Victoria Doviner

The activating receptor NKp46 is essential for the development of type 1 diabetes.

The mechanism of action of natural killer (NK) cells in type 1 diabetes is still unknown. Here we show that the activating receptor NKp46 recognizes mouse and human ligands on pancreatic beta cells. NK cells appeared in the pancreas when insulitis progressed to type 1 diabetes, and NKp46 engagement by beta cells led to degranulation of NK cells. NKp46-deficient mice had less development of type 1 diabetes induced by injection of a low dose of streptozotocin. Injection of soluble NKp46 proteins into nonobese diabetic mice during the early phase of insulitis and the prediabetic stage prevented the development of type 1 diabetes. Our findings demonstrate that NKp46 is essential for the development of type 1 diabetes and highlight potential new therapeutic modalities for this disease.

Glucagonoma and the glucagonoma syndrome - cumulative experience with an elusive endocrine tumour

Objective  Glucagonoma is a pancreatic neuroendocrine tumour that arises from alpha cells in the pancreas and is often accompanied by a characteristic clinical syndrome.

H syndrome: the first 79 patients.

BACKGROUND H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3. OBJECTIVE We sought to investigate the clinical and molecular findings in 79 patients with this disorder. METHODS A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature. RESULTS The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3, with no genotype-phenotype correlation. LIMITATIONS In the 31 patients described by others, data were collected from the medical literature. CONCLUSIONS H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3-related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients.

H syndrome: recently defined genodermatosis with distinct histologic features. A morphological, histochemical, immunohistochemical, and ultrastructural study of 10 cases.

This study analyzes the histopathological findings in H syndrome, a recently recognized autosomal recessive genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin in well-defined anatomical areas accompanied by various systemic manifestations. So far, descriptions of the histopathological skin changes in this disorder, as reported in a few small case series, were inconsistent, leading to diverse clinical interpretations. In an attempt to define standardized, diagnostic, morphological criteria that will distinguish this disorder from other fibrosing conditions, we studied skin biopsies from 10 patients with H syndrome. The characteristic morphology included widespread fibrosis (moderate in dermis and severe in subcutis); striking mononuclear infiltrates consisting mainly of monocyte-derived cells (small CD68+ histiocytes and CD34+ and FXIIIa+ dendrocytes) and plasma cells; and thickened, fragmented, and partially calcified elastic fibers, admixed with well-formed psammoma bodies, a previously unrecognized feature in nonneoplastic skin and subcutaneous conditions. In addition, the ultrastructure of CD68+ small histiocytes exhibited distended endoplasmic reticulum and scarcity of lysosomes, features typical for fibroblasts but unusual for histiocytes. These unusual findings in the histiocytes pose a question as to their possible role in the fibrotic cascade in this disorder. We conclude that the above findings are essential for the diagnosis of H syndrome and that incisional biopsies are mandatory for recognition of the full spectrum of histopathological findings.

Early-onset sensorineural hearing loss is a prominent feature of H syndrome

This case report describes two patients with H syndrome, a multisystemic autosomal recessive disorder, caused by mutations in the SLC29A3 gene. It is characterized by cutaneous hyperpigmentation, camptodactyly or flexion contractures and other features, among them hearing loss. The two patients had hearing loss as their presenting symptom, and had mutations in SLC29A3, one of them a novel mutation. The aim of this paper is to increase awareness to this recently described disorder, and to emphasize that H syndrome should be included in the differential diagnosis of congenital or acquired syndromic hearing loss in children.

Unfolding the Diagnosis

A previously healthy, 25-year-old man was admitted to the hospital because of abdominal pain, nausea, vomiting, and weight loss. Two weeks before his admission, fever (temperature up to 40°C), chills, and weakness developed. To control his fever, the patient ingested ibuprofen at a dose of 400 mg four times a day for more than a week. Subsequently, abdominal discomfort and nausea developed, and he presented to the emergency department owing to worsening of epigastric pain and vomiting. Since his gastrointestinal symptoms had started, he had lost about 4 kg of body weight. He reported no hematemesis, hematochezia, or melena. His medical history was remarkable only for a left inguinal hernioplasty 3 years earlier. He did not smoke, ingest alcohol, or use illicit drugs. This patient’s symptoms of fever, chills, and malaise are nonspecific and may occur with viral or bacterial infection or noninfectious inflammation. Protracted vomiting or nausea may lead to Mallory–Weiss tears at the gastroesophageal junction, causing epigastric pain and possibly upper gastrointestinal bleeding. Pancreatitis may also explain this constellation of symptoms, although the patient reports no alcohol ingestion and has no known history of gallstones. Intestinal obstruction is another, more remote possibility. The patient’s use of ibuprofen puts him at risk for nonsteroidal antiinflammatory drug (NSAID)–induced gastritis; prepyloric edema could lead to partial gastric obstruction and vomiting. Treatment with a proton-pump inhibitor may alleviate his symptoms pending further evaluation. On physical examination, the patient was pale and weak but did not appear to be in distress. His blood pressure was 125/75 mm Hg in a supine position and 105/70 mm Hg while he was standing. The pulse rate was 96 beats per minute, and the temperature was 36°C. His tongue appeared dry. His tonsils were not enlarged, and there was no exudate. There was no cervical or axillary adenopathy. He had marked epigastric tenderness without rebound or abdominal rigidity. The spleen and liver were mildly enlarged. There was no rash. The patient’s physical examination is consistent with dehydration, but there is no evidence of peritonitis, which would suggest perforation. The mild hepatic and splenic enlargement may be consistent with a viral illness, which could also explain his recent fever and its absence on admission. Alternatively, the patient’s fever may be intermittent, as in Hodgkin’s disease (Pel–Ebstein fever); the abdominal pain, weight loss, and hepatic and splenic enlargement could also be consistent with this diagnosis.

A case of metastatic adamantinoma responding to treatment with pazopanib.

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