Patient's perspective on long-term complications after superficial parotidectomy for benign lesions: Prospective analysis of a 2-year follow-up.

OBJECTIVE: Evaluation of patients' perspective on long-term complications after superficial parotidectomy for benign lesions. DESIGN: A prospective nonrandomized controlled multicenter study. SETTING: Three university-based tertiary referral centers (Departments of Otorhinolaryngology of Cologne, Jena and Giessen; all in Germany). PARTICIPANTS: 130 adult patients, who underwent a primary superficial parotidectomy for benign tumors of the parotid gland, were consecutively included from 09/2010 to 05/2012. 61 patients completed every follow-up examination. MAIN OUTCOME MEASURES: Complications were evaluated using the validated German-language questionnaire Parotidectomy Outcome Inventory 8 at six, 12 and 24 months after surgery. Pain intensity was assessed on a numeric rating scale (NRS) at each follow-up visit. RESULTS: At 6 months after surgery, 90% characterized hypoesthesia as the most disturbing problem, followed by fear of revision surgery (57%) and scar (56%). Facial palsy (14%) posed the minor problem. Hypoesthesia improved significantly during the follow-up period (all P < .05), but still posed a problem for 78% of the patients after 2 years. Pain, which initially bothered 53% of the patients, significantly decreased, whereas impairment due to Frey's syndrome significantly increased during the follow-up (6 vs 24 months; P = .002 and P = .001, respectively). Scar, substance loss, xerostomia, facial palsy, and anxiety affected patients with unvarying severity during the 2 years (all P > .05). CONCLUSIONS: From patients' perspective, sensation loss posed the major subjective problem after superficial parotidectomy. Appearance of the scar, and fear of revision surgery impaired more than 50% of the patients in their daily life without significant improvement during the 2 years postoperatively. Although superficial parotidectomy is a highly standardized and safe procedure, limited parotidectomy for proven benign parotid salivary gland neoplasms is more likely to result in patients with minimal or no displeasing complications.

Recurrence after primary salivary gland carcinoma: Frequency, survival, and risk factors.

BACKGROUND: Primary salivary gland carcinomas (SGC) are rare neoplasms that present therapeutic challenges especially in recurrent tumors. The aim of this study was to investigate the incidence and distribution of tumor recurrence, associated risk factors, and survival. METHODS: This analysis includes data from 318 patients treated for SGC between 1992 and 2020. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to identify risk factors associated with recurrence. RESULTS: 21.7% of the patients developed recurrent disease after a mean of 38.2 months. In multivariate analysis, positive-resection margins, vascular invasion, and tumor localization in the submandibular gland and small salivary glands were independent factors for recurrence. The 5-year overall survival was 67%, the 5-year disease-free survival was 54%. CONCLUSION: Tumor recurrence in SGC occurred in one out of five patients. In highly aggressive entities and patients with risk factors, treatment intensification should be considered.

Incidence and clinical outcome of primary carcinomas of the major salivary glands: 10-year data from a population-based state cancer registry in Germany.

PURPOSE: The aim of this project was to provide an overview of the epidemiology of primary salivary gland carcinomas (SGC) in terms of incidence, distribution of clinicopathological features and survival in one of the largest cancer registries in Europe. METHODS: Data were collected from patients with SGC of the major salivary glands registered in the population-based state cancer registry (Landeskrebsregister LKR) in North Rhine-Westphalia (NRW), Germany from 01/01/2009 to 12/31/2018. Age standardization of incidence was performed and relative survival estimates were computed by sex, histological group, age group and T-, N-, and M-stage. RESULTS: A total of 1680 patients were included in this analysis. The most frequent tumor localization was the parotid gland (78%). Adenocarcinoma (not otherwise specified) was the most common tumor entity (18.5%). Most tumors were found in stages T1-T3 (29% T1; 29% T2; 28% T3). The age-standardized incidence rate (ASR) for SGC was 0.65/100,000 and remained stable during the observation period. There was an age-dependent incidence increasing especially from the age 70 years and onwards. The overall 5-year relative survival (RS) for all patients with SGC was 69.2%. RS was 80-95.6% for T1-2 stage tumors, 60.3% for T3, 47.3% for T4 stage, 87.4% for N0 and 51.2% for N1-2, 74.4% for M0 and 44.9% for M1. CONCLUSION: Age-standardized incidence for SGC has been stable for the observed 10-year period. Smaller tumors and those without lymph node or distant metastases had a better RS than more advanced tumors.

Expression of Mucins in Different Entities of Salivary Gland Cancer: Highest Expression of Mucin-1 in Salivary Duct Carcinoma : Mucin-1 - highest expression in Salivary Duct Carcinoma.

Therapeutic options for advanced salivary gland cancer (SGC) are rare. Therefore, it was the aim of this study to investigate the extent and intensity of Mucin-1 (MUC1), Mucin-16 (MUC16), and Mucin-5AC (MUC5AC) as potential molecular targets using immunohistochemistry. The medical records of all patients who underwent primary surgery for salivary gland cancer with curative intent in a tertiary referral center between 1990 and 2018 were reviewed. Immunohistochemical staining for MUC1, MUC16, and MUC5AC was performed for all patients with sufficient formalin-fixed paraffin-embedded material, and a semi-quantitative combined score derived from the H-score for the cytoplasmatic, the membranous and the apical membrane was built for the most common entities of SGC. 107 patients with malignancies of the parotid (89.7%) and the submandibular gland (10.3%) were included. The most common entities were mucoepidermoid carcinoma (MuEp; n = 23), adenoid cystic carcinoma (AdCy; n = 22), and salivary duct carcinoma (SaDu; n = 21). The highest mean MUC1 combined score was found in SaDu with 223.6 (±91.7). The highest mean MUC16 combined score was found in MuEp with 177.0 (±110.0). The mean MUC5AC score was low across all entities. A higher MUC1 combined score was significantly associated with male gender (p = 0.03), lymph node metastasis (p < 0.01), lymphovascular invasion (p = 0.045), and extracapsular extension (p = 0.03). SaDu patients with MUC16 expression showed a significantly worse 5-year progression-free survival than those without MUC16 expression (p = 0.02). This is the first study to give a comprehensive overview of the expression of MUC1, MUC16, and MUC5AC in SGC. Since advanced SGCs lack therapeutic options in many cases, these results warrant in vitro research on therapeutic targets against MUC1 in SaDu cell lines and xenograft models.

Bacterial ice-nucleation proteins.

Certain bacteria possess proteins that enable them to nucleate crystallization in supercooled water. These ice-nucleation proteins are thought to produce templates for the assembly of very small seed crystals of ice. The proteins from different species have related, internally repetitive primary structures, which may be directly responsible for aligning the water molecules of the seed crystal.

Analysis of smoking behaviour in patients with peritonsillar abscess: a prospective, matched case-control study.

OBJECTIVE: Smoking is purported to increase the risk of peritonsillar abscess formation, but prospective data are needed to confirm this hypothesis. This prospective study aimed to identify this correlation. METHODS: Fifty-four patients with peritonsillar abscess were prospectively asked about their smoking behaviour using a questionnaire that was designed and approved by the Robert Koch Institute (Berlin, Germany) to analyse smoking behaviour in epidemiological studies. Afterwards, a consecutive control group (without peritonsillar abscess), matched in terms of age and gender, was surveyed using the same questionnaire. A classification of smoker, former smoker and non-smoker was made, and the numbers of pack-years were calculated and compared. RESULTS: Statistical analysis of both groups revealed a significant correlation between peritonsillar abscess and smoking experience (p = 0.025). Moreover, there were significantly fewer non-smokers in the non-peritonsillar abscess group (p = 0.04). The number of pack-years was higher in the peritonsillar abscess group (p = 0.037). CONCLUSION: There is a statistically significant association between peritonsillar abscess and smoking.

Sequelae of carpal tunnel surgery: rationale for the design of a surgical approach.

The sequelae of carpal tunnel surgery were reviewed and were presumed to be associated with the linear vertical section of the transverse carpal ligament because this was the common element in the reported series. The authors adopted a modified approach, substituting a parabolic incision that left a protective flap of the ligament to cover the structures within the tunnel in the area of maximum convexity of the wrist. The results from a recent series of 100 cases were contrasted with a control series of 770 previous cases. Untoward postoperative sequelae were significantly reduced through this modified approach. The improved results, the authors conclude, were attributable to a reduction of pressure within the carpal tunnel, while avoiding the wide gaping of the tunnel space that is associated with vertical incisions, which may allow an anterior displacement of the median nerve and flexor tendons between the cut ends of the transverse carpal ligament and sometimes result in a continuous scar through the skin.

Surgical management of extreme lateral lumbar disc herniations: review of 138 cases.

Extreme lateral disc herniations in the authors' series account for 10% of all lumbar herniations; 80% occurred at the L3, L4 and L4, L5 interspaces. The authors review the clinical findings in 138 patients and point to the characteristic features of the clinical syndrome. They compare the accuracy of various diagnostic studies and conclude that computed tomography is highly accurate and should be used before other diagnostic studies. Discography is still helpful as a confirmatory study in some cases, whereas myelography is particularly useful in disclosing other associated lesions. Analysis of the operative series revealed a high percentage of extruded fragments (60%) and a significant number of double herniations on the same side and at the same level (15%). These two findings may respectively preclude chemonucleolysis and microsurgery from the surgical management of extreme lateral herniations. Double herniations explain some discrepancies in the clinical picture and are emphasized as a potential source of error in diagnosis. The surgical technique allows exploration for herniations within the intervertebral canal as well as for extraforaminal herniations without sacrifice of the facet. Operative results are presented.

Molecular aspects of microbial ice nucleation.

Certain organisms nucleate the crystallization of ice. This requires a small volume of water to be induced, probably by lattice-matching with a solid template, to form an 'ice embryo'--a region sharing at least some of the characteristics of macroscopic ice. It is of particular interest to understand the structure and function of biological structures capable of lattice-matching (or otherwise inducing a quasi-crystalline state). Some strains of the Gram-negative eubacterial genera Erwinia, Pseudomonas, and Xanthomonas, and the mycobionts of certain lichens, display ice-nucleating activity. In bacteria, the activity is conferred by a protein that contains three nested periodicities of repetition, which probably reflects a hierarchy of three motifs of structural repetition. Thus the tertiary structure of the ice-nucleation protein is likely to be regular, consistent with the expectation of its forming a template for lattice-matching. Even within a clonal culture, the nucleating sites formed by bacteria and lichens vary considerably in the threshold temperatures at which they display activity; this indicates wide variations in either the size of the template, or its structural regularity, or both. However, ice-nucleating sites of lichen and bacterial origin are clearly differentiated by their sensitivities to experimental treatments.

Fluorescence lifetime and time-resolved polarization anisotropy studies of acyl chain order and dynamics in lipid bilayers.

The time-resolved fluorescence intensity and anisotropy decays of cis- and trans-parinaric acids and phosphatidylcholines labeled with trans-parinaric acid have been characterized in bilayers formed by several phosphatidylcholines and by dipalmitoylphosphatidylcholine-cholesterol mixtures, at several temperatures. Both a conventional free-running nitrogen flashlamp and the novel synchrotron source at the Stanford Linear Accelerator Center (SLAC) were used as excitation sources for a modified single photon counting fluorescence lifetime apparatus. The measured emission decay kinetics of both isomers of parinaric acid were biexponential in all but one of the lipid systems examined. The fluorescence anisotropy of parinaric acid was large and constant in gel phase lipids, but showed a very rapid (approximately 2 GHz) decay of large amplitude in fluid lipids. In all lipid systems studied, the fluorescence anisotropy decayed to a nonzero asymptote, in striking contrast to the behavior observed in viscous solvent solutions. The asymptotic anisotropy was used to calculate an "order parameter" of the emission transition dipole. The value of the order parameter is quite close to that obtained by deuterium NMR. Cholesterol increased the order parameter measured in fluid dipalmitoylphosphatidylcholine but did not substantially affect the rate of angular relaxation. Experiments conducted with trans-parinaroylphosphatidylcholines yielded results virtually identical with those obtained with trans-parinaric acid.

An analytic solution to the Förster energy transfer problem in two dimensions.

An analytic solution of the Förster energy transfer problem in two dimensions is presented for the case in which the orientation factor is independent of the donor-acceptor distance, and both the donors and acceptors are randomly distributed in a plane. A general solution based on the method of Förster is possible since all distances are measured in units of R0. The analytic solution is extended to the cases of donors embedded in structures that exclude acceptors, and donors that bind acceptors. The validity of the analytic solutions is demonstrated by comparison with numerical simulation calculations. Numerical approximations to the exact solutions are given for ease of computation. Specific applications to the case of fluorescence quenching of a membrane-bound donor by membrane-bound acceptors are presented.

Conserved repeats in diverged ice nucleation structural genes from two species of Pseudomonas.

Sequence analysis shows that an ice nucleation gene (inaW) from Pseudomonas fluorescens is related to the inaZ gene of Pseudomonas syringae. The two genes have diverged by many amino acid substitutions, and have effectively randomized the third bases of homologous codons. By reference to their potential for change, it is shown that certain conserved features must have been maintained by selection pressure. In particular, their conservation of internal sequence repetition, with three orders of repeat periodicity in each gene, suggests that the pattern of repetition is significant to the gene products' function. We propose models for the structure of the gene products in which each order of periodicity would be required for the nucleation function.

Bilayer acyl chain dynamics and lipid-protein interaction: the effect of the M13 bacteriophage coat protein on the decay of the fluorescence anisotropy of parinaric acid.

Nanosecond fluorescence polarization anisotropy decay is used to determine the effect of the bacteriophage M13 coat protein on lipid bilayer acyl chain dynamics and order. The fluorescent acyl chain analogues cis- and trans-parinaric acid were used to determine the rate and extent of the angular motion of acyl chains in liquid crystalline (39 degrees C) dimyristoylphosphatidylcholine bilayers free of coat protein or containing the coat protein at a protein:lipid ratio of 1:30. Subnanosecond time resolution was obtained by using synchrotron radiation as the excitation source for single photon counting detection. Previous measurements of Förster energy transfer from coat protein tryptophan to cis- or trans-parinaric acid have shown that these probes are randomly distributed in the bilayer with respect to the protein. The anisotropy decay observed for pure bilayers has the form of a rapid drop, followed by a nonzero constant region extending from roughly 3 ns to at least 12 ns. The magnitude of the anisotropy in the plateau region is simply related to the acyl chain order parameter. The effect of the M13 coat protein is to increase the acyl chain order parameter significantly while having only a small effect on the rate of angular relaxation. This behavior is rationalized in terms of a simple microscopic model. The order parameters for pure lipid and coat protein containing bilayers are compared to 2H-NMR values.

Retinal migration during dark reduction of bacteriorhodopsin.

When the retinal Schiff base in chymotryptically cleaved bacteriorhodopsin is reduced to a secondary retinylamine by prolonged exposure to 10% (wt/vol) sodium cyanoborohydride, at pH 10, in the absence of light, approximately 45% of the retinal is found linked to Lys-41 and 22% to Lys-40, and the remainder is scattered over various sites on the large chymotryptic fragment, including the physiological site at Lys-216. The retinal-binding site is destroyed or blocked by the reduction conditions, but the bacteriorhodopsin lattice remains intact. The results demonstrate that artifactual linkage to Lys-40/41 is possible under special conditions. Under these conditions, the epsilon-amino groups of Lys-40/41 show an enhanced ability to form retinylidene linkages with the retinal released by the physiological linkage site at Lys-216, due to some combination of close proximity to the normal linkage site, and increased reactivity with respect to other lysine epsilon-amino groups. The results are of interest for the characterization of the two newly discovered rhodopsin-like proteins, halorhodopsin and slow rhodopsin.

Photochemical dimerization of parinaric acid in lipid bilayers.

Parinaric acid (9,11,13,15-octadecatetraenoic acid), a conjugated tetraene fatty acid, undergoes a second-order photochemical reaction in phospholipid bilayers. The reaction results in the loss of the characteristic absorption of this chromophore and the development of new absorption demonstrating the presence of a triene chromophore. The progress of this reaction is easily monitored by measurement of the decrease in the fluorescence intensity from a uniformly illuminated sample. The reaction rate measured in this way is sensitive to the thermal phase transition of the bilayer and to the presence of cholesterol. The relationship of the second-order rate constant to the lipid diffusion coefficient is discussed. This relationship differs from that previously used for the analysis of similar photochemical processes.

Ice nucleation activity of Pseudomonas fluorescens: mutagenesis, complementation analysis and identification of a gene product.

A DNA fragment of 7.5 kb from Pseudomonas fluorescens MS1650 confers an ice nucleation phenotype when cloned in Escherichia coli. This DNA encodes a protein with an apparent mol. wt of 180 kd, which is found in both inner and outer membrane fractions of transformed E. coli cells. Insertion mutations throughout a 3.9-kb region cause deficiency in ice nucleation, and eliminate the 180-kd protein. Complementation is not observed between any pair of mutations, suggesting that the nucleating phenotype is encoded by a single transcriptional unit. Mutations in most parts of the 3.9-kb region are not completely deficient in phenotype: they still generate ice nuclei at low frequency. One insertion mutation was found to generate pseudowild revertants, which had undergone deletions of the entire insertion and some of the adjacent sequence; these could account for the incomplete deficiency. These deletions displayed depressed nucleation temperatures, but their nucleation frequencies were close to that of the wild-type gene.

Mapping of the triazine binding site to a highly conserved region of the QB-protein.

A number of herbicide classes, including the s-triazines and ureas (atrazine, diuron) inhibit photosynthetic electron transport via a direct interaction with the QB-protein. This protein, also known as the 32-kDa protein or herbicide binding protein, is believed to bind the plastoquinone QB, which functions as the second stable electron acceptor at the reducing side of Photosystem II. The site of covalent attachment of the photoaffinity herbicide analog azido-[14C]atrazine to the QB-protein of spinach chloroplast thylakoid membranes has been determined. Two amino acid residues are labeled; one residue is methionine-214, the other lies between histidine-215 and arginine-225. Both residues are within a region of the amino acid sequence which is highly conserved between the QB-protein and the L and M reaction center proteins of Rhodopseudomonas capsulata and R. sphaeroides. This region includes the site of a mutation which results in diuron resistance in Chlamydomonas reinhardi (valine-219). However, this region is well removed from point mutations at phenylalanine-255 (which gives rise to atrazine resistance in C. reinhardi) and at serine-264, (which results in extreme atrazine resistance in C. reinhardi and naturally occurring weed biotypes). The patterns of labeling and mutation imply that the quinone and herbicide binding site is formed by at least two protein domains.

Nonlinear relationship between concentration and activity of a bacterial ice nucleation protein.

The expression level of an ice nucleation gene (inaZ) was varied in Escherichia coli to observe the relationship between activity and gene product. The ice nucleation activity increased as the 2nd to 3rd power of the membrane concentration of the inaZ gene product, implying that molecules of InaZ protein interact cooperatively in groups of two to three at the rate-limiting step of ice nucleus assembly. The 2nd to 3rd power relationship was independent of the threshold temperature at which ice nucleation was measured and was consistent over a 500-fold range of protein concentration. Such a relationship indicates that the same rate-limiting step must be common to the formation of ice nuclei displaying all the various threshold temperatures within a bacterial population. Observations of Pseudomonas syringae, expressing the inaZ gene at various levels, were consistent with a similar relationship and hence a similar mechanism of ice nucleus assembly in Pseudomonas.