Unilateral vocal fold paralysis post-thyroidectomy: does early intervention allow for better voice recovery?

OBJECTIVE: Thyroidectomy is the primary cause of unilateral vocal fold paralysis (UVFP). A delay in rehabilitation may cause dysfunctional phenomena and worsen dysphonia. The main aim is to investigate the impact of early Speech Therapy (ST) on voice recovery in UVFP post-thyroidectomy and propose an appropriate treatment schedule. PATIENTS AND METHODS: 93 patients with UVFP were analysed. 72 presented transient paralysis and 21 permanent ones. Individuals with permanent paralysis were retrospectively divided in two groups. Group A was composed of 11 patients (8 F, 3 M; mean age: 50.5 ± 8.6) who received ST within 8 weeks; Group B comprised 10 patients (7 F, 3 M; mean age: 57 ± 11.5) treated after more than 8 weeks. Videolaryngostroboscopy (VLS) was assessed and both objective and subjective voice parameters were collected. The non-parametric Wilcoxon test was applied to the sample. RESULTS: The resolution of supraglottic compensations was observed in 91% of cases in Group A, whereas in only 40% of cases in Group B. A functional glottal closure occurred in 73% of patients in group A, while it was completely absent in group B. Group A showed a statistically significant difference between the values of Jitter, NHR, TMF and VHI collected pre-ST compared to that collected after 1 year. Conversely, a statistically significant difference was found only for VHI values in group B. CONCLUSIONS: Early ST brings benefits to patients with permanent UVFP, both on voice recovery and on quality of life. A ST protocol should be applied both before and after thyroidectomy. The ST treatment should start early after surgery.

Sapienza Global Bedside Evaluation of Swallowing after Stroke: the GLOBE-3S study.

BACKGROUND AND PURPOSE: Dysphagia occurs in up to 50% of all patients with acute stroke. There is debate regarding which is the most effective screening tool in identifying aspiration in patients with acute stroke. We assessed the accuracy of the Sapienza Global Bedside Evaluation of Swallowing after Stroke (GLOBE-3S), which combines the Toronto Bedside Swallowing Screening Test (TOR-BSST©) with oxygen desaturation and laryngeal elevation measurement during swallowing. METHODS: We prospectively enrolled consecutive patients with stroke within 72 h of symptom onset. All patients with stroke firstly underwent a standard neurological examination, then the GLOBE-3S evaluation and finally the fiberoptic endoscopic evaluation of swallowing (FEES). Two different assessors, a neurologist and a speech pathologist, blind to both the clinical data and each other's evaluation, administered the GLOBE-3S and FEES examination. We assessed the accuracy of the GLOBE-3S in detecting post-stroke swallow impairment with aspiration using the FEES as the standard. RESULTS: We enrolled 50 patients with acute stroke, 28 of whom (56%) had swallowing impairment with aspiration at FEES evaluation. A total of 33 patients (66%) failed the GLOBE-3S evaluation. The GLOBE-3S reached a sensitivity of 100% and a specificity of 77.3% (negative predictive value, 100%; positive likelihood ratio, 4.34). The median time required for the GLOBE-3S to be performed was 297 s. CONCLUSIONS: GLOBE-3S is quick to perform at the bedside and can accurately identify aspiration in patients with acute stroke. By including the measurement of laryngeal elevation and monitoring of oxygen desaturation, it could represent a highly sensitive instrument to avoid the misdiagnosis of silent aspirators.

Methylene blue MMX® tablets for chromoendoscopy. Bioavailability, colon staining and safety in healthy volunteers undergoing a full colonoscopy.

Methylene blue-MMX® tablets are proposed as an aid for detection and visualisation of adenomas and carcinomas in patients undergoing colonoscopy, by improving their detection rate and highlighting the presence of the intestinal dysplastic lesions. Single total doses of 100 and 200 mg were administered to healthy volunteers undergoing a bowel cleansing preparation and a full colonoscopy to investigate the colonic staining. The pharmacokinetics of methylene blue and the safety after exposure to the tablets were also investigated. With 200 mg, the best staining, assessed as the sum of acceptable and good staining, was achieved in the ascending colon and rectosigmoid (75% subjects each), the transverse and the descending colon (approximately 63% each). Absence of staining or overstaining were reported for no colonic region of interest in any subject. Similar results were observed in the 100 mg dose group. Methylene blue blood concentrations reached a peak (Cmax) in a median time (Tmax) of 12 h with 100 mg and 16 h with 200 mg. AUC0-t was 10.7 ±â€¯6.7 µg/mLxh after 100 mg and 25.2 ±â€¯7.4 µg/mLxh after 200 mg. Half-life ranged between 9 and 22 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative urinary excretion was about 28% after 100 mg and about 39% after 200 mg up to 60 h post-dose. The overall frequency of adverse events after single dose of the test product administered along with a bowel cleansing preparation was 39%, but only one was related to the test product: abnormal transaminases. The most frequent adverse event was a transient polyuria (17%). One serious adverse event (gastrointestinal haemorrhage) led the subject to study discontinuation and hospitalisation and another subject withdrew the study due to one adverse event (haematemesis). Either event was not related to methylene blue.

ALK-positive adenocarcinoma of the lung expressing neuroendocrine markers and presenting as a "pituitary adenoma".

We report an ALK-rearranged adenocarcinoma of the lung presenting as a pituitary metastasis, clinically simulating a pituitary adenoma. The patient, a 50 year-old, former-smoking woman was admitted with a Parinaud's syndrome characterized by progressive oculomotor impairment of visual verticality, bitemporal hemianopsia and nystagmus. Imaging studies showed a sellar tumor and the biopsy revealed a TTF-1 and napsin positive lung adenocarcinoma strongly expressing synaptophysin and CD56, also harboring ALK rearrangement. A subsequent CT scan disclosed the primary lung mass of the left upper lobe. The patient progressed after 4 cycles of cisplatin/pemetrexed as first line treatment, but showed a partial response and a significant clinical benefit from the combination of ceritinib and nivolumab in a phase Ib trial. Despite its central nervous system tropism, ALK-rearranged adenocarcinoma manifesting with pituitary gland involvement was never reported. Second generation ALK inhibitors seem the best therapeutic strategy.

Morpho-functional patterns of physiologic oropharyngeal swallowing evaluated with dynamic fast MRI.

With the advent of dynamic fast MRI sequences the act of deglutition can be dynamically visualized in cine-mode. Twenty-three healthy volunteers were enrolled in this study to define the morpho-functional patterns of oral and pharyngeal deglutition using new dynamic MRI techniques. All subjects were previously submitted to video endoscopic assessment, to exclude swallowing abnormalities. As contrast material a combination of yogurt mixed with gadolinium-diethylene diamine pentaacetic acid was used. The protocol was divided into three parts: (a) preliminary assessment of the oral cavity, pharynx and laryngeal structures; (b) morphologic assessment of tongue, soft palate, pharynx, epiglottis and larynx-hyoid bone; (c) dynamic assessment of swallowing without administrating any contrast media and, in subsequent phase, by injecting 5 ml of yogurt-based contrast medium in the patient's mouth. The time resolution was 3-4 images/s. The MR protocol revealed to be effective in the evaluation of normal motility patterns of the structures involved in swallowing. Moreover, the evaluation of the bolus progression, slowdown or stagnation, was possible. On the contrary problems were encountered in calculating precisely the bolus progression time, because of the insufficient temporal resolution. However, more energy should be invested to optimize the spatial and temporal resolution of turbo-FLASH sequences, to obtain a better dynamic representation of a complex function such as deglutition.

Placental gene expression responses to maternal protein restriction in the mouse.

OBJECTIVE: Maternal protein restriction has been shown to have deleterious effects on placental development, and has long-term consequences for the progeny. We tested the hypothesis that, by the use of microarray technology, we could identify specific genes and cellular pathways in the developing placenta that are responsive to maternal protein deprivation, and propose a potential mechanism for observed gene expression changes. METHODS: We fed pregnant FVB/NJ mice from day post-coitum 10.5 (DPC10.5) to DPC17.5, an isocaloric diet containing 50% less protein than normal chow. We used the Affymetrix Mouse 430A_2.0 array to measure gene expression changes in the placenta. We functionally annotated the regulated genes, and examined over-represented functional categories and performed pathway analysis. For selected genes, we confirmed the microarray results by use of qPCR. RESULTS: We observed 244 probe sets, corresponding to 235 genes, regulated by protein restriction (p<0.001), with ninety-one genes being up-regulated, and 153 down-regulated. Up-regulated genes included those involved in the p53 pathway, apoptosis, negative regulators of cell growth, negative regulators of cell metabolism and genes related to epigenetic control. Down-regulated genes included those involved in nucleotide metabolism. CONCLUSIONS: Microarray analysis has allowed us to describe the genetic response to maternal protein deprivation in the mouse placenta. We observed that negative regulators of cell growth and metabolism in conjunction with genes involved in epigenesis were up-regulated, suggesting that protein deprivation may contribute to growth restriction and long-term epigenetic changes in stressed tissues and organs. The challenge will be to understand the cellular and molecular mechanisms of these gene expression responses.

PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma.

The detection of PHOX2B mutations in a small proportion of patients affected with either familial or sporadic neuroblastoma (NB), has arisen interest on the possible pathogenic role of this gene in the disease determination. In this light, we have carried out a quantitative expression analysis of PHOX2B and its paralogue PHOX2A on a panel of NB cell lines and NB tumour samples to identify a possible differential expression between NB cells and their normal counterpart (adrenal medulla cells). Our results revealed that both PHOX2A and PHOX2B are over-expressed in tumour samples and NB cell lines. Particularly, the expression levels of the two genes in NB cell lines show a highly significant correlation, suggesting their possible synergistic role or a coordinated expression regulation. Furthermore, PHOX2 gene over-expression in NB tumours and cell lines suggests these genes may be widely involved in NB development through either a direct mechanism of up-regulation or a failure in maintaining proper transcript levels after embryonic development.

808-nm laser with exogenous chromophores for the treatment of benign oral lesions.

OBJECTIVE: The aim of this study was to verify the effectiveness and safety of the 808-nm wavelength for use on benign lesions of the oral cavity that are stained with toluidine blue solution. MATERIALS AND METHODS: The toluidine blue solution according to Mashberg is used in stomatology for the detection of leuko-erythroplasic lesions. In our experience, we have used it to stain even serous cysts, angiomas, and fibromas. We chose a 808-nm wavelength emitted from a power diode laser, because it is well absorbed by the blue color and barely by the healthy mucosa. The non-contact photocoagulation kept the surrounding borders intact when we used the pulsed-emission, 50 ms 7 W, without anesthesia. No sutures were needed. The leukoplasic borders of the lesions were histologically examined before and after the treatment. RESULTS: The vaporized lesions healed completely in about 5-7 days without any kind of treatment, leaving some slight elastic white scars. A mild edema-erythema followed the treatment for 5-7 days. CONCLUSIONS: The selective results confirm the effectiveness of this therapeutic procedure on pigmented benign lesions, pre-treated with exogenous chromophores and photocoagulated without bleeding, with a minimum energy 808-nm laser.

Two-year follow-up results of copper bromide laser treatment of striae.

OBJECTIVE: The aim of our study was to follow-up 15 patients with stretch marks treated positively with the CuBr laser (577-511 nm) in 1998-99 and followed-up for 2 years. MATERIALS AND METHODS: The patients were Italian women, young to middle age (average 30 years old), with skin coloration classified as Fitzpatrick II-III. Biopsies were taken on some patients before the treatment and 1 month after the first treatment. Double-blind histological, histochemical and photographic evaluation was performed. Results obtained as well as to the contradictory effects reported elsewhere in the literature were compared. RESULTS: On average, the results were positive and there were some pathogenic considerations that justified the use of laser.

Atypical (bizarre) leiomyoma of the nasal cavity with prominent myxoid change.

A 72 year old woman presented complaining of nasal obstruction, rhinorrea, and epistaxis. At examination, a polypoid mass on the right posterior choana was revealed and subsequently removed. Light microscopic findings consisted of a diffuse proliferation of spindle shaped, pleomorphic cells with eosinophilic cytoplasm and blunt ended nuclei in a prominent myxoid background. The presence of numerous plurinucleate, bizarre cells made it very difficult to determine the malignant potential. Immunohistochemical evidence for leiomyogenic markers coupled with the low mitotic rate, the lack of an infiltrating growth pattern, and the indolent clinical course led to the diagnosis of atypical leiomyoma with prominent myxoid change. A literature survey confirmed that such a tumour is extremely rare at this site, but the biological behaviour seems to be similar to its uterine counterpart. Clinicians should be aware of this occurrence to prevent misdiagnosis because a conservative therapeutic approach is necessary in this disease.

[Carcinosarcoma of the larynx: immunohistochemical study, clinical considerations, therapeutic strategies]. / Il carcinosarcoma della laringe: studio immunoistochimico, considerazioni cliniche, strategie terapeutiche.

Carcinosarcoma is a rare laryngeal neoplasm accounting for less than 1% of all malignancies involving this organ. Given its double epithelial, mesenchymal nature, this neoplasm is described in the literature in many ways: sarcomatoid carcinoma, variants of squamous cell carcinoma with fused cells, pseudoscarcoma, pleumorphous carcinoma, polypoid carcinoma, metaplastic carcinoma. Although not invalidating, cytokeratin positive immunohistochemistry is fundamental for diagnosis. Given the different histopathological pictures, the rareness and heterogeneous natural history of such tumors, it is not surprising there is as yet no agreement as to the treatment of choice. An accurate analysis of the literature indicates that both the therapeutic approach and prognosis are the same as those found for normal squamous cell carcinoma. The authors describe a case of laryngeal carcinosarcoma, analyzing the clinical-therapeutic aspects, histopathological features and immunohistochemistry of this rare neoplasm.

Primary high-grade mucosa-associated lymphoid tissue-type lymphoma of the cervix presenting as a common endocervical polyp.

Lymphomas of the uterine cervix are uncommon neoplasms and typically appear as diffuse cervical enlargement. We describe a rare case of primary high-grade lymphoma of mucosa-associated lymphoid tissue of the uterine cervix in a 46-year-old white woman. The tumor, incidentally disclosed at gynecological examination, appeared as a single common polyp. Immunohistochemical investigation found the lesion to consist of a monomorphic CD20-positive infiltrate of large blasts and rare intermingling centrocyte-like lymphoid cells. A dense area of monotypic (lambda light-chain restriction) plasma cells was found beneath the endocervical mucosa; only a few scattered lymphoepithelial lesions were present. The neoplastic cells did not stain for CD5, CD10, CD23, CD43, or cyclin D1. A bone marrow biopsy displayed a paratrabecular, centrocyte-like B-cell infiltration, but no lymphadenopathy was detected by instrumental examination (computed tomographic scan, magnetic resonance imaging). The tumor was successfully treated by multiagent chemotherapy followed by total hysterectomy. To our knowledge, this case represents the second reported example of mucosa-associated lymphoid tissue-type lymphoma occurring in the uterine cervix. We highlight the very unusual gross appearance of this case and emphasize the difficulty of interpreting lymphoid infiltrates in the lower genital tract by microscopy.

Exclusion of candidate genes and chromosomal regions in familial neuroblastoma.

Two families with recurrence of neuroblastoma one Italian and one British with three and two affected children respectively were genotyped using polymorphic markers on chromosome 1 spanning the p32-p36 region frequently deleted in neuroblastoma tumor cells. Linkage to this region was excluded by haplotype inspection and negative lod scores. Furthermore, the exclusion of genes involved in neurocristopathies sometimes associated with neuroblastoma was carried out by typing the Italian family with polymorphic markers located in or near the corresponding genes. Finally, linkage analysis in the two families showed negative lod scores for markers spanning the 16p12-13 chromosomal region where a locus for familial neuroblastoma has been recently mapped. Our findings indicate that different genes are involved in the pathogenesis of familial neuroblastoma.

Cerebral artery K(ATP)- and K(Ca)-channel activity and contractility: changes with development.

The present study was designed to test the hypothesis that in cerebral arteries of the fetus, ATP-sensitive (K(ATP)) and Ca(2+)-activated K(+) channels (K(Ca)) play an important role in the regulation of intracellular Ca(2+) concentration ([Ca(2+)](i)) and that this differs significantly from that of the adult. In main branch middle cerebral arteries (MCA) from near-term fetal ( approximately 140 days) and nonpregnant adult sheep, simultaneously we measured norepinephrine (NE)-induced responses of vascular tension and [Ca(2+)](i) in the absence and presence of selective K(+)-channel openers/blockers. In fetal MCA, in a dose-dependent manner, both the K(ATP)-channel opener pinacidil and the K(Ca)-channel opener NS 1619 significantly inhibited NE-induced tension [negative logarithm of the half-maximal inhibitory concentration (pIC(50)) = 5.0 +/- 0.1 and 8.2 +/- 0.1, respectively], with a modest decrease of [Ca(2+)](i). In the adult MCA, in contrast, both pinacidil and NS 1619 produced a significant tension decrease (pIC(50) = 5.1 +/- 0.1 and 7.6 +/- 0.1, respectively) with no change in [Ca(2+)](i). In addition, the K(Ca)-channel blocker iberiotoxin (10(-7) to 10(-6) M) resulted in increased tension and [Ca(2+)](i) in both adult and fetal MCA, although the K(ATP)-channel blocker glibenclamide (10(-7) to 3 x 10(-5) M) failed to do so. Of interest, administration of 10(-7) M iberiotoxin totally eliminated vascular contraction and increase in [Ca(2+)](i) seen in response to 10(-5) M ryanodine. In precontracted fetal cerebral arteries, activation of the K(ATP) and K(Ca) channels significantly decreased both tension and [Ca(2+)](i), suggesting that both K(+) channels play an important role in regulating L-type channel Ca(2+) flux and therefore vascular tone in these vessels. In the adult, K(ATP) and the K(Ca) channels also appear to play an important role in this regard; however, in the adult vessel, activation of these channels with resultant vasorelaxation can occur with no significant change in [Ca(2+)](i). These channels show differing responses to inhibition, e.g., K(Ca)-channel inhibition, resulting in increased tension and [Ca(2+)](i), whereas K(ATP)-channel inhibition showed no such effect. In addition, the K(Ca) channel appears to be coupled to the sarcoplasmic reticulum ryanodine receptor. Thus differences in plasma membrane K(+)-channel activity may account, in part, for the differences in the regulation of contractility of fetal and adult cerebral arteries.

Cerebral artery sarcoplasmic reticulum Ca(2+) stores and contractility: changes with development.

To test the hypothesis that sarcoplasmic reticulum (SR) Ca(2+) stores play a key role in norepinephrine (NE)-induced contraction of fetal and adult cerebral arteries and that Ca(2+) stores change with development, we performed the following study. In main branch middle cerebral arteries (MCA) from near-term fetal ( approximately 140 days) and nonpregnant adult sheep, we measured NE-induced contraction and intracellular Ca(2+) concentration ([Ca(2+)](i)) in the absence and presence of different blockers. In adult MCA, after thapsigargin (10(-6) M), the NE-induced responses of tension and [Ca(2+)](i) were 37 +/- 5 and 47 +/- 7%, respectively, of control values (P < 0.01 for each). In the fetal artery, in contrast, this treatment resulted in no significant changes from control. When this was repeated in the absence of extracellular Ca(2+), adult MCA increases in tension and [Ca(2+)](i) were 32 +/- 5 and 13 +/- 3%, respectively, of control. Fetal cerebral arteries, however, showed essentially no response. Ryanodine (RYN, 3 x 10(-6) to 10(-5) M) resulted in increases in tension and [Ca(2+)](i) in both fetal and adult MCA similar to that seen with NE. For both adult and fetal MCA, the increased tension and [Ca(2+)](i) responses to RYN were essentially eliminated in the presence of zero extracellular Ca(2+). These findings provide evidence that in fetal MCA, in contrast to those in the adult, SR Ca(2+) stores are of less importance in NE-induced contraction, with such contraction being almost wholly dependent on Ca(2+) flux via plasma membrane L-type Ca(2+) channels. In addition, they suggest that in both adult and fetal MCA, the RYN receptor is coupled to the plasma membrane Ca(2+)-activated K(+) channel and/or L-type Ca(2+) channel.

Epithelioid sarcoma of the penis: a case report and review of the literature.

A rare case of epithelioid sarcoma (ES) of the penis is presented. The patient, a 35-year-old man, was initially treated as having Peyronie's disease, but the subsequent appearance of a subcutaneous nodule displayed a 'distal-type' ES. At immunohistochemical phenotypification, the tumor was positive for vimentin, cytokeratins and epithelial membrane antigen (EMA), as well as for some other multidirectional antibodies, including a membranous reaction for CD99. The review of 11 similar cases so far reported in the literature led to the conclusion that the clinicopathological characteristics of penile ES are basically the same as those of tumors in more classical locations: the age at diagnosis ranged from 23 to 43 years, the interval between first manifestations and diagnosis averaged 37 months (delayed diagnosis being common because of the slow growth rate and the harmless appearance of the lesion), the typical sign was a superficial nodule or mass, usually accompanied (better preceded) by urethral stenosis, dysuria and erectile disturbances. Total or partial penectomy was the treatment of choice in most patients, but lack of adequate follow up did not permit any definitive conclusion to be reached regarding its efficacy.

Addiction: part II. Identification and management of the drug-seeking patient.

The medications most often implicated in prescription drug abuse are opioid analgesics, sedative-hypnotics and stimulants. Patients with acute or chronic pain, anxiety disorders and attention-deficit disorder are at increased risk of addiction comorbidity. It is important to ask patients about their substance-use history, including alcohol, illicit drugs and prescription drugs. Patients who abuse prescription drugs may exhibit certain patterns, such as escalating use, drug-seeking behavior and doctor shopping. A basic clinical survival skill in situations in which patients exert pressure on the physician to obtain a prescription drug is to say "no" and stick with it. Physicians who overprescribe can be characterized by the four "Ds"-dated, duped, dishonest and disabled. Maintaining a current knowledge base, documenting the decisions that guide the treatment process and seeking consultation are important risk-management strategies that improve clinical care and outcomes.

Elizabeth M. Ramsey and the evolution of ideas of uteroplacental blood flow and placental gas exchange.

During the past century a number of investigators have contributed to an understanding of the regulation of uteroplacental blood flow and its influence on placental respiratory gas exchange and fetal oxygenation. Among these, Elizabeth M. Ramsey is noteworthy for her contributions to embryology and placental development. In addition, with several colleagues she performed pioneering cineangiographic studies on the patterns of blood flow in the primate placenta.