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Affinity cytochemistry analysis of mast cells in skin lesions: a possible tool to assess the timing of lesions after death.

The histamine content in vital wounds is known to increase, with a zenith after 3 h, and then decrease until 24 h after wounding. We addressed whether this biochemical alteration has a morphological counterpart. Since the main source of skin histamine are mast cells, the distribution and number of these cells was assessed upon labeling with fluorescent avidin and with antibodies to the mast cell specific enzymes, chymase and tryptase. Analyses were performed on skin from 15 healthy controls (from surgical biopsies), from 15 post-mortem lesions and 75 vital lesions, obtained at autopsy from subjects who had survived from a few seconds to 24 h. The number of mast cells per unit area of section surface increased progressively with survival time, up to a maximum in subjects who survived 1-3 h ( p<0.01), and decreased thereafter becoming less than in the controls if lesions had occurred earlier than 6 h before death ( p<0.01). Samples from post-mortem lesions had significantly fewer mast cells than those of any other groups of samples ( p<0.01). We suggest that in association to other histological and circumstantial evidence the analysis of mast cells by affinity cytochemistry can help to discriminate vital from post-mortem lesions and to estimate survival time after lesions.

Adult↗

How high should total pain-relief score be to obviate the need for analgesic remedication in acute pain? Estimation using signal detection theory and individual-patient meta-analysis.

BACKGROUND: A pain relief score 50% of the maximum is often used as a clinically meaningful outcome in meta-analyses of analgesic trials. This arbitrary value requires validation. OBJECTIVE: To determine the optimum pain relief score for predicting pain relief sufficient to obviate the need for analgesic remedication in acute post-surgical pain. DESIGN: Individual-patient meta-analysis of randomized controlled trials and use of signal detection theory to identify the optimum cut-off point on the total pain relief score (TOTPAR). Analgesic remedication was used as the clinical outcome. DATA SOURCES: Seven parallel-group, active and placebo-controlled trials of minor analgesics. RESULTS: The predictive value of the TOTPAR score [expressed as a percentage of the maximum score (%maxTOTPAR)] for remedication was excellent for all the trials. The pooled estimate of the area under the receiver operating curve, an index of discriminative power, was outstanding 0.96 (95% CI 0.95-0.97). The pooled estimate of the optimal %maxTOTPAR for predictive purposes was 44.11 (95% CI 44.00-44.23). CONCLUSION: The analysis suggests that the arbitrary 50% cut-off point TOTPAR score often used in meta-analyses of analgesic trials in dental pain is reasonably acceptable. This is different to the 33% cut-off point reported for analgesic trials of acute breakthrough cancer pain and some chronic pain states such as diabetic neuropathy and postherpetic neuralgia. These differences deserve careful consideration when reading reports of analgesic trials and meta-analyses. Remedication itself should be considered as the preferred outcome measure for analgesic trials.

Acetaminophen↗

Brachytherapy with iridium-192 for bladder cancer.

OBJECTIVE: Patients with invasive bladder cancer often need radical cystectomy with its implications on quality of life. Bladder preservation combining surgery and radiotherapy could maintain quality of life without compromising tumor control. STUDY DESIGN: Twenty-eight selected patients with different stages of invasive bladder cancer were treated with preoperative external beam radiotherapy in a dosage depending on the tumor stage. Subsequently they underwent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading with iridium-192. A close follow-up consisted of 3-monthly urine cytology, cystoscopy and yearly CT scan. RESULTS: Sixteen patients (57%) are alive with no evidence of disease. Five patients (18%) have died of non-cancer-related causes without evidence of recurrent tumor. Tumor progression was seen in 7 patients (25%). CONCLUSIONS: Interstitial radiation can result in long-term complete remission in patients with small solitary invasive bladder tumors. The afterloading technique is safe and effective. The selection of patients is the most relevant key to success.

Adult↗

The role of torus longitudinalis in equilibrium orientation measured with the dorsal light reflex.

The torus longitudinalis (TL) is a paired elongated structure reciprocally connected with the optic tectum in actinopterygian fishes. Electrophysiological recordings have revealed a sustained neural discharge in TL inversely related to luminance [Northmore, 1984]. This photometric response may play a role in the comparison of light levels between the two eyes, which must occur for the dorsal light reflex (DLR) to orient the body in the environment. Based on the luminance response of TL, it was hypothesized that TL ablation would result in a reduced DLR. Individual goldfish (Carassius auratus) were observed with variable and constant light sources on opposite sides of a test tank. The DLR was measured with respect to angle (degree) and duration (seconds) of body tilt about the longitudinal axis. After baseline readings were obtained, the intertectal commissure was cut and TL was removed bilaterally. Surgical control fish had only the intertectal commissure cut. Following surgery, TL ablatees showed a significantly reduced DLR compared to controls. The results are consistent with the suggestion by Northmore [1984] that TL may be involved in the processing of luminance information.

Animals↗

Ex vivo secretion of tumor necrosis factor and interleukin-2 by rat splenocytes after intestinal ischemia and shock.

We studied the ex vivo secretion of tumor necrosis factor (TNF) and interleukin 2 (IL-2) by splenocytes after circulatory shock induced by intestinal ischemia and reperfusion in rats. Shock was induced by total occlusion of the superior mesenteric artery followed by reperfusion. In a second group, vascular occlusion was maintained throughout the experimental protocol. A third group of sham rats and a fourth group of control rats with a negligible surgical procedure were also studied. "Spontaneous" (untriggered) secretion of TNF by splenocytes was higher in the ischemia-reperfusion group than in all other groups (p < 0.01), but did not increase significantly after stimulation with LPS. Splenocytes from control rats exhibited a marked increase in TNF secretion after stimulation with LPS to values similar to those in the ischemia-reperfusion group. A diminished, though statistically significant increase in LPS-stimulated secretion of TNF was detected in the sham and ischemia only groups of rats (p < 0.05) from untriggered values in each. Untriggered secretion of IL-2 was similar in all groups. However, when compared to control rats, splenocytes from the three surgically manipulated groups exhibited suppressed secretion of IL-2 in response to stimulation with Con A (p < 0.05). These results support the role played by TNF in mediation of shock and point to spleen macrophages as a source of TNF after intestinal ischemia and reperfusion. Our results also demonstrated postinjury alteration in immune function manifested by depressed ability of splenocytes to increase the production of IL-2 after stimulation with Con A.

Animals↗

Optimal excision margins for primary cutaneous melanoma: a systematic review and meta-analysis.

OBJECTIVE: To determine in patients with localized primary melanoma of the trunk or extremities the optimal excision margin that achieves the highest disease-free survival and overall survival and the lowest local recurrence rate. DATA SOURCES: Trials comparing 2 different excision margins were identified by searching MEDLINE from 1966 to May 2002 using the term "melanoma," subheading "surgery," and limiting the search to human studies and randomized controlled trials (RCTs). Additional studies were found using the MeSH term "surgical procedures, operative," combining with "melanoma," and limiting to human studies. We searched EMBASE and the Cochrane Library in May 2002 using similar terminology. No language restriction was applied. STUDY SELECTION: We selected studies for the overview using the following inclusion criteria: design--an RCT with wide excision versus narrower excision (margin width was not specified a priori); population--adult patients (> 18 yr) with cutaneous melanoma of the trunk or extremities without evidence of metastasis; intervention--surgical excision of the primary melanoma; and outcomes--at least 1 of overall survival, disease-free survival, local recurrence, wound complications and necessity for skin grafting. DATA EXTRACTION: Information was abstracted for each outcome reported in the studies, and results were pooled by consensus. Statistical analysis was performed using RevMan 4.1 (The Cochrane Collaboration) software program. Relative risk and risk difference were reported with 95% confidence intervals. The number needed to harm was calculated for the need for skin grafting by taking the inverse of the risk difference. DATA SYNTHESIS: Three trials and their follow-up studies met the inclusion criteria and included 2087 adults with localized cutaneous melanoma of the trunk or extremities. No statistically significant differences were found between wide surgical excision (margins ranging from 3-5 cm) and narrower surgical excision (margins ranging from 1-2 cm) with respect to mortality, disease-free survival or local recurrence rate. CONCLUSIONS: Surgical excision margins no more than 2 cm around a melanoma of the trunk or extremities are adequate; overall survival, disease-free survival and recurrence rate are not adversely affected compared with a wider excision. There is more data to support a 2-cm margin than a 1-cm margin as the minimum margin of excision. Surgical margins should be no less than 1 cm around the primary melanoma.

Biopsy↗

The role of mitomycin C in preventing synechia and stenosis after endoscopic sinus surgery.

BACKGROUND: Synechia and stenosis formation after endoscopic sinus surgery (ESS) represents a potential source of surgical failure. Mitomycin C (MMC) has been used successfully in other fields to decrease postoperative scar formation. We hypothesize that the topical application of MMC reduces the incidence of stenosis and synechia formation after ESS. METHODS: This study is a randomized, controlled, single-blinded study based in a tertiary care teaching hospital. After routine ESS, a pledget soaked in MMC (0.5%) was randomly placed into the middle meatus of one nasal cavity for 5 minutes and a pledget soaked in saline was placed in the contralateral side in each patient. A blinded observer followed the patients for any evidence of stenosis or synechia formation. The medical records of enrolled patients were reviewed for demographics, diagnosis, prior surgery, type of sinus surgery, complications, incidence of stenosis/synechia, and need for further procedures. RESULTS: Twenty-nine patients were included in the final analysis. The mean follow-up period was 15 months (range, 3-32 months). There were no complications in this series. Eight patients experienced 10 episodes of synechia formation and one patient experienced 1 episode of synechia formation and 1 episode of stenosis of the maxillary sinus ostium. Seven of the 12 episodes of synechia/stenosis occurred on the side of the MMC application and the remaining 5 episodes occurred on the side opposite to the MMC application. This difference was not statistically significant. CONCLUSION: The topical application of MMC did not decrease the incidence of stenosis and synechia formation after ESS.

Administration, Topical↗

Changes in serum creatine kinase and lactate dehydrogenase caused by acute perioperative myocardial infarction and by transatrial cardiac surgical procedures.

A prospective clinical study was conducted to ascertain if a patient's postoperative elevation in serum creatine kinase MB isoenzyme coupled with determination of the lactate dehydrogenase1/lactate dehydrogenase2 ratio could differentiate whether atrial or ventricular myocardium was the source of these changes. Animal studies have shown that atrial myocardium is as rich a source of creatine kinase MB as is ventricular myocardium. Atrial myocardium has a lactate dehydrogenase1/lactate dehydrogenase2 ratio less than 1.00, whereas in ventricular myocardium the ratio is greater than 1.00. Sixty-four patients were assigned to six groups on the basis of serial electrocardiograms and vectorcardiograms by a cardiologist who was unaware of their clinical courses. The control group (Group 1) consisted of 16 patients admitted to the coronary care unit who had no electrocardiographic changes. Three surgical groups without electrocardiographic or vectorcardiographic evidence of perioperative myocardial infarction were studied: 10 patients undergoing routine coronary artery bypass procedures (Group 2), six adults undergoing repair of secundum atrial septal defect (Group 3), and 13 patients having mitral valve replacement (Group 4). Two groups of surgical patients who had acute perioperative transmural myocardial infarctions confirmed by serial electrocardiograms and vectorcardiograms were studied: 15 patients (Group 5) who had elective coronary artery bypass procedures and four (Group 6) who had mitral valve replacement. This study suggests that serum creatine kinase MB levels in excess of 50 IU/L on the postoperative day 1 and day 2 samples coupled with serum lactate dehydrogenase1/lactate dehydrogenase2 ratios greater than 1.00 on the postoperative day 2 and day 3 samples support the diagnosis of acute myocardial infarction. Patient groups undergoing procedures necessitating atriotomies had average elevations in serum creatine kinase MB and in the lactate dehydrogenase1/lactate dehydrogenase2 ratio, but these were significantly less than those seen when acute perioperative myocardial infarction had occurred.

Adult↗

Risk factors for acquisition of Serratia marcescens in a surgical intensive care unit.

Between January 1996 and May 1997, a four-fold increased rate of isolation of Serratia marcescens was observed amongst patients admitted to the surgical Intensive Care Unit (SICU) of the Leiden University Medical Center compared to the preceding years. Random amplification of polymorphic DNA showed the involvement of genotypically distinct strains, implicating multiple different sources. After improvement of hygienic measures the frequency of isolation of S. marcescens returned to baseline. A case-control study was performed to assess patient-related risk factors for acquisition of S. marcescens. Nineteen cases and 38 controls were included. Hospital- and SICU-stay were significantly longer in case patients than in controls. By univariate analysis, statistically significant differences were found in body weight, the duration of mechanical ventilatory support, the cumulative use of antimicrobial agents, the use of aminoglycosides, parenteral nutrition and tube feeding. The sum of the number of days per invasive device (deep intravenous lines, arterial lines, wound drains and urinary catheters) was higher in cases than in controls (P = 0.08). Categorically, a cumulative number of device-days > 25 was a statistically significant risk factor for acquisition of S. marcescens. Multivariable logistic regression analysis showed that body weight, parenteral feeding and mechanical ventilation were independent predictors of acquisition of S. marcescens. As transmission of S. marcescens appears to be by the hands of personnel, the identified risk factors may act by necessitating an increased frequency and intensity of direct contacts.

APACHE↗

Aprotinin.

OBJECTIVE: To review the clinical pharmacology of aprotinin in patients undergoing surgical procedures involving major blood loss, namely, coronary artery bypass graft (CABG). DATA SOURCES: A MEDLINE search was used to identify French- and English-language publications on aprotinin using the indexing terms aprotinin, cardiothoracic surgery, and hemorrhage. The MEDLINE search was supplemented by review of article bibliographies. Data also were obtained from the approved Canadian and US product labels. STUDY SELECTIONS: All abstracts and uncontrolled and controlled clinical trials were reviewed. DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. DATA SYNTHESIS: Aprotinin, a serine protease inhibitor isolated from bovine lung tissue, decreases bleeding after cardiac surgery by mechanisms including antifibrinolytic activity and preservation of platelet function. Several trials have shown that aprotinin reduced blood loss and transfusion requirements in patients undergoing CABG. Its use in other surgical procedures involving major blood loss has been reported. Aprotinin is well tolerated, with minor allergic reactions being the most frequently reported adverse effect. Although unsubstantiated, the possibility that aprotinin could create a prothrombic state leading to early graft occlusion and formation of microthrombi in renal and coronary vasculatures is of concern. CONCLUSIONS: Aprotinin is an effective hemostatic agent in CABG. Clear definitions of indications, dosing, safety, and repeated use remain to be investigated thoroughly.

Aprotinin↗

Atrial arrhythmias in adults after repair of tetralogy of Fallot. Correlations with clinical, exercise, and echocardiographic findings.

BACKGROUND: The long-term success of intracardiac repair of tetralogy of Fallot is hampered by the occurrence of arrhythmias. Numerous studies have stressed the potential role of ventricular arrhythmias. However, the importance of other arrhythmias in the morbidity of these patients appears to be underestimated. Furthermore, most follow-up studies have been limited to children or adolescents, whereas many patients have reached adulthood after earlier repair of tetralogy of Fallot. The aim of the present study was to determine the incidence of atrial fibrillation, atrial flutter, and other supraventricular arrhythmias in adult patients after intracardiac repair for tetralogy of Fallot and their correlation with surgical and clinical findings. METHODS AND RESULTS: The study group consisted of 53 consecutive patients referred to the Thoraxcenter adult congenital heart disease clinic. They underwent repair at a mean age of 9.1 years (range, 0.7 to 55 years). The median age at the time of study was 23.2 years (range, 15 to 57 years; mean age, 26.6 years), and the mean duration of follow-up of 17.5 years (range, 1.4 to 32 years) after surgery. Records were reviewed extensively for evidence of arrhythmias. The follow-up study included routine 12-lead ECG, 24-hour continuous ambulatory monitoring, and echocardiography, and 46 patients underwent exercise testing. Sinus node dysfunction was recorded in 19 patients (36%), of whom 4 required a permanent pacemaker. Atrial fibrillation or flutter was found in 12 patients, and other supraventricular tachycardias were found in 6. The former were more frequently of older age at follow-up. Antiarrhythmic therapy and cardioversion were typically directed at control of atrial (and not ventricular) tachyarrhythmias. Ten patients (19%) showed nonsustained ventricular tachycardia; they were older at initial surgery and older at follow-up and had more intracardiac repairs and longer cardiopulmonary bypass times. CONCLUSIONS: Despite an emphasis on ventricular ectopy in past series, the main sources of morbidity in adult patients after surgical correction of tetralogy of Fallot emanated from atrial arrhythmias, which were present in one third of the patients.

Adult↗

[Kineplastic reconstruction after upperlimb amputation (author's transl)].

In our country the preprosthetic surgical reconstruction of the upper-limb stumps based on the idea of kinematization has become a separate part of reconstructive surgery. Kineplastics- the formation of the skin-muscular canals-aimed at controlling the prosthetic-orthotic devices has acquired a new trend closely connected with the achievements of prosthetics, particularly with the development of the upper-limb externally powered prostheses. At the Leningrad Research Institute of Prosthetics 80 patients underwent kineplastic operations and 102 skin-muscular canals were formed in the period of 1975-1980. Most of the patients were severely disabled; among 65 cases there were upperlimb amputations, congenital deficiencies of the proximal shoulder girdle and disarticulations of shoulder joints. The authors improved the technique of the kineplastic operations, developed the original operations for fastening the prostheses and controlling the functional externally powered prostheses. The physiological investigations showed that the skin-muscular canals possessed a required number of commands and may be a reliable source of control. The skin-muscular canals are used for controlling prostheses, holding different devices for self-help, work and sports. This complex treatment enables the amputees not only to control the prostheses and aid devices, but also to become highly skilled workers.

Amputation, Surgical↗

Superoxide anion production by leukocytes exposed to post-ischemic skeletal muscle.

Superoxide anion (O2-) and polymorphonuclear leukocytes (PMNs) have been implicated in the genesis of skeletal muscle ischemia-reperfusion (I-R) injury, but the source of (O2-) has not been established. We studied PMNs as a potential source of O2- using a ferricytochrome reduction assay in 5 anesthetized dogs. Using a gracilis muscle model of I-R, 6 hours of ischemia was followed by 2 hours of reperfusion. The contralateral muscle served as control. Prior to ischemia and after 0.5 and 2.0 hours of reperfusion, PMNs were separated from the gracilis venous effluent of ischemic (I) and control (C) muscles. Central venous samples were also obtained prior to surgical preparation and after reperfusion. Assays for O2- were performed with and without zymosan (Z) activation. Results are expressed as nmol O2-/2 x 10(6) PMNs +/- SEM. Baseline production of O2- was 0.49 +/- 0.54 in central venous samples; Z increased the values to 6.77 +/- 2.13. After 2 hrs of reperfusion, central O2- was 1.57 +/- 0.75, which increased to 7.1 +/- 1.04 with Z. Gracilis venous samples O2- values with and without Z are reported in Table I. One way measures of analysis of variance showed no significant (p > 0.05) differences between samples. Our results demonstrate that PMNs are not the sole source of O2- in the pathophysiology of skeletal muscle I-R injury. PMN associated injury may be mediated by mechanisms other than O2- production.

Analysis of Variance↗

The effect of weight loss on C-reactive protein: a systematic review.

BACKGROUND: Several studies suggest that weight loss reduces C-reactive protein (CRP) level; however, the consistency and magnitude of this effect has not been well characterized. Our objective was to test the hypothesis that weight loss is directly related to a decline in CRP level. DATA SOURCES: We searched the Cochrane Controlled Trials Register and MEDLINE databases and conducted hand searches and reviews of bibliographies to identify relevant weight loss intervention studies. STUDY SELECTION: We included all weight loss intervention studies that had at least 1 arm that was a surgical, lifestyle, dietary, and/or exercise intervention. Abstracts were independently selected by 2 reviewers. DATA EXTRACTION: Two reviewers independently abstracted data on the characteristics of each study population, weight loss intervention, and change in weight and CRP level from each arm of all included studies. DATA SYNTHESIS: We analyzed the mean change in CRP level (milligrams per liter) and the mean weight change (kilograms), comparing the preintervention and postintervention values from each arm of 33 included studies using graphical displays of these data and weighted regression analyses to quantify the association. RESULTS: Weight loss was associated with a decline in CRP level. Across all studies (lifestyle and surgical interventions), we found that for each 1 kg of weight loss, the mean change in CRP level was -0.13 mg/L (weighted Pearson correlation, r = 0.85). The weighted correlation for weight and change in CRP level in the lifestyle interventions alone was 0.30 (slope, 0.06). The association appeared roughly linear. CONCLUSION: Our results suggest that weight loss may be an effective nonpharmacologic strategy for lowering CRP level.

Biomarkers↗

Intraoperative radiotherapy: current thinking.

Intraoperative radiotherapy (IORT) refers to the delivery of irradiation at surgery. A large single dose of irradiation is delivered to a surgically defined area, while uninvolved and dose-limiting tissues are displaced, the final goal of IORT being enhanced locoregional tumour control. IORT is used in most modern protocol studies as a boost radiation component of multidisciplinary treatment approaches. More recently, high activity radiation sources or mobile operating room treatment machines are used to facilitate the IORT procedure. Clinical experiences have shown that IORT may improve local control and disease-free survival, especially when used in adjuvant setting, combined with external beam irradiation in some neoplasms such as cancer of the stomach, pancreas, colorectum, and soft tissue sarcoma.

Colorectal Neoplasms↗

Increased metabolic activity of fibroblasts derived from cords compared with nodule fibroblasts sampling from patients with Dupuytren's contracture.

BACKGROUND: The pathogenesis of Dupuytren's contracture is characterized by progress in several stages. The disease process includes two structurally distinct fibrotic elements, the so-called nodule and the cord. Several hypotheses have been proposed regarding the cause. Until now, there has been ongoing discussion regarding whether cords or nodules are the primary source of the disease. METHODS: Tissues from 24 patients with Dupuytren's disease were obtained during hand surgery, providing samples from nodules and cords for cell culture. Tissue from the flexor retinaculum excised from healthy patients during surgical procedures on the hand served as control. By using the explant culture technique, fibroblasts were isolated and grown in standard medium. Besides morphological analysis, XTT proliferation tests were performed at various time periods to measure the metabolic activity of the cultivated fibroblasts. RESULTS: Statistical analysis revealed significant differences of nodule- and cord-derived fibroblasts after 1 hour (p = 0.0150), 8 hours (p < 0.0001), and 16 hours (p < 0.0001). CONCLUSIONS: The authors suggest that distinct proliferative properties of Dupuytren-derived fibroblasts are dependent on the cells' origin. Conclusions about the cause or pathogenesis cannot yet be drawn. Further investigation concerning their apparently different fibroproliferative properties is necessary.

Cells, Cultured↗

An outbreak of Norwegian scabies in a surgical ward.

An outbreak of Norwegian scabies in a surgical ward of a teaching hospital was reported. The source of infestation was an elderly diabetic. The epidemic involved 28 of 32 medical personnel in the ward and 3 family contacts. All infected individuals were given a two-course treatment with hexachlorcyclohexane gel. Control of the outbreak was achieved by strict handwashing after patient contact, application of gowns and gloves for contact with skin lesions and the treatment of infected persons. Norwegian scabies in institutions is on the rise, vigilance for its occurrence is needed.

Cross Infection↗