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Biomedical subjects

C M Kunin

Publications and source records attributed to C M Kunin.

At least 55 records · Page 3Linked to original sources

Effect of NaCl-induced osmotic stress on intracellular concentrations of glycine betaine and potassium in Escherichia coli, Enterococcus faecalis, and staphylococci.

Staphylococci are more salt tolerant than are enterococci or Escherichia coli. They have a more rigid cell wall and higher internal turgor pressure. The mechanisms of NaCl-induced osmotic tolerance among these bacteria were examined by determining the generation of osmoprotective activity of cellular extracts and intracellular concentrations of glycine betaine and potassium (K+) in response to graded amounts of NaCl. Staphylococci as well as E. coli were shown to require choline or glycine betaine to achieve maximal salt tolerance. In response to 0.9 mol/L NaCl, E. coli exhibited a marked increase in osmoprotective activity, a 168-fold rise in glycine betaine, and a 2.3-fold rise in K+. Enterococcus faealis exhibited a small increase in osmoprotective activity, a 9.3-fold increase in glycine betaine, and a twofold increase in K+. In contrast, strains of Staphylococcus aureus, S. epidermidis, and S. saprophyticus were found to have considerably greater osmoprotective activity, glycine betaine, and K+ than other organisms, even in the absence of external osmotic stress. Glycine betaine rose in some strains, but K+ remained virtually unchanged as the concentration of NaCl was increased. The high concentrations of glycine betaine and K+ in staphylococci, even in the absence of osmotic stress, may explain in part their remarkable salt tolerance and high turgor pressure.

Betaine↗

Natural history of "lower" urinary tract infections.

Our current knowledge of the long-term outcome of uncomplicated urinary tract infections in women is based on a re-evaluation of the criteria for defining pyelonephritis at autopsy, careful description of the causes of renal disease among patients entering dialysis and transplant programs, long term observation of patients, and epidemiologic studies which have attempted to determine the association of bacteriuria with mortality. The weight of the evidence favors the conclusion that although urinary tract infections can produce severe impairment of renal function, this is rare in the absence of a major predisposing factor such as obstruction, calculus, reflux, abnormalities of the voiding mechanism or diabetes. The predisposing lesions, however, may go undetected until heralded by episodes of acute pyelonephritis or by renal failure. Unfortunately, urinary tract infections are so common that it is difficult to distinguish the population at greatest risk. The possible role of renal damage produced by autoimmune mechanisms following infection needs continued study.

Adult↗

The implications for Europe of revised FDA guidelines for clinical trials with anti-infective agents.

This article summarizes the current collaborative effort between the US Food und Drug Administration and the Infectious Diseases Society of America for the purpose of generating new General and Disease/Organism Specific Guidelines for the evaluation of anti-infective agents. Examples of proposed changes from draft documents are presented. The final documents may assist European colleagues in their efforts to establish a standardized new drug registration process by 1992. An area of mutual interest is the acceptability of safety and efficacy data from international clinical trials. In the interest of human and financial economies, both US and European Guidelines need to clarify the conditions, or criteria, for the conduct of valid 'off-shore' clinical trials.

Anti-Infective Agents↗

Purchase of antibiotics without prescription in Manila, the Philippines. Inappropriate choices and doses.

The purchase of antimicrobial agents in drugstores in a district in Manila. The Philippines was examined in order to determine how these agents might be used. Most antimicrobial agents are imported as bulk products and repackaged by a large number of small firms into 1491 different preparations including 206 marketed as combinations with other drugs. Antimicrobial agents accounted for 20.1% of all drug purchases. Purchases were made without prescription in 66.3% of 1608 transactions. Most of these were aminopenicillins or penicillins G or V (40.0%). The most common perceived indications were respiratory tract infections (20.2%), tuberculosis (8.8%), "prophylaxis" (8.6%) and gastrointestinal infection (8.3%). Almost 90% of purchases were for 10 or less capsules or tablets. The median number of units purchased was 3. Customers with written prescriptions purchased a mean of 8 while those who self-prescribed purchased a mean of 4 units (p = less than 0.05). We believe that these practices can provide only limited clinical efficacy and should favor emergence of resistant bacteria.

Anti-Bacterial Agents↗

Blockage of urinary catheters: role of microorganisms and constituents of the urine on formation of encrustations.

Long-term indwelling urinary catheters may become blocked in some patients by formation of encrustations made up of aggregated struvite crystals while other patients rarely develop blocked catheters. We have designated these groups as "blockers", "intermediates" or "non-blockers". To further understand this phenomenon we followed 32 catheterized elderly women in a nursing home. Catheters were changed six times at 2 week intervals. Patients tended to remain as "blockers", "intermediates" or "non-blockers" consistently over time. There were no significant differences in use of antibiotics, clinical manifestations of urinary infection or fever among the groups. "Blockers" were significantly more often colonized with Proteus mirabilis and Providencia stuartii than "non-blockers", and significantly less often with Klebsiella pneumoniae. However, there was no evidence of interference among the organisms. "Blockers" excreted a significantly more alkaline urine, and lesser amounts of magnesium, urea and phosphate in their urine. Two "blockers" in whom Proteus sp. were eliminated by coincidental antimicrobial therapy converted to "non-blockers". These findings support the concept that "blockers" are patients who have prolonged colonization with urease producing Proteus mirabilis and Providencia stuartii.

Aged↗

Postmortem microbiological findings of two total artificial heart recipients.

This report describes the postmortem microbiological findings and related gross pathology from two patients who had the longest survival after implantation of the Jarvik-7-100 total artificial heart. We documented extensive polymicrobial colonization at the site of the device and adjacent structures; however, the internal drive lines were remarkably free of bacterial colonization despite evidence of infection at the skin junction and in close proximity to the artificial heart. The polyurethane polymer (Biomer) on the external surface of the device was discolored and pitted in appearance and the Velcro material that attaches the two ventricles together was eroded. A nonspecific mass of tissue that was adherent to the device and to portions of the drive lines contained inflammatory cells, fibrinous debris, and colonies of microorganisms.

Autopsy↗

Infectious complications in four long-term recipients of the Jarvik-7 artificial heart.

This article describes the infectious complications that occurred among four of the longest-term recipients of the Jarvik-7 artificial heart. Infection arising from the drive lines, with spread to the mediastinal periprosthetic space, was the major limiting factor in long-term use of the device in these patients. Periprosthetic infections were due to coagulase-negative staphylococci, Staphylococcus aureus, Pseudomonas aeruginosa, and other Pseudomonas species. Other infectious complications incurred by some of the patients included pneumonia, empyema, urinary tract infection, and intravascular line sepsis with Candida. Intensive antimicrobial therapy for prolonged periods seemed to suppress but not to eradicate infection and was accompanied by the appearance of multiresistant bacterial strains. Complications of antimicrobial therapy included diarrhea secondary to overgrowth with Clostridium difficile in two patients. Use of the current device for more than 30 days should be considered extraordinary and should be reserved for patients for whom no other form of life support is available.

Adult↗

E pluribus unum.

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History, 20th Century↗

Indwelling urinary catheters in the elderly. Relation of "catheter life" to formation of encrustations in patients with and without blocked catheters.

In order to define the natural history of indwelling urinary catheters in the elderly, 50 patients aged 65 years or older were followed. Their catheters had been in place for a mean of 33.2 days. When removed, 40.4 percent were blocked or showed poor flow. After the catheters were changed, the 14-day "catheter life" was 78 percent. About half the population had blocked catheters. They had a 14-day "catheter life" of only 31.8 percent (p = less than 0.01). Patients with blocked catheters ("blockers") excreted more alkaline urine, calcium, protein, and mucin than patients without blocked catheters ("nonblockers"), but urea-splitting bacteria were no more frequent. The mortality was not significantly different. Flow of water through catheters was closely related to extent of encrustations. Encrustations formed uniformly throughout the catheter lumen except when the tip was obstructed. The distribution and number of species of microorganisms (three and a half per specimen) were virtually identical in catheter and bladder urine, but the counts in the catheter urine were more frequently greater than 100,000 cfu/ml (p = less than 0.01). Patients with blocked catheters appear to be metabolically different from patients without blocked catheters and should have their catheters changed at seven to 10 days to avoid obstruction.

Aged↗

Formation of encrustations on indwelling urinary catheters in the elderly: a comparison of different types of catheter materials in "blockers" and "nonblockers".

In order to determine the effect of catheter materials on formation of encrustations in long-term indwelling urinary catheters in the elderly we performed a crossover study utilizing commercially available silicone, silicone-coated, teflon-coated and latex catheters that were left in place for 14 days. The study was conducted with #18 french catheters fitted with a 30 ml. balloon since smaller size catheters frequently fell out spontaneously. The distinction between patients who were "blockers" and "nonblockers" was found to be clinically useful since "nonblockers", who constituted about half the population, did well regardless of type of catheter material used. Formation of encrustations and blockage was significantly less in "blockers" with silicone than with teflon-coated or latex catheters. The more rapid flow-time through silicone catheters appears to be related to a larger bore. Although this study supports the use of silicone catheters for "blockers" on long-term drainage the results should not be interpreted to imply that they are preferable to other types of catheters for short-term use or to changing less expensive catheters more frequently when needed.

Aged↗

Enteric colonization with antibiotic resistant bacteria in nurses working in intensive care units.

To determine whether nurses who worked in an intensive care unit (ICU) might acquire enteric colonization with Gram-negative aerobic bacteria from their patients, rectal swabs were obtained from the patients and nurses in the ICU, from nurses working in a coronary care unit (CCU) and from young women with urinary tract infection who had not been exposed to the hospital environment. The healthy women differed from the patients in that their enteric flora contained greater numbers of lactose fermenting bacteria, they were less often colonized by resistant organisms and when resistant bacteria were present they were less abundant than in the patients. Nurses who had been treated with antimicrobial agents during the preceding six months were colonized more often with antibiotic resistant enteric bacteria. There was no evidence of transmission of antibiotic resistant Escherichia coli from patients to nurses largely because this species had been virtually eliminated from the patients by intensive use of antimicrobial agents. Instead, several multiresistant species of Klebsiella, Citrobacter and Pseudomonas were isolated from the patients and ICU nurses. It was difficult, however, to define clearly patient-nurse controls who had no exposure to the ICU patients. These observations and those of other investigators emphasize the need for examination of control populations and of therapeutic use of antibiotics when examining the issue of environmental acquisition of antibiotic resistant bacteria.

Adolescent↗

Morbidity and mortality associated with indwelling urinary catheters in elderly patients in a nursing home--confounding due to the presence of associated diseases.

A prospective study was conducted in a nursing home among elderly residents treated with and without indwelling catheters. Most of the patients were white females with a mean age of 82.3 years. The mortality at 6 months among catheterized patients was 30.2% compared with 10.1% among the noncatheterized groups (P less than 0.001). Patients with catheters differed significantly from those without in having more impaired mental status and diminished activities of daily living. They also differed significantly for eight of 30 diseases. Cerebrovascular and hypertensive disease were significantly more common in catheterized patients. In contrast, fractures and musculoskeletal disorders were significantly more common among noncatheterized patients. Catheterized patients had significantly more days with fever and symptomatic urinary tract infections and received antibiotics more often than did noncatheterized patients. We conclude that: (1) direct comparisons of morbidity and mortality among catheterized and noncatheterized populations are not valid because of confounding by the presence of associated life-threatening illnesses; and (2) catheterized patients have more clinical episodes of urinary tract infections and fever and are treated more frequently with antibiotics.

Activities of Daily Living↗

Dimethylthetin can substitute for glycine betaine as an osmoprotectant molecule for Escherichia coli.

Glycine betaine is believed to be the most active naturally occurring osmoprotectant molecule for Escherichia coli and other bacteria. It is a dipolar ion possessing a quaternary ammonimum group and a carboxylic acid group. To examine the molecular requirements for osmoprotective activity, dimethylthetin was compared with glycine betaine. Dimethylthetin is identical to glycine betaine except for substitution of dimethyl sulfonium for the quaternary nitrogen group. Dimethylthetin was found to be about equally as effective as glycine betaine in permitting E. coli to grow in hypertonic NaCl, and both compounds were recovered almost completely from bacterial cells grown in the presence of hypertonic NaCl. 3-Dimethylsulfonioproprionate, an analog of dimethylthetin observed in marine algae, and 3-Dimethylsulfonio-2-methylproprionate were found to be less active. Dimethylthetin may prove useful as a molecular probe to study betaine metabolism and as a model for the development of antibacterial agents.

Betaine↗

Isolation of glycine betaine and proline betaine from human urine. Assessment of their role as osmoprotective agents for bacteria and the kidney.

Human urine is osmoprotective for enteric bacteria, permitting E. coli to grow with high concentrations of NaCl and other salts and even higher concentrations of sucrose and mannitol but not urea. The active material in urine is soluble in methanol and is precipitated by ammonium reineckate at acid pH. Using gel filtration and high-pressure liquid chromatography, we have identified two major osmoprotective compounds in urine. One is glycine betaine; the other is proline betaine as demonstrated by nuclear magnetic resonance, mass spectrum scanning, and chemical synthesis. Proline betaine has not been described previously to our knowledge in vertebrate tissues. It is known to be a cell volume-regulating agent for marine red algae and the euryhaline mollusk Elysia chloritica. We suggest that the presence of glycine and proline betaines in human urine may reflect an osmoprotective role for the kidney and that they protect bacteria in the urine only fortuitously.

Betaine↗