Hairy leukoplakia: an AIDS-associated opportunistic infection

Hairy leukoplakia has been defined and confirmed as a specific oral mucosal marker for human immunodeficiency virus infection. Light microscopic findings include alteration of spinous layer cells, which contain nuclear chromatin abnormalities. Enlargement of spinous cells with ballooning degeneration is also characteristic. Ultrastructural morphology has defined the presence of large numbers of herpes-type virus particles within the intranuclear, cytoplasmic, and intercellular regions. Morphologically, the criteria of Epstein-Barr virus are satisfied. Southern blot analysis has confirmed the virus to be Epstein-Barr virus. Further hybridization analyses failed to show any evidence of human immunodeficiency virus or human papillomavirus in the lesions themselves. We conclude that hairy leukoplakia may represent an epithelial opportunistic Epstein-Barr virus infection. Finally, the production and shedding of Epstein-Barr virions into the oral cavity from the sites of hairy leukoplakia can occur separate from the usual tonsillar and oropharyngeal sites.     

Calcified meconium balls in a newborn: an unusual case with imperforate anus,rectourinary fistula,colpocephaly, and agenesis of corpus callosum

Calcified intraluminal meconium is a rare finding in newborn infants. It is often associated with communication between the urinary and gastrointestinal tracts. Intra-abdominal calcifications are unusual radiographic findings in the newborn and can easily be misinterpreted as meconium peritonitis. We report on a newborn infant with anorectal malformation, meconium balls, intraluminal calcifications, colpocephaly, and agenesis of the corpus callosum, a rare association.     

Reversal of papilloma growth in rabbits therapeutically vaccinated against E6 with naked DNA and/or vesicular stomatitis virus vectors

Persistent infection with high-risk human papillomaviruses (HPVs) is the greatest risk factor for the development of HPV-associated cancers. In this study rabbits bearing persistent and potentially malignant papillomas were used to test the efficacy of vaccination with a recombinant DNA and/or vesicular stomatitis virus (VSV) targeting the cottontail rabbit papillomavirus (CRPV) E6 protein. Immune responses were primed with either vector and boosted twice with the homologous or heterologous E6 vector. Over the course of 18 weeks, E6 vaccination reduced papilloma volumes to one third the volume in the controls, and the rabbits boosted with an heterologous vector tended to mount stronger responses. Small and medium-sized papillomas responded significantly but only slightly better than large papillomas. Finally the initial papilloma burden per rabbit, ranging from <100 mm³ to >1000 mm³, was not prognostic of antitumor efficacy. In summary both E6 vaccines elicited significant therapeutic immunity, and their sequential use tended to be advantageous.     

Patients' and physicians' interpretation of chemotherapy‐induced peripheral neurotoxicity

To test if and how chemotherapy‐induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI‐PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation (“impossible”) generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%‐65% of patients; 76%‐78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%‐56% of them. In Group 3 strength reduction was observed in 49%‐50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.     

Physiological movement disorder-like features during typical motor development

Aim

To compare physiological age-relatedness between dyskinesia (dystonia/choreoathetosis), dystonia and ataxia rating scale scores in healthy children.

The Martin-Gruber innervated hand

Two patients with a complete ulnar nerve lesion at the elbow and a median nerve lesion at the wrist secondary to leprosy neuropathy retained good function of the first dorsal interosseous and flexor pollicis brevis muscles. One patient also lacked the typical finger clawing associated with ulnar and median paralyses. These findings were attributed to the presence of Martin-Gruber anastomoses that were confirmed by nerve-conduction studies.     

Application of infrared thermography for the analysis of rewarming in patients with cold intolerance

Cold intolerance is a serious long-term problem after injury to the ulnar and median nerves, and its pathophysiology is unclear. We investigated the use of infrared thermography for the analysis of thermoregulation after injury to peripheral nerves. Four patients with injuries to the ulnar nerve and four with injuries to the median nerve (4-12 years after injury) immersed their hands in water at 15 degrees C for 5 minutes, after which infrared pictures were taken at intervals of 2-4 minutes. The areas supplied by the injured nerves could be identified easily in the patients with symptoms of cold intolerance. At baseline temperature distribution of the hand was symmetrical, but after testing the injured side warmed up much slower. We concluded that the infrared profile of the temperature of the hand after immersion in cold water is helpful to assess thermoregulation after injury to peripheral nerves.     

Directing the use of DDR kinase inhibitors in cancer treatment

Introduction: Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval of three different PARP inhibitors for the treatment of ovarian cancer provides the impetus for further developing targeted inhibitors of many of the kinases involved in the DDR, including inhibitors of ATR, ATM, CHEK1, CHEK2, DNAPK and WEE1.

Areas covered: We summarise the current stage of development of these novel DDR kinase inhibitors, and describe which predictive biomarkers might be exploited to direct their clinical use.

Expert opinion: Novel DDR inhibitors present promising candidates in cancer treatment and have the potential to elicit synthetic lethal effects. In order to fully exploit their potential and maximize their utility, identifying highly penetrant predictive biomarkers of single agent and combinatorial DDR inhibitor sensitivity are critical. Identifying the optimal drug combination regimens that could used with DDR inhibitors is also a key objective.     

The clinical treatment of laryngeal papillomas with hematoporphyrin therapy

Photodynamic activation of hematoporphyrin derivative was originally developed for the treatment of cancer. This article demonstrates that it may also be an effective therapy for papillomavirus infections of the larynx. Seventy-two hours prior to surgery, hematoporphyrin derivative (6 mg/kg) was given intravenously to two patients with the adult-onset form of this disease. Three days later, endoscopic surgery was performed and 32 J/cm2 was delivered to the endolarynx via an argon pump dye laser with a red light output of 630 nm. No significant complications such as swelling or hemorrhage occurred. At follow-up (13 months) there has been no recurrence of the laryngeal papilloma in either of these patients. The surgical technique, molecular biology, and clinical implications of this work to control laryngeal papillomatosis are described.