Antibiotic use: is appropriateness expensive?

Antibiotics are prone to misuse. In this study, 37% of 600 antibiotic prescriptions in three hospitals were considered unnecessary. When antibiotic therapy was indicated, 45% were considered to be inadequate. In multivariate analyses, the indicated treatments were found to be more expensive than the unjustified ones, probably because the latter were more often oral regimens. However, for indicated treatments, the cost of adequate and inadequate treatments did not differ significantly.

[Febrile cellulitis surrounding a scar revealing a large immunoblastic B-cell lymphoma]. / Dermohypodermite fébrile péricicatricielle révélatrice d'un lymphome B immunoblastique à grandes cellules.

BACKGROUND: Secondary skin sites of lymphoma appear in the advanced stages of the disease. We report the first case of a pericicatricial skin infiltration, mimicking febrile dermohypodermitis, revealing diffuse immunoblastic large B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Four months after decompressive cervical laminectomy, a 56-year-old man presented an inflammatory pericicatricial patch evoking cellulitis in a setting of hyperthermia and lymphadenopathy. Blood cultures and bacteriological analysis of skin biopsy samples were negative. The images showed infiltration of the soft subcutaneous areas and polyadenopathy. Two weeks later, several subcutaneous nodules appeared on the trunk. Histological analysis and immunolabelling pointed to immunoblastic large B-cell non-Hodgkin's lymphoma. A clone of B lymphocytes CD45+, CD20+, CD79a+, Bcl2+, CD5+, MUM1+, CD3-, CD10-, CD23- and Bcl6- was seen. The remainder of the extension examination was negative. CHOP-rituximab polychemotherapy resulted in complete regression of all lesions, notably the inflammatory cervical plaque. DISCUSSION: Secondary skin manifestations of lymphoma are generally non-specific (pruritus, ichthyosis, purpura, etc.) rather than specific in terms of lymphoid infiltration. As in our patient, certain cutaneous sites of lymphoma may have a misleading clinical presentation, histological analysis alone was able to provide a conclusive diagnosis. In our patient, the highly specific infiltration seen around the entire scar could either suggest a Koebner phenomenon or point to a role of the cutaneous aggression within the development of an inflammatory process contributing to pericicatricial infiltration by lymphoid cells. Locoregional invasion from the osseous part of the cervical spine and not macroscopically diagnosed during neurosurgery could also be responsible.

[Syringotropic and pilotropic cutaneous T-cell lymphoma without follicular mucinosis]. / Mycosis fongoïde syringotrope et pilotrope sans mucinose folliculaire.

BACKGROUND: Mycosis fongoides rarely exhibits predilection for infiltration of hair follicles and eccrine glands. We report the case of a patient with cutaneous T-cell lymphoma with syringotropism and pilotropism without follicular mucinosis. CASE REPORT: A 51-year-old man presented with erythematous infiltrated patches with alopecia and anhydrosis, cystic lesions, comedon-like lesions, follicular keratosis and an ulcer over the lower left leg. Clinical examination revealed no palpable adenopathy or hepatosplenomegaly. The patient complained about hypohydrosis. Histological examination of skin biopsies evidenced pilotropic cutaneous T-cell lymphoma without follicular mucinosis. Immunohistological examination and T-cell receptor B-chain gene rearrangement analysis showed a clonal population of T-cells. Moreover sweat glands and sweat ducts were infiltrated by atypical lymphocytes with syringolymphoid hyperplasia. DISCUSSION: Syringolymphoid hyperplasia and folliculotropism without follicular mucinosis are rarely seen in mycosis fongoides. Deep biopsies of adnexal structures are required for this critical diagnosis and clonal rearrangement of TCR genes is a reliable means of assessing clonality. Syringolymphoid hyperplasia and pilotropism without mucinosis are variants of cutaneous T-cell lymphomas.

The size of selected human skull foramina in relation to skull capacity.

An anatomical study was undertaken in order to investigate whether the sizes of selected human skull foramina with significant venous compartments correlated significantly with skull capacity. A total of 100 macerated human skulls were examined to determine the diameter of the foramina and the skull capacity. Measurements of the surface area of the foramina were made using a computerised digital analysis system. Only the size of the hypoglossal canal and jugular foramen were found to correlate significantly with the capacity of the skull. This correlation, together with the considerable size of the hypoglossal canal, indicated its important role in the venous drainage of the brain. There was considerable centralisation of venous outflow from the brain, with 60% of the area of all venous foramina of the skull occupied by jugular foramina. Asymmetry between the right and left jugular foramina was identified, with an average ratio of 1.6 (ranging between 1 and 3.47). In the case of right-sided domination the correlation between the skull capacity and the size of both jugular foramina was negative (the larger the skull cavity, the less the asymmetry), while in the case of left-sided domination the correlation was positive. Perhaps the left-sided domination is less advantageous for the haemodynamics of blood outflow, as the left brachiocephalic vein is longer and is often compressed by the sternum and aortic arch.

[Acrodermatitis enteropathica-like syndrome secondary to branched-chain amino acid deficiency during treatment of maple syrup urine disease]. / Pseudo-acrodermatite entéropathique secondaire à un déficit en acides aminés ramifiés au cours du traitement d'une leucinose.

INTRODUCTION: Clinical pictures resembling acrodermatitis enteropathica have been described in acquired zinc deficiency and deficiencies of other nutrients such as biotin, essential fatty acids and amino acids as well as biotin metabolism disorders. We describe the case of an infant with maple syrup urine disease who developed an acrodermatitis-like syndrome due to iatrogenic valine and isoleucine deficiency. CASE-REPORT: A diagnosis of maple syrup urine disease was made in a 5-month-old infant girl with severe neurologic disorders with extremely high levels of the three branched-chain amino acids (leucine, valine and isoleucine) in plasma and urine. Seven days after the start of therapy with a diet excluding these branched-chain amino acids, plasma isoleucine and valine concentrations were low while plasma leucine remained elevated. At the same time, a periorificial and acral dermatitis appeared together with diarrhea. Serum zinc concentrations were normal. A diagnosis of acrodermatitis enteropathica-like syndrome secondary to isoleucine and valine deficiency was suspected. Valine and isoleucine supplementation resulted in rapid resolution of the eruption. DISCUSSION: Several cases of acrodermatitis enteropathica-like eruptions resulting from therapeutic protein restriction diets have been described in infants with different aminoacidopathies. The accompanying dermatosis was associated with a raised plasma leucine/isoleucine ratio and/or isoleucine deficiency, or valine deficiency. While the exact pathogenesis of the skin lesions has not been established, these observations show that branched-chain amino acids are essential for normal growth and differentiation of keratinocytes. The essential role of isoleucine is further substantiated by the fact that its presence is critical in keratinocyte culture media, with growth arrest occurring upon its depletion.

X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair.

DNA duplexes containing unnatural base-pair surrogates are attractive biomolecular nanomaterials with potentially beneficial photophysical or electronic properties. Herein we report the first X-ray structure of a duplex containing a phen-pair in the center of the double helix in a zipper like stacking arrangement.

Novel methods for biocatalyst screening.

There have been a number of recent advances in catalysis assays applicable for screening biocatalyst libraries in high-throughput format. These include instrumental assays such as high-performance liquid chromatography, mass spectrometry, capillary electrophoresis and IR-thermography, reagent-based assays producing spectroscopic signals (UV/VIS or fluorescence) in response to reaction progress, and assays based on fluorogenic or chromogenic substrates. These fluorogenic substrates enable the assaying of a variety of enzymes in enantioselective and stereoselective manner, including alcohol dehydrogenases, aldolases, lipases, amidases, epoxide hydrolases and phosphatases.

High-throughput screening for biocatalysts.

Recent progress in high-throughput enzyme assays includes new examples of fluorogenic and chromogenic substrates, fluorescence resonance energy transfer substrates, and applications of the pH and pM indicator methods. Recent developments of Horeau's pseudo-enantiomer derivatisation method to screen enantioselectivities in high-throughput have also been reported.

[Problems posed by the therapeutic use of photosensitizers in dermatology]. / Problèmes posés par l'utilisation thérapeutique des photosensibilisateurs en dermatologie.

Three phototherapeutic regimens with photosensitization are now used in dermatology: PUVA (psoralen + UVA), TUV (crude coaltar + UV), PRT (phototherapy with hematoporphyrin derivative). The efficiency of PUVA and TUV is well known in several dermatoses. PRT is now being tested experimentally. For TUV, the lack of a standardized regimen does not allow a clear-cut evaluation of the therapy. For PUVA, late side-effects, particularly carcinogenicity have to be considered. To improve efficiency and minimize the side-effects of PUVA some procedures, such as association with retinoïds, pharmaco-kinetic studies for individual adaptation of the therapeutic regimen and the use of new less mutagenic psoralens are helpful. The persistent phototoxicity following treatments with hematoporphyrin derivative constitutes the major side-effect observed, for this phototherapy.

Stereoselective inhibition of alpha-L-fucosidases by N-benzyl aminocyclopentitols.

[structure: see text] (1R,2R,3R,4R,5R)-4-Amino-5-methylcyclopentane-1,2,3 -tr iol 8, its 4S stereoisomer 9, and their acyclic analogues (R)- and (S)-2-aminobutanol 11 and 12 are selective but moderate inhibitors of alpha-L-fucosidases. N-Benzylation selectively enhances inhibition potency for aminocyclopentitol 8 (--> 1, K(i) = 6.8 x 10(-)(7) M) but decreases inhibition for its 4S-stereoisomer 9 (--> 2, K(i) = 1.1 x 10(-)(4) M) and for the aminobutanols 11 (--> 13, no inhibition) and 12 (--> 14, no inhibition).

Anomer-selective inhibition of glycosidases using aminocyclopentanols.

[reaction: see text] (1S,2S,3S,4R,5R)-4-amino-5-(hydroxymethyl)cyclopentane-1,2,3-triol 1 is prepared stereoselectively from D-lyxose and displays anomer-selective inhibition for beta-galactosidase (Ki = 3.0 x 10(-6) M) and beta-glucosidase (Ki = 1.5 x 10(-7) M), over alpha-galactosidase (Ki = 2.3 x 10(-5) M) and alpha-glucosidase (IC50 = 1.0 x 10(-4) M). There is no observable cross-reactivity with alpha-mannosidase, beta-mannosidase, or alpha-L-fucosidase.

Synthesis and evaluation of aminocyclopentitol inhibitors of beta-glucosidases.

[reaction: see text] (1R,2S,3S,4R,5R)-4-Amino-5-(hydroxymethyl)cyclopentane-1,2,3-triol 1, prepared from D-glucose, inhibits beta-glucosidases from Caldocellum saccharolyticum (Ki = 1.8 x 10(-7) M) and from almonds (Ki = 3.4 x 10(-6) M). Inhibition is not influenced by N-ethylation (--> 15) but is strongly reduced upon N-acetylation (--> 12). Inversion of stereochemistry at C(5) (--> 14) has little effect on inhibition of beta-glucosidases. These experiments suggest that 1 acts as an analogue of a protonated beta-glucoside.

Tissue oxygen tension and other indicators of blood loss or organ perfusion during graded hemorrhage.

Currently employed clinical indicators of perfusion provide inadequate warning of developing hazards caused by marginal perfusion in certain vital organs or "peripheral" tissues that are pivotal to postsurgical wound healing. In this study, mean arterial blood pressure, cardiac output, and transcutaneous and subcutaneous oxygen tensions (PtcO2 and PsqO2) were investigated during serial hemorrhage, as indicators of the degree of both hypovolemia and perfusion to specific tissues. Blood was removed in stages (10%, 20%, 30%, 40%, 55%, 60%, and 65% of original volume) from anesthetized dogs. Injections of variously radiolabeled microspheres allowed assessment of blood flow at each stage of hemorrhage in bone, brain, colon, heart, kidney, liver, muscle, pancreas, skin, small intestine, spleen, stomach, and subcutaneous tissue. PsqO2 was correlated more highly with blood volume lost than was PtcO2. Furthermore PsqO2 was more sensitive to blood loss than was either cardiac output or PtcO2 and, also during the early loss (0% to 40%), was more sensitive than mean arterial pressure. Some organs (e.g., pancreas) appeared to lose considerable blood flow with only small loss of blood volume, but their blood flow then stabilized at a low level despite further hemorrhage. Other organs, notably the kidney, appeared to be relatively unaffected by substantial loss of blood volume (20% to 40%), after which, however, their blood flow quite abruptly became sensitive to further hypovolemia. This explains why blood flow-related performance of the kidney (e.g., urine volume) may not adequately predict a developing hazard or peripheral perfusion. Some indicators were found to be better indexes of blood flow in some organs than in others (e.g., cardiac output and PsqO2 correlated more closely with skin, spleen, and intestinal flows [and one another] than with vital organ flows).

Rural psychiatric services in western Australia.

The literature pertinent to the delivery of psychiatric services to rural areas is briefly surveyed. Existing rural psychiatric services in Western Australia, the largest State in Australia and a vast sparsely populated area, are described. These services are currently only of a rudimentary nature. Lack of appropriate professional staff is the major factor inhibiting further development of the services. Possible alternative models for the future are described. Flexibility and diversity of services to meet local conditions and staff availability are advocated.

The relationship between distance from inpatient facilities and the rate of psychiatric admissions in Western Australia.

Western Australia is the largest and most sparsely populated state in Australia with all its specialised psychiatric inpatient facilities in Perth, the capital city. This study tested a number of hypotheses concerning the effect of distance from Perth, firstly, on total hospitalisation rates for psychiatric illness of the rural population and secondly, on the proportion who were hospitalized in Perth. High rates of alcoholism in males and of neuroses in females, together with local conditions in various rural centres, rather than distance from Perth, were major determining factors affecting both total hospitalisation and th proportion sent to Perth. The major exception was that the proportion of male alcoholics admitted to Perth hospitals decreased the further the patient lived from Perth. These findings were contrary to those reported in the literature. However the distances from Perth were much greater than those usually reported elsewhere. It was concluded that beyond a certain distance from psychiatric facilities, distance per se was not a major factor governing admissions to these facilities.

Statistical study of individual variations in sunburn sensitivity in 303 volunteers without photodermatosis.

Variations in individual sunburn sensitivity have been studied using erythema as the photobiologic criterion. The minimal erythema dose (MED), the minimal dose necessary to elicit an intense erythema (MED++), and an edema (MOD), were determined by Saidman's method. The irradiation was performed with a 2,500-W xenon arc solar simulator fitted with a water filter and WG 305 Schott filter. The high correlation between MED, MED++, and MOD and the existence of saturation phenomenon confirm that determination of MED is the best photobiologic criterion. The average MED and the pathologic threshold for total light spectrum irradiation are, respectively, 889 mJ/cm2 and 347 mJ/cm2. A statistically significant variation in MED as a function of age, sex, complexion, eye color, hair color, and Fitzpatrick skin type has been established. Finally, complexion has been shown to be the best clinical criterion for the characterization of sunburn sensitivity and a new classification of the epidermis for UV therapy and artificial photoprotection is proposed.

Use of broad spectrum antibiotics in six non-university Swiss hospitals.

PRINCIPLES: Broad-spectrum antibiotics (BSAs) are costly and prone to misuse. Their use is associated with the emergence of resistant bacteria. This article describes the first step of an interhospital programme for the appropriate use of BSAs. METHODS: BSAs were defined as the i.v. antibiotics present in the formulary shared by the six participating institutions and considered to be antipseudomonal agents (i.e. cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem, piperacillin/tazobactam) plus trovafloxacin. Annual utilisation rates and interhospital comparisons were provided to each institution using the "defined daily dosages" (DDDs) of the World Health Organization. RESULTS: From 1997 to 1999, the overall utilisation rate of BSAs increased from 20.6 treatment days (TD)/1000 patient days (PD) to 36.5 TD/1000 PD. Significant interhospital differences were detected (range: 12.1 TD/1000 PD in 1997-66.5 TD/1000 PD in 1999). The highest relative risk for treatment with any BSA for each individual hospital in comparison to the others was determined for 1999 (RR = 2.92; 95% confidence interval: 2.81-3.04). In 1999, the most frequently used BSAs were cefepime, imipenem, and piperacillin/tazobactam respectively. CONCLUSIONS: Although this programme does not provide information on the indications for using BSAs in various hospitals, it helps to identify those institutions where the selection pressure for resistant bacteria is highest, and that could particularly benefit from specific interventions aiming at decreasing this pressure and controlling drug expenditure. Moreover, the feedback of utilisation rates and interhospital comparisons to the prescribing physicians might have a positive impact on BSA use.

Mastoid emissary in man. An anatomical-clinical study.

The purpose of the study was establishing differences in the situation of the external orifice of the emissary, its size and angle at which it leaves the skull. It is necessary for optimizaing of position for the internal coil of the speech processor of cochlear implant. As yet, the variability of external foramen of this emissary have not been sufficiently studied, especially in the clinical aspect with respect to the use of cochlear implants. The authors examined 200 skulls of adults of both sexes. The statistically significant differences were observed between sexes and between sides of the body, and they showed a definite regularity. The variability of the site of the emissary is presented in a form useful for clinical purposes.

[Cutaneous argyria: an electron microscopic study of four eases with microanalysis X study of one case (author's transl)]. / Etude en microscopie électronique et en microanalyse X de 4 cas.

This study was done in order to follow the fate of silver in the dermis of chronic argyria. Silver was easily recognizable in the tissue as irregular aggregates of elementary granules round or ovoid in shape, ranging from 30 to 40 mm in size. The microanalysis X showed that the metal was bound with sulfur. In the cases of recent intoxication, the main location of silver was intracellular: the granules were found in the lysosomes as elementary particle or as dense heterogen bodies. In the cases where intoxication had been stopped a long time ago, silver was found either on fibrillar component of the connective tissue or in the basal material of sweat glands. The results show that silver is at first phagocytized by macrophages but this cell is unable to perform complete degradation of the silver salt or metal. Then silver is found on connective fibers where it remains on sulfated glycoproteins.

[Cutaneous symptoms of carcinoid tumours of the small bowel (author's transl)]. / Les manifestations cutanées des carcinoïdes du grêle.

Cutaneous symptoms of carcinoid tumours are classified in 4 groups: --Acute type: flusch and vasomotor signs (the caracters of which are described). --Chronic type: telangiectasia, hyperpigmentation, sclerodermia-like, cutaneous maetastasis. --Rare type with non-diagnostic sign. --Types in association with other dermatological conditions either unrelated disease or with a likely related disease such as phacomatosis. Dermatological diagnosis is generally easy as cutaneous symptoms is concomitant with metastatic tumours and increased levels of serotonin and 5-H.I.A. The carcinoid syndrom may take place in the concept of the tumours of the A.P.U.D. system on clinical, embryological, histological and biochemical basis.