Evaluation of liver iron overload with R2* relaxometry with versus without fat suppression: both are clinically accurate but there are differences.

OBJECTIVES: To assess clinically relevant difference in hepatic iron quantification using R2* relaxometry with (FS) and without (non-FS) fat saturation for the evaluation of patients with suspected hepatic iron overload. METHODS: We prospectively enrolled 134 patients who underwent 1.5-T MRI R2* relaxometry with FS and non-FS gradient echo sequences (12 echoes, initial TE = 0.99 ms). Proton density fat fraction for the quantification of steatosis was assessed. Linear regression analyses and Bland-Altman plots including Lin's concordance correlation coefficient were performed for correlation of FS R2* with non-FS R2*. Patients were grouped into 4 severity classes of iron overload (EASL based), and agreement was evaluated by contingency tables and the proportion of overall agreement. RESULTS: A total of 41.8% of patients showed hepatic iron overload; 67.9% had concomitant steatosis; and 58.2% revealed no iron overload of whom 60.3% had steatosis. The mean R2* value for all FS data was 102.86 1/s, for non-FS 108.16 1/s. Linear regression resulted in an R-squared value of 0.99 (p < 0.001); Bland-Altman plot showed a mean R2* difference of 5.26 1/s (SD 17.82). The concordance correlation coefficient was only slightly lower for patients with steatosis compared with non-steatosis (0.988 vs. 0.993). The overall agreement between FS and non-FS R2* measurements was 94.8% using either method to classify patients according to severity of iron storage. No correlation between R2* and proton density fat fraction was found for both methods. CONCLUSION: R2* relaxometry showed an excellent overall agreement between FS and non-FS acquisition. Both variants can therefore be used in daily routine. However, clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. We therefore recommend choosing a method and keeping it straight in the context of follow-up examinations. KEY POINTS: • Both variants of R2* relaxometry (FS and non-FS) may be used in daily routine. • Clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. • It seems advisable choosing one method and keeping it straight in the context of follow-up examinations.

Post-discharge nausea and vomiting after total intravenous anaesthesia and standardised PONV prophylaxis for ambulatory surgery.

BACKGROUND: The incidence of post-discharge nausea and vomiting (PDNV) after ambulatory anaesthesia using total intravenous anaesthesia with a risk-stratified anti-emetic approach is not well documented in the literature. In this study, we outline such an approach. The goal was to achieve an acceptably low rate of PDNV both immediately and the day after surgery. METHODS: With ethics committee approval, adult patients undergoing outpatient surgery received a Propofol-based general anaesthetic plus standardised PONV-prophylaxis corresponding to their Apfel risk-score (0-4); ondansetron (risk-score 2), additional dexamethasone (risk-score 3), and additional droperidol (risk-score 4). On post-operative days one and two, patients scored PDNV and pain (numeric rating scale (NRS); 0 = none at all; 10 = worst imaginable). On post-operative day two, patients indicated the level of interference of PDNV and/or pain with their quality of life. Data are descriptive (%) or mean. RESULTS: There were 222 patients included (age 43 years, 44% female, anaesthesia time 95 min). On the day of surgery, 69.4% of patients did not experience any nausea, 10.4% complained about severe (NRS > 6) nausea, 6.3% experienced vomiting or retching. On the first and second postoperative day, nausea was absent in 88.7% of patients and 97.3%, respectively. Quality of life was impacted (NRS ≥ 4) more by pain (32.8% of cases), than by PDNV (13.6%). CONCLUSION: Acceptably low rates of PDNV were achieved with the proposed standardised approach to PDNV prophylaxis. For almost 90% of patients, PDNV was not an issue the first day after surgery. Pain after discharge was a more common problem.

Factors influencing the level of patients using the internet to gather information before anaesthesia: a single-centre survey of 815 patients in Switzerland : The internet for patient information before anaesthesia.

BACKGROUND: Aim of this study was to identify factors associated with patients using the internet to find information about their upcoming surgery in general, and more specifically about anaesthesia. METHODS: With Ethics committee approval, 1000 consecutive patients seen before elective surgery in the anaesthesia preoperative clinic of a Swiss Level 2 hospital were asked to complete a questionnaire. Primary outcome were patients using the internet to gather any medical information related to their upcoming hospital stay, secondary outcome patients using the internet to gather information regarding the upcoming anaesthesia. Multiple regression was performed to identify independent factors associated with internet use. RESULTS: Eighty-two percent of the patients (n = 815) participated. 97% of those were ASA physical status 1 or 2; 83% (n = 676) had experience with previous anaesthetics, 86% (n = 700) reported to use the internet in general. Overall, about one-third of the participants used the internet to learn more about their medical condition, 26% regarding their upcoming surgical procedure. Only 7% (n = 55) obtained information about the anaesthetic. In multivariate analyses, factors associated with internet use were generally doing so, and planned moderate compared to minor surgery; not using the internet was associated with previous anaesthetic experience. Of those who did not use the Internet to learn about their anaesthetic, 34% indicated that they would have visited a trusted website. CONCLUSION: Only few patients used the internet to obtain information about their upcoming procedure and the anaesthetic part played an even smaller role. However, many patients would have appreciated guidance to find trustworthy internet sites. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00005434 ; date of registration: 27th December 2013); date of enrolment of first patient: 1st August 2013; study retrospectively registered.

Midazolam plasma concentration after anesthesia premedication in clinical routine - an observational study : Midazolam plasma concentration after anesthesia premedication.

BACKGROUND: Midazolam is commonly used as a pre-anesthesia anxiolytic. It`s elimination may not be fast enough for short procedures. In orally premedicated patients we obtained midazolam plasma concentrations at the end of surgical procedures and compared those to concentrations at anesthesia induction. METHODS: The study was conducted prospectively with consent of the local ethics committee (Ethikkomission Kanton Thurgau, Switzerland) and carried out with written informed consent of each patient. Female patients aged 20 to 60 years undergoing elective procedures with general anesthesia were included, and were divided in two groups according to the planned surgical time: group S (<30 min) and group L (90-120 min), respectively. All patients received 7.5 mg Midazolam po as premedication. Blood samples were drawn at anesthesia induction, and at the end of surgery. Data were compared with t-test (independent samples; significance level p <0.05). RESULTS: Twenty-five patients per group were included. Four patients were excluded from analysis, since midazolam was not detectable in any samples. Time of premedication to the 1st blood sample was not statistically different between groups, neither were Midazolam plasma levels at this time point (p = 0.94). None of the patients from group L (n = 24), but five patients in group S (n = 22) did have a higher plasma level of Midazolam at the end of the case compared to the beginning. CONCLUSIONS: The elimination half-life of oral Midazolam can lead to higher plasma levels at the end of a short procedure compared to those at induction of anesthesia. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien), DRKS00005429 ; date of registration 3rd January 2014.

Alemtuzumab in chronic lymphocytic leukemia: final results of a large observational multicenter study in mostly pretreated patients.

This retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced B-cell chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (B-PLL) to definitely describe the impact of this antibody in clinical routine use. Data were collected from 208 consecutive, mainly pretreated, patients with CLL (n = 202), and B-PLL (n = 6) who had received alemtuzumab. Response, progression-free survival (PFS), and overall survival (OS) in various settings were assessed, and toxicities were documented. In these routine patients, a comparably low cumulative dose of alemtuzumab (median, 403 mg) was applied. In CLL, overall response rate was 32 %, and various pre-therapeutic parameters were predictive for inferior response, among them, the prior administration of ≥3 therapy lines (P < 0.001), refractoriness to fludarabine (P = 0.002), and bulky lymphadenopathy (P = 0.003). PFS and OS after start of alemtuzumab were 6.2 and 21.0 months, respectively. Bulky lymphadenopathy was the prominent risk factor for both inferior PFS (P < 0.001) and OS (P = 0.002). In B-PLL, four patients experienced a fatal outcome, whereas two patients had some benefit with alemtuzumab. The main adverse effects were CMV reactivation (20 %) and a broad spectrum of infections, which together were the main reasons for treatment interruption and/or premature termination. In conclusion, alemtuzumab administered even at low dose levels was effective but overall considerably toxic in routine CLL patients. We emphasize that alemtuzumab remains an important therapeutic option in subsets of CLL patients.

Reduction of complement factor H binding to CLL cells improves the induction of rituximab-mediated complement-dependent cytotoxicity.

A main effector mechanism of rituximab (RTX) is the induction of complement-dependent cytotoxicity (CDC). However, this effector function is limited, because CLL cells are protected from complement-induced damage by regulators of complement activation (RCAs). A prominent RCA in fluid phase is factor H (fH), which has not been investigated in this context yet. Here, we show that fH binds to CLL cells and that human recombinant fH-derived short-consensus repeat 18-20 (hSCR18-20) interferes with this binding. In complement-based lysis assays, CLL cells from therapy-naive patients were differently susceptible to RTX-induced CDC and were defined as CDC responder or CDC non-responder, respectively. In CDC responders, but notably also in non-responders, hSCR18-20 significantly boosted RTX-induced CDC. Killing of the cells was specific for CD20(+) cells, whereas CD20(-) cells were poorly affected. CDC resistance was independent of expression of the membrane-anchored RCAs CD55 and CD59, although blocking of these RCAs further boosted CDC. Thus, inhibition of fH binding by hSCR18-20 sensitizes CLL cells to CDC and may provide a novel strategy for improving RTX-containing immunochemotherapy of CLL patients.

Actinomycin D induces p53-independent cell death and prolongs survival in high-risk chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most prevalent lymphoid malignancy in the elderly of the Western world. Although treatment options have improved over the past two decades, 10-15% of patients still have a poor prognosis and are often resistant to therapy. Aberrations in the p53 pathway, such as a deleted (del17p13) or mutated p53 gene, are highly enriched in this class of patients. In an extensive screen for p53-independent apoptosis inducers, actinomycin D was identified from 1496 substances and shown to induce apoptosis in primary CLL cells derived from high-risk patients including those with aberrant p53, revealing a novel p53-independent mechanism of action. Both pro-survival genes BCL2 and MCL1 are targeted by actinomycin D, in contrast to fludarabine the backbone of current treatment schedules. In the well-established TCL1 transgenic mouse model for high-risk CLL, actinomycin D treatment was more effective in reducing tumor load than fludarabine, with no evidence of resistance after three treatment cycles and an overall survival increase of over 300%. Tumor load reduction was coupled to BCL2 downregulation. Our results identify the clinically approved compound actinomycin D as a potentially valuable treatment option for CLL high-risk patients.

The volatile anaesthetic sevoflurane attenuates lipopolysaccharide-induced injury in alveolar macrophages.

Acute lung injury (ALI) is a well-defined inflammation whereby alveolar macrophages play a crucial role as effector cells. As shown previously in numerous experimental approaches, volatile anaesthetics might reduce the degree of injury in pre- or post-conditioning set-ups. Therefore, we were interested to evaluate the effect of the application of the volatile anaesthetic sevoflurane on alveolar macrophages regarding the expression of inflammatory mediators upon lipopolysaccharide (LPS) stimulation in vitro. Alveolar macrophages were stimulated with LPS. Two hours later, cells were exposed additionally to air (control) or to sevoflurane-containing air for 4, 6, 8, 12 or 24 h. Tumour necrosis factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant-1 (CINC-1), macrophage-inflammatory protein-2 (MIP-2) and monocyte chemoattractant protein-1 (MCP-1) proteins were determined and chemotaxis assays were performed. To evaluate possible cellular signalling pathways phosphorylation of the kinases extracellular-regulated kinase (ERK) and Akt was assessed. In the early phase of sevoflurane post-conditioning expression of TNF-alpha, CINC-1, MIP-2 and MCP-1 was attenuated, leading to a diminished chemotaxis reaction for neutrophils. Phosphorylation of ERK seems to be a possible cellular mechanism in the sevoflurane-induced protection in vitro. Pharmacological post-conditioning of alveolar macrophages with sevoflurane immunmodulates the inflammatory response upon stimulation with endotoxin. This might be a possible option for a therapeutical approach in ALI.

Postconditioning with a volatile anaesthetic in alveolar epithelial cells in vitro.

Acute lung injury is a common complication in critically ill patients. The present study examined possible immunomodulating effects of the volatile anaesthetic sevoflurane on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (AEC) in vitro. Sevoflurane was applied after the onset of injury, simulating a "postconditioning" scenario. Rat AEC were stimulated with LPS for 2 h, followed by a 4-h co-exposure to a CO(2)/air mixture with sevoflurane 2.2 volume %; control cells were exposed to the CO(2)/air mixture only. Cytokine-induced neutrophil chemoattractant-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, as well as the potential protective mediators inducible nitric oxide synthase (iNOS)2 and heat shock protein (HSP)-32, were analysed. Additionally, functional assays (chemotaxis, adherence and cytotoxicity assay) were performed. A significant reduction of inflammatory mediators in LPS-stimulated, sevoflurane-exposed AEC was found, leading to reduced chemotaxis, neutrophil adherence and neutrophil-induced AEC killing. While iNOS2 was increased in the sevoflurane group, blocking experiments with iNOS2 inhibitor did not affect sevoflurane-induced decrease of inflammatory mediators and AEC killing. Interestingly, sevoflurane treatment also resulted in an enhanced expression of HSP-32. The data presented in the current study provide strong evidence that anaesthetic postconditioning with sevoflurane mediates cytoprotection in the respiratory compartment in an in vitro model of acute lung injury.

Ep-CAM expression in pancreatic and ampullary carcinomas: frequency and prognostic relevance.

AIMS: Pancreatic adenocarcinoma is an aggressive gastrointestinal malignancy with only a few long-term survivors even after radical surgery. Patients with ampullary cancer have a better prognosis but adjuvant therapy needs further improvement. Epithelial cell adhesion molecule (Ep-CAM) is strongly expressed in a variety of epithelial cancers and represents a promising target for immunological tumour therapy. Thus, the aim of this study was to investigate Ep-CAM expression and its potential prognostic impact in pancreatic and ampullary carcinomas. METHODS: Ep-CAM expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series of consecutive patients with pancreatic (n = 153) and ampullary cancer (n = 34). RESULTS: Ep-CAM overexpression was observed in 85 of 153 pancreatic cancer specimens (56%) and in 29 of 34 ampullary cancer samples (85%). Overall, Ep-CAM failed to be an independent prognostic marker. However, subgroup analyses showed that Ep-CAM overexpression correlated with shorter overall survival among patients with ampullary cancer and advanced stage pancreatic cancer. In the latter subgroup, survival gradually worsened with increasing Ep-CAM scores. Furthermore, in ampullary cancer, Ep-CAM overexpression was found to correlate with tumour stage. CONCLUSIONS: Ep-CAM overexpression was detectable in the majority of cases with pancreatic and ampullary cancer. Therefore, Ep-CAM represents an attractive target for immune-based therapeutic interventions in these tumour entities. However, the prognostic value of Ep-CAM overexpression remains undetermined.

Purine antagonists for chronic lymphocytic leukaemia.

BACKGROUND: Recent trials suggest improved response rates for purine antagonists compared to alkylator-based regimens in the treatment of B-CLL. However, none was able to show a survival advantage. OBJECTIVES: To determine if there is any advantage of purine antagonists compared to alkylating agents (alone or in combination) in the treatment of patients with previously untreated B-CLL. SEARCH STRATEGY: Medical databases (Cochrane Library, MEDLINE, EMBASE), conference proceedings and internet-based trial registers were searched electronically and/or by hand (1990-2003). All references were checked for further trial information. We also contacted experts in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing purine antagonists as single agents with alkylator-based regimens in patients with previously untreated B-CLL were included. We included full-text and abstract publications as well as unpublished data. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were done in duplicate by two independent reviewers. Missing data were obtained from original authors. Endpoints included overall survival, overall response rate, rate of complete remissions, progression-free survival, treatment-related morbidity and mortality. MAIN RESULTS: Five trials with 1838 randomised patients were included. There is some evidence for improved overall survival after treatment with purine antagonists compared to alkylators, but statistical significance was not reached (HR 0.89 [95% CI 0.78-1.01], 4 trials, n=1638). However, the relative risk for achieving an overall response (RR 1.22 [95% CI 1.13-1.31], 5 trials, n=1751) and complete remission (RR 1.94 [95% CI 1.65-2.28], 5 trials, n=1751) was significantly higher, resulting in a longer progression-free survival (HR 0.70 [95% CI 0.61-0.82], 4 trials, n=1638). Incidence of grade III/IV infections was significantly higher in patients receiving treatment with purine antagonists (RR 1.83 [95% 1.30-2.58], 4 trials, n=1620). There was no significant difference concerning the relative risk for grade III/IV neutropenia (RR 1.14 [95% CI 0.98-1.34], 4 trials, n=1620) and therapy-related mortality (RR 0.94 [95% CI 0.45-1.95]). Overall incidence of hemolytic anemia was low, but significantly increased in the purine antagonist group (RR 3.36 [95% CI 1.27-8.91], 3 trials, n=1258). AUTHORS' CONCLUSIONS: Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent purine antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of purine antagonists also augments the risk for grade III/IV infections and hemolytic anemia.

Large-vessel arteritis and myelodysplastic syndrome: report of two cases.

Myelodysplastic syndrome (MDS) is frequently associated with autoimmune diseases such as polymyalgia, arthritis, and rarely, with systemic vasculitis. The pathogenesis of these autoimmune complications remains unknown, but there is increasing evidence of profound immune dysregulation in MDS. In the few cases reported so far, vasculitides associated with MDS affected mainly cutaneous vessels. Here we describe two cases of acute large-vessel vasculitis in association with MDS. The first patient is a 67-yr-old male presenting with a massive large-vessel arteritis as primary manifestation of refractory anemia with excess of blasts type 1 (RAEB-1). The second patient is a 60-yr-old male, who presented with acute thoracic aortitis after a 2-yr history of refractory anemia with ringed sideroblasts (RARS). Both patients received immunosuppressive treatment with steroids, leading to rapid improvement of systemic inflammatory symptoms, vessel wall injury and peripheral blood counts. Whereas the first patient displayed sustained favorable hematologic responses under long-term steroid therapy, there was a rapid transformation into secondary acute myeloid leukemia in the second patient. We conclude that large-vessel vasculitis should be added to the list of potential autoimmune complications in MDS. In this clinical setting, steroid therapy may alleviate inflammatory symptoms and result in beneficial hematologic responses.

Low-dose thalidomide for multiple myeloma: interim analysis of a compassionate use program.

BACKGROUND: Despite recent advances in systemic and supportive therapies, multiple myeloma remains an incurable plasma cell malignancy. Novel therapeutic approaches are thus needed. Thalidomide has recently been recognized as an effective new agent for previously untreated, refractory or relapsed myeloma. PATIENTS AND METHODS: To evaluate the efficacy and tolerability of thalidomide in myeloma, we performed a retrospective analysis of 21 consecutive patients receiving thalidomide alone or in combination with dexamethasone and/or intermittent cyclophosphamide as first-line, maintenance or salvage therapy within a compassionate use program. RESULTS: Of the 21 patients, 16 (76.2%) had refractory or relapsed disease, including 7 (33.3%) patients relapsing after autologous stem cell transplantation. Three patients received thalidomide as maintenance therapy after having achieved a partial remission following autologous stem cell transplantation or conventional chemotherapy. Two patients were given thalidomide as first-line treatment for indolent disease. During long-term treatment (median 12 months, range 1-27 months), patients tolerated only low doses of thalidomide (50-150 mg/day) due to cumulative neurotoxicity. At a median follow-up of 16 months (range 1.5-28 months), we observed an overall response rate of 61.9% (50% for the subgroup receiving thalidomide alone; 77.8% for combination therapy) consisting of 1 complete response, 2 near-complete responses, 8 partial responses and 2 minor responses. Median progression-free survival was 20 months. CONCLUSIONS: We conclude that low-dose thalidomide (50-100 mg/day) alone or in combination is a safe, well-tolerated and effective form of therapy for patients with myeloma at various stages of disease.

Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survival.

Recent studies have demonstrated cyclooxygenase 2 (COX-2) overexpression in various human malignancies, especially in breast cancer, where COX-2 turned out to be a predictor of poor survival. To evaluate the relation of COX-2 and Ep-CAM overexpression and its prognostic significance, we performed a retrospective study on 212 breast cancer patients with a median follow-up time of 10.5 years. Overexpression of COX-2 in tumour tissue samples was assessed by immunohistochemistry. COX-2 overexpression was found in 48.6% of the tumour samples and was predictive for poor disease-free and overall survival. Univariate analysis revealed a strong correlation between COX-2 and Ep-CAM overexpression (P=0.009). Concurrent COX-2 and Ep-CAM overexpression was present in 21.7% of tumour specimens and had an additive negative impact on disease-free and overall survival. Determination of both tumour markers should help in guiding new therapeutic strategies in patients with invasive breast cancer.

Efficacy and safety of cefdinir in the treatment of maxillary sinusitis.

Cefdinir is a new, extended-spectrum, orally active, third-generation cephalosporin that is resistant to bacterial beta-lactamase production. To evaluate efficacy and safety of the antibiotic in maxillary sinusitis, its use was compared with amoxicillin/clavulanate (amox/clav), which is a well-accepted beta-lactamase-resistant antibiotic. In this investigator-blinded multicenter phase III clinical study, 569 patients were randomly assigned to one of three treatment regimens: one daily dose of cefdinir 600 mg (OD), cefdinir 300 mg every 12 h (BD), and amox/clav 500/125 mg every 8 h. All antibiotics were administered orally for 10 days. Maxillary sinusitis was documented by typical clinical signs and symptoms and was confirmed by X-ray imaging. Before treatment, the genus and species of any pathogens were determined from sinus aspirates. Cultures were tested for beta-lactmase production and in vitro resistance to cefdinir and amox/clav. The effectiveness of antibiotic treatment was evaluated 7-14 days after therapy and whether or not recurrent clinical symptoms or persistent infection was determined 21-35 days post-therapy. The appearance of any adverse events was classified as associated or not associated with the medication of the study. Present findings showed that the in vitro susceptibility of pathogens to cefdinir and amox/clav was similar. Cefdinir OD or BD was therapeutically as effective as or better than amox/clav, although cefdinir BD was not as useful as amox/clav clinically. Cefdinir OD and BD and amox/clav were well tolerated. The statistical incidence of adverse events was the same among the three treatment groups, although cefdinir OD treatment had significantly fewer treatment discontinuations due to adverse events than BD and amox/clav.

Angiogenesis as a target for tumor treatment.

Angiogenesis is a key step in tumor growth, invasion and metastasis. Thus, antiangiogenic therapy was postulated to be an attractive approach for antitumor treatment. Based on today's knowledge, at least three strategies for inhibition of angiogenesis are feasible: (1) inhibition of release of angiogenic factors from tumor cells and/or neutralization of angiogenic molecules that have already been released: (2) inhibition of vascular endothelial cell proliferation and migration, and (3) inhibition of the synthesis and turnover of vessel basement membrane. To date, a number of antiangiogenic agents have been identified. In animal models, treatment with angiogenesis inhibitors has proven antitumor effects. Early clinical experience with angiogenic inhibitors indicates that optimal antiangiogenic therapy in the future is likely to be based on the long-term administration to cancer patients in adjunct to surgery, radiotherapy and conventional chemotherapy.

Soft-tissue effects of the holmium:YAG laser: an ultrastructural study on oral mucosa.

BACKGROUND AND OBJECTIVE: The specifics of the ablation mechanism of the holmium:YAG laser remain largely unexplored. Following laser exposure to the oral mucosa of rats, the ultrastructural damage profile obtaining to varying degrees in blood vessels, erythrocytes, nerves, and muscle cells was examined. An attempt was made to relate the cytoplasmatic alterations to the tissue ablation modes of midinfrared lasers described in the literature. STUDY DESIGN/MATERIALS AND METHODS: The biological effects of a new pulsed holmium:YAG laser (lambda = 2,120 nm) on the oral mucosa of rats were examined by light and transmission electron microscopy. Laser incisions reaching into the muscle layer were made on different sites of the tongue of white rats. Laser energy (400 mJ, 2.5 microseconds pulse, 2 Hz) was delivered to the target via 400 microns nylon fibers. RESULTS: The fine-structural morphology of the sublingual mucosa after laser surgery of the epithelial surface revealed no carbonization layer but a 150-micron-wide zone of lacunar structures extending to the lamina propria. In the muscle cells there is partial decomposition of the cell contents resulting in the development of electron optically empty spaces within the cortical cytoplasm underneath the intact plasma membrane of the muscle cell. The organelles within the cell remain ultrastructurally intact. CONCLUSION: These features support the assumption of an additional nonthermal holmium:YAG laser-tissue interaction.

Case report: sicca syndrome due to primary amyloidosis.

Sicca syndrome consists of two major clinical findings: keratoconjunctivitis sicca and xerostomia due to destruction of the lacrimal and salivary gland parenchyma. Although it is most often due to Sjögren's syndrome, a variety of other diseases causes sicca syndrome. We report the rare case of a patient with gland infiltration in primary amyloidosis. Sonographic, computed tomographic and magnetic resonance findings are presented.