Accelerated cellular senescence in solid tumor therapy.

Accelerated cellular senescence (ACS) is an emerging concept that implicates sustained, telomere-independent cell cycle arrest of neoplastic cells in response to chemotherapeutic agents, ionizing radiation, oxidative stress, or the presence of selective oncogenic stimuli. Recent evidence suggests that a subset of tumor cells induced in a state of reversible ACS can escape cell cycle arrest and resume proliferation accounting for cancer progression. The purpose of this review is to describe our current understanding of ACS including signaling pathways of senescence escape, role of senescence biomarkers, and rationale for senescence-based therapy. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".

Indium 111-labeled leukocyte scintigraphy in evaluating head and neck infections.

This retrospective study looked at the role of indium 111-labeled white blood cell (111In WBC) scintigraphy in head and neck infections. The efficacy of 111In WBCs was compared to gallium 67 citrate (67Ga) and technetium Tc99m methylene diphosphonate (99mTc MDP) scintigraphy in detecting and monitoring the resolution of infection. For 22 active infections, the sensitivities for 111In WBC, 67Ga, and 99mTc MDP scintigraphy were 94%, 56%, and 86%, respectively, and the specificities for 111In WBC, 67Ga, and 99mTc MDP scintigraphy were 100%, 43%, and 0%, respectively. For 8 successfully treated infections, all seven 111In WBC studies became negative after therapy, in as short an interval as 1 month. In contrast, all seven 99mTc MDP images remained positive for as long as 6 months after therapy. The seven 67Ga studies had variable results, with four (57%) remaining positive, including two (28%) positive at 6 months after therapy. These results suggest that 111In WBC scintigraphy should be the initial radionuclide imaging tool in detecting active head and neck infections because of its greater accuracy, and its ability to revert to normal much sooner than 67Ga or 99mTc MDP scintigraphs when applied to a subset of patients with resolved infections.

Hemifacial spasm. Occurrence in multiple sclerosis.

We present six patients with hemifacial spasm and multiple sclerosis. To our knowledge, this association has not been described previously in the North American literature. Magnetic resonance imaging was obtained in all the patients and plaques consistent with multiple sclerosis were identified. In two patients the plaques were seen in the area of the facial nucleus on the involved side. We suggest that hemifacial spasm can be a manifestation of multiple sclerosis. These cases illustrate the utility of magnetic resonance imaging in the investigation of hemifacial spasm. Our findings also support a central (nuclear) origin in multiple sclerosis associated with hemifacial spasm.

Central neurofibromatosis: a clinical-pathological correlation.

Central neurofibromatosis is a genetic disorder of neural crest tissue derivatives that includes bilateral acoustic neuromas and other central nervous system tumors, usually meningiomas or gliomas. This is different from peripheral neurofibromatosis because of the primary central nervous system manifestations and frequent lack of accompanying peripheral neurofibromas and café au lait spots as well as different alterations of nerve growth factor. We present the temporal bone histopathology of a unique case of unsuspected central neurofibromatosis that included bilateral acoustic neuromas invading the cochlea and an asymptomatic glioblastoma multiforme occurring in the absence of a family history and without any accompanying peripheral stigmata of neurofibromatosis. As bilateral tumors frequently invade the cochlea, the modified transotic rather than the translabyrinthine approach is recommended for complete tumor removal. Contralateral tumor removal should be delayed while useful hearing remains.

Atypical osteomyelitis of the skull base.

Most cases of osteomyelitis of the skull base occur as a result of inadequately treated localized malignant otitis externa. We present four patients with osteomyelitis of the skull base who did not present initially as malignant otitis externa. Increased morbidity may occur when these atypical cases are not promptly recognized and treated.

Osteomyelitis of the base of the skull.

Infection in the marrow of the temporal, occipital, and sphenoid bones is an uncommon, but increasing occurrence. It is usually secondary to infections beginning in the external auditory canal and is caused almost uniformly by the gram negative Pseudomonas aeruginosa bacteria. Technetium and gallium scintigraphy help in the early detection of such infections while CT scans demonstrate dissolution of bone in well-developed cases. Headache is the predominant symptom. Dysphagia, hoarseness, and aspiration herald the inevitable march of cranial nerves. We have diagnosed and treated 17 cases of osteomyelitis of the skull base. Although the total mortality rate is 53%, it is now a curable disease. Six of our last 8 patients remain alive, although 1 is still under treatment. Treatment is medical and requires the long-term concomitant intravenous administration of an aminoglycoside and a broad spectrum semisynthetic penicillin effective against the causative organism.