great deal of plasticity in their responses to natural selection.

Animals↗

Oral immunoadjuvant activity of Lactobacillus casei subsp. casei in dextran-fed layer chickens.

We recently reported that synbiotic Lactobacillus casei subsp. casei together with specific substrate dextran elicited an enhancement in humoral immune response against bovine serum albumin (BSA) as a model antigen in BALB/c mice. The present study was designed to evaluate the oral immunoadjuvant effects of the synbiotic in layer chickens. Using a PCR assay, L. casei subsp. casei was detected specifically in the intestinal chyme of chickens (10 d of age, Julia strain) fed ad libitum on a diet supplemented with 75 mg dextran/kg (dextran-supplemented diet, DSD) and administered orally with 10(7) colony-forming units (CFU) L. casei subsp. casei in 0.1 ml PBS with the aid of an intubation needle at 1, 2 and 3 d of age. Furthermore, oral administration of 10(7) CFU L. casei subsp. casei at 1-3 d of age significantly enhanced the production of anti-BSA antibody in DSD-fed chickens (60 d of age) administered orally with 1 mg BSA at 32 and 33 d of age and subcutaneously with 5 microg BSA at 33 d of age. In addition, among bacterial numbers tested, 10(6) CFU L. casei subsp. casei together with dextran induced an effective increase in humoral immune response to mixed inactivated vaccines against Newcastle disease and avian infectious bronchitis, and the treatment may be advantageous in protecting against these infectious diseases in chickens in actual application. These results suggest that dietary supplementation of L. casei subsp. casei with dextran leads to immunomodulation of humoral immune responses.

Adjuvants, Immunologic↗

Dynamic bulbocavernosus reflex: dyssynergia evaluation following SCI.

High urethral resistance caused by detrusor-sphincter dyssynergia (DSD) occurs following spinal cord injury (SCI) and results in poor voiding. A major pelvic floor reflex that may be involved in DSD is the bulbocavernosus reflex (BC) and evaluation of this reflex during the micturition cycle may provide additional information regarding this role. The periodic BC observed during micturition via cystometry is described as a dynamic bulbocavernosus reflex (DBC). The DBC was induced in upper motor neuron SCI patients using periodic dorsal penile nerve stimulation; the evoked reflex response was recorded with an anal sphincter pressure sensing balloon. Stimulation of 15-50 mA was applied at the base and dorsal side of the penis with surface electrodes, pulsed at a rate of 0.25 Hz. By applying the stimulation during cystometry, the BC reflex could be evaluated throughout the entire micturition cycle. Results showed that the DBC increased during bladder filling and bladder contractions. These findings indicate that an enhanced BC reflex is a major factor causing increased urethral resistance during micturition.

Adult↗

Donald Munro Lecture 2003. Neurogenic bladder: past, present, and future.

The foundation of the management of neurogenic bladder can be attributed to a pioneer in spinal cord injury medicine. Dr. Donald Munro, a neurosurgeon, who also had experience in urologic surgery, established the first Spinal Cord Injury Service of 10 beds in the Boston City hospital in the 1930s. He later became adviser to the US Army and the Veterans Administration (VA). On his recommendation, paraplegic centers were created in US army hospitals and later in the VA hospitals from 1943 to 1945. This article reviews the evolution of the management of neurogenic bladder in patients with spinal cord injuries from the past century to the present. The role of urodynamics in defining neurologic lesions is critical to the appropriate management of the voiding dysfunction. Key advances, such as the diagnosis of detrusor sphincter dyssynergia (DSD), recognition of its association with autonomic dysreflexia, and its definitive management, have been emphasized. The role of transrectal linear array sonography using a rectal probe was found useful for defining bladder outlet dysfunction during urodynamics. It also helped to recognize secondary bladder neck obstruction and diagnose false passages in the urethra. Clean technique intermittent catheterization (IC) was evaluated and recommended. In about 28% patients with DSD that led to secondary bladder neck obstruction, a consequence of IC was reported. Transurethral laser sphincterotomy (TURS) was first reported by me in 1991, and later, durable 7-year follow-up results were reported in 78% of the first 99 patients. We reported a surgical technique to lengthen the penis. We also reported the long-term success with semirigid implants in 92% of patients with SCI. This technique helped maintain external condom drainage on a small phallus and improved the sex life of patients, as well as their quality of life. The author's pertinent areas of interest in the past one-half century were aimed at recognizing specific urologic problems associated with neurologic impairment. Management was aimed at preventive care, early recognition, and timely management to reduce secondary complications and enhance quality of life.

Humans↗

Influence of population density on antibiotic resistance.

Antibiotic consumption and population density as a measure of crowding in the community were related to the prevalence of antibiotic resistance of three cities in three different countries: St Johns in Newfoundland (Canada), Athens in Greece and Groningen in The Netherlands. Antibiotic consumption was expressed in DDD (defined daily dose), as DID (DDD/1000 inhabitants/day) and as DSD (DDD/km(2)). The prevalence of antibiotic-resistant Escherichia coli and enterococci was determined in faecal samples of healthy volunteers. In both Newfoundland (28 DID) and Greece (29 DID) the overall consumption of antibiotics was more than three times higher compared with that of The Netherlands (9 DID). The lowest prevalence of resistant E. coli against the majority of antibiotics tested was found for the samples from Newfoundland and was significant (P < 0.05) for cefazolin, oxytetracycline and trimethoprim. A poor correlation between the number of DID and the prevalence of resistance was observed [the Pearson correlation coefficient (Pcc) ranged between -0.93 and 0.87]. However, when population density was taken into consideration and antibiotic consumption was expressed in DSD, a strong correlation was observed (and Pcc ranged between 0.86 and 1.00). This study suggests that population density is an important factor in the development of antibiotic resistance and warrants special attention as a factor in resistance epidemiology.

Canada↗