Kartagener's syndrome. A blinded, controlled study of cilia ultrastructure

We investigated respiratory mucosa cilia ultrastructure in patients homozygous for the gene for Kartagener's syndrome (KS) and patients apparently phenotypic for KS who had bronchiectasis and sinusitis but without situs inversus. Parents, as obligate carriers of the recessive KS gene, were also evaluated among other control groups. The four patients with KS had significantly fewer cilia outer dynein arms than normal subjects or parents of patients with KS. Two of five patients apparently phenotypic for KS demonstrated distinctive ultrastructural changes. No other subjects demonstrated explicit ultrastructural abnormalities. Internal control specimens showed that the number of outer dynein arms was consistent within a subject compared with variation between subjects. The outer dynein arm serves as a dependable ultrastructural marker. Carriers of KS do not demonstrate distinctive morphologic cilia abnormalities. Not every patient with chronic bronchiectasis and sinusitis demonstrates abnormal cilia ultrastructure.     

Is there a relation between mastoid aeration and Körner’s septum?

The purpose of this study is to investigate the prevalence of Körner’s septum (KS) in temporal bones with varying degrees of pneumatization and to evaluate any relationship between the degree of pneumatization and the presence of KS. Data were obtained retrospectively from 356 temporal bone high-resolution computed tomography of 178 patients who underwent tympanoplasty. Mastoid bone pneumatization was classified as aerated, diploic and sclerotic. The presence of Körner’s septum was also investigated. The relationship between the presence of Körner’s septum and the type of mastoid pneumatization was assessed. KS was encountered in 98 out of total 356 ears. Prevalence of KS was not statistically different between aerated (31%, n = 36), diploic (24.7%, n = 27) and sclerotic mastoids (26.9%, n = 35; p > 0.05). In conclusion, there is no relationship between the presence of KS and the degree of pneumatization. The presence of KS does not necessarily corroborate the presence of poor pneumatization.     

Local treatment of AIDS-associated bulky Kaposi's sarcoma in the head and neck region

Kaposi’s sarcoma (KS) is frequently seen in the head and neck regions of HIV-infected patients. We report two cases of patients with AIDS who consulted the ENT clinic. One patient came to our clinic complaining of abnormal sensations in the pharynx, and dysphasia due to a gross KS in the oropharynx. The excision of the tumor improved the difficulty of swallowing. The other patient complained of masticatory problems and tongue pain due to a bulky KS on the dorsal side of the tongue. We treated the tongue lesion with intralesional chemotherapy. The administration of intralesional vinblastine resulted in a partial response. Unless systemic chemotherapy is effective enough to improve a functional disorder, it is thought that local therapy employing excision or intralesional chemotherapy is one of the common therapeutic option of the otolaryngologist, because this treatment avoids severe side effects caused by systemic chemotherapy or radiotherapy.     

Oropharyngeal kaposi sarcoma in related persons negative for human immunodeficiency virus

OBJECTIVES: Kaposi sarcoma (KS) is a vascular tumor that can affect the mucosa of the upper aerodigestive tract. Although KS is the most common malignancy in patients with acquired immunodeficiency syndrome, it is rare in immunocompetent persons. We describe an unusual presentation of KS in 2 related individuals and describe our attempts to determine whether oropharyngeal KS is associated with human herpesvirus 8 (HHV-8). METHODS: All relevant clinical and surgical information, including information on tumor histopathologic and human immunodeficiency virus (HIV) serologic tests, was abstracted from the patient charts and electronic databases. HHV-8 immunohistochemistry was performed on paraffin-fixed specimens. RESULTS: Both patient 1 and patient 2 (the nephew of patient 1) were referred for workup of a tonsillar mass that was pathologically confirmed to be KS. In each case, HIV serologic testing was negative, and a screening immunologic workup, including a quantitative natural killer cell count, a B- and T-lymphocyte count, and immunoglobulin analysis, also yielded findings that were within normal limits. Immunohistochemistry performed on 1 pathological specimen showed positive staining for the presence of HHV-8, the etiologic agent of KS. CONCLUSIONS: The presence of oropharyngeal KS in 2 related HIV-negative individuals supports a role for genetic factors in susceptibility to KS, a common exposure to an infectious agent such as HHV-8, or both. Whereas most KS cases in industrialized countries are associated with immunodeficiency, clinical and laboratory data do not suggest that either of the patients described in this report are immunodeficient. Their susceptibility to KS may be secondary to a subtle inherited defect in host resistance to HHV-8, or another unknown factor.     

Primary Kaposi’s sarcoma of the nasal cavity not associated with AIDS

Kaposi’s sarcoma (KS) is an unusual vascular tumor characterized by multiple reddish blue nodules, which usually present on the skin of the lower and upper extremities. KS may also involve mucosal sites, lymph nodes and visceral organs. During the last two decades, with the large increase in the incidence of this tumor associated with the acquired immune deficiency syndrome (AIDS), there have been increasing number of cases with KS presenting on the skin or mucosa of the head and neck. A review of the literature revealed that only six cases of primary KS of the nasal cavity have previously been published and only one of them presented in a patient not associated with AIDS. We report the case of a 59-year-old woman who presented 4 years ago with nasal obstruction and intermittent minor epistaxes. Physical examination revealed the presence of a fleshy tumor arising from the left nasal septum, which was excised. Histological examination of the tumor showed morphological and immunohistochemical features of KS. A complete physical and laboratory examination revealed no other pathological findings. The patient received no further treatment and 4 years later, she is in excellent condition. In the present study, we report the second case where the primary manifestation of the KS was in the nasal cavity in a patient with an adequate immune system.     

Classic (Mediterranean) Kaposi’s sarcoma of the true vocal cord: a case report and review of the literature

Kaposi’s sarcoma (KS) is a rare subcutaneous lesion linked mainly with patients suffering from acquired immunodeficiency syndrome. The aim of the present study is to present the first documented case of classic Kaposi’s sarcoma (CKS) located in the right true vocal cord. A 62 year old male presented with cough and hoarseness for 2 months. Clinical examination revealed a nodule on the right vocal cord. The patient underwent surgery and the lesion was removed and biopsied. The histopathology report showed that the lesion was KS but with no complete removal of the lesion, since the surgical margins of the nodule were not healthy. The patient, although fully informed, refused any further treatment. Further laboratory tests were performed, revealing an HIV-negative immunodeficiency profile. Although (Mediterranean) CKS is not an aggressive malignancy, surgery with complete removal of the affected area is indicated when it is applicable. Moreover, conservative treatment and follow up of the patient is essential in order to prevent relapse or other primary lesions.     

Defective monocyte chemotaxis in patients with epidermoid tumors of the head and neck

The function of the immune surveillance system has been studied extensively in patients with neoplastic disease. Defective monocyte chemotaxis has been demonstrated in a variety of neoplastic conditions. We have assayed chemotaxis in monocytic and polymorphonuclear leukocytes taken from patients with epidermoid tumors of the head and neck. Multiwell chemotaxis chambers and the chemoattractant, formyl-methionyl-leucyl-phenylalanine, were used. Polymorphonuclear leukocytes responded normally, but monocytes from all tumor patients studied displayed marked reductions in random migration (86% inhibition) and in chemotaxis (77% inhibition) toward formylpeptide.     

Detecting novel mutations and combined Klinefelter syndrome in Usher syndrome cases

Background: Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, vision loss, and occasionally vestibular dysfunction. Klinefelter syndrome (KS) is an X chromosome polyploidy characterized by one or more additional X chromosomes in males. To date, there has been no report of USH combined with KS.

Objectives: This study examined the causative genes in three Chinese probands with congenital hearing loss.

Material and methods: Targeted next-generation sequencing (NGS) was performed to identify mutations in three probands with hearing loss. Low-coverage whole-genome sequencing (WGS) analysis of aneuploidy was used to verify the chromosome aneuploidy.

Results: Four novel MYO7A mutations were identified in two USH1 probands who were initially diagnosed with nonsyndromic hearing loss until the onset of vision loss. Another case was initially diagnosed with nonsyndromic hearing loss and USH2 and KS were discovered incidentally after the genetic analysis.

Conclusions: Our findings expand the mutation spectrum of MYO7A. This is also the first report of concomitant USH and KS. Genetic testing can help with clinical management, particularly if an unrecognized syndromic disorder is identified before the onset of additional symptoms. A clinical genetic evaluation is recommended as part of the diagnostic work-up in congenital hearing loss.     

Oral cavity and oropharyngeal tumors in human immunodeficiency virus-positive patients: acute response to radiation therapy.

BACKGROUND: The survival of patients with human immunodeficiency virus (HIV) has improved considerably with modern medical management. However, there remains surprisingly little information on treating head and neck neoplasms in HIV-positive patients. OBJECTIVE: To report our recent experience treating oral cavity and oropharyngeal tumors in HIV-positive patients. DESIGN AND PATIENTS: Retrospective analysis of a cohort of 8 HIV-positive patients with Kaposi sarcoma (KS), lymphoma, or squamous carcinoma of the oral cavity or oropharynx who were consecutively treated during a single year with radiation therapy at a tertiary care referral center. Length of follow-up was at least 2 years (mean, 2.5 years). RESULTS: All patients had partial and complete responses to treatment lasting until the last follow-up. However, we found that treatment was considerably better tolerated by patients with non-KS tumors, with fewer acute reactions and significantly less weight loss, despite larger treatment volumes and higher radiation doses, compared with patients with KS. Patients with non-KS tumors received a mean radiation dose of 62.6 Gy to 2636 cm3, yet lost only a mean of 0.1 kg in weight, whereas patients with KS were treated with a mean radiation dose of 19 Gy to a mean volume of 568 cm3, but lost a mean of 5.8 kg during treatment (P = .005) and on average sustained an additional grade of severity on a standard scale of mucosal reaction (P = .01). CONCLUSIONS: Oral cavity and oropharyngeal tumors in HIV-positive patients respond to radiation therapy, but there is a marked difference in the degree of acute reactions to treatment between patients with and without KS. Infection with HIV is not a contraindication when aggressive radiation therapy is needed in select patients.     

Retroviruses in Kaposi's sarcoma in acquired immune deficiency syndrome (AIDS)

The ultrastructure of Kaposi's sarcoma (KS) of the oral mucosa in patients with acquired immune deficiency syndrome (AIDS) was examined electron microscopically. The tumour consisted of pleomorphic vascular endothelial structures and spindle cell formations. The KS cells contained characteristically numerous multivesicular bodies, a large number of tubuloreticular structures and abundant Weibel-Palade bodies in their cytoplasm. Virus particles, 100-120 nm in diameter, were observed budding from the plasma membrane or as free particles already separated from the plasma membrane. Many mature virions manifested a dense cylindrical-shaped core. These virus particles and the human T-cell lymphotropic retroviruses subgroup HTLV-III are ultrastructurally identical. This report is based on recent immunological research.     

Kaposi's sarcoma and community-acquired immune deficiency syndrome

Kaposi's sarcoma (KS), or idiopathic multiple hemorrhagic sarcoma, has heretofore been considered an indolent disease of the elderly, which also occurs in immunosuppressed hosts. Within the last two years, an epidemic of a community-acquired immune deficiency syndrome (AIDS) and disseminated KS has been reported in various population groups across the United States. The head and neck manifestations of KS in AIDS and our experience at UCLA are reviewed. Of 45 patients with AIDS, 18 (40%) had initial disease in the head and neck region. Most commonly, dermal lesions (44%), oropharyngeal lesions (39%), and cervical lymphadenopathy (33%) were noted. One patient had coexistent lymphoma. Six patients (33%) died of opportunistic infections. Head and neck lesions often herald more extensive disease. Early recognition of AIDS is important for complete patient evaluation as well as for personal safety.     

Ultrastructural abnormalities of the cilia in human nasal epithelia

Nasal mucosal cilia were observed with electron microscope in 14 patients with immotile cilia syndrome (ICS), 9 with nasal papilloma (NP), 23 with sinobronchial syndrome (SB), 2 with sinusitis combined with dextrocardia (SC), 1 with Kartagener's syndrome (KS), and 5 normal controls (C). Abnormalities such as complex cilia, cilia with abnormal axonemes and cilia with randomly oriented central microtubules were frequently found in the groups of ICS (8.1%) and NP (10.4%) while less in other groups: SB (4.9%), SC (5.3%), KS (4.7%) and C (3.9%). The percentage of cilia with defective dynein arms (DA) was the highest in the ICS group (94.0%), followed by the groups of SC (53.7%), SB (47.5%), NP (41.2%), C (35.8%) and KS (33.3%). The ICS group was found to be the largest in the number of defective DA per a cilium (4.1), followed by the groups of NP (1.0), SB (0.6), SC (0.7), KS (0.4) and C (0.4). Increased rates of defective DA were also recognized in cilia of tracheal mucosa and flagella of sperm in 7 patients with ICS examined. In conclusion, neither abnormal cilia nor defective DA of cilia are specific findings for ICS. However, when we observe these findings in high percentage in nasal mucosa as well as in other organs, we may define this condition as ICS.     

Chemoradiation in Advanced Head and Neck Cancers: A Comparison of two Radiosensitizers, Paclitaxel and Cisplatin

To compare the locoregional control rates, survival outcome and toxicity profiles between two groups of patients of squamous cell carcinoma (SCC) of Head and Neck (Stage III & IV) receiving concomitant chemo-radiotherapy with Paclitaxel and Cisplatin. A prospective study was done on 94 previously untreated patients of histopathologically proved squamous cell carcinoma of head and neck region-AJCC stage III & IV (T3 & T4 with N0 -N3, M0) treated with concomitant chemoradiation. The patients were divided into two groups. Group A (44 patients) received concomitant chemotherapy (C.T.) with Paclitaxel 40 mgm/m2 while Group B (50 patients) received concomitant chemotherapy with Cisplatin 40 mgm/m2. All the patients in both the groups responded. In Group A (Paclitaxel + R.T.), complete response was seen in 72.7% and partial response in 27.3%. In Group B (Cisplatin +R.T.) complete response was seen in 52% and partial in 48%. At one year follow up, the locoregional control rate (LRC) in Group A was significantly higher as compared to that in Group B (65.9 vs. 46%, P<0.05) while there was no difference in the disease free survival (DFS) and the overall survival (OS). A 3 year estimate of the LRC, DFS and OS using Kaplan Meier Estimator revealed no difference in the LRC, DFS and OS between the 2 groups. There was a higher incidence of skin and mucosal toxicity with Paclitaxel while the gastro-intestinal and hematological toxicity was more with Cisplatin. No significant chronic toxicity except xerostomia was observed in either group. Paclitaxel has better complete response and locoregional control rates at 1?year as compared to cisplatin. However, there is no difference in the estimated 3?year rates of locoregional control, disease free survival and overall survival between the 2 groups.     

基于NK公式和KS公式预测ICL术后早期拱高的一致性研究

目的 探讨基于CASIA OCT的NK和KS公式预测有晶状体眼人工晶体术后拱高的一致性.方法 前瞻性病例研究.选取植入ICL矫正中高度近视患者25例(50眼).采用CAISA OCT分析术后1d、1周、1个月拱高(Vault)变化情况以及NK、KS公式的预测拱高值和实际拱高值的差异以及一致性.各时间点拱高变化数据采用单...     

Immunological responses in acute low-tone sensorineural hearing loss and Ménière's disease

OBJECTIVE: The autoimmune response appears to play an important role in some types of acute sensorineural hearing loss. Endolymphatic hydrops associated with fluctuating hearing loss has also been suggested to be caused by an immunological mechanism. Acute low-tone hearing loss (ALHL) associated with Ménière's disease (MD) is characterized by fluctuating hearing loss, and its etiology is thought to involve endolymphatic hydrops. The aim of this study was to attempt to determine the etiology of ALHL in MD. MATERIAL AND METHODS: A flow cytometer was used to analyze intracellular cytokine levels in peripheral blood from 19 patients with ALHL and 26 patients with MD and the data compared to those obtained from age- and gender-matched healthy volunteers. RESULTS: The patients with ALHL showed significantly increased levels of Th1 subsets (interferon-gamma-producing helper T cells) as compared to those in normal controls. The levels of Th2 (IL-4-producing helper T cells) subsets did not differ from those in the control group and thus Th1 predominated in ALHL patients. The patients with MD showed significantly increased natural killer cell activity but no Th1 dominance. These patients had no obvious systemic or local disease except in the inner ear. CONCLUSION: An abnormality of the Th1/Th2 balance in ALHL and increased natural killer cell activity in MD are thought to relate to inner ear disorder. These results are consistent with the possibility that the etiology of ALHL and MD involves an immune response.     

Investigation of vitamin D levels in patients with Sudden Sensory-Neural Hearing Loss and its effect on treatment

BackgroundDue to high prevalence of vitamin D deficiency and the possible association with Sudden Sensory-Neural Hearing Loss (SSNHL) finding the main causes and appropriate treatments are highly essential. This study aimed to investigate vitamin D levels in patients suffering SSNHL and its effect on response to treatment.Materials and methodsThis cross-sectional study was performed on two groups of case (34 SSNHL patients) and control (34 healthy subjects without risk of hearing loss). All patient information such as age, sex, audiogram illustration of hearing frequency and the level of vitamin D were recorded at baseline. Patients with SSNHL received routine treatments such as 10 days of 1 mg/kg/day steroid and the response or lack of complete response to treatment was recorded and analyzed according to the audiometry.ResultsVitamin D level in SSNHL group with a mean of 19.28 ± 9.56 ng/ml was significantly less than the control group (25.71 ± 11.21 ng/ml; P value < 0.001). After treatment, 76.5% were completely recovered and 23.5% did not recover completely. Factors such as age, sex and level of initial hearing loss did not have a significant effect on the response to treatment, but the level of vitamin D in these patients had a significant relationship with the response to treatment (P value = 0.004); so that all patients with sufficient vitamin D level had completely recovered, versus 87.5% of patients with vitamin D deficiency and 12.5% of insufficient vitamin D had no response to treatment.ConclusionAccording to the results of the present study, the prevalence of vitamin D deficiency in patients with SSNHL was more than healthy people. SSNHL patients with deficient vitamin D had the highest percentage of no response to treatment.     

Detection of neutrophil inhibition factor (NIF) in patient with carcinoma of larynx using skin-window technique

Tumour antigen-induced leucocyte inhibition was studied in vivo in patients with laryngeal carcinomas (squamous-cell type in 13 and transitional cell type in 1 case) and benign tumours (squamous cell papilloma in 2, fibroepithelial polyp in 1 and mixed mesenchymal tumour in 1 case). All the patients were biopsied and autologous tumour-antigen (ATA) was used in vivo skin window test. Release of of ATA-induced neutrophil inhibition factor (NIF) was detected in 12 of 14 (85.7%) malignant cases. Basophilic chemotaxis occurred in 4 malignant cases, following exposure to ATA. Furthermore, 4 other malignant cases also gave positive ATA-induced delayed hypersensitivity (DH) response. Results of this study suggest possible role of immunological factors in limiting tumour dissemination.     

In vivo effects of thymostimulin treatment on monocyte polarization,dendritic cell clustering and serum p15E-like trans-membrane factors in operable head and neck squamous cell carcinoma patients

Head and neck squamous cell carcinoma patients have been characterized by impairments in their cell-mediated immune system, particularly by decreased chemotactic function of monocytes and impairments in the function of the monocyte-derived dendritic cells (viz, a decreased capability to form cell clusters). These impairments are thought to be due to immunosuppressive factors of low molecular mass released by tumor, the so-called p15E-like factors. These suppressive effects of p15-like factors can be neutralized in vitro by thymic peptides, such as thymostimulin (TP1). In a randomized double-blind, placebo-controlled multicenter trial in the Netherlands, 41 patients with operable head and neck squamous cell carcinomas (HNSCC) were treated for 10 days prior to surgery with intramuscular TP1 in one of three dosages (0.5 mg/kg; 1.0 mg/kg or 2.0 mg/kg body weight) or treated with placebo. Assessment of monocyte chemotaxis, the capability of dendritic cells to form clusters and the presence of p 15E-like low-molecular-mass factors (LMMFs) in serum was performed before TP1 treatment and on the day of surgery. Findings demonstrated that TP1 in a dose of 1.0 mg/kg and 2.0 mg/kg resulted in normalization of impaired monocyte chemotactic capability. Although the cluster capability of dendritic cells after TP1 treatment improved, values only reached statistical significance for the 0.5 mg/kg group. Serum p15E-like LMMF levels were not affected by TP1 treatment in any of the patient groups. Contrary to expectations we found no correlation between elevated immunosuppressive LMMFs and defective monocyte chemotaxis or cluster capability of dendritic cells. We conclude that treatment with TP1 can improve monocyte chemotaxis in HNSCC patients but an effect on the production of p15E-like factors by carcinoma cells could not be demonstrated.     

鼻息肉调节激活正常T细胞表达和分泌因子的测定及其意义

目的 探讨在鼻息肉形成过程中,上皮应答时产生调节激活正常Ｔ细胞表达和分泌因子（ｒｅｇｕｌａｔｅｄ ｕｐｏｎ ａｃｔｉｖａｔｉｏｎ,ｎｏｒｍａｌＴｃｅｌｌ ｅｘｐｒｅｓｓｅｄ ａｎｄ ｓｅｃｒｅｔｅｄ,ＲＡＮＴＥＳ）对嗜酸粒细胞趋化、移行、局部聚集的影响。方法 采用无血清原代细胞培养法培养鼾症患者下鼻甲上皮细胞和鼻息肉上皮细胞,经炎性介质ＩＬ－１β（２５ｕｇ／Ｌ,５０ｕｇ／Ｌ）刺激后收集２４ｈ和４８     

Ultrastructure of Kaposi's sarcoma in acquired immune deficiency syndrome (AIDS)

We used electron microscopy to examine the ultrastructural morphology of Kaposi's sarcoma (KS) of the oral mucosa in patients with acquired immune deficiency syndrome (AIDS). The tumors manifested endothelial vascular proliferation and neoplastic spindle cell formations. The endothelial tumor cells contained several multivesicular bodies and a large number of tubuloreticular structures within the endoplasmic reticulum. Ultrastructural changes in the other cytoplasmic organelles included defective cell junctions that seemed to facilitate the migration and extravasation of erythrocytes through endothelial gaps, after which erythrophagocytosis occurred. Tumor cells contained viral particles which were 100-120 nm in diameter and contained dense cylindrical cores. We believe that this is the first time these particles have been identified in KS cells of the oral mucosa in patients with AIDS. These viral particles are also ultrastructurally identical to the human T-cell lymphotropic retroviruses subgroup HTLV-III. Our observations are discussed in the light of recent immunological findings.