In Vitro and In Vivo Efficacy of β-Lactams against Replicating and Slowly Growing/Nonreplicating Mycobacterium tuberculosis

Beta-lactams, in combination with beta-lactamase inhibitors, are reported to have activity against Mycobacterium tuberculosis bacteria growing in broth, as well as inside the human macrophage. We tested representative beta-lactams belonging to 3 different classes for activity against replicating M. tuberculosis in broth and nonreplicating M. tuberculosis under hypoxia, as well as against streptomycin-starved M. tuberculosis strain 18b (ss18b) in the presence or absence of clavulanate. Most of the combinations showed bactericidal activity against replicating M. tuberculosis, with up to 200-fold improvement in potency in the presence of clavulanate. None of the combinations, including those containing meropenem, imipenem, and faropenem, killed M. tuberculosis under hypoxia. However, faropenem- and meropenem-containing combinations killed strain ss18b moderately. We tested the bactericidal activities of meropenem-clavulanate and amoxicillin-clavulanate combinations in the acute and chronic aerosol infection models of tuberculosis in BALB/c mice. Based on pharmacokinetic/pharmacodynamic indexes reported for beta-lactams against other bacterial pathogens, a cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%T_MIC) of 20 to 40% was achieved in mice using a suitable dosing regimen. Both combinations showed marginal reduction in lung CFU compared to the late controls in the acute model, whereas both were inactive in the chronic model.     

Intrathyroidal thymic tissue mimicking a thyroid nodule in a 4‐year‐old child

A 4 year‐old girl was referred for CT of her neck for suspected submental lymphadenopathy and was found to have an incidental low‐attenuation thyroid mass. Subsequent thyroid ultrasound showed a heterogeneous thyroid mass with punctate areas of increased echogenicity. Cytologic examination was consistent with ectopic intrathyroidal thymic nodule. We review the presentation of ectopic thymic tissue, especially in the thyroid gland. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 41:319–320, 2013     

TUBERCULOSIS OF THE THYROID GLAND: A CLINICOPATHOLOGICAL PROFILE OF FOUR CASES AND REVIEW OF THE LITERATURE

Four cases of tuberculosis of the thyroid with different presentations including chronic sinus (following drainage of thyroid abscess), thyrotoxicosis, severe dysphagia clinically mimicking malignancy and euthyroid multinodular goitre are described. Except in the case presenting with chronic sinus (discharging acid-fast bacilli), the diagnosis was a pathological surprise (cytopathology in one and histopathology in two). Only in one case was there evidence of disease outside the cervical region. All cases showed multiple coalescing and caseating epitheloid cell granulomas along with giant cells, which are considered as diagnostic of tuberculous thyroiditis even if acid fast bacilli cannot be demonstrated. The literature is reviewed and the pathogenesis discussed.     

Diazepam as an adjuvant analgesic to morphine for pain due to skeletal muscle spasm

Side effects of morphine are common when it is given in titrated doses to control severe pain in advanced cancer. We describe a case of severe back pain resistant to parenteral morphine accompanied by muscle spasm, in which the addition of diazepam both had an opioid-sparing effect and provided superior symptomatic relief. Diazepam appears to have a specific role as an adjuvant analgesic for pain due to skeletal muscle spasm associated with painful vertebral metastases.     

Inhibition of contractions and 45Ca influx by adenosine in rabbit aorta.

The effects of adenosine on contractility and 45Ca-uptake in rabbit aorta have been examined and compared with those of nifedipine. Both adenosine (10(-5) M) and nifedipine (10(-8) M) inhibited contractions caused by CaCl2 (0.1-10 mM) in K(+)-depolarized preparations. Nifedipine (10(-7) M) significantly inhibited the contractions of noradrenaline (NA) at all doses (10(-8)-10(-4) M), while adenosine inhibited the contractions induced only by lower doses of NA (10(-8) and 10(-7) M) without affecting those at higher doses (greater than 10(-7) M). Adenosine (10(-8) M) and nifedipine (10(-7) M) inhibited K(+)-stimulated 45Ca-uptake by aortic strips by 75 and 100%, respectively. Similarity, NA (10(-4) M)-stimulated 45Ca influx was inhibited by about 70% by both these agents. The results suggest that adenosine inhibits inward Ca2+ movement involving both voltage-operated and receptor-operated calcium channels in rabbit aortic smooth muscle.     

Synthesis of Pro-Leu-Gly-NH2 analogues modified at the prolyl residue and evaluation of their effects on the receptor binding activity of the central dopamine receptor agonist, ADTN

Several analogues of L-prolyl-L-leucylglycinamide (PLG) were synthesized wherein the prolyl residue was replaced with other heterocyclic amino acid residues. Among the analogues synthesized were D-Pro-Leu-Gly-NH2 (2), less than Glu-Leu-Gly-NH2 (3), Thz-Leu-Gly-NH2 (4), Pip-Leu-Gly-NH2 (5), Aze-Leu-Gly-NH2 (6), L-delta 3,4-Pro-Leu-Gly-NH2 (7), and D-delta 3,4-Pro-Leu-Gly-NH2 (8). These analogues were tested for their ability to enhance the binding of the agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene to central dopamine receptors. Analogues 2, 3, and 5-7 showed activity comparable to that of PLG, while the tripeptides 4 and 8 were found to be inactive. The results show that the N-terminal prolyl residue of PLG is not an essential requirement for this tripeptide's ability to modulate dopamine receptors.