Superficial versus total parotidectomy for metastatic cutaneous squamous cell carcinoma and melanoma of the head and neck: a systematic review.

OBJECTIVE: The extent of parotidectomy in the management of regional metastatic disease is controversial. This systematic review aimed to appraise data from studies evaluating superficial and total parotidectomy in metastatic cutaneous squamous cell carcinoma and cutaneous malignant melanoma of the head and neck. METHOD: A systematic search of PubMed, Embase and Cochrane Library was performed. The protocol was registered with Prospero (CRD42020217962). RESULTS: A total of five studies evaluated cutaneous malignant melanoma. Only one compared outcomes of superficial and total parotidectomy: they found higher parotid area recurrence following superficial parotidectomy. Seven studies reported outcomes following cutaneous squamous cell carcinoma; some studies found higher regional recurrence and reduced survival in total parotidectomy, but there was likely selection bias in these studies. Others found no difference in survival between superficial and total parotidectomy. CONCLUSION: The effect of the extent of parotidectomy on outcomes is unclear in cutaneous malignant melanoma and cutaneous squamous cell carcinoma. This systematic review highlights the need for well-designed studies to direct better care.

Lateral rectus muscle palsy secondary to sphenoid sinusitis.

Isolated sphenoid sinus disease is a rare, often misdiagnosed condition of the paranasal sinus. If left untreated, it can lead to complications involving pituitary gland, cavernous sinus, neurological and vascular structures nearby. Early recognition and treatment are critical to prevent the progression of the disease. We present a case of a 60-year-old woman with a history of severe left-sided headache, facial pain, diplopia and left lateral rectus palsy. She was initially referred to ophthalmology and rheumatology for possible giant cell arteritis. Magnetic resonance imaging revealed opacification in left sphenoid sinus with cavernous sinus/superior orbital fissure involvement consistent with left sphenoid sinusitis. She was then referred to the ear, nose and throat department and had endoscopic transnasal sphenoidotomy in theatre. Culture results showed Haemophilus influenza and fungal pseudohyphae. She recovered three months later after a course of antibiotics and antifungals. The onset of isolated sphenoid sinus disease is often insidious and the diagnosis of this condition remains a challenge. Magnetic resonance imaging and computed tomography remain the best diagnostic tools to recognise and manage this condition.

Large-scale two-dimensional MoS2 photodetectors by magnetron sputtering.

We report on the demonstration of photodetectors based on large scale two-dimensional molybdenum disulfide (MoS2) transition metal dichalcogenides. Excellent film uniformity and precise control of the MoS2 thickness down to a monolayer (~0.75nm) were achieved by magnetron sputtering synthesis approach. In particular, the photodetectors integrated with five MoS2 monolayers exhibit a high photoresponsivity of 1.8 A/W, an external quantum efficiency exceeding 260%, and a photodetectivity of ~5 x 10(8) Jones for a wavelength of 850 nm, surpassing the performance of mechanically exfoliated based photodetectors.

Coronary artery spasm (CAS) simulating inferior ST elevation myocardial infarction (STEMI).

Coronary arteries vasospasm (CAS) is commonly seen in invasive cardiology laboratory during diagnostic catheterization or coronary intervention. Though the incidence of Printzmetal angina is uncommon, coronary vasospasm resulting in acute myocardial infarct is rare, especially if there is no significant atherosclerotic plaque within the coronary vasculature.

Esophageal tissue engineering: an in-depth review on scaffold design.

Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patient's own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non-biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design.

Durian induced hyperkalaemia.

Hyperkalaemia is a life threatening acute medical emergency. Patients with end stage renal failure are more prone to get hyperkalaemia as potassium is normally excreted via the kidneys. Therefore, patients with end stage renal failure should avoid food with high potassium contents. Bananas are well known to have high potassium content. However, the 'king of fruits' the durian, has higher potassium content compared to bananas. We describe a case of life threatening hyperkalaemia in a lady with end stage renal failure who ate durians prior to her presentation.

Engineered antibody for treating lymphoma.

One approach to improving the results of antibody treatment of posttransplant and other lymphomas is to alter the geometry of the antibody molecule so as to enhance its cytotoxicity. When antibody alights on a cell, cytotoxicity can be exerted by initiation of apoptotic signals at the cell surface, and by recruitment of effectors to specific sites on the antibody Fc region. Other routes to cytotoxicity have been described but their generality is debatable. The effectors consist of complement, and a series of potentially cytotoxic cells (macrophages, NK cells, neutrophils and others) bearing Fc-receptors (FcR). Recent evidence suggests that the FcR-bearing cells are the more important in dealing with antibody-coated autologous cells, including tumor cells. If the antibody happens to be of the host IgG class then its Fc region (Fcgamma) will contain a site for attachment of a non-cytotoxic FcR known as FcRB (the Brambell receptor): it is this receptor, present on endothelial cells, which recycles the molecule intact if it happens to be endocytosed and thus prolongs its metabolic life. Replacement of the mouse Fcgamma by human Fcgamma is expected to have three beneficial effects: better recruitment of human effector cells, better persistence of the antibody in extracellular fluid, and removal of a major source of immunogenic epitopes. Chemical manipulations of Fab'gamma and Fcgamma modules, linking them in different geometries via their hinge regions, offers constructs with further enhancements of cytotoxicity. These include Fab2Fc2, in which the presence of dual Fc regions enhances recruitment of both complement and cellular effectors; and bispecific antibody of the same modular formula in which one of the Fab arms is specific for tumor while the other is specific for, and recruits powerfully, a cellular effector.

Thioether-bonded constructs of Fab'gamma and Fc gamma modules utilizing differential reduction of interchain disulfide bonds.

We describe a two-stage preparation of chemically engineered Ab constructs, employing as modules Fab'gamma from mAb or rAb, and Fc from human normal IgG1. A multivalent, optionally multispecific F(ab')(n) core is formed in stage one, and one or more Fc modules added in stage two. Examples include bispecific Fab(2)Fc(2) (for simplicity, primes and Greek letters are omitted from names of final constructs) and trivalent Fab(3)Fc(2), which are designed to kill neoplastic cells. An essential element in the construction is the availability of the Fab' in two reduced forms, Fab'(-sulfhydryl (SH))(5) and Fab'-SH. The first is obtained by full reduction of the interchain disulfide bonds (SS) in the F(ab')(2) fragment of IgG. Fab'-SH is obtained by disulfide-interchange reactions on Fab'(-SH)(5), whereby the gamma-light SS is reconstituted, an unusual intrachain SS forms in the gamma-chain hinge, and one hinge SH remains. F(ab')(2) and F(ab')(3) cores are built using partially reduced modules, being given intermodular thioether links that resist reduction. These cores are then fully reduced, making available SH groups for addition of the Fcgamma modules. In the final constructs, all intermodular links embody tandem thioether bonds arising at hinge-region cysteines. Cytotoxic activities of representative constructs, and some enhancements deriving from multiple modules, are assessed. In guinea pigs, catabolism of Fab(2)Fc(2) yielded a t(1/2) similar to that of human IgG1, although the serum Fab(2)Fc(2) revealed some proteolytic breakdown not shown by the IgG1. Immunotherapy of a guinea-pig leukemia confirmed the ability of these constructs to kill target cells in vivo.

Preparation of fcgamma for addition to sulfhydryl-expressing ligands with minimal disturbance of the hinge.

We described previously a scheme for linking functionally intact human normal Fcgamma1, via a thioether linkage emerging from its hinge, to any molecule expressing a free sulfhydryl group (SH). The scheme entails reducing the Fc to release four SH from the two inter-gamma disulfide bonds (SS) in the hinge, blocking one SH by a stochastic alkylation, restoring by SS-interchange the inter-gamma SS whose two SH are still available, and attaching a bismaleimide linker to the one remaining SH. One thereby obtains Fc with a single maleimide group (Fc-maleimide) for attachment to the SH-displaying partner. Restoration of the inter-gamma SS is necessary if the final chimeric construct is to be able to activate the classical complement pathway. However, during this preparation of Fc-maleimide, there is apparently some SS-formation between non-homologous SH, so that not all hinges emerge with a reconstituted inter-gamma SS. To reduce this error we have modified the preparative procedure after investigating an initial partial reduction of the hinge, and reviewing the conditions for stochastic alkylation. During partial reduction by dithiothreitol, the two hinge SS were cleaved apparently randomly: there was no evidence for one bond being more susceptible to reduction than the other, and little indication that the reduction of one bond enhanced the susceptibility of the other. By limiting reduction to an average of one SS per molecule, and alkylation to 0.8 SH per molecule, a final Fc-maleimide product is obtained in which most of the molecules have passed through the entire preparation with one of their hinge SS, and by inference much of the hinge conformation, remaining intact.

Stimulation of cartilage resorption by extracellular ATP acting at P2-purinoceptors.

Net loss of the cartilage extracellular matrix occurs in all forms of arthritis, and it is important to identify the factors that initiate and maintain this process. Extracellular ATP can elicit biological responses via P2-purinoceptors, and we have obtained evidence for the presence of these receptors at the surface of cultured human articular chondrocytes. We have extended this work by examining whether exogenous ATP also promotes cartilage resorption. Cultured explants of bovine nasal cartilage were used, and breakdown of proteoglycans was monitored by measuring the release of glycosaminoglycans. ATP, GTP, CTP, UTP, ITP, 2-methylthioadenosine 5'-triphosphate, and adenosine 5'-O-(3-thiotriphosphate) all promoted release of glycosaminoglycans, whereas ADP, AMP, adenosine, and adenosine 5'-(alpha,beta-methylene)triphosphate were inactive. On lowering the concentration of foetal calf serum in the tissue culture medium from 10% (v/v) to 2.5% (v/v), the response to ATP was enhanced and the minimum effective concentration was reduced. The ATP-elicited release of glycosaminoglycans was also enhanced by interleukin 1 beta, tumour necrosis factor alpha, and transforming growth factor-beta, although only high concentrations of the latter were effective. These data provide further evidence for the presence of P2-purinoceptors in cartilage, and indicate that if ATP arises extracellularly, it could have potentially deleterious effects. The enhancement of the response to ATP by interleukin 1 beta and tumour necrosis factor alpha suggests an additional mechanism whereby these cytokines can promote cartilage resorption.

Induction of enhanced responsiveness of human articular chondrocytes to extracellular ATP by tumour necrosis factor-alpha.

1. We have observed previously that extracellular ATP acting at P2-purinoceptors promotes the production of prostaglandin E2 by human articular chondrocytes, and that this response is enhanced synergistically by interleukin-1 beta. Since other cytokines that influence the metabolism of articular cartilage may have a similar effect, we have investigated whether tumour necrosis factor-alpha also modulates the stimulation of the production of prostaglandin E2 in these cells by ATP. 2. Tumour necrosis factor-alpha enhanced the response of cultured human articular chrondrocytes to a maximally stimulating concentration of ATP (100 mumol/l). This effect was present when the cells were co-incubated with tumour necrosis factor-alpha and ATP for 4 h, was augmented when the cells were also preincubated with the cytokine for 24 h, and remained constant or decline on extending the preincubation period to 72 h. The enhancement of responsiveness to ATP by tumour necrosis factor-alpha was dose-dependent, and the minimum effective concentration (6 pmol/l) did not consistently increase prostaglandin E2 production when the cytokine was tested alone. The presence of tumour necrosis factor-alpha during the incubation with ATP was required for maximum enhancement of the response. Tumour necrosis factor-alpha did not alter the minimum concentration of ATP that stimulated production of prostaglandin E2. 3. Cytokines such as interleukin-1 and tumour necrosis factor-alpha are involved in the pathogenesis of some forms of arthritis, and these data provide additional evidence that their actions in articular cartilage may be modulated by other agents which originate from chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin-1 beta enhances the response of human articular chondrocytes to extracellular ATP.

It has been observed that both interleukin-1 (IL-1) and extracellular ATP stimulate the production of prostaglandin E (PGE) by human articular chondrocytes in monolayer culture. The combined effects of recombinant human IL-1 beta and ATP were therefore studied using these cells. IL-1 beta rapidly enhanced the response to a maximally effective concentration of ATP (100 microM). On continuous exposure of the cells to the cytokine, its effect was greatest after approx. 24 h and tended to decline thereafter. The enhancement of the response to 100 microM ATP by IL-1 beta was dose-dependent. Removal of IL-1 beta prior to treating the cells with 100 microM ATP did not affect the degree of enhancement of the response. The effect of the cytokine on the response to suboptimal concentrations of extracellular ATP was also tested. IL-1 beta lowered the minimum concentration of ATP required to elicit an increase in the production of PGE by human articular chondrocytes. These findings are of interest, since they indicate a synergistic interaction between a cytokine and a purinergic agonist. Moreover, since both the sensitivity of the cells to extracellular ATP and the maximum response to this agent were enhanced, it is possible that IL-1 modulates more than one step in the process of P2-purinoceptor-mediated stimulation of PGE production. These observations may be relevant to the pathogenesis of some forms of arthritis.

Evidence for the presence of P2-purinoceptors at the surface of human articular chondrocytes in monolayer culture.

Extracellular purines can act at purinoceptors to influence metabolic processes. Nucleotide-metabolizing ectoenzymes may modulate such purinergic effects, and their occurrence in a tissue may suggest the presence of purinoceptors. Thus, following the identification of ecto-nucleoside triphosphate pyrophosphatase in cultured human articular chondrocytes, we have studied whether these cells express P2-type purinoceptors. Release of prostaglandin E (PGE) was monitored, since articular chondrocytes synthesize and secrete PGE, and activation of P2-purinoceptors frequently results in enhanced prostaglandin production. Extracellular ATP and ADP stimulated PGE production, whereas AMP and adenosine had only limited effects. ATP concentrations as low as 5 microM were effective, and maximal responses were achieved at 50-100 microM ATP. GTP, UTP and ITP also elicited responses, but tended to be less effective than ATP at equivalent concentrations. Of the analogues of ATP that were tested, only adenosine 5'-(beta,gamma-methylene)triphosphate stimulated PGE production. The response to extracellular ATP was virtually abolished by indomethacin. Treatment of the cells with the P1-purinoceptor antagonist, 8-phenyltheophylline, or with pertussis toxin reduced both basal and ATP-stimulated PGE production, but did not substantially decrease the ratio of ATP-stimulated to basal PGE production. These results indicate the presence of P2-purinoceptors in cultured human articular chondrocytes, and suggest that extracellular ATP may have physiological and pathological effects in human articular cartilage.

Submicromolar manganese dependence of Golgi vesicular galactosyltransferase (lactose synthetase).

1. Manganese(II) buffers were set up with inorganic triphosphate, trimethylenediaminetetraacetate and tetramethylenediaminetetraacetate to study the Mn dependence of beta 1,4-galactosyltransferase (lactose synthetase) in preparations of rat mammary gland. 2. In intact particulate preparations, treated with the calcium ionophore A23187, lactose synthesis was abolished by chelators and restored by bivalent transition metal ions in a manner characteristic of activation site I of the pure enzyme. Ni(II) also activated, as did Mg at high concentration. 3. Only Mn(II) could restore endogenous rates, giving an apparent Km of 0.1-0.2 microM, and eliciting about 70% full activity without addition of a site II activator. 4. In purified Golgi membrane vesicles, Mn gave an apparent Km of 0.4 microM. This increased sharply to about 10 microM on permeabilization with filipin, lysis with detergents, solubilization with Triton X-100, or in the pure enzyme. Preparations of chemically undamaged Golgi vesicles, known to include a proportion of the enzyme on exposed membranes, exhibited both low-Km and high-Km components. 5. The response of particulate galactosyltransferase to apparently physiological concentrations of free Mn(II) ion is interpreted as either due to a sensitizing factor within the Golgi lumen, or to the accumulation of Mn at elevated concentrations. Alternatively, the high Km of the soluble enzyme may reflect proteolytic damage.