Biomedical subjects
Publications and source records attributed to T John.
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PURPOSE: The incidence of Peyronie's disease is up to 7% in some series. While there are numerous nonsurgical methods of treatment, they do not have a high rate of success. Nesbit plication was once the accepted surgery for Peyronie's disease. Tunical lengthening procedures became popular because they avoided penile shortening caused by the Nesbit procedure. More urologists now perform plaque incision or excision, followed by grafting with different materials. Small intestinal submucosa offered promise as an ideal graft material. It is available off the shelf as 1 or 4-ply graft material. In several studies it appeared to function as a collagen based scaffold with graft incorporation in host tissue. MATERIALS AND METHODS: A single reconstructive urologist performed plaque incision and small intestinal submucosa grafting in 4 cases of Peyronie's disease using the same surgical technique. RESULTS: Although early results were positive, we have achieved less than satisfactory results with this material. The penis was straight in the immediate postoperative period but there was recurrent curvature in 3 of the 4 patients, of whom 2 had recurrence within 4 months of the procedure. CONCLUSIONS: We observed disappointing results with small intestinal submucosa for Peyronie's disease surgery with a high percent of recurrent curvature. Further studies are needed to determine if 1 or 4-ply small intestinal submucosa is an ideal graft material for the tunica albuginea.
Leiomyosarcoma of the scrotum is a rare tumor. Cutaneous and subcutaneous leiomyosarcomas constitute the two subtypes. We report a case of cutaneous leiomyosarcoma of the scrotum in a 73-year-old man. Cutaneous leiomyosarcoma arises from the smooth muscle of the dartos or arrectores pilorum. It is often mistaken for a benign lesion. We describe the clinical and pathologic features and review the published reports of this uncommon malignancy. It is best treated by wide local excision. Inguinal lymph node dissection is not advocated, unless a high degree of suspicion is present for lymph node metastasis. Long-term follow-up is essential, because of the risk of delayed local recurrence and distant metastasis.
Pelvic injuries represent a thorny and stubborn therapeutic challenge. Because major forces are required to fracture the pelvis, pelvic ring disruption, more than any other fracture, can lead to life-threatening associated injuries such as massive bleeding, organ injuries, and open fractures including hemipelvectomy. The rapid diagnosis and effective treatment ("damage control") of those injuries play the key role in the patient's survival, inasmuch as the mortality of multiply injured patients with pelvic ring disruption remains high with 20-35%. Exsanguinating hemorrhage represents the most dreaded acute complication of pelvic injuries. Therefore, diagnostic and therapeutic procedures have to be primarily adapted to the hemodynamics of the patient, secondarily to injuries of the brain and the torso. The time point and the techniques of definitive pelvic ring stabilization may be different in the patient with multiple injuries compared to isolated pelvic ring injuries.
Limited supplies of tendon tissue for use in reconstructive surgery require development of phenotypically stable tenocytes cultivated in vitro. Tenocytes in monolayer culture display an unstable phenotype and tend to dedifferentiate, but those in three-dimensional culture may remain phenotypically and functionally differentiated. In this study we established a three-dimensional high-density culture system for cultivation of human tenocytes for tissue engineering. Human tenocytes were expanded in monolayer culture before transfer to high-density culture. The synthesis of major extracellular matrix proteins and the ultrastructural morphology of the three-dimensional cultures were investigated for up to 2 weeks by electron microscopy, immunohistochemistry, immunoblotting and quantitative, real-time PCR. Differentiated tenocytes were able to survive over a period of 14 days in high-density culture. During the culture period tenocytes exhibited a typical tenocyte morphology embedded in an extensive extracellular matrix containing cross-striated collagen type I fibrils and proteoglycans. Moreover, expression of the tendon-specific marker scleraxis underlined the tenocytic identity of these cells. Taken together, we conclude that the three-dimensional high-density cultures may be useful as a new approach for obtaining differentiated tenocytes for autologous tenocyte transplantation to support tendon and ligament healing and to investigate the effect of tendon-affecting agents on tendon in vitro.
The aim of the study was to validate the Routine Assessment of Patient Progress (RAPP), an instrument for assessment by nurses, among patients with psychosis in South India. One hundred consecutive patients with psychosis admitted to the Department of Psychiatry, Christian Medical College, Vellore, India, were assessed on day five and day 19 using the RAPP, the PANSS, and the CGI scales. The correlation of the RAPP with the other scales, its change over time, the inter-rater reliability, and factor structure were assessed. The subscales of RAPP correlated significantly with those of the other scales at intake and at follow-up. The RAPP scores changed significantly after treatment. Its inter-rater reliability as measured by the intra-class correlation coefficient was 0.98. The Cronbach's alpha, used to measure the internal consistency of the scale, was 0.87. The split-half reliability (Spearman-Brown) was 0.89. Principal component analysis with varimax rotation revealed six factors, which explained 67.4% of the variance. Items related to life skills explained a major proportion of the variance. The good psychometric properties, concurrent validity, high inter-rater reliability and sensitivity to change make it a useful instrument for nurses to employ to assess patients with psychoses.
High-density cultures are widely used as an in vitro model for studies of embryonic cartilage formation. In the present study we investigated the suitability of high-density cultures for the redifferentiation of dedifferentiated chondrocytes. When primary human chondrocytes were cultured in alginate beads, some cells emigrated into Petri dishes. These cells were cultured for one to eight passages (each passage lasting about 3 days) in monolayer culture. At each passage, monolayer cells were removed and allowed to grow in high-density cultures at the medium-air interface and subsequently investigated with morphological, immunolocalization and biochemical methods for the production of cartilage-specific markers, i.e. collagen type II and cartilage-specific proteoglycans. When such dedifferentiated chondrocytes from monolayer passages P1-P4 were introduced in high-density culture, they regained a chondrocyte phenotype and formed cartilage nodules surrounded by fibroblast-like cells. Cells were interconnected by typical gap junctions and after a few days in culturing produced cartilage-specific extracellular matrix, notably collagen type II and cartilage-specific proteoglycans. In contrast, cells taken from monolayer passages P5-P8 did not produce these chondrocyte-specific extracellular materials when grown in high-density culture. We conclude that the growth of dedifferentiated chondrocytes in high-density culture promotes their redifferentiation and reveals their chondrogenic potential. Such high-density cultures might serve as a model system to initiate and promote the redifferentiation of chondrocytes and to provide sufficient quantities of differentiated chondrocytes for autologous chondrocyte transplantation.
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BIMD of Aspergillus nidulans belongs to a highly conserved protein family implicated, in filamentous fungi, in sister-chromatid cohesion and DNA repair. We show here that BIMD is chromosome associated at all stages, except from late prophase through anaphase, during mitosis and meiosis, and is involved in several aspects of both programs. First, bimD(+) function must be executed during S through M. Second, in bimD6 germlings, mitotic nuclear divisions and overall cellular program occur more rapidly than in wild type. Thus, BIMD, an abundant chromosomal protein, is a negative regulator of normal cell cycle progression. Third, bimD6 reduces the level of mitotic interhomolog recombination but does not alter the ratio between crossover and noncrossover outcomes. Moreover, bimD6 is normal for intrachromosomal recombination. Therefore, BIMD is probably not involved in the enzymology of recombinational repair per se. Finally, during meiosis, staining of the Sordaria ortholog Spo76p delineates robust chromosomal axes, whereas BIMD stains all chromatin. SPO76 and bimD are functional homologs with respect to their roles in mitotic chromosome metabolism but not in meiosis. We propose that BIMD exerts its diverse influences on cell cycle progression as well as chromosome morphogenesis and recombination by modulating chromosome structure.
We previously have reported that the mitogen-activated protein kinase (MAPK) pathway is stimulated by adhesion of human chondrocytes to anti-beta(1)-integrin antibodies or collagen type II in vitro. These mechanisms most likely prevent chondrocyte dedifferentiation to fibroblast-like cells and chondrocyte death. To investigate whether this pathway plays an essential role for the differentiation, phenotype, and survival of chondrocytes, we blocked mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) (MEK), a kinase upstream of the kinase Erk by using U0126. Exposure of chondrocytes to U0126 caused activation of caspase-3 in a dose-dependent manner. Western blot analysis with an antibody specific for dually phosphorylated Erk shows that collagen type II induced phosphorylation of Erk1/2 was specifically blocked by U0126 in a dose-dependent manner. Immunohistochemical analysis showed that treated chondrocytes were caspase-3 positive. In treated chondrocytes, the cleavage of 116-kDa poly(ADP-ribose)polymerase resulted in the 85-kDa apoptosis-related cleavage fragment and was associated with caspase-3 activity. Analysis by electron microscopy showed typical morphological signs of apoptosis, such as crescent-shaped clumps of heterochromatin, and a degraded pericellular matrix. Thus, these results indicate that the MEK/Erk signal transduction pathway is involved in the maintenance of chondrocytes differentiation and survival. These data stimulate further investigations on the role of mitogen-activated protein kinase pathways in human chondrocytes.
PURPOSE: To evaluate in vitro adherence of Staphylococcus epidermidis to silicone punctal plugs and collagen implants. SETTING: Loyola University Medical Center, Maywood, Illinois, USA. METHODS: Silicone punctal plugs and collagen implants were exposed to S epidermidis (3 x 10(8) colony forming units/mL) for 0, 5, 30, and 60 minutes, rinsed in sterile saline, and processed for light, scanning (SEM), and transmission (TEM) electron microscopy. Scanning electron microscopy (x2000) was used to quantify bacteria/mm2 adhering to the devices. RESULTS: The mean S epidermidis/mm2 +/- (SD) adhering to each device were as follows: baseline, silicone punctal plug, 1593 +/- 899, and collagen implant, 7168 +/- 2895 (P =.000, paired Student t test); 5 minutes, silicone punctal plug, 3833 +/- 537, and collagen implant, 6571 +/- 2240 (P =.008); 30 minutes, silicone punctal plug, 13 988 +/- 9076, and collagen implant, 10 404 +/- 1731 (P =.2616); and 60 minutes, silicone punctal plug, 12 644 +/- 10 402, and collagen implant, 11 748 +/- 2685 (P =.8056). CONCLUSIONS: Staphylococcus epidermidis adhered significantly more to collagen implants than to silicone punctal plugs at 0 and 5 minutes. No significant difference in bacterial adherence was seen at 30 and 60 minutes. For both devices, bacterial adherence increased with increasing exposure.
PURPOSE: To report blockage of a commercially available ciprofloxacin bottle by white crystalline deposits. This study evaluated the ultrastructural features of the ciprofloxacin crystals. METHODS: A patient underwent intensive topical treatment of an infectious corneal ulcer with commercially available ciprofloxacin 0.3% ophthalmic solution. During treatment, the patient was unable to obtain medication from the ciprofloxacin bottle and required a new prescription. Examination of the bottle revealed that about 50% of the medication remained, but compression of the bottle with any amount of force failed to deliver any medication. On closer examination, a white material partially filled the nozzle track of the bottle and was on the outer bottle near the nozzle and the inner surface of the bottle cap. These white crystalline deposits were evaluated by scanning electron microscopy. RESULTS: Plate-like, needle, cable and spaghetti-like crystals were found. The needle crystals formed multiple petaloid patterns. CONCLUSIONS: This is the first report of blockage of a commercially available ciprofloxacin 0.3% bottle by ciprofloxacin crystals and the inability to deliver medication from the bottle. Ultrastructural study of the white crystalline deposits revealed four types of ciprofloxacin crystals.
PURPOSE: Pterygium excision is often followed by recurrence that may be more severe than the initial lesion. This study evaluated the efficacy of conjunctival mini-autograft following surgical excision of pterygium. METHODS: Eight patients underwent pterygium excision with a conjunctival mini-autograft. All patients had decreased visual acuity secondary to involvement of the central cornea by the pterygium. Following the excision, dissection of a conjunctival mini-autograft was performed. The mini-autograft was then transposed to the area of excision and secured in place with interrupted Vicryl and a few nylon sutures. Follow-up periods ranged from 5 to 9 years. RESULTS: All eyes healed with no post-operative complications and no recurrences of the pterygium in any patient up to a maximum follow-up period of 9 years 10 months. CONCLUSION: Conjunctival mini-autograft with excision of the pterygium is an effective procedure for the surgical management of pterygium.
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PURPOSE: To determine whether preserved human amniotic membrane (AM) can be used to treat ocular burns in the acute stage. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Thirteen eyes from 11 patients with acute burns, 10 eyes with chemical burns and 3 with thermal burns of grades II-III (7 eyes) and grade IV (6 eyes), treated at 7 different facilities. METHODS: Patients received amniotic membrane transplantation (AMT) within 2 weeks after the injury. MAIN OUTCOME MEASURES: Integrity of ocular surface epithelium and visual acuity during 9 months of follow-up. RESULTS: Ten patients were male and one patient was female; most were young (38.2 +/- 10.6 years). For a follow-up of 8.8 + 4.7 months, 11 of 13 eyes (84.63%) showed epithelialization within 2 to 5 weeks (23.7 +/- 9.8 days), and final visual acuity improved > or = 6 lines (6 eyes), 4 to 5 lines (2 eyes), and 1 to 3 lines (2 eyes); only one eye experienced a symblepharon. Eyes with burns of grade II to III showed more visual improvement (7.3 +/- 3 lines) than those with burns of grade IV (2.3 +/- 3.0 lines; P < 0.05, unpaired t test). In the group with grade II or III burns, none had limbal stem cell deficiency. All eyes in the group with grade IV burns did experience limbal stem cell deficiency. CONCLUSIONS: Amniotic membrane transplantation is effective in promoting re-epithelialization and reducing inflammation, thus preventing scarring sequelae in the late stage. In mild to moderate burns, AMT alone rapidly restores both corneal and conjunctival surfaces. In severe burns, however, it restores the conjunctival ocular surface without debilitating symblepharon and reduces limbal stromal inflammation, but does not prevent limbal stem cell deficiency, which requires further limbal stem cell transplantation. These results underscore the importance of immediate intervention in the acute stage of eyes with severely damaged ocular surface. Further prospective randomized studies including a control group are required to determine the effectiveness of AMT in acute chemical and thermal burns of the eye.
PURPOSE: To evaluate the incidence of anterior chamber bacterial contamination during no-stitch, 1-handed, small incision phacoemulsification. SETTING: Little Company of Mary Hospital, Evergreen Park, Illinois, USA. METHODS: This study comprised 53 eyes of 46 patients. Topical gentamicin sulfate was administered 1 hour preoperatively. After povidone-iodine cleansing solution and povidone-iodine paint (5% and 10%) were applied, the eyes were draped in a sterile manner. Aqueous fluid was aspirated upon entering the anterior chamber and at the end of surgery; the specimens were cultured for up to 14 days. All eyes had no-stitch, 1-handed, small incision phacoemulsification with implantation of a foldable acrylic posterior chamber intraocular lens through a 3.5 mm scleral tunnel incision. RESULTS: Three specimens (5.7%) aspirated on entry into the anterior chamber were positive for microorganisms. Of the cultures obtained at the end of surgery, 4 (7.5%) were positive for microorganisms. All posterior lens capsules were intact. The following organisms were cultured at the end of phacoemulsification: alpha-streptococci, micrococci, saprophytic mold, alpha-viridans streptococci, coagulase-negative Staphylococcus species, and anaerobic positive cocci. No eye developed endophthalmitis. CONCLUSIONS: The incidence of anterior chamber bacterial contamination was low. Bacterial contamination of the anterior chamber occurred at the beginning and toward the end of phacoemulsification. Staphylococcus species was the most common organism in the beginning, while Streptococcus species was the most common at the end. Saprophytic mold was present only at the end. No eye developed endophthalmitis.
We have examined the mechanism by which collagen-binding integrins co-operate with insulin-like growth factor-I (IGF-I) receptors (IGF-IR) to regulate chondrocyte phenotype and differentiation. Adhesion of chondrocytes to anti-beta1 integrin antibodies or collagen type II leads to phosphorylation of cytoskeletal and signalling proteins localized at focal adhesions, including alpha-actinin, vinculin, paxillin and focal adhesion kinase (FAK). These stimulate docking proteins such as Shc (Src-homology collagen). Moreover, exposure of collagen type II-cultured chondrocytes to IGF-I leads to co-immunoprecipitation of Shc protein with the IGF-IR and with beta1, alpha1 and alpha5 integrins, but not with alpha3 integrin. Shc then associates with growth factor receptor-bound protein 2 (Grb2), an adaptor protein and extracellular signal-regulated kinase. The expression of the docking protein Shc occurs only when chondrocytes are bound to collagen type II or integrin antibodies and increases when IGF-I is added, suggesting a collaboration between integrins and growth factors in a common/shared biochemical signalling pathway. Furthermore, these results indicate that focal adhesion assembly may facilitate signalling via Shc, a potential common target for signal integration between integrin and growth-factor signalling regulatory pathways. Thus, the collagen-binding integrins and IGF-IR co-operate to regulate focal adhesion components and these signalling pathways have common targets (Shc-Grb2 complex) in subcellular compartments, thereby linking to the Ras-mitogen-activated protein kinase signalling pathway. These events may play a role during chondrocyte differentiation.