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Histopathological analysis in experimental macular surgery with trypan blue.

AIM: To analyse the effect of trypan blue on the retina in an experimental setting of macular surgery. METHODS: Porcine eyes were used within 3 hours after death. The eyes were hemisected and the vitreous removed. Trypan blue (0.15%) was applied over the trephined posterior pole, whereas the rest of the eye cup was filled with a balanced salt solution (BSS). The dye and the BSS were removed after 1 minute and the complete eye cup irrigated and filled with fresh BSS. Both the treated and untreated retinas were illuminated with a standard surgical light pipe and source at maximum power for 10 minutes. Both the trypan blue exposed retina and the non-treated surrounding retina were processed for histology. RESULTS: Exposure of the retina to trypan blue for 1 minute, followed by illumination caused no histologically detectable damage compared to the controls. No microarchitectural disorganisation, cellular disruption, or affection of the vitreoretinal interface was detected. CONCLUSIONS: These findings indicate that a 1 minute exposure of trypan blue followed by illumination does not cause an acute morphologically detectable toxic effect on the porcine retina.

Animals↗

Adenoid cystic carcinoma of major and minor salivary gland origin.

The records of 76 patients with adenoid cystic carcinoma of major and minor salivary gland origin seen at the Washington University Medical Center from 1963-1980 were reviewed to determine factors involved in local control, development of distant metastasis, and survival. Twenty-four (32%) patients were initially treated with surgery alone, 36 (47%) with combined surgery and irradiation, and 16 (21%) with irradiation alone. Local control after treatment was determined for all patients and was analyzed with respect to extent of surgery and dose of irradiation. Of 75 patients evaluable for local control, 30 (40%) failed with a median time of less than 5 years. There was no significant difference for patients treated vigorously for local recurrences after surgery. Patients who had a complete surgical resection (i.e., negative margins) survived significantly longer than patients treated by incomplete resection or biopsy alone followed by irradiation. Distant metastases developed in 50% of patients regardless of local control. Median survival after development of distant metastases was 40 months. There was no difference between major and minor gland sources for development of metastases. Lymph node involvement was rare. Our data indicate that complete and radical surgery results in the best survival. Combined modality therapy with surgery and irradiation optimizes the control of local disease. However, since distant metastases develop in spite of local control, in most instances we cannot recommend mutilating surgery for this disease entity.

Adult↗

Analysis of lipid peroxidation and electron microscopic survey of maturation stages during human cataractogenesis: pharmacokinetic assay of Can-C N-acetylcarnosine prodrug lubricant eye drops for cataract prevention.

Morphological and biophysical techniques described in this study have shown that membrane derangement occurs in human cataractous lenses. The data suggest that these disruptions were globules, vacuoles, multilamellar membranes and clusters of highly undulating membranes. Deleterious structural damage of the lens fibre cell plasma membranes serve as the primary light-scattering centres that cause the observed lens opacity. Nuclear cataract, a major cause of loss of lens transparency in the aging human, has been thought to be associated with oxidative damage, particularly at the site of the nuclear plasma membrane. Phospholipid molecules modified by oxygen accumulate in the lipid bilayer, change its geometry and impair lipid-lipid and protein-lipid interactions in lenticular fibre membranes. Lipid peroxidation (LPO) is a causative and pathogenic factor in cataract. Increased concentrations of primary molecular LPO products (diene conjugates, lipid hydroperoxides, oxy-derivatives of phospholipid fatty acids) and end-fluorescent LPO products have been detected in the lipid moieties of aqueous humour samples and human lenses obtained from patients with senile and complicated cataracts as compared with normal donors. In the present study, a rapid and simple high-performance liquid chromatographic (HPLC) assay for determination of imidazole-containing dipeptides in the aqueous humour of the eye was developed. The method was applied to determine the pharmacokinetic parameters and the time-course of N-acetylcarnosine and L-carnosine-related product in the eye, following a single dosage of topical ocular administration of peptide. Utilising data from pharmacokinetic studies and the specific purity of the N-acetylcarnosine (NAC) ingredient as a source of the pharmacological principle L-carnosine, we have created an ophthalmic time-release prodrug form including the US FDA-approved carboxymethylcellulose lubricant and other essential ingredients (Can-C, private label Nu-Eyes). This formulation increases the intraocular absorption of L-carnosine in the aqueous humour and optimises its specific antioxidant activity in vivo while reducing the toxic effects of lipid peroxides on the crystalline lens. L-carnosine that enters the aqueous humour can accumulate in the lens tissue for a reasonable period of time. The presence of L-carnosine in transparent crystalline lenses during normal aging was detected and its concentration in this case was about 25 microM. At different stages of cataract development, the level of L-carnosine drastically decreased, reaching about 5 microM in ripe human cataracts. However, administration of pure L-carnosine (1% solution) to the rabbit eye (instillation or subconjunctival injection) does not lead to accumulation of this natural compound in the aqueous humour at the time level over 30 minutes at a concentration exceeding that in placebo-treated matched eyes, and its effective concentration is exhausted more rapidly. Use of NAC prodrug eye drops optimises the clinical effects of L-carnosine in the treatment of ophthalmic disorders (such as prevention and reversal of cataracts in human and animal [canine] eyes). The data provided predict a clinical effect with NAC ophthalmic prodrug, and show that the magnitude and duration of this effect are directly related to the bioavailability of L-carnosine released from NAC in the aqueous humour of the anterior eye segment. The ophthalmic NAC drug shows promise in the treatment of a range of ophthalmic disorders that have a component of oxidative stress in their pathogenesis (including cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, and corneal, retinal and systemic diseases [such as diabetes mellitus and its ophthalmic complications]). There is a need for further and better collaboration between Innovative Vision Products' cataract control and ophthalmic services, improved education of people affected by cataract, a commitment that N-acetylcarnosine eye drops will be the preferred treatment before orthodox cataract surgery is attempted, and consideration of outcomes and a possible role of the NAC drug cataract treatment as source of referral for orthodox surgical, ophthalmic and optometric services.

Adolescent↗

IL-18-binding protein expression by endothelial cells and macrophages is up-regulated during active Crohn's disease.

The pathogenesis of Crohn's disease (CD) remains under intense investigation. Increasing evidence suggests a role for mature IL-18 in the induction of proinflammatory cytokines and Th1 polarization in CD lesions. The aim of this study was to investigate the contribution of the IL-18-neutralizing (a and c) and non-neutralizing (b and d) isoforms of IL-18-binding protein (IL-18BP) during active CD. Intestinal endothelial cells and macrophages were the major source of IL-18BP within the submucosa, and this IL-18BP production was also found to be relevant to other types of endothelial cells (HUVEC) and macrophages (peripheral monocytes). IL-18BP messenger transcript and protein were significantly increased in surgically resected specimens from active CD compared with control patients, correlating with an up-regulation of IL-18. Analysis of the expression of the four IL-18BP isoforms as well as being free or bound to IL-18 was reported and revealed that unbound IL-18BP isoforms a and c and inactive isoform d were present in specimens from active CD and control patients while isoform b was not detected. IL-18/IL-18BP complex was also detected. Interestingly, although most was complexed, free mature IL-18 could still be detected in active CD specimens even in the presence of the IL-18BP isoform a/c. These results demonstrate that the appropriate neutralizing isoforms are present in the intestinal tissue of patients with active CD and highlights the complexity of IL-18/IL-18BP biology.

Adult↗

New frontiers in brachytherapy.

Brachytherapy gives a high dose to a tumor (better cell kill) because the sources are close to or within the tumor. Because of the location of the source (usually within target volume), the surrounding normal tissues are spared, resulting in lower morbidity. In the past, radiation exposure hazard to caregivers was a major disadvantage of brachytherapy; however, this concern has been reduced with the use of low energy isotopes and remote controlled afterloading techniques. The need for surgical exposure and its associated trauma has been overcome by using percutaneous, image-guided brachytherapy techniques. Use of brachytherapy to treat prostate and intravascular sites can be expected to increase.

Brachytherapy↗

Upper GI-bleeding--value and consequences of emergency endoscopy and endoscopic treatment.

Emergency endoscopy permits the early detection and prognostic evaluation of a source of hemorrhage. It serves as a "baseline" for decision-taking with regard to subsequent therapeutic measures. Today, modern endoscopic hemostatic procedures provide us with effective means of achieving primary control of the bleeding. Endoscopic emergency treatment can reduce the rebleed rate and help reduce the number of emergency surgical operations that need to be performed. A significant reduction in mortality rate has, so far, been observed in only a few comparative studies. When hemostasis has been accomplished, interdisciplinary discussions with the surgeon are needed in order to determine how to proceed in the individual case.

Emergencies↗

Comparison of nonwoven and woven gown and drape fabric to prevent intraoperative wound contamination and postoperative infection.

In a prospective, controlled clinical trial, nonwoven, disposable gown and drape fabrics were no better barriers to intraoperative wound contamination or postoperative wound infection than reusable cotton poplin. We observed no difference between the two study groups in either the frequency or level of intraoperative wound contamination as judged by cultures of specimens collected at the time of wound closure. Of procedures in which reusable fabrics were used, 13.1 percent had positive cultures compared with 15.5 percent of those in which disposable fabrics were used (difference not statistically significant). We recovered coagulase-negative Staphylococci from more than 95 percent of contaminated wounds. Rates of postoperative wound infection were virtually identical in the two groups. Our data suggest that either both fabrics were similar in their ability to block bacteria that were shed from skin surfaces from entering the wound, or that bacteria which contaminate the wound in clean surgical procedures are derived from sources other than skin.

Clinical Trials as Topic↗

Source and route of methicillin-resistant Staphylococcus epidermidis transmitted to the surgical wound during cardio-thoracic surgery. Possibility of preventing wound contamination by use of special scrub suits.

The objective of this study was to trace the source and route of transmission of methicillin-resistant Staphylococcus epidermidis (MRSE) in the surgical wound during cardio-thoracic surgery, and to investigate the possibility of reducing wound contamination by wearing special scrub suits. In total 65 elective operations for coronary artery bypass grafting (CABG) with or without concomitant valve replacement were investigated. All staff present in the operating room wore conventional scrub suits during 33 operations and special scrub suits during 32 operations. Samples were taken from the hands of the scrubbed team after surgical scrub but before putting on sterile gowns and gloves, and from patients' skin (incisional area of sternum and vein harvesting area of legs) after preoperative skin preparation with chlorhexidine gluconate. Air samples were taken during operations. Samples were also taken from the wound just before closure. Total counts of bacteria on sternal skin and from the wound (cfu/cm2) were calculated as well as total counts of bacteria in the air (cfu/m3). Strains of MRSE recovered from the different sampling sites were compared by pulsed field gel electrophoresis (PFGE). It was found that wearing special scrub suits did not reduce the number of air-samples where MRSE was found compared with conventional scrub suits. The risk factor most strongly associated with MRSE in the wound at the end of the operation was preoperative carriage of MRSE on sternal skin; RR 2.42 [95% CI 1.43-4.10], P= 0.021. By use of PFGE, it was possible to identify the probable source for four MRSE isolates recovered from the wound. In three cases the source was the patients own skin. Finding MRSE in air-samples, or on the hands of the scrubbed team, were not risk factors for the recovery of MRSE in the wound at the end of operation. In conclusion, with a total bacterial air count around 20 cfu/m3 and a low proportion of MRSE, the reduction of total air counts by use of tightly woven special scrub suits did not reduce air counts of MRSE or wound contamination with MRSE. The patients' sternal skin was the main source for wound contamination with MRSE

Adult↗

Mesenteric arteriovenous fistula causing portal hypertension and bleeding duodenal varices.

We report a case of portal hypertension associated with a non-traumatic arteriovenous fistula, presenting with bleeding duodenal varices. The patient was admitted for melaena. Emergency endoscopy showed oesophageal varices with no signs of recent bleeding and with no blood in the upper gastrointestinal tract. Arteriography of the coeliac axis and superior mesenteric artery failed to detect any bleeding source. Endoscopy was repeated because of persistent bleeding and revealed active bleeding from varices in the distal duodenum. The patient underwent surgery and a large paraduodenal varicose vein associated with an arteriovenous fistula was found. Resection of the paramural varix and surgical occlusion of the arteriovenous fistula were effective in the control of bleeding. Liver biopsy revealed mild portal fibrosis without cirrhosis. Three years after surgery the patient still has oesophageal varices but has not had recurrent bleeding. There was regression of intraduodenal varices.

Aged↗

[Computer-assisted placement for after-loading procedures with iridium 192].

Extremely high precision is needed to place radiation sources in the after-loading technique, but localisation techniques so far described do not offer the required accuracy. We used the computer-assisted surgery (CAS) localising system for the placement of after-loading probes in patients with head and neck carcinoma. Surgical instruments can be positioned without visual control using the CAS system. Since 1989 after-loading tubes have been placed using the CAS method. We evaluated the accuracy to be better than 1 mm. Ten after-loading treatments with iridium 192 of head and neck carcinomas were carried out between August 1989 and February 1991 with exact placement of the after-loading tubes in the nasopharynx. It seems feasible to treat cerebral tumours as well as tumours of the pelvic region by computer-assisted after-loading brachytherapy.

Adult↗

Are bile bacteria relevant to septic complications following biliary surgery?

Bile bacteriology, wound sepsis and the effect of prophylactic antibiotics have been studied in a controlled prospective double blind randomized trial on 375 patients undergoing elective cholecystectomy at a district general hospital. We have examined the overall prevalence of bacteria in bile and have identified several factors associated with an increased incidence. The identity of organisms isolated from a total of 21 patients with infected wound swabs was compared with isolates from the bile at operation, and in only two instances was there a correlation. Cephazolin, given either pre-operatively, or into the wound, reduced wound infection rates compared with a control group (from 11.8 to 2.4 per cent, P less than 0.005). We conclude that the majority of wound infections in this series were caused by organisms from the patients' skin or exogenous sources, rather than by bacteria from the biliary system.

Adolescent↗

Serum adenosine deaminase and total superoxide dismutase activities before and after surgical removal of cancerous laryngeal tissue.

In this study, pre- and post-operative serum activities of adenosine deaminase (ADA) and total superoxide dismutase (SOD) enzymes were measured in patients with squamous cell laryngeal cancer. Activities of both enzymes were found to be higher in cancerous patients compared to the controls. No significant differences were found however between pre- and post-operative values for both enzymes in the patient group. It has been suggested that ADA and SOD enzymes leak from the cancerous laryngeal tissues into the blood stream. The absence of differences between pre- and post-operative serum enzyme activities has two possible explanations: Firstly, removal of previously released enzymes from the blood stream takes a much longer period than one month; and secondly, cancerous laryngeal tissue is not the only source of the enzymes mentioned even after removal of cancerous tissue by surgical operation, other sources such as adjacent tissues and/or metastatic tissues etc, still release these enzymes into the blood stream.

Adenosine Deaminase↗

Automatic connector devices for proximal anastomoses do not decrease embolic debris compared with conventional anastomoses in CABG.

OBJECTIVE: Emboli generated during cardiac surgery have been associated with aortic clamping and manipulation. Proximal anastomotic devices are thought to be less traumatic by eliminating partial clamping, potentially resulting in fewer adverse outcomes. Intra-aortic filtration has been shown to effectively capture particulate debris. We compared the amount of debris released using intra-aortic filtration and the clinical outcomes between conventionally handsewn and automated proximal anastomoses. METHODS: Seventy-seven patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass were enrolled in a prospective randomized study. Patients were assigned to the anastomotic device Group I (Symmetry Aortic Connector, n = 39) or the conventional handsewn anastomosis control Group II (n = 38). Proximal anastomoses were performed before cardiopulmonary bypass in both groups. Intra-aortic Filter 1 (EMBOL-X)was deployed prior to partial clamping or puncturing the aorta for device application and removed after the proximal anastomosis was completed. Prior to cross-clamp removal, a second filter was inserted (Filter 2). A core laboratory performed quantitative and histologic analyses of the debris captured. Clinical outcomes included adverse events, neurocognitive test scores, graft patency, and mortality. RESULTS: Preoperative variables and risk factors were not significantly different between Groups I and II (EuroSCORE 3.9+/-2.6 vs. 4.2+/-2.5). Filter analyses showed no significant difference between Groups I and II in Filter 1 or 2 for either surface area of particles or total number of particles (P> 0.005). There was a significant decrease between Filters 1 and 2 in both Groups for surface area of particles (Group I: 18.5+/-23.8 mm2 vs. 10.7+/-16.3 mm2, P = 0.017; Group II: 15.0+/-15.4 mm2 vs. 6.9+/-.6.5 mm2, P = 0.004), and for total number of particles in Group II (8.6+/-3.7 vs. 7.1+/-2.4, P = 0.023). No significant differences were observed between Group I (device) and Group II (control) outcomes for myocardial infarction, neurocognitive deficit, stroke, length of stay, graft occlusion, or mortality. CONCLUSIONS: The application of proximal aortic connectors without partial clamping does not reduce particulate emboli or affect clinical outcomes compared with conventional anastomoses. Cross-clamping during cardiopulmonary bypass produces less particulate debris than conventional or automated proximal anastomoses performed off-pump, suggesting a major source of emboli is the anastomotic process.

Adult↗

Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb.

The treatment of soft tissue sarcoma of the limb by function-saving resection and brachytherapy (BRT) was systematically studied from 1975 to 1990 at the Memorial Sloan-Kettering Cancer Center, using iridium-192 temporary tumor-bed implants. Initial experiences showed an 88% local control rate in 33 patients who had locally advanced sarcomas, many of which would have required treatment by amputation. The technique also controlled 70% of tumors that abutted or invaded a major neurovascular bundle that was dissected out and preserved. A prospective randomized study (BRT vs no BRT) confirmed the highly significant efficacy of BRT in preventing local recurrence. This salutary effect is mainly seen in high-grade tumors. Major complications of wound healing occurred in the earlier years of this experience. Adoption of improved techniques of surgical wound repair, standardization of radiation dose planning, and in particular, postponing the loading of radiation sources until after the fifth postoperative day has reduced the rate of serious wound complications, to a level not significantly different from that seen after surgical resection alone. These results rival those currently achieved in centers experienced in external beam therapy of soft tissue sarcomas, and offer the advantage of completion of treatment in one relatively short hospital stay.

Amputation, Surgical↗

Encapsulated cell technology.

The potential therapeutic applications of encapsulated cells are enormous. In the US alone, it has been estimated that nearly half-a-trillion dollars are spent each year to care for patients who suffer tissue loss or dysfunction. Over 6 million patients suffer from neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, over 14 million patients suffer from diabetes, and millions more from liver failure, hemophilia, and other diseases caused by the loss of specific vital cellular functions. It appears likely that by the end of the decade clinical trials of encapsulated cells to treat many of these diseases will become a reality. The Food and Drug Administration has already authorized studies to evaluate the safety and biological activity of several types of systems. A number of issues will have to be addressed, including the sourcing of raw materials, the design and building of manufacturing facilities, the scale-up and optimization process, storage and distribution of the product, and quality control.

Animals↗

Outbreak of osteomyelitis/septic arthritis caused by Kingella kingae among child care center attendees.

OBJECTIVE: Kingella kingae often colonizes the oropharyngeal and respiratory tracts of children but infrequently causes invasive disease. In mid-October 2003, 2 confirmed and 1 probable case of K kingae osteomyelitis/septic arthritis occurred among children in the same 16- to 24-month-old toddler classroom of a child care center. The objective of this study was to investigate the epidemiology of K kingae colonization and invasive disease among child care attendees. METHODS: Staff at the center were interviewed, and a site visit was performed. Oropharyngeal cultures were obtained from the staff and children aged 0 to 5 years to assess the prevalence of Kingella colonization. Bacterial isolates were subtyped by pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the 16S rRNA gene was performed. A telephone survey inquiring about potential risk factors and the general health of each child was also conducted. All children and staff in the affected toddler classroom were given rifampin prophylaxis and recultured 10 to 14 days later. For epidemiologic and microbiologic comparison, oropharyngeal cultures were obtained from a cohort of children at a control child care center with similar demographics and were analyzed using the same laboratory methods. The main outcome measures were prevalence and risk factors for colonization and invasive disease and comparison of bacterial isolates by molecular subtyping and DNA sequencing. RESULTS: The 2 confirmed case patients required hospitalization, surgical debridement, and intravenous antibiotic therapy. The probable case patient was initially misdiagnosed; MRI 16 days later revealed evidence of ankle osteomyelitis. The site visit revealed no obvious outbreak source. Of 122 children in the center, 115 (94%) were cultured. Fifteen (13%) were colonized with K kingae, with the highest prevalence in the affected toddler classroom (9 [45%] of 20 children; all case patients tested negative but had received antibiotics). Six colonized children were distributed among the older classrooms; 2 were siblings of colonized toddlers. No staff (n = 28) or children aged <16 months were colonized. Isolates from the 2 confirmed case patients and from the colonized children had an indistinguishable PFGE pattern. No risk factors for invasive disease or colonization were identified from the telephone survey. Of the 9 colonized toddlers who took rifampin, 3 (33%) remained positive on reculture; an additional toddler, initially negative, was positive on reculture. The children of the control child care center demonstrated a similar degree and distribution of K kingae colonization; of 118 potential subjects, 45 (38%) underwent oropharyngeal culture, and 7 (16%) were colonized with K kingae. The highest prevalence again occurred in the toddler classrooms. All 7 isolates from the control facility had an indistinguishable PFGE pattern; this pattern differed from the PFGE pattern observed from the outbreak center isolates. 16S rRNA gene sequencing demonstrated that the outbreak K kingae strain exhibited >98% homology to the ATCC-type strain, although several sequence deviations were present. Sequencing of the control center strain demonstrated more homology to the outbreak center strain than to the ATCC-type strain. CONCLUSIONS: This is the first reported outbreak of invasive K kingae disease. The high prevalence in the affected toddler class and the matching PFGE pattern are consistent with child-to-child transmission within the child care center. Rifampin was modestly effective in eliminating carriage. DNA sequence analysis suggests that there may be considerable variability within the species K kingae and that different K kingae strains may demonstrate varying degrees of pathogenicity.

Anti-Bacterial Agents↗

The health professional's role in preventing nosocomial infections.

Despite their best intentions, health professionals sometimes act as vectors of disease, disseminating new infections among their unsuspecting clients. Attention to simple preventive strategies may significantly reduce disease transmission rates. Frequent hand washing remains the single most important intervention in infection control. However, identifying mechanisms to ensure compliance by health professionals remains a perplexing problem. Gloves, gowns, and masks have a role in preventing infections, but are often used inappropriately, increasing service costs unnecessarily. While virulent microorganisms can be cultured from stethoscopes and white coats, their role in disease transmission remains undefined. There is greater consensus about sterile insertion techniques for intravascular catheters-a common source of infections-and their care. By following a few simple rules identified in this review, health professionals may prevent much unnecessary medical and financial distress to their patients.

Catheterization, Central Venous↗

Management of rhinosinusitis in children: consensus meeting, Brussels, Belgium, September 13, 1996.

OBJECTIVES: To (1) provide definitions for the different forms of pediatric rhinosinusitis, with an enumeration of the main symptoms and signs; (2) provide indications for microbiological, allergic, and immunologic assessment as well as for imaging studies; (3) suggest standard medical management with judicious use of antimicrobial agents; and (4) discuss indications for surgery. DATA SOURCES: Clinical studies and literature data relevant to the different topics of pediatric rhinosinusitis. CONCLUSIONS: Rhinosinusitis in children is a multifactorial disease in which the importance of several predisposing factors changes with increasing age. Continued study to obtain a better understanding of the disease and carefully controlled comparative evaluations of medical and surgical therapies are suggested.

Child, Preschool↗