Efficacy of alternative fidaxomicin dosing regimens for treatment of simulated Clostridium difficile infection in an in vitro human gut model.

BACKGROUND: Fidaxomicin treatment reduces the risk of recurrent Clostridium difficile infection (CDI) compared with vancomycin. Extending duration of fidaxomicin therapy may further reduce recurrence. We compared the efficacy of four extended fidaxomicin regimens in an in vitro model of CDI. METHODS: Four gut models were primed with human faeces, spiked with C. difficile spores (PCR ribotype 027) and clindamycin instilled (33.9 mg/L, four-times daily, 7 days) to induce simulated CDI. Four extended fidaxomicin treatment regimens were evaluated: model 1, 20 days, 200 mg/L twice daily; model 2, 5 days 200 mg/L twice daily, 5 days rest, 5 days 200 mg/L twice daily; model 3, 5 days 200 mg/L twice daily, 5 days rest, 10 days 200 mg/L once daily; and model 4, 5 days 200 mg/L twice daily, 20 days 200 mg/L once every other day. C. difficile populations, toxin, gut microbiota and antimicrobial levels were monitored daily. RESULTS: All fidaxomicin regimens successfully resolved simulated CDI without recurrence. Five days of fidaxomicin instillation was barely sufficient to resolve CDI (models 2-4). A second pulse or tapered dosing further reduced C. difficile and toxin detection. All regimens were sparing of microbiota, affecting only enterococci and bifidobacteria. Pulsed or tapered regimens allowed greater bifidobacteria recovery than the extended (20 day) regimen. Bioactive fidaxomicin persisted throughout the experiment in all models at concentrations inhibitory to C. difficile. CONCLUSIONS: Pulsed or tapered fidaxomicin regimens may enhance suppression of C. difficile whilst allowing microbiota recovery; clinical studies are required to ascertain the potential of this approach in further reducing recurrent CDI.

Optimal timing and technique for endoscopic management of dysphagia in pediatric aerodigestive patients.

INTRODUCTION: The best strategy to manage an interarytenoid defect [Type 1 laryngeal cleft (LC-1) or deep interarytenoid groove (DIG)] in pediatric aerodigestive patients with dysphagia remains uncertain. This study compared benefit of interarytenoid augmentation (IAA) to suture repair or clinical observation alone in pediatric patients. METHODS: A 3-year retrospective, single-center analysis of children with dysphagia undergoing endoscopic airway evaluation was performed. Physician preference guided treatment plan: suture repair with CO2 laser, IAA (carboxy methylcellulose or calcium hydroxyapatite), or observation. Primary outcome was improved post-operative diet. Significance was assumed at p < 0.05. RESULTS: 449 patients underwent diagnostic endoscopy. Mean age (±SD) at procedure was 21 ± 13 months, with nearly one fourth (28 %) of children ≤ 12 months. Eighty (18 %) had either an LC-1 (n = 55) or DIG (n = 25). Of these, 35 (42 %) underwent suture repair, 22 (28 %) IAA, and 23 (30 %) observation only. Aspiration improved overall in the interventional groups compared to observational controls (58 % vs. 9 %, p < 0.05), with no change in benefit observed by age of intervention. IAA was as effective as suture repair (59 % vs 55 %, p = 0.46). In patients with only a DIG, IAA intervention alone significantly improved swallow function (66.6 % vs. 0 %, p < 0.05). CONCLUSION: In pediatric aerodigestive patients with dysphagia, 18 % of children have an addressable lesion. IAA or suture repair similarly improves dietary advancement. IAA improves swallow function in patients with DIG. These findings support a novel protocol to intervene in dysphagia patients with LC-1 or DIG via IAA at the initial operative evaluation.

Risk of complications and mortality following recurrent and non-recurrent Clostridioides difficile infection: a retrospective observational database study in England.

BACKGROUND: Clostridioides difficile infection (CDI) increases the risk of complications and mortality. We assessed the magnitude of these outcomes in a large cohort of English patients with initial and recurrent CDI. AIM: To compare the risk of complications and all-cause mortality, within 12 months, among hospitalized patients ≥18 years old with hospital-associated- (HA-) CDI and recurrent CDI. METHODS: Patients with HA-CDI during 2002-2013 were identified using inpatient hospital data linked to primary care and death data. Each HA-CDI case was frequency matched to two hospitalized patients without CDI on age group, sex, calendar year of admission, admission method and number of hospital care episodes. A second CDI episode starting on days 13-56 was defined as recurrence. Risks of mortality and complications at 12 months were analysed using Cox proportional hazard models. FINDINGS: We included 6862 patients with HA-CDI and 13,724 without CDI. Median age was 81.0 years (IQR 71.0-87.0). Patients with HA-CDI had more comorbidities than those without CDI, and significantly higher risks of mortality (adjusted hazard ratio (95% confidence interval) 1.77 (1.67-1.87)) and complications (1.66 (1.46-1.88)) within 12 months from hospital admission. Of those with HA-CDI, 1140 (16.6%) experienced CDI recurrence. Patients with recurrent versus non-recurrent CDI also had significantly increased risk of mortality (1.32 (1.20-1.45)) and complications (1.37 (1.01-1.84)) in the 12 months from the initial CDI. CONCLUSIONS: HA-CDI (versus no CDI) and recurrent CDI are both associated with significantly higher risks of complications or death within 12 months of the initial CDI episode.

The role of motivation in the performance of conditioned reflex switching of a maze skill in response to substitution of food reward quality in ants of the species Myrmica rubra.

The characteristics of learning in ants - active Myrmica rubra foragers - were studied in a maze at different levels of colony carbohydrate food need with reinforcement consisting of carbohydrate (sugar syrup) or protein (pupae of Lasius niger ants). Measures of the maze skill during learning reinforced with syrup were somewhat worse than those during learning reinforced with pupae, especially in terms of time-based measures. Ants were able to modify the acquired conditioned reflex reaction when the quality of reinforcement changed. At high levels of food need (" hungry" colony), substitution of syrup with larvae and vice versa was followed by transformation of the previously formed skill; this occurred at both experimental periods (training and testing). At low levels of motivation ("sated colony"), the optimized maze habit formed with protein reinforcement was replaced in the test with carbohydrate reinforcement by a "stochastic," unoptimized behavior with a dominance of investigative activity. These experiments demonstrated that conditioned reflex switching can occur in higher social insects - ants - in which the different forms depend on the level of colony need for food and, respectively, on the level of social food-related motivation of forager ants. The special importance of using the switch activating the corresponding motivational system before changing the reinforcement food quality is emphasized.

[The role of motivation in the performance of a conditioned switching-over of the maze habit in ants Myrmica rubra after a change in the quality of the food reinforcement].

Active foragers Myrmica rubra were trained in a maze under conditions of different levels of colony need in food with carbohydrate (sugar syrup) or protein (ants Lasius niger pupae) reinforcement. Acquisition of the maze habit was better under conditions of reinforcement with pupae, especially by its time indices. Ants were able to modify the acquired habit when the reinforcement quality was changed. It was shown that learning was possible only when the colony and after a change pupae for the syrup was "hungry". Under these conditions, after a change of the syrup for pupae or visa versa the previously acquired optimum habit was transferred. Several hours later, with satiation of the colony, food reactions learned with protein reinforcement switched-over to "stochastic" non-optimized behavior with the dominance of exploratory reactions. Thus, it was shown that higher social insects ants were capable for conditioned switching-over. Different forms of this phenomenon depended on the level of the colony need in food and, consequently, on the level of the social food motivation of foragers ants.

Pulmonary aspergillosis: an analysis of 41 patients.

During the period 1969 to 1974, 41 patients having cultures positive for aspergillus were seen on the thoracic surgical services of the University of Maryland and Mt. Wilson State Hospitals. Intracavitary mycetoma was present in 36 patients. In 32 the underlying disease was chronic cavitary tuberculosis, 5 had decreased immunity due to other diseases, and in 3 no underlying disease was noted. One final patient developed a mycetoma following repair of tetralogy of Fallot. Hemoptysis, the predominant symptom, occurred in 23 patients, all of whom were from the group with intracavitary mycetoma. Hemoptysis was life-threatening in 8 patients, severe but not life-threatening in 12, and minimal in 3. Fifteen patients underwent pulmonary resection with 2 deaths. Both patients who died had undergone emergency resection for life-threatening hemoptysis; the fungus ball had developed following a previous resection for tuberculosis, and both had poor pulmonary reserve. Of 10 patients with hemoptysis who were not treated surgically, chiefly because they were poor operative risks, 4 died. This study suggests that pulmonary aspergillosis, particularly of the intracavitary type, is a potentially life-threatening disease. Because of the suddenness with which massive hemoptysis may occur, pulmonary resection is recommended for all patients with intracavitary mycetoma who do not constitute prohibitive operative risks.

An outbreak of Shiga bacillus dysentery in KwaZulu/Natal, South Africa.

An outbreak of Shiga bacillus (Shigella dysenteriae type 1) infection has been detected for the first time in South Africa. Forty-eight cases of this epidemic that presented to a referral hospital were clinically evaluated. Patients presented with dysentery from all age groups and 16 (33%) were admitted to hospital. There were two geographical regions where 32 (67%) of the patients resided. The isolates were demonstrated to be pathogenic by in vitro testing for invasion and toxin production, and were found to be resistant to first line antibiotics that have been used for the treatment of shigellosis i.e. ampicillin, cotrimoxazole, tetracycline and chloramphenicol. However, they were susceptible to nalidixic acid, ceftriaxone and ciprofloxacin. Urgent, public health measures are needed to prevent further spread of this epidemic.

Intravenous lidocaine and small-intestinal size, abdominal fluid, and outcome after colic surgery in horses.

Twenty-eight horses with the diagnosis of an intestinal disorder requiring surgical intervention were randomly assigned to lidocaine (n = 13) or saline (control, n = 15) treatment groups. After induction of anesthesia, treated horses received a loading dose of 2% lidocaine (0.65 mg/kg) intravenously, followed by a continuous rate of infusion of 1% lidocaine (0.025 mg/kg/min) until the discontinuation of anesthesia. Upon recovery from anesthesia, a 2nd loading dose of 2% lidocaine (1.3 mg/kg) was administered, followed by an infusion of 1% lidocaine (0.05 mg/kg/min) for 24 hours postoperatively. The control group received equivalent volumes of saline. Lidocaine-treated horses had significantly better minimum jejunal cross-sectional area scores (P = .011), minimum jejunal diameter scores (P = .002), and intestinal ultrasound index (IUI) (P = .007). Peritoneal fluid was detected by percutaneous ultrasound examination in 8 of the 15 control animals but in none of the treated animals (P = .003). Failure to obtain fluid via abdominocentesis was significantly more frequent for lidocaine-treated horses (P = .025). No significant differences between the groups were found in the presence of gastrointestinal sounds, time to passage of 1st feces, number of defecations in the 1st 24 hours, presence of gastric reflux, duodenal or jejunal wall thickness, maximum duodenal or jejunal diameter or cross-sectional area, minimum duodenal diameter or cross-sectional area, duodenal and jejunal intraluminal echogenicity, small-intestinal contractions per minute, rate of complications, or outcome. On the basis of this study, lidocaine infusion may have some desirable effects on jejunal distension and peritoneal fluid accumulation and was well tolerated perioperatively in horses with colic. The low incidence of small-intestinal lesions and gastric reflux in the study makes it difficult to assess the use of lidocaine in the prevention of postoperative ileus (POI).

The behavior of ants in a maze in response to a change from food motivation to protective motivation.

The ability of Myrmica rubra scout ants to modify the foraging habit, formed in a symmetrical multiple-choice maze, in the situation in which the reinforcement (syrup) was replaced with a brood of the same species was studied. When the "test" was performed at the same high level of food motivation of the family as applied during training, the ants were able successfully to transfer to another type of social behavior - transporting of the brood. When the high-level food motivation was replaced with a low-level motivation, some of the ants were unable to modify the habit. Preliminary utilization in these conditions of reinforcement as a switching factor addressing the motivational system for protective behavior promoted successful performance of the "test." Criteria allowing identification of different methods of modifying behavior during the switch from food motivation to protective motivation were developed. A total of 37.5% of the ants transferred the strategy formed during training: 40.6% showed gradual remodeling. while 21.9% of individuals immediately used the new strategy.

Sedation and chemical restraint in the dog and cat.

Small animal patients must often undergo veterinary procedures that are painful or distressful, for which judicious use of sedatives or other agents with anesthetic or analgesic properties can be useful. If the degree of sedation is profound enough, such "chemical restraint" may be employed to provide immobilization for radiographs or minor surgical procedures. The choice of agents to be used will depend upon the physiologic state and cooperative nature of the patient and the desired endpoint, ie, anxiolysis versus deep sedation with analgesia. This report discusses important features of patient assessment, preparation, equipment needs, consideration of the types of procedures for which sedation is useful, and recovery considerations. A brief review is included of the useful effects and contraindications for the various agents employed, and doses for each are listed. Algorithms are presented for a given category of patient, leading the practitioner through a decision making strategy to arrive at examples of sedation or chemical restraint protocols that are commonly found to be effective by the author.

Sedation and anesthesia of pet rabbits.

Pet rabbits frequently become stressed when handled and may require sedation or chemical immobilization for procedures such as blood collection, IV catheter placement, radiography, deep ear cleaning, and dentistry. Common surgical procedures requiring general anesthesia include spay, castration, gastrotomy, cystotomy, and orthopedic procedures. Rabbits may be difficult to safely sedate or anesthetize. Individual rabbits may have varying sensitivity to the depressant effects of anesthetics. The apparent sensitivity of the rabbit's respiratory center to anesthetic drugs and the narrow range between anesthetic and toxic doses in this species add to the unpredictable character of rabbit anesthesia. Furthermore, mortality following anesthesia and surgery in sick rabbits is common. Strategically, safe anesthesia of rabbits must include the planning of procedures so that anesthetic time is minimized. Clinicians must be on guard for individual variation in response to drugs. Minimizing the use of cardiovascular depressant agents, use of agents with a high therapeutic index, and careful titration of doses to effect, along with thorough cardiorespiratory monitoring, will permit attainment of appropriate anesthetic depth with the widest margin of safety. This article presents several injectable and inhalant anesthetic protocols that may assist in effective management of many types of rabbit patient.

[Asymmetry of movement direction of Myrmica rubra ants during maze learning motivated by food]. / Asimmetriia napravleniia dvizheniia u murav'ev Myrmica rubra pri obuchenii v labirinte v usloviiakh pishchevoi motivatsii.

Asymmetry in direction of motion was found in Myrmica rubra ants at their learning in a symmetrical multi-alternative maze in conditions of "social" alimentary motivation. It was manifested in the form of preferable stay in the right half of the maze and was significant by several parameters: total number of motions, approaches to "false" spots and right turns. Unequal degrees of spatial-motor asymmetry (individual and for the whole sample) was revealed by various parameters. Most clearly the right-sided spatial preference was seen in the insects which had more approaches to goal with reinforcement taking than "exploratory" approaches. It is suggested that the parameters of motion direction asymmetry in ants learning in the maze depend on the level of alimentary "social" motivation.

[Ant maze behavior during switch from food motivation to defense motivation]. / Povedenie murav'ev v labirinte pri smene pishchevoi motivatsii na zashchitnuiu.

It was shown that scout ants Myrmica rubra are capable for an adequate modification of foraging habit acquired in a multichoice symmetrical maze following a reward change (syrup for the species brood). Under conditions of the high level of food motivation of a family both during learning and "examination" (i.e., brood transportation) all the ants succeed in a conditioned switchover of heterogeneous reflexes. If the high level of motivation during learnings is changed for its low level during examination, some ant do not realize the new task. The unconditioned switch (preliminary 1-3 brood takes at the start ares) facilitates the successful performance. In different experimental sessions a certain ratio was revealed between the ants realizing different ways of correct decision making. Specially developed criteria made it possible to identify different individual types of behavior during examination: transfer of acquired strategy, its gradual adaptation, and fast switchover to the new strategy. The adequate maze method and learning on the basis of specific forms of social behavior of ants (foraging, brood transportation, and exploratory activity) promote the rapid and efficient acquisition of the habit and its modification.

[The behavioral strategy of ants with a change in the level of food motivation]. / Strategiia povedeniia murav'ev pri izmenenii urovnia pishchevoi motivatsii.

Learning of ants was studied in a symmetrical multi-choice maze at different levels of food "social" motivation. A capability was shown of scout ants Myrmica rubra for changing rapidly behavioral strategy when the motivation level of a family changed from the low one for the high or vice versa. In the satiated state the ants demonstrated a clear-cut research activity. This activity was associated with high variability and instability of the maze habit. In the "hungry" state movement trajectories were rapidly minimized, the majority of ants used one dominant scheme of moving. Initial level of motivation determined the peculiarities of and learning and ability to transform behavioral strategies.

[The asymmetry of movement direction in freshwater shrimp (Gammarus oceanicus) in the open-field test]. / Asimmetriia napravleniia dvizheniia u gammarusov (Gammarus oceanicus) v teste otkrytogo polia.

Behaviour of Gammarus oceanicus was studied in the open field test. For the whole except (n = 204) spatial-motor asymmetry was found. It was manifested in significantly greater number of movements clockwise (to the right) than counterclockwise (to the left). Animals with significant asymmetry dominated, forming 93.5% of the except. The asymmetry was characterized by distinct right-sided direction. Motor activity and spatial-motor asymmetry at repeated tests in the main weakened; the changes in "right" and "left" animals were manifested differently. The essential factor which disturbed the behaviour of the animals in the open field test (including the asymmetry of movement direction) proved to be a toxicant (oil pollution) action.

[The capacity of ants for multiple alterations in the maze habit]. / Sposobnost' murav'ev k mnozhestvennym peredelkam labirintnogo navyka.

Ability was shown of ants Myrmica rubra to multiple reconstructions of the habit elaborated in symmetrical multialternative maze under motivation of care for the progeny (transportation of breed of the own species). Reconstruction consisted in the change of reinforcement location on the left or right aim spot. The ants showed the ability to carry out the series of eight reconstructions during one-two days. An improvement took place of the fulfillment of the last reconstructions in comparison with the first ones. Peculiarities of learning and reconstructions were found in two groups of animals differing by conditions of learning: at reinforcement on both ain spors or on one of them. The results obtained are considered as indices of high plasticity of the behaviour of ants of the studied species.

[Plasticity of the behavior of Myrmica rubra ants during learning in a multi-alternative symmetric labyrinth]. / O plastichnosti povedeniia murav'ev Myrmica rubra pri obuchenii v mnogoal'ternativnom simmetrichnom labirinte.

The ability was studied of Myrmica rubra ants to change the habit of passing through a multialternative symmetric labyrinth at motivation of the care for posterity. In exams the location of reinforcement was changed: in the first exam the progeny was carried from both aim places to those symmetric to them relatively to labyrinth cross axis; in the second exam the reinforcement was left on one aim place non-preferred during learning. The first exam was passed by 62.5% of ants, the second--by 87.5%. In the first exam such parameters were worse as the first correct decision, the mean number of movements in the cycle, the total number of correct cycles. At elaboration of new motor habits and increase and inversion were observed of the initial spatial-motor asymmetry. Individual variations in ants behaviour increased. The ants who failed to solve the task, showed pronounced signs of preneurotic state. The obtained results testify to a high plasticity of ants behaviour and their ability to modify their activity according to changes of experimental situation.

[Late results of gamma-teletherapy for lung cancer]. / Otdalennye rezul'taty distantsionnoi gamma-terapii raka legkogo

As a result of distance gamma-therapy on Rocus-123 machine in patients with pulmonary cancer in stage II-IV, the survival for a year period and longer was noted in 57.5 +/- 4.5%, over 3 years--in 19.5 +/- 3.6%; over 5 years--in 7.2+/- 2.4%. An average life survival was 21.6 +/- 1.8%.

[Morphohistochemical and electron microscopic characteristics of malignant tumors of the upper respiratory tract after combined local hyperthermia and radiotherapy]. / Morfogistokhimicheskaia i élektronno-mikroskopicheskaia kharakteristika zlokachestvennykh opukholei verkhnikh dykhatel'nykh putei pri sochetanii lokal'noi gipertermii i luchevoi terapii.

The paper discusses morphohistochemical and electron microscopic characteristics of 15 primary tumors of the upper respiratory tract removed following preoperative irradiation in combination with local hyperthermia as a radio-modifying factor. Eighteen tumors removed after irradiation alone served as controls. Application of local microwave hyperthermia resulted in a higher degree of irreversible tumor cell dystrophia and damage. Hyperthermia--induced damage included disorders in ultrastructure of intracellular membranes and cell organelles mainly due to derangement of membrane--binding proteins, protein--lipid and nucleotide complexes. Thermoradiotherapy stimulated protective reaction of surrounding tissue which took the form of increase in fraction of leukocytes and macrophages with high acid phosphatase level in areas of tumor cell damage.