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Abstract: Changes in the gut microbiome have been increasingly shown to accompany oncogenesis across various tumors. Similarly, microbial dysbiosis was found to be associated with pancreatic cancer progression and survival outcomes, expanding the field of tumor microenvironment research in pancreatic cancer. Mechanistic studies in pancreatic cancer models implicate components of the gut and pancreatic cancer microbiome in regulating tumorigenesis by altering cancer cell signaling, modulating immune function, and influencing the efficacy of current therapies in pancreatic cancer. This review discusses the outcomes of microbial modulation across various preclinical and clinical studies and highlights ongoing trials targeting the microbiome for pancreatic cancer therapy., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Understanding the mechanisms involved in the development of asthma and allergic diseases is expanding, due in part to sequencing advances that have led to the identification of new viral strains such as human rhinovirus strain C (HRV-C) and the human microbiome project., Recent Findings: Recent studies have identified new ways in which viral and microbial exposures in early life interact with host genetic background/variants to modify the risk for developing asthma and allergic diseases. Recent research suggests that HRV-C is the main pathogenic agent associated with infant wheeze, hospitalizations and likely the subsequent development of asthma. Pulmonary He MRI suggests that HRV infection in early childhood and subsequent immune responses initiate airway remodeling. Numerous studies of the microbiome indicate that intestinal and airway microbiome diversity and composition contribute to the cause of asthma and allergic diseases., Summary: Susceptibility to asthma and allergic diseases is complex and involves genetic variants and environmental exposures (bacteria, viruses, smoking, and pet ownership), alteration of our microbiome and potentially large-scale manipulation of the environment over the past century.

Tazobactam is a new, irreversible inhibitor of bacterial beta-lactamases of staphylococci, plasmid-mediated beta-lactamases of the TEM and SHV types found in Escherichia coli and Klebsiella species and beta-lactamases of anerobes such as Bacteroides species. Its combination with piperacillin, a broad spectrum ureido-penicillin, would be expected to improve the activity of piperacillin against staphylococci, TEM and SHV beta-lactamase producing Gram negative bacteria and anerobes. Minimal inhibitory concentrations (MIC) of piperacillin/tazobactam were determined for 1952 individual patient isolates of Gram positive and negative bacteria causing significant infections and compared with MIC values for cefotaxime, ceftazidime, ciprofloxacin, imipenem, ticarcillin/clavulanic acid. MICs were determined by agar dilution (NCCLS 1990 and 1992). Piperacillin/tazobactam had excellent activity against methicillin susceptible staphylococci, Streptococcus pneumoniae, Haemophilus influenzae, enterococci and organisms of the Bacteroides fragilis group. It was also active against the majority of Enterobacteriaceae and Pseudomonas aeruginosa isolates tested. It was not active against extended spectrum beta-lactamase (ESBL) producing Klebsiella species and some high level TEM and SHV beta-lactamase producing E. coli and Klebsiella species. Activity against Gram negative organisms capable of producing chromosomally mediated beta-lactamases was good, since in most organisms tested, the enzymes were not induced in sufficient quantities to cause antibiotic resistance. However some Enterobacter species were derepressed hyperproducing mutants; these isolates showed resistance to piperacillin/tazobactam since tazobactam does not inhibit these Class I beta lactamases. Activity was superior to ticarcillin/clavulanic acid for Gram negative rods. Imipenem was the most active agent against ESBL producing Klebsiella species. Piperacillin/tazobactam has a suitable spectrum of activity in vitro to suggest its use in monotherapy of mixed anerobic infections, mixed respiratory infections such as aspiration pneumonia and, in combination with an aminoglycoside, it would provide Gram positive as well as Gram negative cover of febrile episodes in immunosuppressed patients.

Background: Intermittent self-administered nitrous oxide has long had widespread use as an analgesic in labor, but its efficacy has not been adequately established. Questions about its effect on maternal oxygenation between labor contractions also have been raised., Methods: Twenty-six women were recruited to participate in a randomized, double-blind, cross-over, placebo-controlled study to assess the effect of intermittent nitrous oxide inhalation on labor pain and maternal hemoglobin oxygen saturation (SPO2) during the first stage of labor. Visual analog scale pain scores for each of five consecutive labor contractions were measured after administration of either nitrous oxide or compressed air., Results: Mean visual analog scale pain scores for five contractions were 5.1, 5.2, 5.7, 5.2, and 5.6 (nitrous oxide) and 4.9, 5.2, 6.1, 5.6, and 5.7 (compressed air). There were no statistically significant differences in pain when nitrous oxide as compared with compressed air was administered. Pain scores did not differ significantly over time as a function of inhaled substance (F = 0.41, P = 0.53). The mean lowest SPO2 observed between these contractions after self-administration of nitrous oxide and air were 97, 97, 97, 97, and 97% (nitrous oxide) and 97, 96, 96, 96, and 96% (compressed air). SPO2 was significantly higher after nitrous oxide administration (F = 8.8, P = 0.007)., Conclusion: While intermittent self-administered 50% nitrous oxide in oxygen does not appear to predispose parturient women to hemoglobin oxygen desaturation, its analgesic effect has yet to be clearly demonstrated.

In April 1992 an outbreak of Legionnaires' disease occurred in south western Sydney. Twenty four patients were diagnosed as having Legionnaires' disease either on the basis of a positive culture of Legionella pneumophila serogroup I from a respiratory specimen (14 patients) or a four-fold or greater rise in antibody titre or isolated convalescent titre > 1024 with IgM antibodies present (10 patients). This is the largest outbreak in New South Wales since 44 cases of Legionnaires' disease were reported in Wollongong in 1987. Culture and direct immunofluorescent staining (DFA) were performed for early laboratory diagnosis. The DFA test and a set of defined clinical criteria were then used to classify patients as probable cases of Legionnaires' disease for subsequent Public Health investigations. The DFA test had a predictive value for a positive culture of 45.8% and for a negative culture of 97.1%. Its positive predictive value for a definite diagnosis of Legionnaires' disease (either positive culture or seroconversion), however, was 78.3% with a negative predictive valve of 95.1%. During a 27 day period DFA and culture for Legionella species were performed on 198 specimens from 127 patients. Cultures became positive after a mean of 5 days incubation (range 1-11 days). The use of both selective and non-selective media is recommended for optimal recovery of L. pneumophila since some isolates were obtained on only one culture plate. After an initial evaluation of heat decontamination of specimens this process was abandoned, since in 8/63 specimens so treated, L. pneumophila was recovered prior to but not following heat decontamination and was not grown only in heated specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Neisseria elongata subsp. nitroreducens (formerly CDC group M-6) is a newly-recognized cause of particularly destructive endocarditis, frequently requiring valve replacement. We describe an Australian case of endocarditis caused by this organism, summarizing the clinical and microbiological features of this rarely isolated subspecies.

Immediately following thoracotomy, 22 patients were entered into a randomized, double blind study comparing the effects of three lumbar epidural doses of sufentanil on postoperative pain and respiratory pattern. Patients were given either 30 micrograms (group I), 50 micrograms (group II), or 75 micrograms (group III) of epidural sufentanil in 20 ml N saline. Repeat doses were given on request for the 24-h study period. Linear analogue pain score (PS), heart rate (HR), and mean arterial pressure (MAP) were measured at 15-min intervals after each dose. Respiratory depression was assessed by the presence of: 1) slow respiratory rate (SRR--less than 10 breaths per minute for greater than 5 min), 2) apnea (AP--cessation of tidal ventilation for greater than 15 s), and 3) increased PaCO2 in arterial blood gases (ABG) drawn at regular intervals. SRR and AP were measured using respiratory inductive plethysmography (RIP). A further group of ten patients (group IV) underwent preoperative RIP monitoring during sleep and in the absence of any drug. Maximum analgesia was achieved within 15 min after a dose of sufentanil for all groups. Analgesia was not significantly prolonged by increasing the dose of sufentanil. SRR occurred in all four groups (group I: 2/9; group II: 2/6; group III: 7/7; group IV: 2/10 P less than 0.05 I, IV:II, I, IV:III, II:III). The number of episodes of SRR/hr was highest in group II (group I: 0.6 +/- 0.8, group II: 4.12 +/- 0.6, group III: 1.8 +/- 2.0, group IV: 0.5 +/- 0.2) (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibacterial activity of enoxacin was evaluated against more than 3,700 clinical isolates using the agar-dilution method and an inoculum of 10(4)-10(5) cells per site. For comparison other antibiotics appropriate for each species were also included. For most enterobacteria and for Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, the MIC90 of enoxacin was below 2 mg/l. Serratia marcescens was more resistant; the MIC90 being 4 mg/ml. Enoxacin also showed high activity against Campylobacter jejuni and Neisseria gonorrhoeae. Streptococci were comparatively resistant, 32 mg/l to 64 mg/l of the compound being required to inhibit 90% of strains.