[Prospective analysis of risk factors for perioperative infections in clean and clean-contaminated surgeries in dogs and cats with special reference to perioperative and postoperative antibiotic use]. / Prospektive Analyse von Risikofaktoren für perioperative Infektionen bei sauberen und sauber-kontaminierten Eingriffen bei Hund und Katze unter besonderer Berücksichtigung des perioperativen und postoperativen Antibiotikaeinsatzes.

INTRODUCTION: With every surgical procedure there is a risk of postoperative infection (surgical site infection = SSI). This risk of infection can be influenced by various factors, including perioperative antibiotic prophylaxis. In terms of antibiotic stewardship, antibiotics should only be used if there is a proven benefit for the patient. However, this advantage has not yet been conclusively proven, especially for clean and clean-contaminated surgeries. The aim of our study was to document various relevant influencing factors on the infection rate after clean and clean-contaminated surgeries in dogs and cats. In particular, it was documented to what extent a reduced use of antibiotics affects the infection rate in the context of all influencing factors. Over a period of eleven months, 807 clean and clean-contaminated surgeries in dogs and cats were prospectively analyzed with possible influencing factors (gender, ASA classification, underlying endocrinological diseases, duration of anesthesia, duration of surgery, type of surgery, perioperative antibiotic prophylaxis (POA), duration of hospitalization) affecting the infection rate. After surgery all cases were followed up either 30 or 90 days, if implants were used. The effect of the various factors was evaluated using multivariable logistic regression analysis. SSI was detected in 25/664 clean and 10/143 clean-contaminated surgeries. Longer hospitalization, without antimicrobial prophylaxis, and male animals had a significantly higher risk of SSI. In clean surgeries, SSI occurred in 2,3 % of all cases with POA and 5,3 % without POA. The SSI in clean-contaminated was 3,6 % with POA and 9 % without. This difference resulted mainly from the results of osteosynthesis, gastrointestinal and skin surgeries. However, other types of surgeries, such as castrations, neurological interventions, abdominal and thoracic surgeries, and surgeries in the head and neck region, showed comparable infection rates with and without POA.

INTRODUCTION: Toute intervention chirurgicale comporte un risque d'infection postopératoire (infection du site opératoire = ISO). Ce risque d'infection peut être influencé par différents facteurs, dont l'antibioprophylaxie périopératoire. En termes de gestion responsable des antibiotiques, les antibiotiques ne devraient être utilisés que s'il existe un avantage prouvé pour le patient. Cependant, cet avantage n'a pas encore été prouvé de manière concluante, en particulier pour les chirurgies propres et propres-contaminées. L'objectif de notre étude était de documenter divers facteurs d'influence pertinents sur le taux d'infection après des chirurgies propres et propres-contaminées chez les chiens et les chats. Nous avons en particulier cherché à savoir dans quelle mesure une utilisation réduite des antibiotiques affecte le taux d'infection en tenant compte de tous les facteurs d'influence. Sur une période de onze mois, 807 chirurgies propres et contaminées chez des chiens et des chats ont été analysées prospectivement avec les facteurs d'influence possibles (sexe, classification ASA, maladies endocrinologiques sous-jacentes, durée de l'anesthésie, durée de la chirurgie, type de chirurgie, prophylaxie antibiotique périopératoire (POA), durée de l'hospitalisation) affectant le taux d'infection. Après la chirurgie, tous les cas ont été suivis durant soit 30 soit90 jours si des implants avaient été utilisés. L'effet des différents facteurs a été évalué par une analyse de régression logistique multivariable. Des ISO ont été détectées dans 25/664 chirurgies propres et 10/143 chirurgies contaminées propres. Une hospitalisation plus longue sans prophylaxie antimicrobienne ainsi que les animaux mâles présentaient un risque significativement plus élevé d'ISO. Dans les chirurgies propres, les ISO sont survenues dans 2,3 % des cas avec POA et 5,3 % sans POA. Dans les opérations propres-contaminées, les ISO étaient de 3,6 % avec POA et de 9 % sans POA. Cette différence était principalement due aux résultats des ostéosynthèses, des chirurgies gastro-intestinales et cutanées. En revanbche, d'autres types de chirurgies, comme les castrations, les interventions neurologiques, les chirurgies abdominales et thoraciques et les chirurgies de la tête et du cou ont montré des taux d'infection comparables avec et sans POA.

Entanglement of dark electron-nuclear spin defects in diamond.

A promising approach for multi-qubit quantum registers is to use optically addressable spins to control multiple dark electron-spin defects in the environment. While recent experiments have observed signatures of coherent interactions with such dark spins, it is an open challenge to realize the individual control required for quantum information processing. Here, we demonstrate the heralded initialisation, control and entanglement of individual dark spins associated to multiple P1 centers, which are part of a spin bath surrounding a nitrogen-vacancy center in diamond. We realize projective measurements to prepare the multiple degrees of freedom of P1 centers-their Jahn-Teller axis, nuclear spin and charge state-and exploit these to selectively access multiple P1s in the bath. We develop control and single-shot readout of the nuclear and electron spin, and use this to demonstrate an entangled state of two P1 centers. These results provide a proof-of-principle towards using dark electron-nuclear spin defects as qubits for quantum sensing, computation and networks.

Atomic-scale imaging of a 27-nuclear-spin cluster using a quantum sensor.

Nuclear magnetic resonance (NMR) is a powerful method for determining the structure of molecules and proteins1. Whereas conventional NMR requires averaging over large ensembles, recent progress with single-spin quantum sensors2-9 has created the prospect of magnetic imaging of individual molecules10-13. As an initial step towards this goal, isolated nuclear spins and spin pairs have been mapped14-21. However, large clusters of interacting spins-such as those found in molecules-result in highly complex spectra. Imaging these complex systems is challenging because it requires high spectral resolution and efficient spatial reconstruction with sub-ångström precision. Here we realize such atomic-scale imaging using a single nitrogen vacancy centre as a quantum sensor, and demonstrate it on a model system of 27 coupled 13C nuclear spins in diamond. We present a multidimensional spectroscopy method that isolates individual nuclear-nuclear spin interactions with high spectral resolution (less than 80 millihertz) and high accuracy (2 millihertz). We show that these interactions encode the composition and inter-connectivity of the cluster, and develop methods to extract the three-dimensional structure of the cluster with sub-ångström resolution. Our results demonstrate a key capability towards magnetic imaging of individual molecules and other complex spin systems9-13.

The influence of age, gender and race/ethnicity on the composition of the human axillary microbiome.

OBJECTIVE: The microbial community plays an important role in the generation of human axillary odour by transforming odourless natural secretions into volatile odorous molecules. A limited number of traditional culturing methods and molecular based research have been performed to characterize the human axillary microbiome in small collection sample sizes. Moreover, only a few have considered the interpersonal variations across age, gender or race/ethnicity, and none have included all three variables within one single study. The aim of this study was to characterize the axillary microbiome of healthy subjects across different age groups, genders and races/ethnicities in a large sample size. METHODS: The underarm skin swab samples were collected from 169 healthy subjects. The axillary microbiome was analysed by IS-pro, a clinically validated high-throughput DNA fingerprinting technique. RESULTS: The results indicate that the senior subjects (55+) tend to have a higher number of total bacterial than younger adults (of a defined age). The diversity of odour causing bacteria, e.g. corynebacteria, increases with age. Among the three races/ethnicities studied, East Asians have a unique microbial composition compared to Caucasians and Hispanics, which may contribute to the different odour profiles observed among the races/ethnicities studied. CONCLUSION: Human axillary microbiome varies by age, gender and race/ethnicity. This study has provided an unprecedented fundamental knowledge about the axillary microbiota as a function of age, gender and race/ethnicity.

OBJECTIF: La population microbienne joue un rôle important dans la génération de l'odeur axillaire par la transformation de sécrétions naturelles inodores en molécules odorantes et volatiles. Un nombre limité d'études par culture traditionnelle et de recherches moléculaires ont été réalisées pour caractériser le microbiome axillaire humain dans des échantillons de prélèvements de petite taille. En outre, seules quelques-unes de ces études ont tenu compte des variations interpersonnelles à travers l'âge, le sexe ou la race/l'origine ethnique, et aucune n'a inclus les trois variables dans une seule et même recherche. Le but de cette étude est de caractériser le microbiome de sujets sains est de réunir différents groupes d'âge, sexes et races/origines ethniques dans un échantillon important. MÉTHODES: Les échantillons de frottis cutanés de l'aisselle ont été recueillis sur 169 sujets sains. Le microbiome axillaire a été analysé par ISpro, une technique cliniquement validée d'empreinte ADN à haut débit. RÉSULTATS: Les résultats indiquent que les sujets séniors (55 ans et plus) ont tendance à présenter un plus grand nombre de bactéries que les adultes plus jeunes (d'un âge défini). La diversité des bactéries odorantes, par exemple, de type corynebacterium, augmente avec l'âge. Parmi les trois races/origines ethniques étudiées, les populations asiatiques présentent une composition microbienne unique par rapport aux populations caucasiennes et hispaniques, ce qui pourrait contribuer aux différents profils d'odeur observés dans les races/origines ethniques prises en compte. CONCLUSION: Le microbiome axillaire varie selon l'âge, le sexe et la race/l'origine ethnique. Cette étude fournit une connaissance fondamentale sans précédent sur la flore axillaire en fonction de l'âge, du sexe et de la race/l'origine ethnique.

[Awake ECMO therapy in airway stenosis. Bronchoscopic treatment using laser resection]. / Wach-ECMO-Therapie bei Atemwegsstenose. Bronchoskopische Behandlung mithilfe der Laserresektion.

This article presents the case of a 62-year-old patient with cancer in the left upper pulmonary lobe who underwent lobe resection with postoperative respiratory insufficiency. The right upper lobe had already been resected 5 years earlier because of an adenocarcinoma. Prior to the present surgery a computed tomography scan detected a narrow stenosis at the former resection site; however, both pulmonary lobes beyond this stenosis appeared to be sufficiently ventilated. After resection of the left upper lobe attempted extubation was unsuccessful due to insufficient global gas exchange as the stenosis prevented ventilation of the right lung. Bronchoscopy provided evidence of a normal diameter of the bronchus behind the stenosis so both lobes were to be recruited after possible correction of this section. A veno-venous extracorporeal membrane oxygenation device (ECMO) was established as bridging therapy to attain normal gas exchange. As the patient showed no muscle weakness and was cooperative, extubation was performed and spontaneous breathing occurred without any support while still under ECMO treatment. The stenosis was reduced by bronchoscopic laser resection within seven consecutive sessions. Each of these surgeries was conducted with the patient under general anesthesia with oral intubation and jet ventilation in combination with the ECMO. The patient was extubated after each treatment session and weaned from ECMO after the final resection within 2 days. This case demonstrates the use of ECMO in combination with surgical procedures in a spontaneously breathing patient as a causal therapy and option for selected patients to prevent complications from long-term ventilation.

Opposite effect of fluticasone and salmeterol on fibronectin and tenascin-C expression in primary human lung fibroblasts.

BACKGROUND: Airway remodelling is a key feature of asthma and chronic obstructive pulmonary disease (COPD). The remodelling process involves the deposition of extracellular matrix (ECM) proteins within the airways. Current therapies for asthma and COPD consist of inhaled corticosteroids and long-acting beta(2)-agonists (LABA). However, their effect on airway remodelling is not well understood so far. OBJECTIVE: In this study we investigated the effect of fluticasone and salmeterol, either alone or in combination, on fibronectin and tenascin-C protein, isoform, and mRNA levels in primary human lung fibroblasts. METHODS: In our model, fibroblasts cultured in serum-free medium represented a non-inflammatory condition and stimulation with 5% fetal calf serum and/or TGF-beta(1) mimicked a pro-fibrotic environment with activation of tissue repair. Using these two different conditions, the effects of fluticasone and salmeterol on fibronectin and tenascin-C protein and mRNA levels were analysed by immunoblotting and semi-quantitative RT-PCR. RESULTS: In both conditions, fluticasone increased fibronectin transcript and protein levels, whereas it decreased those of tenascin-C. Salmeterol neither affected fibronectin and tenascin-C synthesis significantly nor did it influence the effect of fluticasone when applied in combination. Furthermore, we found that treatment with fluticasone had an opposite effect on extra domain A and B containing fibronectin isoforms generated by alternative splicing compared with total fibronectin transcript levels, whereas tenascin-C isoforms were not differently modulated by fluticasone. CONCLUSIONS: Our results indicate that standard therapies for inflammatory lung disorders influence ECM protein composition and relative expression levels. In contrast to corticosteroids, LABA did not significantly alter the expression of tenascin-C and fibronectin in cultures of primary human lung fibroblasts.

[Bronchioloalveolar carcinoma of the lung associated with a highly positive pANCA-titer and clinical signs of microscopic polyangiitis]. / Bronchioloalveoläres Karzinom der Lunge assoziiert mit einem hochpositiven pANCA-Titer und dem klinischen Bild einer mikroskopischen Polyangiitis.

Autoimmune paraneoplastic processes are investigated in detail concerning the Lambert-Eaton-Myasthenic-Syndrome for bronchial carcinomas. For the cutaneous leukocytoclastic vasculitis as a non-ANCA-associated vasculitis the paraneoplastic genesis is described. Litttle is known about ANCA-associated vasculitis as a paraneoplastic autoimmune phenomenon. We present the case of a 62 year old woman referred to our hospital presenting air-space shadows mainly in both upper lobes, skin rash with petechial bleeding and a highly positive pANCA-titer. A bronchioloalveolar carcinoma was diagnosed by surgical biopsy. The patient developed renal failure postsurgically and died a few weeks after the diagnosis was established. This is the 5 (th) case in literature of the temporal concurrence of a bronchial carcinoma and an ANCA-associated vasculitis. So far only 24 cases of a solid tumor occuring simultaneously with an ANCA-positive vasculitis are reported in literature.

Sequential therapy with azelastine in seasonal allergic rhinitis. Deutsche Rhinitis Studiengruppe (German Rhinitis Study Group).

A sequential therapy treatment with azelastine (Allergodil) in seasonal allergic rhinitis is introduced. In the critical early stage, treatment begins with a combination of azelastine tablets (azelastine hydrochloride, CAS 79307-93-0) and azelastine nasal spray (azelastine, CAS 58581-89-8), and after five days only the nasal spray is administered. This sequential therapy model aims at achieving the quickest and most complete effect without reducing the tolerability. The investigation was carried out as a randomized, controlled double-blind phase IV study of parallel group design with 300 patients during 14 days. In the first five days, one group was given one puff (0.14 mg) of azelastine nasal spray twice daily and one 2 mg tablet of azelastine at night. The other group received nasal spray and a placebo tablet. Beginning on day six, both groups received nasal spray only. Both treatments proved to be effective; the combination therapy, however, was significantly more effective beginning as early as the first treatment. The superiority of the combination therapy increased until day five. Thereafter, the two curves grew closer together; however, the superiority of the combination treatment remained. The tolerability of both treatments was similar.

The use of a shotgun for euthanasia of stranded cetaceans.

A 12-gauge shotgun, loaded with either a solid 28 g lead slug or buckshot consisting of nine individual lead pellets with a total mass of 28 g, was used to shoot the heads of one dead common dolphin (Delphinus delphis) and five dead long-finned pilot whales (Globicephala melaena) varying in length from 2.5 m to 5 m. The dolphin and the smallest pilot whale were shot with both projectiles from the dorsal surface of the head. The projectiles penetrated the head and dorsal surface of the skull, but not the base of the cranium. This site using buckshot was not effective in the larger animals. Two whales between 3 and 4 m in length were shot with buckshot through the lateral side of the head caudal to and above the eye, without penetration of the contralateral side of the head. It is concluded that shooting smaller cetaceans with a shotgun can be effective and safe. Further work is required to develop more suitable projectiles for cetaceans up to the size of mature pilot whales.

Pharmacokinetics of a sulphamethoxazole/trimethoprim formulation in pigs after intravenous administration.

Plasma disposition, metabolism, protein binding and renal clearance of sulphamethoxazole (SMZ) and trimethoprim (TMP) were studied in four pigs after intravenous administration at a dose of 40 and 8 mg/kg, respectively. SMZ and TMP were quickly eliminated (mean elimination half-lives: 2.7 and 2.4 h, respectively). SMZ was predominantly acetylated; no hydroxy and glucuronide derivates could be detected in plasma and urine. TMP was 0-demethylated into 4-hydroxytrimethoprim (M1) and 3-hydroxytrimethoprim (M4) metabolite and subsequently extensively glucuronidated. SMZ, TMP and its M1 metabolite were excreted predominantly by glomerular filtration, while N4-acetylsulphamethoxazole and glucuronide conjugates of the M1 and M4 metabolites of TMP were actively eliminated by tubular secretion. The proportional drug percentage being present in the urine as parent compound was 13.1% for TMP and 16.0% for SMZ. The glucuronide conjugates of the M1 and M4 metabolites formed the main part (81.5%) of urinary TMP excretion pattern.

Pharmacokinetics of sulphadimidine in carp (Cyprinus carpio L.) and rainbow trout (Salmo gairdneri Richardson) acclimated at two different temperature levels.

The influence of temperature (10 degrees C and 20 degrees C) on pharmacokinetics and metabolism of sulphadimidine (SDM) in carp and trout was studied. At 20 degrees C a significantly lower level of distribution (Vdarea) and a significantly shorter elimination half-life (T(1/2)beta) was achieved in both species compared to the 10 degrees C level. In carp the body clearance parameter (ClB(SDM)) was significantly higher at 20 degrees C compared to the value at 10 degrees C, whereas for trout this parameter was in the same order of magnitude for both temperatures. N4-acetylsulphadimidine (N4-SDM) was the main metabolite of SDM in both species at the two temperature levels. The relative N4-SDM plasma percentage in carp was significantly higher at 20 degrees C than at 10 degrees C, whereas there was in trout no significant difference. In neither species was the peak plasma concentration of N4-SDM (Cmax(N4-SDM)) significantly different at two temperatures. The corresponding peak time of this metabolite (Tmax(N4-SDM)) was significantly shorter at 20 degrees C compared to 10 degrees C in both carp and trout. In carp at both temperatures, acetylation occurs to a greater extent than hydroxylation. Only the 6-hydroxymethyl-metabolite (SCH2OH) was detected in carp, at a significant different level at the two temperatures. Concentrations of hydroxy metabolites in trout were at the detection level of the HPLC-method (0.02-micrograms/ml). The glucuronide metabolite (SOH-gluc.) was not detected in either species at the two temperatures.

Pharmacokinetics of sulphamethoxazole in calves and cows.

The kinetics of sulphamethoxazole (SMZ) in plasma and milk, and its metabolism, protein binding and renal clearance were studied in three newborn calves and two dairy cows after intravenous administration. SMZ was predominantly acetylated; no hydroxy and glucuronide derivatives could be detected in plasma and urine. Age-dependent pharmacokinetics and metabolism of SMZ were observed. The plasma concentration-time curves of the N4-acetyl metabolite in the elimination phase were parallel to those of the parent drug; the N4-acetyl metabolite plasma percentage depended on age and ranged between 100% (new-born) to 24.5% (cow). SMZ was rapidly eliminated (elimination half-lives: 2.0-4.7 h) and exhibited a relatively small distribution volume (VDarea: 0.44-0.57 l/kg). SMZ was excreted predominantly by glomerular filtration, while its N4-acetyl metabolite was actively eliminated by tubular secretion.

Thrombocytosis associated with a myeloproliferative disorder in a dog.

A dog with a myeloproliferative disorder and thrombocytosis had clinical signs that were consistent with a diagnosis of essential thrombocythemia. The dog was treated with aspirin, radioactive phosphorus, and melphalan. Eighteen months after referral, the disorder progressed to chronic granulocytic leukemia, and treatment was switched to hydroxyurea. Fourteen months later, the dog was euthanatized because of uncontrollable atrial fibrillation.

Pharmacokinetics and renal clearance of sulphadimidine, sulphamerazine and sulphadiazine and their N4-acetyl and hydroxy metabolites in pigs.

The effect of molecular structure on the drug disposition and protein binding in plasma, the urinary recovery, and the renal clearance of sulphamerazine (SMR), sulphadiazine (SDZ), and sulphadimidine (SDM) and their N4-acetyl and hydroxy derivatives were studied in pigs. Following IV administration of SDM, SMR and SDZ, their mean elimination half-lives were 12.4 h, 4.3 h and 4.9 h respectively. The plasma concentrations of parent sulphonamide were higher than those of the metabolites, and ran parallel. The acetylated derivatives were the main metabolites; traces of 6-hydroxymethylsulphamerazine and 4-hydroxysulphadiazine were detected in plasma. The urine recovery data showed that in pigs acetylation is the major elimination pathway of SDM, SMR and SDZ; hydroxylation became more important in case of SMR (6-hydroxymethyl and 4-hydroxy derivatives) and SDZ (4-hydroxy derivatives) than in SDM. In pigs methyl substitution of the pyrimidine side chain decreased the renal clearance of the parent drug and made the parent compound less accessible for hydroxylation. Acetylation and hydroxylation speeded up drug elimination, because their renal clearance values were higher than those of the parent drug.

Pharmacokinetics and metabolism of sulphadimidine in kids at 12 and 18 weeks of age.

The pharmacokinetics and metabolism of sulphadimidine (SDM) following intravenous administration of 100 mg/kg were studied in seven dwarf preruminant kids at 12 weeks of age, and again at the ruminant stage, when the animals were 18 weeks old. The persistence of SDM in 18-week-old kids was prolonged in comparison to the 12-week-old animals: a lower total body clearance and a prolonged elimination of SDM were obtained in the older animals. The renal clearance values of SDM and its metabolites were the same at both ages. The decrease of SDM clearance is related to the significant reduction in SDM hydroxylation at the older age. The reduced oxidative hepatic metabolism may result from the sexual maturation of the kids.

Pharmacokinetics, metabolism and renal clearance of sulphatroxazole in calves and cows.

The pharmacokinetic analysis of plasma concentration--time curves after a single i.v. dose of 20 mg/kg sulphatroxazole (STZ) to calves and cows revealed a small distribution volume of STZ (mean VD(area) = 0.22-0.26 l/kg) and an age dependent elimination (mean t1/2 6.6-18.8 h). In calves and cows, STZ was extensively metabolized into the N4-acetyl and 5-hydroxy derivatives. In the plasma of calves, the N4-acetyl metabolite (N4-STZ) was present in greater amounts than the hydroxy metabolite (5-OH-STZ), while in cows' plasma concentration of these two metabolites were similar. In the milk of dairy cows STZ concentrations paralleled those of the metabolites and were approximately 21 times lower than corresponding plasma concentrations. The mean plasma protein binding of STZ and its metabolites ranged from 36.4 to 82.5% of total concentration. The N4-STZ derivative was excreted by tubular secretion; the 5-OH-STZ and the parent compound, mainly by glomerular filtration. In calves the majority of STZ administered was excreted as N4-STZ (40-52%), while in cows the parent drug dominated the urinary excretion (36%).

A lower size limit exists for export of fragments of an outer membrane protein (OmpA) of Escherichia coli K-12.

The ompA gene codes for a 346 residue precursor of a 325 residue protein of the outer membrane of Escherichia coli K-12. Internally and/or COOH-terminally deleted genes were constructed that encode 123, 116, 88, 72 or 68 residue precursors. The former three were processed and localized to the periplasmic space; the latter two were not processed and remained cytosolic. These data suggest that the signal sequence has to interact with a component of the export apparatus (the Sec pathway) before translation is finished. Comparison of these results with others obtained for prokaryotic and eukaryotic systems shows that: (1) a very similar lower size limit exists for membrane translocation of the 147 residue chicken prelysozyme or the 229 residue bovine preprolactin; (2) precursors smaller than those reported here can be translocated in both systems; (3) the latter translocation, in contrast to, for example, the ompA gene products, does not depend on the cellular export machinery but most likely requires folding of the precursors into an export-competent conformation. In general, at least two quite different, not necessarily mutually exclusive, mechanisms for translocation of a protein across or assembly into a membrane appear to exist.

Pharmacokinetics, metabolism, and renal clearance of sulfadiazine, sulfamerazine, and sulfamethazine and of their N4-acetyl and hydroxy metabolites in calves and cows.

The effect of molecular structure on the drug disposition and protein binding in plasma and milk, the urinary recovery, and the renal clearance of sulfadiazine, sulfamerazine, and sulfamethazine and of their N4-acetyl and hydroxy derivatives were studied in calves and cows. Sulfadiazine was highly acetylated and was slightly hydroxylated. Sulfamerazine and sulfamethazine were hydroxylated predominantly at the methyl group of the pyrimidine side chain; hydroxylation of the pyrimidine ring itself was more extensive for sulfamethazine than for sulfamerazine. At dosages between 100 and 200 mg/kg of body weight, sulfamethazine had a capacity-limited elimination pattern, which was not observed for sulfadiazine or sulfamerazine. The concentrations of the parent sulfonamide and its metabolites in plasma and milk were parallel, the latter being lower. Metabolite concentrations in milk were at least 8 times lower than those of the parent drug. Metabolism speeds drug elimination, producing compounds with renal clearance values higher than those of the parent drug. The effect on the metabolism and renal clearance of methyl substitution in the pyrimidine side chain is discussed.