Neurofibromatosis type 1 and the "elephant man's" disease: the confusion persists: an ethnographic study

Background: In 1986, two Canadian geneticists had demonstrated that Joseph Merrick, better known as the Elephant Man, suffered from the Proteus syndrome and not from neurofibromatosis type 1 (NF1), as was alleged by dermatologist Parkes in 1909. Despite this and although the two diseases differ at several levels: prevalence, diagnostic criteria, clinical manifestations and transmission, the confusion between NF1 and the "elephant man's" disease continues in medical and social representations by current linguistic usage, and in some media reports. With this article, we want to 1) document the persistence and extent of this fallacy, 2) identify certain critical factors that contribute to its persistence, and 3) evaluate its impact on the health and well being of patients with NF1 and their family members.Methodology: Participant observation in the course of an ethnographic study on intergenerational dialogue between individuals with neurofibromatosis and their parents - Analysis of the scientific literature and of pinpoint articles in the print and online news media.Findings: Our findings show that because physicians have little knowledge about NF1, several print and online news media and a lot of physicians continue to make the confusion between NF1 and the disease the "elephant man". This misconception contributes to misinformation about the disease, feeding prejudices against affected patients, exacerbating the negative impacts of the disease on their quality of life, their cognitive development, their reproductive choices, as well as depriving them of proper care and appropriate genetic counseling.Conclusion: If family physicians and pediatricians were properly informed about the disease, they could refer their patients with NF1 to NF clinics and to specialists. Thus, patients and their family members would benefit from better-tailored clinical management of their cases, perhaps even optimal management. [corrected]     

Vascular Manifestations of von Recklinghausen's Disease

A casual relationship between von Recklinghausen''s disease, or neurofibromatosis, and arteriolar abnormalities has been reported in the European literature. A patient was seen who had biopsy-proved neurofibromatosis and renovascular hypertension and retroperitoneal bleeding. An arteriographic study showed multiple small aneurysms throughout the coeliac axis, the superior mesenteric artery and in several small intrarenal vessels. Renal vein renin levels were elevated particularly in the right renal vein, supporting the diagnosis of renovascular hypertension. Both the aneurysms seen in angiographic studies and the retroperitoneal hemorrhage are probably vascular manifestations of von Recklinghausen''s disease. Support for this conclusion is enhanced by the absence of clinical, laboratory or histologic data supporting the only tenable differential diagnosis, periarteritis nodosa.     

Diffuse large B cell lymphoma presenting as Horner's syndrome in a patient diagnosed with neurofibromatosis type 1: a case report and review of the literature

Introduction

Horner's syndrome has a variety of etiologies ranging from benign to serious life-threatening conditions and has been infrequently reported as a presenting symptom of patients with lymphoid neoplasms. Only one case of Burkitt's lymphoma presenting with toothache, paresthesia, and Horner's syndrome has been described and no case reports of diffuse large B-cell lymphoma as the etiology of Horner's syndrome currently exist in the literature. In addition, lymphoid neoplasms have rarely been reported to occur in patients with neurofibromatosis type 1 despite an increased risk of many types of cancer in such cases.

Case presentation

A 28-year-old Thai man presented with a progressively enlarged left supraclavicular mass together with a significant weight loss and night sweating for four months. He also noticed hoarseness and ptosis of his left eye associated with double vision for two months. Physical examination revealed large supraclavicular lymphadenopathy and Horner's syndrome (ptosis, miosis, and anhydrosis) on the left side of his face. A large mediastinal mass was clearly detected by chest X-ray and computed tomography and subsequent lymph node biopsy provided a diagnosis of diffuse large B-cell lymphoma. Interestingly, the patient was also definitely diagnosed with neurofibromatosis type 1 from multiple café au lait macules, axillary freckles, three neurofibromas, multiple Lisch nodules, and a history of affected family members. He subsequently received chemotherapy with a good response. Twenty-seven cases of various types of lymphoid neoplasms previously reported to occur in neurofibromatosis type 1 patients were also extracted from the literature. All cases were non-Hodgkin lymphoma and the major subtype was T-cell. Only nine cases were B-cell lymphoma. The majority of cases were young with a median age at lymphoma diagnosis of 9.4 years (range 1.1 to 77 years). Two-thirds of the cases were boys or men. Other concomitant malignancies were brain tumor, colorectal cancer, pheochromocytoma, and acute lymphoblastic leukemia.

Conclusions

We describe for the first time a case of diffuse large B-cell lymphoma that occurred in a neurofibromatosis type 1 patient with Horner's syndrome. Horner's syndrome can be an initial manifestation of diffuse large B-cell lymphoma. Patients who present with a classical triad of Horner's syndrome should always be fully investigated for lymphomatous involvement, especially in the thorax. The exact molecular mechanism for diffuse large B-cell lymphoma development in neurofibromatosis type 1 cases remains to be elucidated.     

Multiple endocrine neoplasia associated with von Recklinghausen's disease.

Details were studied of three patients with duodenal carcinoid tumour in association with neurofibromatosis and phaeochromocytoma, and of four patients with duodenal carcinoid and either von Recklinghausen''s disease or phaeochromocytoma. The rarity of these endocrine tumours, together with the unusual morphological features and somatostatin content of the two duodenal carcinoids examined, suggest that this combination of tumours is not a chance association. It is suggested that this linkage of neurofibromatosis, phaeochromocytoma, and duodenal carcinoid is a specific multiple endocrine neoplasia syndrome.     

SIR JOSEPH DALTON HOOKER IN THE KEW ARCHIVE

Sir Joseph Dalton Hooker was born in Halesworth, Suffolk in 1917. The second son of Sir William Jackson Hooker, Joseph Hooker would, throughout the course of his life, become one of the most famous and lauded scientists of his day. At its pinnacle, Joseph Hooker's career would see him hold the post of Director of the Royal Botanic Gardens, Kew for 20 years (1865–1885), and be the first botanist after Joseph Banks to be elected President of the Royal Society between 1873 and 1878. His archives and letters, which are described here, are held in the Library, Art and Archives at Kew.     

An appreciation of A.E. Malloch,MB, MD (1844-1919): a forgotten surgical pioneer

Dr. Archibald Edward Malloch was a surgeon whose life and work were greatly influenced by Joseph Lister and his revolutionary system of antiseptic surgery. This paper describes how a young Canadian medical man came to introduce Lister''s system to North America in 1869 and studies his career in the light of Lister''s surgical epoch.     

Acute Myocardial Infarction Attributable to Adrenergic Crises in a Patient with Pheochromocytoma and Neurofibromatosis 1

ObjectiveTo describe a rare case of acute myocardial infarction in a patient with neurofibromatosis 1 and pheochromocytoma and to review the literature on the coexistence of these 2 diseases, the causes of myocardial injury in patients with pheochromocytoma, and the utility of genetic testing and pheochromocytoma screening for those patients and their families.MethodsWe present a case report, including the detailed clinical, laboratory, and radiographic data, results of adrenal mass pathology, and results of coronary angiography. We also survey other relevant reports available in the literature.ResultsA 43-year-old woman with a history of longstanding hypertension, neurofibromatosis 1, headaches, sweating, and palpitations presented to the hospital with chest pain and shortness of breath. She was found to have an acute myocardial infarction and pulmonary edema, as well as a right adrenal mass. A pheochromocytoma was suspected, and phenoxybenzamine was added to her treatment regimen. Cardiac catheterization showed nonobstructive coronary disease. The levels of plasma catecholamine metabolites were extremely high. The patient underwent uncomplicated laparoscopic right adrenalectomy 2 weeks after this admission. Surgical pathology confirmed the diagnosis of pheochromocytoma.ConclusionAdrenergic crisis attributable to pheochromocytoma can result in acute myocardial infarction even in the absence of obstructive coronary disease. Inclusion of pheochromocytoma in the differential diagnosis of hypertension in patients with neurofibromatosis is very important and helps avoid mistakes in the management of such patients. (Endocr Pract. 2007;13:269-273)     

Modern methods of neuro-visualization of brain pathology in central form of Recklinghausen's disease

The paper reviews the data available in the literature on the diagnosis of brain lesions in the central form of Recklinghausen's disease (neurofibromatosis) by magnetic resonance imaging. The results of a clinical observation of 10 children suffering trom neurofibromatosis and the data of electroencephalography, computed tomography and MRI are given and analyzed. Conclusions are made on the magnitude of and the most common site of MRI changes. It is suggested that MRI shows a higher sensitivity in detecting brain lesions in Recklinghausen's disease than other diagnostic techniques.     

播散性暗色丝孢霉病患者CARD9突变及相关免疫学研究

暗色丝孢霉病是指由暗色真菌引起的皮肤、皮下组织乃至深部组织脏器的感染。本研究探讨1例由皮肤及皮下组织暗色丝孢霉病逐渐进展为播散性暗色丝孢霉病患者的遗传背景及其抗真菌免疫功能。收集患者10余年病情进展的临床资料及真菌检查结果,进行临床资料及真菌学研究;对外周血DNA采用Sanger测序,进行遗传学研究;提取患者及正常人外周血单个核细胞(peripheral blood mononuclear cell,PBMC),采用蛋白免疫印迹法、流式细胞术、化学发光法、酶联免疫吸附试验等进行免疫学研究。结果显示,患者胱天蛋白酶募集域蛋白9(caspase recruitment domain-containing protein 9,CARD9)基因存在新的复合杂合错义突变(p.R35Q和p.E81K),CARD9蛋白表达正常,外周血淋巴细胞(peripheral blood lymphocyte,PBL)Th1和Th17细胞比例均降低;PBMC抗疣状瓶霉感染存在天然及适应性免疫缺陷。本研究首次报道1例播散性暗色丝孢霉病患者存在CARD9基因新发错义突变,同时发现患者PBMC抗真菌的天然及适应性免疫存在缺陷,提示CARD9蛋白在暗色丝孢霉病发病中可能发挥重要作用。     

RETRACING JOSEPH HOOKER'S ROUTES IN THE SIKKIM HIMALAYA

Joseph Hooker was one of the most widely travelled botanists of the Victorian period, having explored regions as far afield as Antarctica, Morocco and North America, though it is for his pioneering exploration of the Sikkim Himalaya that he is perhaps best remembered. Seamus O'Brien led four expeditions to this remote corner of the eastern Himalaya, and the results of these trips will appear in a new biography due to be published by Kew in 2018. He summarises that story here.     

Effect of Crohn's disease mesenteric mesenchymal stem cells and their extracellular vesicles on T‐cell immunosuppressive capacity

Crohn''s disease (CD) is a chronic inflammatory disease of the gastrointestinal intestinal tract and has characteristic hypertrophic adipose changes observed in the mesentery. To better understand the role of the mesentery in the pathophysiology of Crohn''s disease (CD), we evaluated the immunomodulatory potential of mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) derived from Crohn''s patients. MSCs and EVs were isolated from the mesentery and subcutaneous tissues of CD patients and healthy individuals subcutaneous tissues, and were analysed for differentiation, cytokine expression, self‐renewal and proliferation. The varying capacity of these tissue‐derived MSCs and EVs to attenuate T‐cell activation was measured in in vitro and an in vivo murine model. RNA sequencing of inflamed Crohn''s disease mesentery tissue revealed an enrichment of T‐cell activation compared to non‐inflamed subcutaneous tissue. MSCs and MSC‐derived EVs isolated from Crohn''s mesentery lose their ability to attenuate DSS‐induced colitis compared to subcutaneous tissue‐derived cell or EV therapy. We found that treatment with subcutaneous isolated MSCs and their EV product compared to Crohn''s mesentery MSCs or EVs, the inhibition of T‐cell proliferation and IFN‐γ, IL‐17a production increased, suggesting a non‐inflamed microenvironment allows for T‐cell inhibition by MSCs/EVs. Our results demonstrate that Crohn''s patient‐derived diseased mesentery tissue MSCs lose their immunosuppressive capacity in the treatment of colitis by distinct regulation of pathogenic T‐cell responses and/or T‐cell infiltration into the colon.     

HISTORY OF ICHNOLOGY—Ichnological Eccentrics: The Curious Case of Dr. Joseph Barratt of Middletown,Connecticut

Joseph Barratt was a British-born and educated physician who settled in the United States in 1819. He had a great interest in natural history, collecting both plants and insects and studying geology, mycology, ornithology, chemistry, meteorology, Native Americans, and local history. He was apparently a man of great energy and ambition but one who could not focus to see a project to completion. Barratt was active in the early history of the discovery of vertebrate footprints in the Newark Supergroup in the eastern United States but latter developed some very strange theories regarding the age and significance of these deposits. In his latter years, Barratt's mental state deteriorated and he became even more obsessed with trying to publicize his outlandish theories. Dr. Joseph Barratt is remembered in ichnology for basically two things; he sold Edward Hitchcock a superb specimen of vertebrate tracks; and he may have the most elaborate ichnological tombstone ever constructed.     

Cain on Linnaeus: the scientist-historian as unanalysed entity

Zoologist A. J. Cain began historical research on Linnaeus in 1956 in connection with his dissatisfaction over the standard taxonomic hierarchy and the rules of binomial nomenclature. His famous 1958 paper ‘Logic and Memory in Linnaeus's System of Taxonomy’ argues that Linnaeus was following Aristotle's method of logical division without appreciating that it properly applies only to ‘analysed entities’ such as geometric figures whose essential nature is already fully known. The essence of living things being unanalysed, there is no basis on which to choose the right characters to define a genus nor on which to differentiate species. Yet Cain's understanding of Aristotle, which depended on a 1916 text by H. W. B. Joseph, was fatally flawed. In the 1990s Cain devoted himself to further historical study and softened his verdict on Linnaeus, praising his empiricism. The idea that Linnaeus was applying an ancient and inappropriate method cries out for fresh study and revision.     

Solitary subcutaneous hydatid cyst: Review of the literature and report of a new case in the deltoid region

BackgroundSolitary subcutaneous hydatid cyst is not frequent and the only symptom is generally a silent growing mass. Total excision remains the mainstay of treatment. Aim of the study was to present a case surgically treated and perform a statistical analysis reviewing previous published works in order to define a correct approach to diagnosis and treatment.Methods264 documents from Medline database were considered for primary subcutaneous hydatid cyst cases. Data concerning geographic region, gender, age, job, location, evolving time, history and physical, mobility, diameter, laboratory, imaging, locularity (uni- or multilocular cyst), fine-needle aspiration, preoperative diagnosis, neoadjuvant chemotherapy, treatment, spillage, adjuvant therapy, follow-up and recurrences were ordered in a database and analysed performing t-test, Fisher's test and Pearson's test.Results23 cases, included ours, resulted suitable for our study. Lower extremities were involved in most cases (60.9%) and the thigh represented the most common site (34.8%), whereas upper extremities were the rarest location (8.7%). Patients with head and neck located cysts were younger than those with upper extremities cysts (P = 0.037). Patients who underwent multiple imaging approach received a significantly correct first diagnosis (P = 0.001) and ultrasonography, unlike other techniques, appeared to be essential (P = 0.013).Case reportA 68-year-old man who lived and worked in his farm in Sicily (Italy) presented with a 30-year-growing mass in the deltoid region measuring 10 cm. Ultrasonography and magnetic resonance imaging strongly suggested hydatid cyst. Therefore the cyst was excised and pathology confirmed the diagnosis.ConclusionSolitary subcutaneous hydatid cyst must always be considered in the differential diagnosis of silent growing mass in soft tissues. History and physical associated with ultrasound and magnetic resonance imaging are sufficient to achieve a correct preoperative diagnosis.     

Juvenile dermatomyositis: medical,social and economic status in adulthood.

Eighteen adults were studied an average of 18.5 years after the diagnosis of juvenile dermatomyositis had been made. Persistent weakness was found in six patients and recurrent rash in the classic distribution in seven. Other clinical features present were Raynaud''s phenomenon, arthritis and subcutaneous nodules. Minor increases in the serum creatine phosphokinase level were noted in seven patients and did not correlate with the presence of weakness or rash. Educational achievement and employment status were better in this group than in a group of adults with juvenile rheumatoid arthritis or the general adult population of British Columbia. Significant residual disability related to calcinosis and flexion contractures was present in only three of the patients.     

Tumor-induced osteomalacia: a single center experience

ObjectiveTo describe the clinical presentation, localization modalities, and management of patients with tumor-induced osteomalacia (TIO).MethodsWe performed a retrospective analysis of case records of patients diagnosed with TIO between January 1996 and March 2010 at our institution in Mumbai, India.ResultsNine patients (6 female and 3 male) with a mean age of 37.5 ± 17.5 years with biochemical and imaging evidence of TIO were included in the study. Overall, patients presented with proximal muscle weakness and pain. Three patients had neurofibromatosis 1, one had isolated schwannoma, and one had epidermal nevus syndrome. The mean delay in diagnosis was 7.67 years. Biochemical studies revealed normal serum calcium (mean, 9.2 ± 0.8 mg/dL), low serum phosphorus (mean, 1.36 ± 0.54 mg/dL), and low maximal tubular reabsorption of phosphorus factored for glomerular filtration rate (mean, 0.94 ± 0.49 mg/dL). Fibroblast growth factor-23 was increased in 3 of the patients without neurofibromatosis but was normal or near-normal in all the patients with neurofibromas. A fludeoxyglucose F 18 positron emission tomography (FDG PET) scan helped to localize the tumors in 4 of the 5 patients with diagnoses other than neurofibromatosis. Three patients underwent surgical excision and were cured. One patient underwent biopsy and partial excision. Histopathologic findings were suggestive of phosphaturic mesenchymal tumor, benign fibrous histiocytoma, nonossifying fibroma, and sciatic nerve schwannoma.ConclusionThere is a well-known delay in the diagnosis of TIO. FDG PET is a useful modality for localization of tumors. Preoperative localization increases the odds for cure after surgical excision. (Endocr Pract. 2011;17: 177-184)     

The Scarab

Abstract

Joseph McBride Searching for John Ford: A Life St. Martin's Press 834 pp. $40.00     

Book Review

Erdtman's Handbook of Palynology, 2nd revised edition (1992). Edited by Siwert Nilsson and Joseph Praglowski. Munksgaard, International Publishers Ltd. Price DKr. 650.00 + postage.     

Design of lymphedema ultrasound phantom with 3D-printed patient-specific subcutaneous anatomy: A-mode analysis approach for early diagnosis

The secondary lymphedema is mostly caused due to injury of lymphatic system during cancer treatment and its psychological and cosmetic issues are very critical for patients since it can cause severe thickening and swelling of lesions, mostly upper and lower limbs. Therefore, early diagnosis of the secondary lymphedema is more important to treat the symptoms in advance. The amplitude-mode (A-mode) ultrasound is suggested as an early diagnostic modality because it is relatively more cost-effective, portable, and easy to use than other previous diagnostic modalities. In order to see features of the A-mode ultrasound forearly diagnosis of lymphedema, ultrasound lymphedema phantoms were designed and fabricated with patient-specific subcutaneous honeycomb structures at the sub-stages of the international society of lymphedema (ISL) stage II and gelatin- or gelatin-salt based phantom materials. The patent-specific honeycomb structures were segmented from computed tomography (CT) venography images using various image process technologies and printed using a three dimensional (3D) printer for which its printing material shows similar acoustic impedance range with human subcutaneous tissues. The lymphedema phantoms showed similar subcutaneous anatomical features to those of patient's imagesin brightness mode (B-mode) ultrasound examination, and acoustic information originated from the stage-specific honeycomb structures was well represented in A-mode ultrasound examination. In particular, the A-mode wave form well represented stage-specific honeycomb information even with higher impedance value of fibrous fat region. Such stage-specific wave form information of A-mode ultrasound for the corresponding stage-specific lymphedema phantoms at the ISL stage II can be useful for further development of an A-mode ultrasound applications for early diagnosis of the secondary lymphedema.     

Book review

Erdtman's Handbook of Palynology, 2nd revised edition (1992). Edited by Siwert Nilsson and Joseph Praglowski. Munksgaard, International Publishers Ltd. Price DKr. 650.00 + postage. Reviewed By Valentina V. Ukraintseva