The Timed Swallowing Proficiency for Eating and Drinking (SPEAD) Test: Development and Initial Validation of an Instrument to Objectify (Impaired) Swallowing Capacity in Head and Neck Cancer Patients.

Objective swallowing outcomes measure the physical swallowing function, while subjective outcomes measure swallowing perception. A test for swallowing capacity, measuring the ingestion of all consistencies is currently not available. Therefore, the Swallowing Proficiency for Eating And Drinking (SPEAD) test was developed. It entails the timed ingestion of thin liquid, thick liquid and solid. In this study, its feasibility, reliability and validity were evaluated in patients with dysphagia after treatment for head and neck cancer (HNC) and healthy participants. Thirty-eight HNC patients and forty healthy participants were enrolled in this study and performed the SPEAD test three times. Video recordings of the test were evaluated three times by one observer, and once by three additional observers, to assess test-retest, intra-rater and inter-rater reliability. Validity was assessed by calculating effect sizes for the difference between results of patients and healthy participants and by evaluating correlations with objective (e.g., videofluoroscopy and functional oral intake scale) and subjective (e.g., SWAL-QOL) swallowing outcomes. Test-retest, intra-rater and inter-rater reliability of ingestion duration was good to excellent. All hypotheses with regard to magnitude and direction of correlations were confirmed, supporting construct validity of the test. Our initial results suggest that the SPEAD test reliably measures the transport capacity of the upper digestive tract (in grams per second) and that this test can be useful to objectively evaluate and monitor the (safe) swallowing capacity in HNC patients, in both research as well as daily clinical practice.

Effects of Strengthening Exercises on Swallowing Musculature and Function in Senior Healthy Subjects: a Prospective Effectiveness and Feasibility Study.

Head and neck cancer (HNC) patients may develop dysphagia due to muscle atrophy and fibrosis following chemoradiotherapy. Strengthening of the swallowing muscles through therapeutic exercise is potentially effective for improving swallowing function. We hypothesize that a customized Swallow Exercise Aid (SEA), developed for isometric and isokinetic strengthening exercises (against resistance), can help to functionally strengthen the suprahyoid musculature, which in turn can improve swallowing function. An effectiveness/feasibility study was carried out with ten senior healthy volunteers, who performed exercises 3 times per day for 6 weeks. Exercises included chin tuck against resistance (CTAR), jaw opening against resistance (JOAR), and effortful swallow exercises with the SEA. Multidimensional assessment consisted of measurements of maximum chin tuck and jaw opening strength, maximum tongue strength/endurance, suprahyoid muscle volume, hyoid bone displacement, swallowing transport times, occurrence of laryngeal penetration/aspiration and/or contrast residue, maximum mouth opening, feasibility/compliance (questionnaires), and subjective swallowing complaints (SWAL-QOL). After 6-weeks exercise, mean chin tuck strength, jaw opening strength, anterior tongue strength, suprahyoid muscle volume, and maximum mouth opening significantly increased (p < .05). Feasibility and compliance (median 86 %, range 48-100 %) of the SEA exercises were good. This prospective effectiveness/feasibility study on the effects of CTAR/JOAR isometric and isokinetic strengthening exercises on swallowing musculature and function shows that senior healthy subjects are able to significantly increase swallowing muscle strength and volume after a 6-week training period. These positive results warrant further investigation of effectiveness and feasibility of these SEA exercises in HNC patients with dysphagia.

From reactive to proactive tube feeding during chemoradiotherapy for head and neck cancer: A clinical prediction model-based approach.

OBJECTIVES: Feeding tubes are placed unnecessarily in a proportion of head and neck cancer (HNC) patients treated with chemoradiotherapy (CRT) when prophylactic tube placement protocols are used. This may have a negative impact on the risk of long-term dysphagia. Reactive tube placement protocols, on the other hand, might result in weight loss and treatment interruption. The objective of this study is to identify patients at risk for prolonged tube dependency in order to implement a personalized strategy regarding proactive tube placement. MATERIALS AND METHODS: A retrospective study was performed in a consecutive cohort of HNC patients treated with primary CRT for whom a reactive tube placement protocol was used. A prediction model was developed to predict prolonged (> 90 days) feeding tube dependency. Model performance and clinical net benefit of the model were assessed. RESULTS: Of the 336 included patients, 229 (68%) needed a feeding tube during CRT and 151 (45%) were prolonged feeding tube dependent. The prediction model includes the predictors pretreatment BMI, weight loss, Functional Oral Intake Scale and T-stage. Discriminatory ability is fair (area under the ROC-curve of 0.69) and calibration is adequate (Hosmer and Lemeshow test p = .254). The model shows net benefit over current practice for probability thresholds from 35 to 80%. CONCLUSION: The developed model can be used to select patients for proactive feeding tube placement during primary CRT for HNC. The nomogram with easily obtainable parameters is a useful tool for clinicians to support shared decision making regarding proactive tube placement.

An intrarenal abscess as presenting symptom of an infection with Nocardia farcinica in a patient after renal transplantation.

A 52-year-old man presented 8 months after transplantation with an intrarenal mass, which proved to be caused by an infection with Nocardia farcinica. Because of the potential fatal course of nocardiosis, transplantectomy was performed and long-term antibiotic treatment was instituted. Three-and-a-half years later, this patient underwent successful re-transplantation under co-trimoxazole prophylaxis. At present, more than 1 year after his second transplant has been performed, there are no signs of recurrence of Nocardia infection. To our knowledge, this is the first report of a patient with nocardiosis with an intrarenal abscess as presenting symptom.

Assessment of voice, speech, and related quality of life in advanced head and neck cancer patients 10-years+ after chemoradiotherapy.

OBJECTIVES: Assessment of long-term objective and subjective voice, speech, articulation, and quality of life in patients with head and neck cancer (HNC) treated with concurrent chemoradiotherapy (CRT) for advanced, stage IV disease. MATERIALS AND METHODS: Twenty-two disease-free survivors, treated with cisplatin-based CRT for inoperable HNC (1999-2004), were evaluated at 10-years post-treatment. A standard Dutch text was recorded. Perceptual analysis of voice, speech, and articulation was conducted by two expert listeners (SLPs). Also an experimental expert system based on automatic speech recognition was used. Patients' perception of voice and speech and related quality of life was assessed with the Voice Handicap Index (VHI) and Speech Handicap Index (SHI) questionnaires. RESULTS: At a median follow-up of 11-years, perceptual evaluation showed abnormal scores in up to 64% of cases, depending on the outcome parameter analyzed. Automatic assessment of voice and speech parameters correlated moderate to strong with perceptual outcome scores. Patient-reported problems with voice (VHI>15) and speech (SHI>6) in daily life were present in 68% and 77% of patients, respectively. Patients treated with IMRT showed significantly less impairment compared to those treated with conventional radiotherapy. CONCLUSION: More than 10-years after organ-preservation treatment, voice and speech problems are common in this patient cohort, as assessed with perceptual evaluation, automatic speech recognition, and with validated structured questionnaires. There were fewer complaints in patients treated with IMRT than with conventional radiotherapy.

Evaluation of long term (10-years+) dysphagia and trismus in patients treated with concurrent chemo-radiotherapy for advanced head and neck cancer.

OBJECTIVES: Assessment of long term (10-years+) swallowing function, mouth opening, and quality of life (QoL) in head and neck cancer (HNC) patients treated with chemo-radiotherapy (CRT) for advanced stage IV disease. MATERIALS AND METHODS: Twenty-two disease-free survivors, participating in a multicenter randomized clinical trial for inoperable HNC (1999-2004), were evaluated to assess long-term morbidity. The prospective assessment protocol consisted of videofluoroscopy (VFS) for obtaining Penetration Aspiration Scale (PAS) and presence of residue scores, Functional Oral Intake Scale (FOIS) scores, maximum mouth opening measurements, and (SWAL-QOL and study-specific) questionnaires. RESULTS: At a median follow-up of 11-years, 22 patients were evaluable for analysis. Ten patients (46%) were able to consume a normal oral diet without restrictions (FOIS score 7), whereas 12 patients (54%) had moderate to serious swallowing issues, of whom 3 (14%) were feeding tube dependent. VFS evaluation showed 15/22 patients (68%) with penetration and/or aspiration (PAS⩾3). Fifty-five percent of patients (12/22) had developed trismus (mouth opening⩽35mm), which was significantly associated with aspiration (p=.011). Subjective swallowing function (SWAL-QOL score) was impaired across almost all QoL domains in the majority of patients. Patients treated with IMRT showed significantly less aspiration (p=.011), less trismus (p=.035), and less subjective swallowing problems than those treated with conventional radiotherapy. CONCLUSION: Functional swallowing and mouth opening problems are substantial in this patient cohort more than 10-years after organ-preservation CRT. Patients treated with IMRT had less impairment than those treated with conventional radiotherapy.

Current assessment and treatment strategies of dysphagia in head and neck cancer patients: a systematic review of the 2012/13 literature.

PURPOSE OF REVIEW: Dysphagia, or swallowing impairment, is a serious sequel of head and neck cancer (HNC) and its treatment. This review focuses on the rapidly growing literature published during the past 2 years about the current assessment and treatment strategies of dysphagia in HNC patients. RECENT FINDINGS: Functional swallowing assessment has become standard of care in many HNC centers, to prevent or identify (silent) aspiration, to optimize functional outcomes, and to determine the appropriate rehabilitation strategy. Also preventive swallowing exercises are considered more and more in the pretreatment setting with promising results on (pharyngeal) swallowing function. However, there is a lack of consensus regarding type, frequency, or intensity of the exercises. Furthermore, long-term follow-up of swallowing function might be necessary, given the potential for long-term sequels following HNC treatment. SUMMARY: Regarding dysphagia evaluation, there is still a lack of a uniform 'gold-standard' for both assessment and treatment strategies. More high-quality data, adequately controlled, adequately powered and randomized, on prophylactic and therapeutic swallowing exercises are needed, with longer follow-up and better adherence to treatment, for better understanding the effects of chemo and radiotherapy dosage, and of frequency, timing and duration of treatment, to improve swallowing function and optimize quality of life.

The organisation of fruiting body formation in Dictyostelium minutum.

The process of culmination was investigated in three strains of the species Dictyostelium minutum. After aggregates have been formed a pulsatile signalling mechanism arises; the centre of signal emission becomes the apex of the developing fruiting structure. In the late aggregate, all cells differentiate into prespore cells. Cells that have reached the apex of the culminating cells mass redifferentiate into stalk cells. In two of the three D. minutum strains, interruption of regular stalk formation, more or less random formation of stalk cells and the synthesis of stalk supporting material from cell debris often takes place. The formation of multiple apices on aggregates and early fruiting structures is characteristic for these two strains. Within the species D. minutum, the exhibition of a marked pulsatile signalling mechanism is correlated with a capacity to form a regularly shaped stalk and to organize relatively large cell masses. The possible function of pulsatile signalling in the culmination process is discussed.

Premetamorphic changes in the ultrastructure of Calliphora fat cells.

In the fat body of Calliphora a drastic reorganization of the cell structure, which is related to premetamorphic functional changes, can be observed during the 3rd larval stage of development. These changes include an accumulation of protein storage granules, a decrease in the relative volume of the mitochondria and the surface area of endoplasmic reticulum membrane, and the disappearance of vacuoles. "Absolute" values obtained for organelle areas and membrane perimeters confirm the assumption that large numbers of organelles are eliminated by autophagic activity prior to the pupation period. A temporary restoration of the endoplasmic reticulum is found immediately before pupariation. Large variations in organelle density were found between individual fat cells and between the nuclear, mid- and peripheral regions of the cytoplasm.

Early recognition of prespore differentiation in Dictyostelium discoideum and its significance for models on pattern formation.

An electron microscopic study revealed that during aggregation the cytoplasm of a number of cells increases in electron density. Increased electron density is shown to be the consequence of cell shrinkage, which causes a close packing of cytoplasmic components. Originally electron-dense cells are spread randomly over the aggregate. The anterior prestalk region of the slug is almost devoid of electron-dense cells. In the posterior prespore region, cells with varying degrees of electron density are intermixed with 15-20% electron-lucent cells. During culmination all cells of the prespore region become very electron dense. Besides introducing a new criterion to recognize prespore cells at an early stage of development, our data give further evidence that induction of prespore cell differentiation is not necessarily position dependent.

Electrophysiological properties of Dictyostelium derived from membrane potential measurements with microelectrodes.

Electrical membrane properties of the cellular slime mold Dictyostelium discoideum were investigated with the use of intracellular microelectrodes. The rapid potential transients (1 msec) upon microelectrode penetration of normal cells had a negative-going peak-shaped time course. This indicates that penetration of a cell with a microelectrode causes a rapid depolarization, which can just be recorded by the microelectrode itself. Therefore, the initial (negative) peak potential transient value Ep (-19mV) should be used as an indicator of the resting membrane potential Em of D. discoideum before impalement, rather than the subsequent semistationary depolarized value En (-5 mV). Using enlarged cells such as giant mutant cells (Ep = -39 mV) and electrofused normal cells (Ep = -30 mV) improved the reliability of Ep as an indicator of Em. From the data we concluded that Em of D. discoideum cells bathed in (mM) 40 NaCl, 5 KCl and 1 CaCl2 is at least -50 mV. This potential was shown to be dependent on extracellular potassium. The average input resistance Ri of the impaled cells was 56 M omega for normal D. discoideum. However, our analysis indicates that the membrane resistance of these cells before impalement is greater than 1 G omega. Specific membrane capacitance was 1-3 pF/cm2. Long-term recording of the membrane potential showed the existence of a transient hyperpolarization following the rapid impalement transient. This hyperpolarization was associated with an increase in Ri of the impaled cell. It was followed by a depolarization, which was associated with a decrease in Ri. The depolarization time was dependent on the filling of the microelectrode. The present characterization of the electrical membrane properties of Dictyostelium cells is a first step in a membrane electrophysiological analysis of signal transduction in cellular slime molds.

The innervation of some proboscis structures involved in feeding behavior of the blowfly (Calliphora vicina).

The microtopology of the motoneurons involved in protraction and retraction of the proboscis of the blowfly (Calliphora vicina) has been studied. In addition, taste input from the labellar hairs was investigated. As a result of this study it appears that protraction movements are controlled by two while retraction movements are guided by three motoneurons on each side. The neurons in each group apear to be in ipsicontralateral communication with each other. The musculi protractores fulcri (MPF) probably contain a proprioceptive cell group which projects to the MPF motoneurons. It is proposed that the proboscis motor system can be modulated by proprioception as well as by chemosensory labellar input. Neurosecretory cells may be involved in adjusting muscle power.

Normal chemotaxis in Dictyostelium discoideum cells with a depolarized plasma membrane potential.

We examined a possible role for the plasma membrane potential in signal transduction during cyclic AMP-induced chemotaxis in the cellular slime mold Dictyostelium discoideum. Chemotaxis, cyclic GMP and cyclic AMP responses in cells with a depolarized membrane potential were measured. Cells can be completely depolarized by two different methods: (1) by treatment with azide; this probably causes inhibition of the electrogenic proton pump, which was shown earlier to regulate plasma membrane potential in D. discoideum. (2) By electroporation, which causes the formation of large non-ion-selective pores in the plasma membrane. It was found that in depolarized cells the cyclic AMP-mediated cyclic AMP accumulation was inhibited. In contrast, chemotaxis to a cyclic AMP source was normal; the cyclic AMP-induced accumulation of cyclic GMP, which is known to mediate the chemotactic response, was also not affected. We conclude that membrane-potential-regulated processes, such as voltage-gated ion channels, do not play an essential role in chemotaxis in D. discoideum.