Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose-based microbicide surrogate or viscosity-matched semen surrogate, labeled with gadolinium-DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium-sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29-102%; P<0.001), as far as the splenic flexure (approximately 60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV-sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Rectally applied drugs have been imaged using radioisotopes and magnetic resonance contrast agents. However, prior studies have not described the distribution and clearance of rectally-applied drugs in quantitative terms with respect to complex three dimensional paths through the gastrointestinal tract. Such tools would allow statistical comparisons of candidate products in development or comparison of drug product with the distribution of a drug target, for example, HIV infected seminal fluid. WHAT THIS STUDY ADDS• New quantitative spatial parameters, derived from three dimensional curve fitting, have been successfully applied in this study to quantify the distribution of rectally-applied gels. Indirect assessment using nuclear medicine techniques avoided the distortion and redistribution associated with sigmoidoscopic sampling. Thus, these measurements can be repeated over time to create concentration-distance-time surfaces to describe rectal product distribution and clearance within the gastrointestinal lumen to inform microbicide and other rectal product development. AIMSWe sought to describe quantitatively the distribution of rectally administered gels and seminal fluid surrogates using novel concentration-distance parameters that could be repeated over time. These methods are needed to develop rationally rectal microbicides to target and prevent HIV infection. METHODSEight subjects were dosed rectally with radiolabelled and gadolinium-labelled gels to simulate microbicide gel and seminal fluid. Rectal doses were given with and without simulated receptive anal intercourse. Twenty-four hour distribution was assessed with indirect single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI), and direct assessment via sigmoidoscopic brushes. Concentration-distance curves were generated using an algorithm for fitting SPECT data in three dimensions. Three novel concentration-distance parameters were defined to describe quantitatively the distribution of radiolabels: maximal distance (Dmax), distance at maximal concentration (DC max ) and mean residence distance (Dave). RESULTSThe SPECT/CT distribution of microbicide and semen surrogates was similar.Between 1 h and 24 h post dose, the surrogates migrated retrograde in all three parameters (relative to coccygeal level; geometric mean [95% confidence interval]): maximal distance (Dmax), 10 cm (8.6-12) to 18 cm (13-26), distance at maximal concentration (DC max ), 3.8 cm (2.7-5.3) to 4.2 cm (2.8-6.3) and mean residence distance (Dave), 4.3 cm (3.5-5.1) to 7.6 cm (5.3-11). Sigmoidoscopy and MRI correlated only roughly with SPECT/CT. CONCLUSIONSRectal microbicide surrogates migrated retrograde during the 24 h following dosing. Spatial kinetic parameters estimated using three dimensional curve fitting of distribution data should prove useful for evaluating rectal formulations of drugs for HIV prevention and other indications.

Adenomyoma is a benign tumor composed of endometrial glands, specialized endometrioid stroma, and smooth muscle. These tumors typically originate within the uterus. An extrauterine adenomyoma is an extremely rare entity. We present the case of a 56-year-old perimenopausal woman with a right adnexal mass, diagnosed histopathologically as an ovarian ligament adenomyoma. This report documents a fourth case of an extrauterine adenomyoma and only the second case in ovarian ligament. The differential diagnosis includes endometrioma, leiomyomatosis peritonealis disseminata, uterus-like mass lesion and extrauterine leiomyoma with entrapped endometrioid glands and stroma. Two theories for the etiology of adenomyoma have been proposed: (i) Müllerian duct fusion defect and (ii) metaplasia.

BackgroundDisseminated tuberculosis (TB) or miliary TB is defined as lymphohematogenous dissemination of Mycobacterium tuberculosis bacilli, which may then affect virtually any organ system. The multiple organ involvement in disseminated TB can mimic metastatic cancer and can make the diagnosis challenging. False negatives are common therefore repeating microbiologic and histologic samples is essential.Case reportWe report the case of a young immunocompetent patient presenting with multiple atypical extra-pulmonary TB involvement. The patient presented with pulmonary, pleural, bilateral testicular and multiple bone involvement including calcanerium abscesses. These lesions were initially described as metastasis by the radiologist. Therefore lymphoma and metastatic testicular cancer as well as TB were high on the differential in this young foreign-born male. Pleural, broncho-alveolar lavage, bone marrow and cerebrospinal fluid acid-fast bacilli smear and microbiologic culture were all negative. However the histologic examination of the trans-bronchial biopsy and pleural biopsy showed necrotizing granuloma and helped to narrow down the diagnosis. The patient improved with RIPE therapy.ConclusionThis case illustrates the diagnostic difficulty of disseminated TB with atypical organ involvement. Culture is the gold standard for diagnosing TB but is a long process and with 23% of culture negative TB in the United-States, the diagnosis sometimes relies on thoroughly ruling-out differential diagnosis and histologic examination.

The results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer.

We report a case of a 6-year-old girl with primary Burkitt's lymphoma (BL) of endometrium and bilateral ovaries of 1-month duration. To the best of our knowledge, few cases of childhood primary BL of bilateral ovaries have been reported worldwide. However, extensive search of the published work did not reveal any case of primary BL of endometrium and both ovaries. Although rare, BL is a potentially curable malignancy with good prognosis.

Lymphedema-associated angiosarcoma also known as lymphangiosarcoma is the commonest type of cutaneous angiosarcoma. Post-mastectomy lymphedema is the most frequent cause, while chronic filarial lymphedema is one of the most uncommon etiology for development of lymphangiosarcoma. We report a case of a 50 year old male suffering from chronic filarial lymphedema of right lower extremity, presented with brownish nodules on the right leg, which were diagnosed histopathologically as lymphangiosarcoma.

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