Clonal replacement of meticillin-resistant Staphylococcus aureus during repeated outbreaks in a long-term care facility.

Meticillin-resistant Staphylococcus aureus (MRSA) is common among residents of long-term care facilities (LTCFs). Analysing the spa types of 22 isolates, mostly bloodstream infections (BSI), revealed five temporally distinct clonal outbreaks occurring in one ward of our local LTCF between 2012 and 2019. Each clone caused episodes of BSI for several months until replaced by another clone. A high MRSA carriage rate of 32% among healthcare workers in this ward was documented during the investigation of the 2019 outbreak. Clonal replacement of MRSA and the role of healthcare workers in transmission are discussed.

Eukaryotic DNAs in solution contain characteristic components of tertiary structure.

For natural eukaryotic DNA in solution, we suggest the existence of secondary-helix components superponed to parts of the DNA double helices. In a previous report we found, for calf thymus DNA in solution and of different mean molar mass Mr, an electrostatically driven rise of the hydrodynamically operative contour length of the double helix. This result was derived from Mr-dependent systematic deviations from the almost but not exactly linear plots of intrinsic viscosity [eta] as a function of 1/cs1/2 (cs = Na+ concentration) accurately determined by a titration technique [K.G. and K.E.R., Nucl. Acids Res. 8, 2807 (1980)]. In order to discriminate between DNA elongation contributions caused by secondary or by tertiary structure effects, respective measurements have now been extended to different temperatures for two eukaryotic and two prokaryotic DNA species. The slope of the curves obtained for the (apparent) gradual elongation effect as a function of temperature is negative for the eukaryotic DNAs investigated and is smaller and positive for the prokaryotic species, thus revealing different underlying main elongation mechanisms. We propose that, for the eukaryotic DNA samples, an electrostatically driven partial abolition of tertiary structure components is responsible for the prevailing part of the DNA elongation effect measured. (A helix elongation of this type may be the result of an abolition of an apparent helix shortening as realized in a very high degree on formation of nucleosome chains or in a less degree by DNA molecules with a respective evolutionarily fitted tertiary structure). For the smaller effects of prokaryotic DNA species something like a base breathing seems to dominate. Recent literature results support such an interpretation.

Physiochemical characterization of substituted chromeno[4,3-b][1,5]benzodiazepine stereoisomers designed as cell membrane active antitumor agents.

As an alternative to naturally occurring pyrrolo[2,1-c][1,4]benzodiazepines (e.g., antramycin) which possess properties of DNA alkylation, we have designed several antileukemic chromeno[4,3-b][1,5]benzodiazepine derivatives with potential activity toward leukemia cell membranes and the cyclic nucleotide system. The cis and trans diastereoisomers were characterized by NMR. The absolute configurations of the enantiomers were established by X-ray diffraction and circular dichroism (CD) measurements. By means of absorption spectroscopy and determinations of fluorescence and fluorescence decay, it was found that the cancerostatically active compound (+)(6aR, 13aS)-3,4-dimethoxy-10,11-dimethyl-6,6a,7,8,13, 13a-hexahydrochromeno[4,3-b][1,5]benzodiazepine (ZIMET 54/79) and its biologically inactive (-) enantiomer (ZIMET 55/79) interact with liposomal membranes. At pH values of 6.0 and 7.3 the long-wave absorption bands of these agents showed weak bathochromic and hypochromic effects upon addition of neutral, and positively and negatively charged phosphatidylcholine and phosphatidylcholine/cholesterol liposomes. Such spectral changes are interpreted as resulting from the binding of both agents to phospholipid bilayers. Steady-state determinations using the membrane probe 1-anilino-8-naphthalenesulfonic acid (1,8-ANS) led to the observation of a small decrease in fluorescence intensity in the presence of either agent. Time-resolved measurements demonstrate that the mechanism of action of the agents occurs mainly through the partial displacement of probe molecules from regions of hydrophobic binding to areas of greater solvent accessibility. No significant differences in binding between the cancerostatically active and inactive enantiomers with liposomes (archiral systems) were detectable on the basis of spectrophotometric and fluorescence determinations. Cell membrane bound adenylate cyclase is stimulated by ZIMET 54/79, resulting in an increase of 103% in the level of cAMP in mouse L1210 leukemia cells. On examination of structure-activity relationships, it was found that the biological activity (leukemia L1210, P388, Lewis lung carcinoma, melanoma B16, increase in cAMP) is correlated with the particular configuration (6aR,13aS) and type of substituent at positions 3 and 4 of the benzo ring in the case of alkoxy groups and positions 10 and 11 for methyl groups. No activity was detected toward DNA/RNA using microbial test systems.

Cationic anticancer drugs and their modes of action.

This report focuses on two groups of cationic cancerostatics, anthracycline antibiotics and 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (ambazone), lining up biophysical and biochemical effects on the level of membranes and membrane constituents. The interaction of both drugs with multilamellar liposomes consisting of phosphatidylcholine used as a simple model membrane system could be ensured by means of steady state and nanosecond time-resolved fluorometric investigations. The biochemical effect on membranes is underlined by the inhibition of the neuraminidase activity of the Sendai virus, modification of the CAMP phosphodiesterase activity of leukemia L 1210 cells of mice and reduction of the lymphocyte blast transformation.

Interaction of DNA with tilorone derivatives: viscometric investigations.

Interaction of DNA with tilorone and six of its derivatives was studied in solution. This was done by viscosity measurements on both low and high molecular weight calf thymus DNA, in order to interpret the experimental results in terms of changes of DNA contour length (intercalation) and of persistence length (stiffening and bending). Qualitative and semiquantitative analysis delivered the following results: The carbonyl derivatives of tilorone bind more strongly to DNA than tilorone itself. The ligands with their two positively charged terminal groups favour DNA-DNA association. All carbonyl derivatives studied intercalate completely whereas the compound with quaternary nitrogens does not. No significant DNA stiffening effects were observed (contrary to the interaction of DNA with anthracycline derivatives) indicating the absence of a strong multipoint clamping between ligand and helix in relatively great distance. Different ligands induce different helix bending effects. The magnitude of the helix bending angle probably depends on the DNA base sequence. For some derivatives this angle is different at low and high ratio vt of added ligand molecules per DNA phosphate. This novel observation suggests the existence of heterogeneous, i.e. specific, binding as also found for tilorone by other authors on the basis of spectroscopic measurements using synthetic polynucleotides.

Surgical management of strictures of the cervical esophagus.

Strictures of the esophagus are difficult and challenging problems. Whether a result of caustic ingestion, trauma, or surgery, or a congenital abnormality, the patient suffers a disruption of the fundamental act of swallowing. The seven cases of stricture of the cervical esophagus presented here were not alleviated by the usual methods of antegrade and retrograde dilation. Each patient underwent a two-stage reconstruction of the esophagus. The strictures in four patients were secondary to a caustic agent, two were congenital, and one was of unknown etiology. All patients no longer require dilation and are essentially cured. This procedure will add to the armamentarium of the surgeon who deals with "hopeless" strictures of the cervical esophagus and, in properly selected cases, should be successful.

Voice change in the pediatric patient. A differential diagnosis.

This paper reviews the causes of voice change in the infant and child. Symptoms of dysphonia can be very early evidence of a serious problem, either within the larynx or resulting from a systemic disease. The need to investigate the cause of voice disturbances is stressed. The large number of diseases in which voice change occurs makes a complete examination of the child, both local and systemic, absolutely necessary in order to arrive at a specific diagnosis. The mechanism of voice change is described in each category of the numerous causes of dysphonia.

Foregut cysts in infants and children. Diagnosis and management.

The charts of 15 patients with foregut cysts were reviewed. The lesions were intrathoracic in 14 patients and in the cervical area in one child. The importance of early diagnosis and surgical management is stressed. In untreated infants with foregut cysts, severe progressive and life-threatening airway obstruction may develop. Since the symptoms of this congenital lesion may simulate other more common diseases of the tracheobronchial tree and esophagus, the physician should become familiar with this disease entity so that proper diagnosis and surgical treatment will not be delayed. The study includes symptomatology, methods of diagnosis, pathologic findings and classification of the cysts.

Papilloma of the larynx and tracheobronchial tree in children. A retrospective study.

One hundred and forty cases of papilloma of the larynx and tracheobronchial tree are documented in the records of the Childrens Hospital of Los Angeles. The records of 90 patients were available and were reviewed intensively. The method of direct laryngoscopy with general anesthesia using apneic technique in most patients and intubation in some was an adequate method of treating patients with laryngeal papillomata. A general anesthetic was never used where obstruction was severe and the airway could not be controlled. The low incidence of papilloma of the tracheobronchial tree and an absence of parenchymal lung seeding in this series is attributed to the avoidance of a tracheotomy and fewer intubation anesthetics thus avoiding trauma to the trachea and bronchi. The immediate removal of the tracheotomy tube seems as alternative if the surgical procedure had been performed. In the patients in this series decannulation was accomplished in a very short period of time. The establishment of an airway seem to be a priority in the treatment of this disease and this can be accomplished by repeated endoscopic procedures rather than tracheotomy. Statistics are given, and prognosis based on the type of lesion and histopathology is documented.

Foreign bodies in the airway. Five-year retrospective study with special reference to management.

The charts of 143 patients with foreign bodies in the larynx and tracheobronchial tree who were admitted to the Chidrens Hospital of Los Angeles during the period 1973 to 1978 were reviewed. Of these children 84 were male and 59 were female. One hundred were private patients and forty-three were clinic patients. Of these foreign bodies 60 were nut meat which is by far the most common foreign body of the tracheobronchial tree. All foreign bodies were successfully removed. One hundred twenty-six were discharged within the first 24 hours after admission and treatment. Fifty-one or 36% of these patients were discharged on the same day after the foreign body was removed. Sixty-two of the foreign bodies were in the left bronchial tree, while 55 were in the right bronchial tree. One hundred thirty-eight were endoscoped under general anesthesia using the apneic technique and five patients were treated with oxygen standby only because of severe respiratory obstruction. A detailed description of the use of apneic technique with profound muscle relaxation, the avoidance of preoperative medication and the team approach to ventilating the patients are all described. The advantage of general anesthesia, and the potential intraoperative and postoperative problems are reviewed. Of the total number of cases 13% were between 4 and 11 months of age, 44% were between 12 and 23 months of age and 57% were over 23 months of age.

Evidence for an increase of DNA contour length at low ionic strength.

The polyion chain expansion of DNA was studied by viscometry within the Na+ concentration range c5 = 0.002 M to 0.4 M. The DNA molecular weights M were between 0.5 x 10(6) and 13 x 10(6). The relative change of intrinsic viscosity [eta] is linearly correlated to c5(-1/2) with a slope that increases with increasing M. This behaviour reflects the predominance of helix stiffening in chain expansion. At c5(112) > 0.01(-1/2 M-1/2 (Debye-Hückel screening radius 1/chi > (1/chi)*=3nm) the relative change of [eta] rises with a steeper slope. This effect increases with decreasing M suggesting that helix lengthening contributes to the chain expansion. Our model enables us to interpret other ionic-strength dependent effects known from literature. The start of the significant duplex elongation at (1/chi)* can be correlated to the polyion-charge arrangement. In accordance with our interpretation (1/chi)* is found to be greater for DNA-intercalator complexes.

Myocardial ischemia from coronary arterial spasm.

Spasm of coronary arteries can cause chest pain indistinguishable from classic angina pectoris in patients without atherosclerosis of these vessels or recognizable heart disease. Associated electrocardiographic changes usually correspond to the coronary artery affected and disappear when the attack of pain ends. Sublingual nitrates are excellent agents for the control of the episodic anginal symptoms. There have been scattered reports of myocardial infarction occurring in patients with normal coronary arteries; a role of arterial spasm in these cases in speculative.

Atmospheric temperature profiles from lidar measurements of rotational Raman and elastic scattering.

Criteria for optimizing system parameters in the lidar measurement of atmospheric temperature profiles from simultaneous Raman and elastic returns by use of a three-channel system are discussed and summarized. It is shown that the filter constraints of earlier techniques are removed thereby eliminating the need for the high rejection capability of spectrometers in this type of measurement. Also, SNR is improved, and a greater freedom in the choice of optimum Raman filters is demonstrated.