Consanguinity among parents of hearing-impaired children in relation to ethnic groups in the Jewish population of Jerusalem

A longitudinal study was performed on Jewish children with moderately-severe to profound hearing impairment born in Jerusalem during a period of 15 years (1967-1982), and the data on consanguineous matings among their parents were analyzed. These data were estimated in relation to the records obtained in an earlier survey performed on Jewish deaf children during the years 1955-1964. The rate of consanguinity among the parents of hearing-impaired children was much lower in the present survey than in the earlier one in both the Ashkenazi (Central and Eastern European origin) and the non-Ashkenazi (Asian-African origin) group. It is assumed that there is a better understanding of the genetic risk in consanguineous unions, especially when a disability such as hereditary deafness is involved.     

Histological,immunohistochemical, and ultrastructural features of a rat medullary thyroid carcinoma transfected with a corticotropin-releasing hormone cDNA expression vector

Clonal cell lines producing corticotropin-releasing hormone (CRH) have been generated by transfection of the W2 rat medullary thyroid carcinoma (MTC) cell with a CRH-encoding CMV/ SV40 expression vector. Here, we report the morphological, immunohistochemical, and ultrastructural features of rat tumors derived by implantation of CRH-producing W2CRH-7 cells and compare them with non-CRH-producing W2 MTCs. Both types of tumors grew rapidly and consisted of sheets and nests of pleomorphic cells infiltrating adjacent adipose tissue. Immunohistochemistry revealed CRH in only W2CRH-7 tumors; scattered cells in these tumors also were immunoreactive for chromogranin and for vasoactive intestinal peptide. Otherwise, the two tumor types exhibited similar profiles of various neuroendocrine markers, including neuron-specific enolase, synaptophysin, calcitonin, and somatostatin. Ultrastructurally, the tumors contained abundant dilated rough endoplasmic reticulum, a prominent Golgi apparatus, and numerous lysosomes. Very few secretory granules were noted in the W2 tumors; by contrast, secretory granules, although still not numerous in the majority of W2CRH-7 cells, were more abundant in scattered cells of those tumors. The positive immunostaining for CRH is consistent with the observations of increased plasma CRH and pituitary-adrenal activation induced by these transplanted tumors. This system provides a valuable model for CRH excess mimicking tumoral CRH-dependent Cushing’s syndrome in human patients.     

Standard and Nonstandard Applications of Sentinel Node-guided Melanoma Surgery

Identification and histologic study of the sentinel node (SN) is an acceptable, yet not firmly established, guide for treating intermediate-thickness melanoma. This study widens the range of applications of this technique. We included 97 patients with intermediate-thickness melanoma lesions or lesions for which there is no standard treatment. Fifty-six underwent preoperative lymphoscintigraphy, and all underwent intraoperative lymphatic mapping (IOLM) using blue dye, followed by frozen section study and total node processing by serial sections. Elective lymph node dissection was performed in cases of metastasis to the sentinel node or technical failures with high risk. Four categories were defined: (A) intermediate-thickness lesions (mean 2.27 mm) (n= 45); (B) thin lesions (mean 1.14 mm) with risk factors of regional failure (n= 27); (C) lesion thickness close to but more than 4 mm (n= 10); and (D) lesions of undetermined thickness (n= 15). Median follow-up was 30 months (range 13–51 months). Intraoperative lymphatic mapping successfully identified the sentinel node (SN) in 93% of basins explored. Metastases were detected in 11 SNs. There were three lymph basin recurrences in patients with previously negative SNs, all salvaged by therapeutic lymph basin dissection and are NED (no evidence of disease). Two SN⁺ patients had systemic recurrences; one died of his disease, and the other is alive with disease. One SN⁻ patient died NED owing to other cause. This technique spared 83% of category A patients from lymph node dissection. It allowed better staging and better decision making for treatment in categories B and D; and it prevented early regional recurrences in category C patients. Intraoperative lymphatic mapping with SN guidance is a novel, low-morbidity approach applicable and advantageous for a wide range and subgroups of melanoma patients.     

Is parotidectomy justified in elderly patients with pleomorphic adenoma? A decision analysis model

PurposeThe value of parotidectomy in older patients is unclear. This study presents a decision model to help resolve this question.Materials & methodsA Markov model with Monte Carlo simulation was used to compare outcomes in patients of different ages with pleomorphic adenoma of the parotid gland treated by surgery or surveillance.ResultsIn 30-year-old patients, surgery conferred a 3.5-year gain in life expectancy whereas in 75-year-olds, it was only 0.74 months. The expected rate of malignant transformation at age 30 years was 6.5% after surgery and 26.5% after surveillance; at age 65, corresponding rates were 0.8% and 10.7%. Sensitivity analysis showed that age was the only parameter that significantly contributed to life expectancy. The benefit of surgery was restricted in older patients.ConclusionOur Markov decision-analysis model suggests that patients older than 65 years with pleomorphic adenoma have a limited survival advantage with surgery compared to surveillance.     

Effects of surgery for obstructive sleep apnea on cognitive function and driving performance

Background

Obstructive sleep apnea (OSA) is associated with a significantly increased risk of motor vehicle accidents in addition to such cognitive impairments as attention and memory deficits. The aim of the study was to examine the effect of upper airway surgery for OSA on driving and cognitive function.

Methods

Adult patients who underwent surgery for OSA at a tertiary medical center in 2016–2019 were prospectively recruited. Patients were assessed before and 3–6 months after surgery with a self-report and neurocognitive battery and a driving simulation platform.

Results

The cohort included 32 patients of average age 46.9 ± 11.6 years. During the 3 years before treatment, 9 patients had been involved in road accidents and 18 were detained by police for traffic violations. After surgery, there was a significant decrease in the Epworth Sleepiness Scale (13.7 vs. 8.1, p 0.043) and a significant reduction in time to completion of the Color Trail Test (part 1: 21.4 vs 18.7 s, p = 0.049; part 2: 46.8 vs 40.5 s, p = 0.038). Improvements in divided attention and selective attention response times were noted on the advanced stages of the Useful Field of Vision Scale (p = 0.013, p = 0.054). Before surgery, patients showed a high tendency to drive over the speed limit and to cross the dividing line to the opposite lane on the simulation test. Nevertheless, all considered themselves good drivers. These tendencies decreased after treatment.

Conclusions

Surgery for OSA can significantly improve driving performance and cognitive function.

     

Histologic and immunohistochemical characterization of tumor and inflammatory infiltrates in oral squamous cell carcinomas treated with local multikine immunotherapy: the macrophage at the front line

Squamous cell carcinomas of the head and neck (SCCHN) are excellent candidates for local immunotherapy owing to their accessibility and their infiltration by mononuclear cells that are susceptible to immunomodulation. A response rate of 25–60% has been reported for treatment with natural IL-2 or a mixture of natural lymphokines. In the present study, biopsies and posttreatment excision specimens from nine patients with operable SCCHN treated systemically with a variety of immunomodulators and locally with natural lymphokines (multikine, CelSci) were analyzed in an attempt to correlate clinical response to histopathological and immunohistochemical changes. Formalin-fixed, paraffin-embedded tissues were stained with antibodies against lymphocytes (CD45, CD3, CD4, CD8, CD20), macrophages (CD68) including dendritic cells (S-100), markers for lymphocyte activation (CD30, HLA-DR), natural killer cells (CD56 and CD57), beta-2-microglobulin and keratin. One patient showed a complete response to treatment and two a partial response. Tumor size was significantly smaller after therapy. Clinical and pathological regression were more prominent in the smaller tumors. Numerous macrophages, both mononucleated and multinucleated, were present along the tumor-stroma interface in the posttreatment specimens of seven patients, most prominently in the three patients with tumor regression. The increase in the number of CD68+ and S-100+ macrophages after treatment was statistically significant. Lymphocytic infiltrates, which showed some increase following treatment, were composed of a mixture of T and B lymphocytes, the former mostly in contact with the tumor and the latter placed more peripherally. CD8+ lymphocytes extended into the tumors, whereas CD4+ lymphocytes showed minimal extension. Intensity of beta-2-microglobulin staining in tumors was significantly higher following therapy and associated with a better outcome. The marked increase in macrophages following treatment may indicate that the macrophage plays a major role in tumor recognition, destruction and clearance. An increase in the number of macrophages in a posttreatment specimen may indicate immunoresponsiveness.This study is a CISEPO project and was supported in part by the Saul A. Silverman Family Foundation.     

Laser surgery for the treatment of glottic carcinomas

PURPOSE: The standard treatment for patients with early glottic carcinoma in Israel has been radiotherapy. In recent years, encouraging results with laryngo-microscopic carbon dioxide laser surgery as a treatment for early glottic carcinoma has changed our treatment strategy. We conducted a retrospective study to investigate the results of carbon dioxide laser excisional technique for early glottic carcinoma (T1, T2). MATERIALS AND METHODS: Twenty-six had squamous cell carcinoma (SCC), (21 patients with T1 and 5 patients with T2 lesions), 3 had carcinoma in situ, (CIS) and 3 had verrucous carcinoma (VC). RESULTS: All patients were free of disease after salvage treatment at the most recent follow-up. CONCLUSIONS: Careful patient selection with endoscopic staging and strict follow-up are essential to secure good results in the treatment of carbon dioxide laser for early laryngeal carcinoma.     

Fistulae in the inner canthus associated with ethmoiditis.

A case of fistulae in the inner canthus arising from the ethmoidal air cell sinuses is presented. This type of complication is very rare, and to the best of our knowledge no similar case has been reported in the literature. Clinical findings, imaging, pathology and treatment are presented and discussed.     

Juvenile mycosis fungoides diagnosed before 18 years of age

The literature regarding mycosis fungoides in children is sparse. To shed further light on the characteristics of mycosis fungoides in the paediatric population we analysed the clinicopathological features of 10 patients in whom this malignancy was diagnosed before the age of 18 years. All were Jews and Arabs with histologically proven patch/early plaque stage disease: 4 in stage IA, 4 in IB and 2 with unilesional disease. Seven patients had hypopigmented lesions either constituting the sole manifestation (2 patients) or in combination with classic lesions (5 patients); of these, 3 had light skin and 4 pigmented skin. Most patients had immunohistochemical features characteristic of mycosis fungoides, with a predominance of CD4+ T cells. Some had deletion of CD7+ cells. In 3 patients, however, the epidermotropic cells were exclusively or predominantly CD8+ cells. All patients responded to conventional therapy and during an average follow-up of 3.4 years only one patient showed stage progression, but without extracutaneous involvement. It is concluded that juvenile mycosis fungoides is characterized by early stage disease, occasionally with unilesional disease, usually with hypopigmented lesions irrespective of skin colour, and a good response to therapy. On the basis of our experience and review of the literature, it appears that the CD8+ phenotype is over-represented in juvenile disease.     

Differential expression of proliferation- and apoptosis-related markers in lentigo maligna and solar keratosis keratinocytes

Keratinocytes influence the number, morphology, and proliferation of melanocytes. An interference in the melanocyte-keratinocyte relationship may contribute to melanoma development. This study examined the expression of apoptotic and proliferative markers in keratinocytes in lentigo maligna to characterize the epidermis permissive to these lesions. Formalin-fixed and paraffin-embedded tissues from 25 samples of lentigo maligna, 20 samples of solar keratoses, and 5 samples each of normal sun-exposed and non-sun-exposed skin (controls) were immunostained with antibodies directed against the proapoptotic markers bax and p53, the antiapoptotic marker bcl-2, and the proliferation marker ki-67. Eight percent of the lentigo maligna samples were positive for keratinocyte expression of bcl-2, 24% were positive for p53, and 76% were positive for bax; respective findings for solar keratoses were 35%, 85%, and 90%. Comparison with normal sun-exposed skin yielded lower rates of keratinocyte proliferation in 56% of the lentigo maligna samples, similar rates in 36%, and higher rates in 8%; for solar keratoses, proliferation was higher than controls in 60% of samples, similar in 35%, and lower in 5%. All these differences were statistically significant. These findings indicate that there are variable patterns of epidermal reaction to chronic sun exposure. The epidermis in lentigo maligna shows overall low proliferation and an apparently low apoptotic tendency. The dysfunctional epidermis may be permissive to aberrant melanocyte proliferation in the early stages of melanoma development.