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Biomedical subjects

M E Ryan

Publications and source records attributed to M E Ryan.

At least 19 recordsLinked to original sources
PubMed1998

Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a multicenter review.

BACKGROUND: Endoscopic therapy of biliary tract leaks was uncommon before laparoscopic cholecystectomy. Studies have demonstrated the efficacy of endoscopic drainage by endoscopic sphincterotomy or stent placement. Various endoscopic therapeutic modalities and long-term follow-up of this problem were studied. METHODS: Members of the Midwest Pancreaticobiliary Group reviewed all patients referred for endoscopic therapy of biliary leaks after laparoscopic cholecystectomy from 1990 to 1994. Long-term follow-up was by direct patient contact. RESULTS: Fifty patients were referred for endoscopic therapy of biliary leaks. Abdominal pain was present in 94%. The mean time from laparoscopic cholecystectomy to referral was 6.9 days. Therapy consisted of sphincterotomy only in 6 patients, stent only in 13, and sphincterotomy with stent in 31. Biliary leaks were healed in 44 patients at a mean of 5.4 weeks. A second or third endoscopic procedure was necessary to achieve healing in five patients. Two stent-related complications were noted. Percutaneous or surgical drainage of biliary fluid collections was required in 16 patients. The mean hospital stay for treatment of the leak was 11.1 days after endoscopic therapy. On follow-up (mean 17.5 months), all patients were well except two with mild abdominal discomfort. CONCLUSIONS: Endoscopic sphincterotomy, stent placement, or sphincterotomy with stent are effective in healing biliary leaks after laparoscopic cholecystectomy. Despite prolonged treatment for the leak, patients did well on long-term follow-up.

Bile↗
PubMed1998

Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms.

A seminal experiment involving a germ-free rat model of connective tissue breakdown (followed soon thereafter by a series of in vitro studies) identified an unexpected non-antimicrobial property of tetracyclines (TCs). This ability of TCs to inhibit matrix metalloproteinases (MMPs) such as collagenase was found to reflect multiple direct and indirect mechanisms of action, and to be therapeutically useful in a variety of dental (e.g., adult periodontitis) and medical (e.g., arthritis, osteoporosis, cancer) diseases. The site on the TC molecule responsible for its MMP-inhibitory activity was identified which led to the development of a series of chemically modified non-antimicrobial analogs, called CMTs, which also have therapeutic potential but do not appear to induce antibiotic side-effects. Longitudinal double-blind studies on humans with adult periodontitis have demonstrated that a sub-antimicrobial dose of doxycycline (previously reported to suppress collagenase activity in the periodontal pocket) is safe and effective and has recently been approved by the FDA as an adjunct to scaling and root planing.

Animals↗
PubMed1998

How do tetracyclines work?

This paper is a summary of a panel discussion by the following panelists: L. Golub, J. te Koppele, G. Nieman, M. Nelson, R. Ashley, T. Sorsa, and S. Simon. The panel discussed the mechanisms by which the tetracyclines and their non-antimicrobial counterparts may provide therapeutic efficacy in a variety of chronic and acute diseases.

Adult↗
PubMed1998

Tetracyclines inhibit protein glycation in experimental diabetes.

Glycation of proteins, which is accelerated in the diabetic state, has been implicated in many of the long-term complications of diabetes. This process can be inhibited by members of the tetracycline family of compounds. This novel finding is supported by studies conducted on drug (streptozotocin)induced Type I and genetic (ZDF/Gmi-fa/fa) Type II diabetic rats. These animals were orally gavaged daily with 5 mg of doxycycline and a variety of non-antimicrobial chemically modified tetracycline derivatives for time periods of 3 weeks to 11 months, while control untreated diabetic and nondiabetic animals were gavaged with vehicle alone (2% CMC). Blood and tissue samples were collected and analyzed for glucose and glycated proteins. None of the treatments had any effect on the severity of hyperglycemia or the intracellular glycation of hemoglobin of either Type I or II diabetic animals. However, the tetracycline analogues did affect the extracellular glycation of several proteins such as those found in the serum as well as skin collagen. In the Type II (ZDF) animals, initial mortality (3-5 months) was seen only in the doxycycline-treated animals, associated with infection by tetracycline-resistant micro-organisms, which was eventually surpassed by mortality rates in the untreated diabetics (6-9 months). CMT treatment not only decreased mortality but also increased longevity in the Type II diabetic animals, most likely by preventing the development of a number of long-term complications of uncontrolled diabetes, including glycation of proteins, that eventually lead to the demise of untreated diabetic animals.

Analysis of Variance↗
PubMed1997

A matrix metalloproteinase inhibitor reduces bone-type collagen degradation fragments and specific collagenases in gingival crevicular fluid during adult periodontitis.

OBJECTIVE AND DESIGN: To determine whether an inhibitor of matrix metalloproteinases (MMPs), administered to human subjects in a dental school research clinic, can reduce bone-type collagen degradation fragments in oral inflammatory exudates containing excessive levels of collagenase. MATERIALS AND SUBJECTS: Gingival crevicular fluid (GCF) was collected from 18 subjects with adult periodontitis whose clinical findings (gingival inflammation, pocket depth, and bone loss on radiographs) predicted excessive MMP activity in their periodontal pockets. TREATMENT: One month before the baseline appointment, plaque and calculus were removed from the teeth by supra- and subgingival scaling. After collection of GCF from 8-12 pocket sites per subject and recording of clinical indices, 12 of the 18 subjects were treated with doxycycline at a low dosage (20 mg b.i.d.) known via an extensive literature to suppress mammalian MMP activity by a non-antimicrobial mechanism. The remaining 6 subjects were followed without drug treatment. METHODS: At the baseline, 1 and 2-month appointments, GCF samples were analyzed for ICTP. (carboxyterminal peptide, a pyridinoline-containing fragment of Type I collagen) and osteocalcin by radioimmunoassay, as well as collagenolytic enzyme activity and MMP species (Western blot). Statistical analyses were determined by ANOVA. RESULTS: GCF ICTP and functional collagenase activity (but not osteocalcin levels) were significantly reduced (p < 0.05) in the doxycycline-treated subjects at both 1 and 2 month evaluations: there was no such change in the non-treated subjects. Western blots revealed that neutrophil-type collagenase (MMP-8) was the predominant MMP; MMP-13, which has been associated with pathologic collagenolysis including bone resorption, was detected in human GCF for the first time and was more substantially reduced than MMP-8. CONCLUSION: This is the first demonstration in human subjects of the simultaneous reduction of excessive MMP activity with concomitant reduction in levels of collagen degradation fragments. The findings are potentially applicable to a wide variety of human diseases characterized by excessive collagenase activity.

Adult↗
PubMed1997

Pitfalls in diagnosis of Lyme disease. What you need to know about serologic testing.

Lyme disease can be difficult to recognize because not all patients have erythema migrans or other classic symptoms. Therefore, laboratory testing has become an important aid to clinical diagnosis. But the story doesn't end there-serologic testing presents another set of problems and concerns. Drs. Still and Ryan explain how aspects of the disease itself and various factors inherent in the available tests can affect laboratory results.

Antibodies, Bacterial↗
PubMed1996

Complications of endoscopic biliary sphincterotomy.

BACKGROUND: Endoscopic sphincterotomy is commonly used to remove bile-duct stones and to treat other problems. We prospectively investigated risk factors for complications of this procedure and their outcomes. METHODS: We studied complications that occurred within 30 days of endoscopic biliary sphincterotomy in consecutive patients treated at 17 institutions in the United States and Canada from 1992 through 1994. RESULTS: Of 2347 patients, 229 (9.8 percent) had a complication, including pancreatitis in 127 (5.4 percent) and hemorrhage in 48 (2.0 Percent). There were 55 deaths from all causes within 30 days; death was directly or indirectly related to the procedure in 10 cases. Of five significant risk factors for complications identified in a multivariate analysis, two were characteristics of the patients (suspected dysfunction of the sphincter of Oddi as an indication for the procedure and the presence of cirrhosis) and three were related to the endoscopic technique (difficulty in cannulating the bile duct achievement of access to the bile duct by "precut" sphincterotomy, and use of a combined percutaneous-endoscopic procedure). The overall risk of complications was not related to the patient's age, the number of coexisting illnesses, or the diameter of the bile duct. The rate of complications was highest when the indication for the procedure was suspected dysfunction of the sphincter of Oddi (21.7 percent) and lowest when the indication was removal of bile-duct stones within 30 days of laparoscopic cholecystectomy (4.9 percent). As compared with those who performed fewer procedures, endoscopists who performed more than one sphincterotomy per week had lower rates of all complications (8.4 percent vs. 11.1 percent, P=0.03) and severe complications (0.9 percent vs. 2.3 percent, P=0.01). CONCLUSIONS: The rate of complications after endoscopic biliary sphincterotomy can vary widely in different circumstances and is primarily related to the indication for the procedure and to endoscopic technique, rather than to the age or general medical condition of the patients.

Age Factors↗
PubMed1996

Potential of tetracyclines to modify cartilage breakdown in osteoarthritis.

For several decades, it has been recognized that an imbalance between activated matrix metalloproteinases, generated locally by both infiltrating and resident cells, and their endogenous inhibitors may play a role in the pathologic breakdown of the joint extracellular matrix in osteoarthritis. This understanding has stimulated the search for a number of synthetic matrix metalloproteinase inhibitors that could serve as potential therapeutic agents. Tetracycline analogues are currently on the threshold of approval as anti-matrix metalloproteinases for another extracellular matrix-destructive disease, periodontitis, and this application could be extended to osteoarthritis and rheumatoid arthritis therapy. In this regard, specially formulated low-dose regimens of a commercially available tetracycline, doxycycline, have been used in long-term clinical trials and were found to reduce extracellular matrix breakdown, including bone loss, in adult periodontitis. Matrix metalloproteinase inhibition by tetracycline analogues is now recognized as complex, and multiple mechanisms have been proposed. A series of recently discovered nonantimicrobial chemically modified tetracyclines are potent inhibitors of several classes of matrix metalloproteinases, preventing collagen breakdown and bone loss in a variety of animal models, although these analogues have not yet been approved for human use. Various tetracyclines have reduced the severity of osteoarthritis in animal models, indicating therapeutic potential for this class of compounds in the future.

Animals↗
PubMed1996

Oxygen consumption calculated from the Fick equation has limited utility.

OBJECTIVE: To determine if oxygen consumption (VO2) calculated using the Fick relationship (calculated VO2) determines total body VO2 accurately and precisely enough to employ this method during clinical assessment of oxygen transport. DESIGN: Methods comparison, using repeated measures during four physiologic states: normal heart/normal lungs, heart failure/normal lungs, normal heart/acute lung injury, heart failure/acute lung injury. SETTING: University research laboratory. SUBJECTS: Thirteen adult Yucatan pigs. INTERVENTIONS: Oleic acid-induced acute lung injury; heart failure was induced with a continuous infusion of esmolol. MEASUREMENTS AND MAIN RESULTS: Calculated VO2 was determined by multiplying thermodilution cardiac output by the arterialvenous oxygen content difference in anesthetized, spontaneously breathing animals. Conditions were tightly controlled so that calculated VO2 would be as accurate as possible. "True" VO2 was measured simultaneously with a water-sealed spirometer (spirometry VO2). Calculated VO2 and spirometry VO2 were determined and analyzed during the four physiologic states listed above. Pooled data also were evaluated. Mean spirometry VO2 and calculated VO2 differed significantly during all four physiologic states and when data were pooled (spirometry VO2 273 +/- 70, calculated VO2 178 +/- 58 mL/min; p < .01). Calculated VO2 consistently underestimated spirometry VO2, as demonstrated by the large, positive bias in pooled data (95 +/- 59 mL of oxygen/min) and in the four physiologic states. Linear regression of data from all four states yielded slopes that were indistinguishable from 1, but y intercepts that varied from -152 to +182. For pooled data, the following equation was used: calculated VO2 = 0.5 x (spirometry VO2 + 46); r2 = .35. Precision in pooled data was 22% of the mean spirometry VO2. Data analysis for the four physiologic states demonstrated results similar to those results obtained when data were pooled. CONCLUSIONS: Even in a tightly controlled, clinical simulation in the laboratory, calculated VO2 from the Fick relationship systematically underestimated VO2 measured with a water-sealed spirometer. If true VO2 changes, the magnitude and direction of change will be reflected by calculated VO2 but with approximately 20% error in the absolute value. Heart failure, acute lung injury, and their combination did not affect the accuracy of calculated VO2. Therefore, calculating VO2 using the Fick relationship is too inaccurate to be used for research purposes. Because assessment of the directional change of VO2 may be clinically useful, calculated VO2 can be employed with discretion during clinical oxygen transport evaluation, bearing in mind the calculation's inherent imprecision.

Animals↗
PubMed1996

Matrix metalloproteinases and their inhibition in periodontal treatment.

Matrix metalloproteinases (MMPs), produced by both infiltrating and resident cells of the periodontium, play a role in physiologic (e.g., tooth eruption) and pathologic (e.g., periodontitis) events. The evidence for the role of MMPs in periodontal destruction has accumulated over three and a half decades, and it is now recognized that an imbalance between activated MMPs and their endogenous inhibitors leads to pathologic breakdown of the extracellular matrix during periodontitis. This understanding has stimulated the search for a number of synthetic inhibitors that could be used as potential therapeutic agents. Tetracycline analogues, as proteinase inhibitors, are currently closer to being used clinically than any other agents in periodontal therapy. Other MMP inhibitors, such as Batimastat (British Bio-technology, Oxford, UK), are currently being tested clinically for inhibition of cancer metastasis and other diseases. Multiple mechanisms of MMP inhibition by tetracycline analogues have been proposed. The nonantimicrobial chemically modified tetracyclines are potent inhibitors of MMPs, preventing collagen breakdown and alveolar bone loss in animal models of periodontitis. In addition, nonantimicrobial low doses of the commercially available semisynthetic tetracycline doxycycline, have been used in human clinical trails to reduce MMP activity in the gingival crevicular fluid and gingival tissues, with a resultant reduction in pocket depth and attachment loss. Of particular interest, periodontal research on the nonantimicrobial properties of tetracycline has generated new therapeutic approaches to a variety of medical disorders characterized by excess MMP activity.

Alveolar Bone Loss↗
PubMed1996

Local and systemic factors in periodontal disease increase matrix-degrading enzyme activities in rat gingiva: effect of micocycline therapy.

We previously reported that both local and systemic factors relevant to the pathogenesis of periodontal disease can increase gingival collagenase activity in rats. Since the degradation of extracellular matrix is an essential feature of periodontal disease and this tissue breakdown requires multiple enzyme interactions, the current study was carried out to determine the effects of bacterial endotoxin (LPS) (a local factor) and diabetes (a systemic factor) on a panel of matrix-degrading enzymes (collagenase, gelatinase, elastase, and beta-glucuronidase) in the gingiva of rats. In addition, the effects of therapy with a semisynthetic tetracycline (minocycline) were investigated. Ten male, Sprague-Dawley rats were made diabetic by IV injection of streptozotocin. Four of the ten rats then received minocycline (10 mg/day) by oral gavage on a daily basis for 3 weeks. Nineteen nondiabetic rats served as controls and 9 of them received 10 microliters of E. coli LPS (10 mg/ml) by injection into the labial gingiva every other day during the last week of the study. The other 10 nondiabetic rats were sham injected with saline into the gingiva. At the end of the 3 week experimental period, gingival tissue and skin were dissected from each rat and extracted for enzyme analysis. Our results showed that diabetes markedly increased the four matrix-degrading enzyme activities in both gingiva and skin. In contrast, local LPS injection increased these enzyme activities in the gingiva alone. Systemic therapy with minocycline completely ameliorated these elevated enzyme levels in diabetic rats in both gingiva and skin. Minocycline added in vitro to the enzyme assay systems containing skin extract from diabetic rats also inhibited collagenase and gelatinase activities, but no inhibition was observed for elastase and beta-glucuronidase activities, indicating that the MMPs and other enzymes were inhibited by minocycline, during diabetes, by indirect and indirect mechanisms, respectively.

Alveolar Bone Loss↗
PubMed1995

Streptococcal preseptal cellulitis complicated by the toxic Streptococcus syndrome.

BACKGROUND: After decades of decline in the incidence of severe infections secondary to group A streptococci, a dramatic increase in the frequency and severity of infections with these organisms has been reported since 1984, including a "toxic Streptococcus syndrome," resembling staphylococcal toxic shock syndrome. To the authors' knowledge, this entity has never been described after ocular infection. METHODS: In a previously healthy 3-year-old boy, preseptal cellulitis developed secondary to minor trauma to the eyelid, progressing rapidly to hypotension, respiratory distress, and an erythrodermic desquamating rash. Ocular and blood cultures grew group A beta-hemolytic streptococci. Appropriate antibiotic coverage and management of systemic manifestations led to rapid improvement, although necrosis developed in the right upper anterior eyelid, requiring skin grafts. RESULTS: More than 3 years since the incident, the patient is free of infection and has a good cosmetic result after skin grafting and revisions for scarring and adhesions. CONCLUSIONS: Streptococcal preseptal cellulitis is not unusual, particularly after trauma. Ophthalmologists must be aware of the re-emergence of more virulent organisms with increased potential for morbidity and mortality.

Anti-Bacterial Agents↗
PubMed1995

Measuring patient satisfaction: a case study.

Health care providers are under tremendous pressure to meet consumer demands in order to compete in the rapidly changing health care arena. Through evaluating patient satisfaction, health care providers can learn what the consumer wants from the health care system. This article informs the reader of issues surrounding patient satisfaction data collection instruments, especially the problem of lack of standardization. That is, each instrument measures satisfaction according to different standards. This article presents a case study analysis of one patient satisfaction data collection instrument entitled the Picker-Commonwealth Survey on Patient-Centered Care. Suggestions for revision and further work are addressed.

Adult↗
PubMed1995

Pitfalls in HIV testing. Application and limitations of current tests.

Enzyme-linked immunosorbent assay (ELISA) and Western blot assay are the most commonly used laboratory tests for HIV infection. Both detect antibodies to HIV. ELISA results are based on detection of antigen-antibody complexes by using antibodies labeled with an enzyme that produces a color change in the presence of a specific substrate. Currently licensed ELISA tests have greater than 98% sensitivity and specificity for HIV. Western blot analysis detects antibodies to specific HIV antigens and is best used as a confirmatory test. In spite of the high sensitivity and specificity of both tests, false-positive and false-negative results do occur. Physicians should be aware of specific causes of inaccurate results. In individual cases, knowledge of the patient's history and the criteria used by the laboratory performing the test is important.

AIDS Serodiagnosis↗