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Expansion of mutant stem cell populations in the human colon.

In general, it is presumed that colonic epithelial stem cells are the principal cell type at risk of incurring the series of somatic mutations leading to carcinoma, since all other epithelial cell types are short-lived. Mutant stem cell clonal expansion increases the risk for subsequent mutations and is therefore a potentially important step in carcinogenesis. The stem cells reside in colonic crypts, simple tubular foldings of the epithelium, and thus counting crypts provides an indirect means to determine stem cell numbers. The normal crypt population is known to expand through a process of crypt replication and this is thought to result in a corresponding expansion of the epithelial stem cell population. A simple mathematical model of the population dynamics of normal and mutant crypts (crypts containing mutant stem cells) is developed and used to estimate a lower bound on the relative rate of expansion of the mutant stem cell population. The model predicts that if mutant and normal crypt populations expand at the same rate, and if the mutation rate is small relative to the rate of growth, then the fraction of clusters of mutant crypts composed of only a single mutant crypt should steadily decrease with age towards one-half. Aberrant crypts are easily recognizable lesions in human colon which have frequently been shown to contain cells with K-ras and occasionally APC gene mutations. Application of the model to recent counts of aberrant crypt cluster sizes indicate that the aberrant crypt population, and the contained mutant stem cell population, is expanding substantially faster than normal.

Cell Division↗

Efficacy of differently concentrated chlorhexidine varnishes in decreasing Mutans streptococci and lactobacilli counts.

The objective of the present prospective trial was to compare the efficacy of differently concentrated chlorhexidine varnishes (EC40) = 40% chlorhexidine and Cervitec = 1% chlorhexidine + 0.1% thymol) on levels of Mutans streptococci (ms), lactobacilli (lb) and plaque formation in interproximal plaque and saliva. Twenty-four volunteers with a high level of ms in saliva were randomized into two groups and treated with the experimental varnishes. Varnish applications were performed in accordance with literature. Over a period of 2 weeks Cervitec was applied three times and EC40 once or twice, depending on ms counts after first application. Four and 12 weeks after final varnish application ms in plaque and saliva were evaluated. Furthermore, lactobacilli (lb) counts in saliva and the effect on plaque formation were recorded. Both varnishes revealed a reduction of ms in interproximal plaque and saliva after 4 and 12 weeks. The highly concentrated varnish revealed a significantly stronger reduction of ms in plaque and saliva compared with the lowly-concentrated varnish. No effect could be demonstrated on lb counts and plaque formation. The results indicate that the chlorhexidine varnishes tested may reduce ms in both interproximal plaque and saliva. However, the application of the highly concentrated varnish EC40 results in a higher decrease of ms in plaque sites and saliva.

Adult↗

Cytokeratin immunostaining for detection of biliary epithelium: its use in counting bile ducts in cases of liver allograft rejection.

AIMS: To see how useful the application of a bile duct specific cytokeratin antibody (AE1) was in identifying and counting bile ducts in liver allograft biopsy specimens. METHODS: Eighteen liver biopsy specimens showing acute rejection and 17 biopsy specimens plus six hepatectomy specimens showing chronic rejection were studied. Serial sections were cut and stained with haematoxylin and eosin and AE1 antibody. Two pathologists (RFH and KP) examined the sections with respect to a range of histological features. RESULTS: Similar numbers of bile ducts were identified on haematoxylin and eosin sections as on corresponding sections stained by AE1 in cases of acute rejection and end stage chronic rejection. Greater numbers of bile ducts were identified by AE1 during the early stages of chronic rejection, especially when dense portal inflammatory infiltrates were present. These were often incomplete structures or individual cells within portal tracts, and bile ducts subsequently disappeared in all cases. Ductular proliferation was clearly shown by AE1 in acute rejection and the extent seemed to correlate with the severity of rejection present. By contrast, no ductular proliferation was observed in chronic rejection. CONCLUSIONS: Haematoxylin and eosin stained sections are adequate for counting bile ducts in most biopsy specimens from patients with suspected chronic rejection. Immunostaining for biliary cytokeratins using AE1 is of limited use in occasional cases where bile ducts are obscured by inflammatory cells.

Acute Disease↗

Detection of adsorption of Ru(II) and Os(II) polypyridyl complexes on gold and silver nanoparticles by single-photon counting emission measurements.

The present study describes a new application of ruthenium(II) tris(bipyridine) (Ru(bpy)3(2+)) and osmium(II) tris(bipyridine) (Os(bpy)3(2+)) as phosphorescent labels for the quantification of surface binding of molecules to gold and silver nanoparticles. The fraction of Ru(bpy)3(2+) and Os(bpy)3(2+) that is in solution can be distinguished from the surface-bound fraction by the relative lifetimes and integrated emission yields as determined by time-correlated single-photon counting (TCSPC) spectroscopy. Complementary steady-state measurements were carried out to confirm surface attachment of the phosphorescent label molecules. Although the emission of solutions of Ru(bpy)3(2+) and Os(bpy)3(2+) is quenched proportional to the concentration of 10 nm Au or 20 nm Ag nanoparticles, the quenching is static and not diffusional quenching observed in Stern-Volmer plots. The results demonstrate that time-resolved spectroscopy provides a rapid method for the measurement of surface binding of labeled molecules on metallic nanoparticles. While steady-state measurements require the preparation of a series of samples with varying quencher concentrations and a reference, the method described herein requires a single sample plus reference. The mechanism for phosphorescence quenching on Au and Ag nanoparticles is discussed in terms of energy and electron transfer theories.

Adsorption↗

A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss.

BACKGROUND: To pical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in men with androgenetic alopecia and women with female pattern hair loss. Results can be variable, and historic experience suggests that higher concentrations of topical minoxidil may enhance efficacy. OBJECTIVE: The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare the efficacy and safety of 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of female pattern hair loss. METHODS: A total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. Primary efficacy variables were change in nonvellus hair count at week 48, and patient and investigator assessments of change in hair growth/scalp coverage at week 48. RESULTS: After 48 weeks of therapy, 5% topical minoxidil was superior to placebo for each of the 3 primary efficacy measures. The 2% topical minoxidil group demonstrated superiority over placebo for hair count and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. The 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit at week 48. Both 5% and 2% topical minoxidil helped improve psychosocial perceptions of hair loss in women with female pattern hair loss. An increased occurrence of pruritus, local irritation, and hypertrichosis was observed with 5% topical minoxidil versus 2% topical minoxidil and placebo. CONCLUSION: In this 48-week study of 381 women with female pattern hair loss, 5% topical minoxidil was superior to placebo on each of the 3 primary efficacy end points: promoting hair growth as measured by change in nonvellus hair count and patient/investigator assessments of hair growth and scalp coverage. Application of 2% topical minoxidil was superior to placebo for assessments of nonvellus hair counts and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. At week 48, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit. Both concentrations of topical minoxidil were well tolerated by the women in this trial without evidence of systemic adverse effects. With the introduction of numerous herbal remedies for hair loss, of which most have not been tested in randomized, double-blind, placebo-controlled trials, it is important to describe well-controlled trials that demonstrate the efficacy and safety of topical drugs.

Administration, Topical↗

Influence of human wet cerumen on the growth of common and pathogenic bacteria of the ear.

The available data on the effect of human wet cerumen on bacterial growth are not conclusive. Nevertheless it is widely accepted that cerumen has a bactericidal effect. In this study the activity of human wet cerumen on bacterial growth was assessed by applying cerumen suspensions to bacterial cultures. Bacterial counts were performed before and after application of cerumen suspensions. A total of 383 assays was carried out with 73 pools of cerumen that were tested against cultures of Staphylococcus aureus, Staphylococcus epidermidis, Corynebacterium spp., Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens. An increase in growth occurred much more frequently than a decrease in growth in almost every microrganism tested, with the mean increase percentage being much higher than the mean decrease percentage, except in the case of S. aureus. The largest average growth increase was obtained with E. coli. The largest average decrease in bacterial growth was recorded with S. marcescens. Our study does not support the conception of a decrease in bacterial growth produced by humen wet cerumen. In vitro, the most observable effect was in fact an increase in microbial growth.

Adolescent↗

Measurement of bacterial growth potential in a reclaimed water.

The objectives of this paper are to show a bio-assay method using direct total microbial count (DTMC) and to demonstrate the applicability of this method to reclaimed water for evaluating its potential of bacterial growth. We have applied our method to four types of reclaimed water, measuring the time course of DTMC and dissolved organic carbon in a bio-assay process. The experimental findings are summarised as follows: 1) By regulating organic carbon, bacteria growth could be controlled. 2) Reduction of the initial concentration of bacteria was effective to delay their growth, but this operation could not control their maximum level. This implies that the retention time of the storage and distribution system of reclaimed water should be considered in design and operation of the disinfection process. 3) Ozonation increased the growth potential. Carbon adsorption process reduced it, but the ozone plus carbon adsorption process could not improve the biological stability. 4) A linear relationship between DTMC and biodegradable organic carbon has been observed, the gradient of this linear correlation, however, depended on the source of reclaimed water.

Colony Count, Microbial↗

A single-platform approach using flow cytometry and microbeads to evaluate immune reconstitution in mice after bone marrow transplantation.

The monitoring of immune reconstitution in murine models of HC transplantation, using accurate and automated methods, is necessary in view of the recent developments of hematopoietic cell (HC) transplantation (including reduced intensity conditioning regimens) as well as emerging immunological concepts (such as the involvement of dendritic cells or regulatory T cells). Here, we describe the use of a single-platform approach based on flow cytometry and tubes that contain a defined number of microbeads to evaluate absolute blood cell counts in mice. This method, previously used in humans to quantify CD34+ stem cells or CD4+ T cells in HIV infected patients, was adapted for mouse blood samples. A CD45 gating strategy in this "lyse no wash" protocol makes it possible to discriminate erythroblasts or red blood cell debris from CD45+ leukocytes, thus avoiding cell loss. Tubes contain a lyophilized brightly fluorescent microbead pellet permitting the acquisition of absolute counts of leukocytes after flow cytometric analysis. We compared this method to determine absolute counts of circulating cells with another method combining Unopette reservoir diluted blood samples, hemocytometer, microscopic examination and flow cytometry. The sensitivity of this single-platform approach was evaluated in different situations encountered in allogeneic HC transplantation, including immune cell depletion after different conditioning regimens, activation status of circulating cells after transplantation, evaluation of in vivo cell depletion and hematopoietic progenitor mobilization in the periphery. This single-platform flow cytometric assay can also be proposed to standardize murine (or other mammalian species) leukocyte count determination for physiological, pharmacological/toxicological and diagnostic applications in veterinary practice.

Animals↗

The effect of a polyhexamethylene biguanide mouthrinse compared with a triclosan rinse and a chlorhexidine rinse on bacterial counts and 4-day plaque re-growth.

OBJECTIVES: For various clinical applications, polyhexamethylene biguanide hydrochloride (PHMB) has been used for many years as an antiseptic in medicine. Recently, a 0.04% and a 0.12% PHMB mouthwash were shown to inhibit plaque re-growth and to reduce oral bacterial counts. In this study, a 0.2% PHMB mouthrinse (A) was compared with a positive control 0.12% aqueous chlorhexidine solution (B), a commercially available 0.3% triclosan/2.0% polyvinyl methyl ether maleic acid copolymer mouthrinse (Colgate Total Plax) (C), and a negative control placebo rinse (10% ethanol, flavour) (D). MATERIALS AND METHODS: The controlled clinical study was a double blind, randomized, four replicate cross - over design. Plaque re-growth was assessed with the Turesky et al. (1970) modification of the Quigley & Hein (1962) plaque index. The antibacterial effect was assessed by taking bacterial counts on the tooth surface (smears from the buccal surface of 16/26) and mucosa (smears from the buccal mucosa in opposite of area 16/26) after the professional prophylaxis and after the first rinse with the preparations on day 1 and prior to the clinical examination on day 5. Sixteen volunteers participated and, on day 1 of each study period were rendered plaque-free, ceased toothcleaning, and rinsed twice daily with the allocated mouthrinse. On day 5, plaque was scored and smears were collected according to the protocol. A 10-day wash-out period was carried out between each rinse evaluation. Data were analysed using ancova with Bonferroni HSD adjustment for multiple comparisons (colony forming units per sample) with a significance level alpha=0.05. RESULTS: The 0.2% PHMB mouthrinse (A) was significantly better at inhibiting plaque than the placebo (D), but significant less effective than the 0.12% aqueous chlorhexidine solution (B). There is no significant difference between A and the 0.3% triclosan/2.0% copolymer mouthrinse (C). Bacterial count reductions (tooth surface and mucosa) with PHMB (A) were significantly greater compared with the placebo (D) and triclosan (C), but significantly lower compared with chlorhexidine (B) (tooth surface) and equally effective compared with chlorhexidine (B) (mucosa). CONCLUSION: Consistent with previous studies, a PHMB mouthrinse was shown to inhibit plaque re-growth and to reduce oral bacterial counts, indicating that PHMB could be an alternative to established mouthrinses in preventive applications.

Adult↗

Prevention of early mutans streptococci transmission in infants by professional tooth cleaning and chlorhexidine varnish treatment of the mother.

Mutans streptococci (MS) are transmitted in early childhood from the mother to the infant, mostly by saliva. This study evaluated the influence of chlorhexidine (CHX) varnish-mediated suppression of MS in mothers with high salivary MS counts on the frequency of MS colonization in their children at 2 years of age. Professional tooth cleaning followed by CHX varnish application in 16 mothers with high salivary MS counts resulted in a significantly lower number of MS-colonized infants at 2 years of age when compared to a control group of 13 untreated mother-child pairs with high maternal salivary MS levels. The frequency of MS colonization in the CHX-treated group was not significantly different from the one found in a negative control group of 15 mother-child pairs with low maternal salivary MS levels.

Adult↗

Wire chambers revisited.

Detectors used for radioisotope imaging have, historically, been based on scintillating crystal/photomultiplier combinations in various forms. From the rectilinear scanner through to modern gamma cameras and positron cameras, the basic technology has remained much the same. Efforts to overcome the limitations of this form of technology have foundered on the inability to reproduce the required sensitivity, spatial resolution and sensitive area at acceptable cost. Multiwire proportional chambers (MWPCs) have long been used as position-sensitive charged particle detectors in nuclear and high-energy physics. MWPCs are large-area gas-filled ionisation chambers in which large arrays of fine wires are used to measure the position of ionisation produced in the gas by the passage of charged particles. The important properties of MWPCs are high-spatial-resolution, large-area, high-count-rate performance at low cost. For research applications, detectors several metres square have been built and small-area detectors have a charged particle resolution of 0.4 mm at a count rate of several million per second. Modification is required to MWPCs for nuclear medicine imaging. As gamma rays or X-rays cannot be detected directly, they must be converted into photo- or Compton scatter electrons. Photon-electron conversion requires the use of high atomic number materials in the body of the chamber. Pressurised xenon is the most useful form of "gas only" photon-electron convertor and has been used successfully in a gamma camera for the detection of gamma rays at energies below 100 keV. This camera has been developed specifically for high-count-rate first-pass cardiac imaging. This high-pressure xenon gas MWPC is the key to a highly competitive system which can outperform scintillator-based systems. The count rate performance is close to a million counts per second and the intrinsic spatial resolution is better than the best scintillator-based camera. The MWPC camera produces quantitative ejection fraction information of the highest quality. The detection of higher energy gamma rays has proved more problematical, needing a solid photon-electron convertor to be incorporated into the chamber. Several groups have been working on this problem with modest success so far. The only clinical detectors have been developed for positron emission tomography, where thin lead or lead-glass can provide an acceptable convertor for 511 keV photons. Two MWPC positron cameras have been evaluated clinically and one is now in routine use in clinical oncology. The problems of detection efficiency have not been solved by these detectors although reliability and large-area PET imaging have been proven.(ABSTRACT TRUNCATED AT 400 WORDS)

Gamma Cameras↗

Microbiologic counts during outpatient office-based cutaneous surgery.

This study used microbiologic counts to evaluate bacterial contamination during cutaneous surgeries of the head and neck. Aerobic bacterial counts of the surgical field in cases with immediate closure (group A, n = 10 patients) and prolonged procedures such as Mohs micrographic surgery (group B, n = 15 patients) were performed three times during the operation. Cultures were taken before antiseptic application, 30 seconds after application, and before closure. Each group showed a statistically significant reduction in aerobic bacteria both 30 seconds after antiseptic application and before closure. All aerobic bacterial counts at both intervals were less than 100,000 colony-forming units/cm2 in each group. The consistent reduction in aerobic bacteria suggests that a clean technique for the two classes of office operating room surgeries provides low-risk conditions for infection in relatively healthy patients.

Ambulatory Surgical Procedures↗

Effects of molgramostim, filgrastim and lenograstim in the treatment of myelokathexis.

Myelokathexis is a very rare form of chronic hereditary neutropenia resulting from impaired neutrophil releasing mechanism in the bone marrow. The recombinant human granulocyte-macrophage (molgramostim) and granulocyte (filgrastim, lenograstim) colony stimulating factors release the mature granulocytes from the bone marrow. We describe a 43-year-old woman suffering from myelokathexis, with the absolute neutrophil count ranging between 0.03 and 1.35 x 10(9)/L. In the period before the introduction of cytokines, the patient had more than 80 major infectious episodes. Since 1991, infections in this patient have been treated with cytokines, given in conjunction with antibiotics. Initially, she received molgramostim in a daily dose of 5 microg/kg subcutaneously, which stimulated the release of granulocytes from her bone marrow, thereby allowing successful treatment of infection. After the development of hypersensitivity, molgramostim was substituted with filgrastim. Finally, lenograstim was given a trial. With all three cytokines, the patient's neutrophil count always attained normal values already 4 hours after subcutaneous application of the drug in a dose of 5 microg/kg, the highest neutrophil levels were measured at 24 hours post-injection, and the neutrophil count was again close to the baseline value 72 hours after the treatment. A slight neutropenia was present 48 hours after the application of filgrastim. We believe that all three cytokines are equally effective in increasing the neutrophil count in venous blood of patients with myelokathexis.

Adjuvants, Immunologic↗

Interleukin-5 preferentially recruits eosinophils from vessels in nasal mucosa.

Interleukin-5 (IL-5), initially described as possessing eosinophil differentiating and proliferating activity, has now been shown to exert its effects on mature eosinophils. To investigate the ability of recombinant human IL-5 (rhIL-5) to cause the migration of eosinophils in the nasal mucosa in vivo, we compared the eosinophil counts in nasal mucosa without and after the nasal application of rhIL-5. In addition, the percentages of eosinophils in leukocytes within the vascular lumens in the nasal mucosa were counted to determine whether IL-5 recruited eosinophils from the vessels. The total number of eosinophils in both the epithelium and lamina propria, as well as the percentage of eosinophils in leukocytes within the lumens of vessels in the nasal mucosa after the application of IL-5, were higher than those in control nasal mucosa. Conversely, neither the number of neutrophils in the nasal mucosa nor the percentages of neutrophils in vessels differed between the two groups of nasal mucosa. The results strongly suggest that IL-5 preferentially recruits eosinophils from vessels into the lamina propria.

Adult↗

Colcemid alters S phase and other parameters in skin during chronic exposure to benzo(a)pyrene.

The administration of Colcemid for collecting mitotic figures in a carcinogenesis study, using benzo(a)pyrene (BaP), diminished the experimental differences between exposed and control mice. A dose-related increase in noncollected mitotic index (n-mitotic index) was seen in keratinocytes in the dorsal epidermis of mice which received four weekly treatments of BaP at 16, 32 and 64 micrograms in 50 microliters of acetone. In contrast, the number of mitotic figures collected for 4 hr by Colcemid block (c-mitotic index) was depressed at 16 micrograms, unchanged at 32 micrograms, and elevated at 64 micrograms of BaP. Weekly treatments with 4,8 or 16 micrograms BaP for 3-8 months induced an elevation in both n-mitotic and c-mitotic indices. The differences in results produced by the two methods of determining mitotic index depended upon dose and duration of treatment with BaP. The administration of Colcemid to acetone-treated mice increased the labeling index (number of labeled cells) and reduced the rate of DNA synthesis (low grain count per keratinocyte nucleus). After chronic application of BaP, Colcemid abrogated the increase in labeling index, but produced no additional effect on the number of grains per labeled keratinocyte. The modifying effect of Colcemid was greatest when administered during the peak of the tissue response to BaP. A number of significant changes in morphology of the skin associated with chronic exposure to BaP were attenuated by the use of Colcemid.

Animals↗

Diminished embryonic movements of developing embryo by direct exposure of sidestream whole smoke solutions.

Embryonic movements (EM) are considered to be the first sign of life and cigarette smoking during pregnancy has been linked to affect EM. Exposure to sidestream smoke, produced from the emissions of a smoldering cigarette, may result in poor pregnancy outcome and increased risk of serious perinatal morbidity and mortality. In this study, the chicken embryo bioassay was used to systematically assess the effects of short-term exposure to sidestream whole smoke solutions (SSWSS) on EM, recorded in real time by a video camera for 60 min and each EM was counted for every 3-min interval. Application of different types of SSWSS to the embryos caused significant changes in all types of EM from 15 to 18 min of recording time. Extensive reduction (P<0.001) and some time complete stoppage of swing-like movements and whole-body movements were observed in almost all treated embryos. Our data clearly link between exposure of SSWSS and substantial decrease in EM. It is unclear whether nicotine and/or other ingredients present in sidestream smoke are responsible for these alterations in EM. This article provides an outline of the relevance of SSWSS on EM for evolutionary developmental biology and this assay can be used to investigate the complex mixtures with regard to their effects on EM.

Animal Testing Alternatives↗

Single-molecule fluorescence detection in microfluidic channels--the Holy Grail in muTAS?

Both single-molecule detection (SMD) methods and miniaturization technologies have developed very rapidly over the last ten years. By merging these two techniques, it may be possible to achieve the optimal requirements for the analysis and manipulation of samples on a single molecule scale. While miniaturized structures and channels provide the interface required to handle small particles and molecules, SMD permits the discovery, localization, counting and identification of compounds. Widespread applications, across various bioscience/analytical science fields, such as DNA-analysis, cytometry and drug screening, are envisaged. In this review, the unique benefits of single fluorescent molecule detection in microfluidic channels are presented. Recent and possible future applications are discussed.

Biosensing Techniques↗

Histological and biochemical changes of experimental meniscus tear in the dog knee.

BACKGROUND: When degeneration is noted in the meniscus, sutures should not be applied even for a tear of the vascularized region of the meniscus because the meniscus may rerupture after suturing. In this study, the degeneration process of bucket-handle tear of the meniscus was investigated using histological and biochemical markers. METHODS: A bucket-handle tear in the intercondylar notch was prepared in the dog knee. Eight animals each were killed at 2, 4, 12, 24, and 48 weeks; and changes in the articular cartilage were observed. The cell count and morphology in the meniscus were investigated by hematoxylin and eosin staining, and glycosaminoglycans in the matrix were investigated by toluidine blue staining. Glycosaminoglycans were also measured by high-performance liquid chromatography. RESULTS: Erosion was noted in the weight-bearing region of the articular cartilage after 12 weeks. The cell count in the meniscus was markedly decreased at 48 weeks. Regarding cell morphology, fibrochondrocytes remained in the meniscus until 12 weeks. The cell morphology varied at 24 weeks, but the number of cells was maintained. Cell proliferation, mainly fibroblasts, was noted from 2 weeks and 4 weeks after surgery in the periphery and body of the meniscus, respectively. Fibrochondrocyte-like cells proliferated from 12 weeks in the meniscal body, and metachromasia was detected by toluidine blue staining, indicating meniscal repair. A marked decrease in glycosaminoglycans was noted at 48 weeks, which was consistent with the decrease in the cell count in the meniscus. CONCLUSIONS: Early application of sutures is desirable for bucket-handle tear of the meniscus because lesions appear in the cartilage within 12 weeks, but suturing may be performed until 24 weeks because of the absence of obvious meniscal degeneration. However, disorder of the meniscus progresses after 48 weeks and may affect the outcome of the meniscal suture.

Animals↗