Rhabdoid meningioma presenting with subependymal and diffuse meningeal involvement but no mass lesion

Rhabdoid meningiomas are rare, aggressive tumours of the meninges that have a generally poor prognosis. We report a 49-year-old man with a background history of sarcoidosis who presented with nausea and vomiting. Imaging showed generalised leptomeningeal and subependymal enhancement suggestive of chronic meningitis. He had multiple lumbar punctures and a brain biopsy, none of which led to a pathological diagnosis. He died within months, and a postmortem examination was performed. At this stage, a diagnosis of rhabdoid meningioma was made. The clinical and radiological presentation of rhabdoid meningioma as a diffuse leptomeningeal process without a mass lesion is unique. All other published cases of rhabdoid meningioma have been of a discrete lesion. This highlights the importance of a tissue diagnosis in patients where the imaging is non-specific. A brief review of rhabdoid meningioma follows.     

Multiple subcutaneous angiolipomas associated with new-onset diabetes mellitus

A 44‐year‐old Hispanic man, with a past medical history of diabetes mellitus type 2 and cerebrovascular accident, presented to the Mount Sinai Department of Dermatology with sudden, fast‐growing nodules over both of his shins. Approximately 2 months before the appearance of the nodules, the patient was diagnosed with diabetes mellitus type 2 with hemoglobin A_1c (HbA_1c) of 8.5%. The patient was taking metformin orally, 500 mg three times daily, at the time of presentation. Six nodules appeared over a period of days. They caused a burning, throbbing pain upon ambulation. Over a period of 6 months, the lumps decreased in size, and two totally disappeared. The resolution of the nodules coincided with the control of the patient's diabetes, as demonstrated by HbA_1c of 5.5%. The patient denied trauma to the sites of the nodules. The patient denied any associated purpura or ecchymoses over the nodules. The past medical history was significant for a stroke with residual right hemiparesis at 42 years of age. The family history was negative for similar lesions, but an aunt did have diabetes mellitus type 2. The patient denied alcohol use, smoking, or intravenous drug use. Physical examination was positive for six soft, tender, freely mobile, symmetrical, well‐demarcated, round masses, 1–2 cm in diameter and skin colored, over the anterior aspects of both legs. The patient was obese (body mass index, 38.5). Laboratory tests (barring the initially elevated HbA_1c) were normal. One lesion was excised. Histopathology revealed features typical of an angiolipoma (see Fig. 1a,b ). A karyotype of the angiolipoma was not performed.

Figure 1 Open in figure viewer PowerPoint (a) Prominent vessels filled with fibrin thrombi at the periphery of mature fat lobules. (b) At higher magnification     

Nonexposed Variant of Bisphosphonate-associated Osteonecrosis of the Jaw: A Case Series

Purpose

To report a case series of patients with the nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw—a form of jaw osteonecrosis that does not manifest with necrotic bone exposure/mucosal fenestration.

Methods

Among 332 individuals referred to 5 clinical centers in Europe because of development of jawbone abnormalities after or during exposure to bisphosphonates, we identified a total of 96 patients who presented with the nonexposed variant of osteonecrosis. Relevant data were obtained via clinical notes; radiological investigations; patients' history, and referral letters.

Results

The most common clinical feature of nonexposed osteonecrosis was jaw bone pain (88/96; 91.6%); followed by sinus tract (51%), bone enlargement (36.4%); and gingival swelling (17.7%). No radiological abnormalities were identified in 29.1% (28/96) of patients. In 53.1% (51/96) of the patients; nonexposed osteonecrosis subsequently evolved into frank bone exposure within 4.6 months (mean; 95% confidence interval; 3.6-5.6).

Conclusions

Clinicians should be highly vigilant to identify individuals with nonexposed osteonecrosis, as the impact on epidemiological data and clinical trial design could be potentially significant. Although the present case series represents approximately 30% of all patients with bisphosphonates-associated osteonecrosis observed at the study centers, further population-based prospective studies are needed to obtain robust epidemiological figures.     

Molecular bases of beta-thalassemia in the Eastern Province of Saudi Arabia

beta-thalassemia is a group of heterogeneous recessive disorders common in many parts of the world. Al-Qatif and Al-Hassa oases in the Eastern Province of Saudi Arabia are regions known for high frequency of these disorders. Using two molecular methods, based on multiplexing-amplification refractory system and reverse hybridization principles, the spectrum of beta-thalassemia in the region was studied. Sixty-nine subjects with known beta-thalassemia disease and volunteers with high hemoglobin $A(2)(HbA(2))$ and low mean corpuscular volume (MCV) were included in this study. Ten mutations were detected in 91% of the subjects under study. Six of these mutations had previously been observed while the other four mutations are reported here for the first time. In addition, four of the mutations accounted for 76.8% of the subjects studied. IVSII-1 (G > A), IVSI-5 (G > A), and codon 39 (C > T) mutations were found to be the most frequent. However, the frequencies of different mutations reported here are slightly different from those reported earlier. A number of these mutations were also found in the neighboring countries, which can be explained in terms of gene flow.     

Apolipoprotein M promoter polymorphisms alter promoter activity and confer the susceptibility to the development of type 1 diabetes

ObjectivesApolipoprotein M plays an important role in the formation of preβ-HDL and cholesterol efflux to HDL. In the present study, we investigate the potential association between the ApoM promoter polymorphisms and type 1 diabetes.Design and methodsThe study was conducted in Peking Union Medical College, Beijing, China and Karolinska Institutet, Stockholm, Sweden. Two populations, including 493 Han Chinese subjects (177 T1D patients/316 controls) and 225 Swedish (124/101), are enrolled in the present study. Three single nucleotide polymorphisms (SNP) C-1065A, T-855C and T-778C in the promoter region of the ApoM gene are genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Promoter activity was measured by reporter gene assay.ResultsSNP T-778C was strongly associated with T1D in both Han Chinese (p = 0.002, OR = 2.188, CI 95% = 1.338–3.581) and Swedish (p = 0.021, OR = 2.865, CI 95% = 1.128–7.278) populations. The luciferase activity of ?778C promoter was 1.41 times as high as that of ?778T promoter (9.90 ± 1.92 vs. 7.04 ± 0.76, p = 0.001).ConclusionsAllele C of SNP T-778C may increase promoter activity and confer the risk susceptibility to the development of T1D.     

Cholecystokinin (CCK)-33 stimulates insulin secretion from the perfused rat pancreas: studies on the structure-activity relationship

Cholecystokinin (CCK)-33 is known to stimulate insulin secretion. Presently, using the perfused rat pancreas, we have characterized the active site in the CCK-33 molecule that is responsible for this effect by the use of different CCK fragments. We found that CCK-33, CCK-8 and CCK-7 (1 nM) all significantly stimulated insulin secretion in the presence of 4.4 mM or 6.7 mM glucose. However, CCK-7 was much less potent than the longer forms. In contrast, CCK-4, CCK-6 and CCK-33 (1-21) had no effect on insulin secretion. We conclude that the shortest CCK-form that stimulates insulin secretion at 1 nM is the C-terminal heptapeptide CCK-7. However, CCK-8 is much more potent than CCK-7 in this respect.