Faculty Bibliography

PURPOSE: Adenosquamous carcinoma is an uncommon, controversial neoplasm. To further comprehend its natural history, the clinical and pathological features of 12 new cases were reviewed and analyzed collectively with those described in the English literature. MATERIALS AND METHODS: Twelve cases of adenosquamous carcinoma of the upper aerodigestive tract with adequate follow-up and available microscopic slides and paraffin tissue blocks were identified in the anatomic pathology files of Presbyterian Hospital of the University of Pittsburgh Medical Center over the period 1983-2001. RESULTS: The 8 men and 4 women ranged in age from 34 to 81 years (mean, 62.8 years). The larynx (5 cases) and the floor of the mouth (4 cases) were the most common sites of origin. Nine patients had cervical lymph nodes positive for carcinoma (8 at diagnosis), 7 experienced local recurrences, and 2 developed distant metastases. Four of 10 (40%) patients with follow-up died of disease. Combining our cases with those in the literature (total of 58 cases) revealed similar findings: 64.7% were associated with positive cervical lymph nodes, 46.7% experienced local recurrences, 23.1% developed distant metastases, and 42.9% died of their disease at a mean follow-up period of 24.7 months. CONCLUSIONS: Adenosquamous carcinoma is an aggressive neoplasm with a tendency for early lymph node metastasis, frequent local recurrence, occasional distant metastasis, and death from disease, usually within 2-3 years. Surgery with neck dissection is the treatment of choice

Spike timing-dependent modulation of synaptic efficacy is concomitant with changes in dendritic structure (Engert and Bonhoeffer 1999), a process thought to require actin polymerization. Recent studies have indicated both that plasticity-inducing activity modulates spine actin dynamics (Star and Murthy 2002) and that actin assembly is necessary for the maintenance of long-term potentiation (Krucker et al. 2000). We report here that actin dynamics are necessary for spike timing-dependent plasticity (STDP) in visual cortex. Whole-cell recordings were made from L2/3 pyramids and EPSPs were evoked by extracellular stimulation at 0.2 Hz. When the postsynaptic cell spiked less than 25 s before presynaptic activation, LTD was induced (-38+-4%, n=22). When presynaptic stimulation was followed less than 12 ms by a postsynaptic AP, LTP was induced (59+-9%, n=21). However, when 20 muM cytochalasin D, an inhibitor of actin polymerization, was included in the whole-cell pipette, neither LTP (n=4, p>0.4) nor LTD (n=3, p>0.4) could be induced. Latrunculin A, which sequesters monomeric actin, and phalloidin, which stabilizes polymeric actin, were applied intracellularly (10 muM and 100 muM) and prevented induction of LTP (n=3, p>0.6; n=3, p>0.25). These results suggest that dynamic actin turnover is necessary for spike-timing dependent plasticity

Children with profound congenital or prelingual deafness encounter significant difficulties in the development of skills in an oral language such as English. Their language development, however, can be accelerated if they receive a cochlear implant-a sensory aid that facilitates language acquisition by providing important auditory information. The present study used the Reynell Developmental Language Scales (RDLS) to assess language skills pre- and postimplant in 44 pediatric cochlear implant users. All users were profoundly to totally deaf, either at birth or before the age of 3 years. They all received cochlear implants before the age of 6 and were programmed with state-of-the-art stimulation strategies (CIS or SPEAK) since the day of initial stimulation. The main finding was that postimplantation language development proceeded at a pace that was not significantly different from normal. Thus, the language gap present at implantation did not increase after children started using the device, as it would if they had not received cochlear implants. Nevertheless, it is important to conduct further studies to determine whether these conclusions apply when other language skills, such as the use of grammar, are measured

Image Analysis, a complicated field still in the early stages of application to Pathology, has the capability of rendering major contributions to the diagnosis, prognosis, and management of malignancies of the breast. The present review summarizes the main problems and the general approach to the use of this technique for quantitating immunohistochemical stain results, obtaining DNA histograms, and making de novo diagnoses in routine materials of the Pathology service. In the case of diagnosis, the main steps are sampling, segmentation, and measures of chromatin texture. Currently, the limiting factor for all routine applications of image analysis is probably the absence of a reliable automatic nuclear segmentation

Bioresorbable implants (meshs and plates) are increasingly used in reconstructive craniofacial and skull base surgery. Usually these implants must be contoured to fit the complex craniofacial anatomy ex vivo; occasionally final contouring is performed in vivo and must be done without damaging surrounding structures (e.g., dura, brain). We report a precision method for in vivo contouring of bioresorbable implants using the Shaw hemostatic thermal scalpel

Acoustic analysis of a reading passage was used to identify the abnormal phonatory events associated with adductor spasmodic dysphonia (ADSD) pre- and postinjection of Botulinum Toxin A (Botox). Thirty-one patients (age 22 to 74 years) diagnosed with ADSD were included for study. All patients were new recipients of Botox, and the examination of their voice occurred before and after their initial injection of Botox. Acoustic events were identified from reading samples of the Rainbow Passage produced by each of the patients. These events were examined from sentences containing primarily voiced sound segments. Dependent variables included the number of phonatory breaks, frequency shifts, and aperiodic segments--all variables previously defined by the investigators. Additionally, calculated variables were made of the percentage of time these events occurred relative to the duration of the cumulative voiced segments. A sex- and age-matched control group (+/-2 years) was included for statistical comparison. Results indicated that those with ADSD produced more aberrant acoustic events than the controls. Aperiodicity was the predominant acoustic event produced during the reading, followed by frequency shifts and phonatory breaks. Within the ADSD group, the number of atypical acoustic events decreased following Botox injection. It is important that the occurrence of specific abnormal acoustic events was sufficient to differentiate the disordered speakers from the controls following as well as preceding initial Botox injection, as indicated by discriminant function analysis. This paper complements our previous work using this acoustic analysis method for defining the abnormal events present in the voice of those with ADSD and further suggests that these measures can be used in conjunction with perceptual impressions to differentiate speakers on the basis of initial severity

We investigated the effect of chronic administration of morphine on noxious stimulus-induced antinociception (NSIA) produced by intraplantar capsaicin injection. In the untreated (naive) rat, we previously found that NSIA depends on activation of dopamine, nicotinic acetylcholine, and mu- and delta-opioid receptors in nucleus accumbens. Rats chronically implanted with subcutaneous morphine pellets demonstrated tolerance to the antinociceptive effects of acute systemic morphine administration but did not show cross-tolerance to NSIA. Morphine pretreatment, however, significantly reduced NSIA dependence on intra-accumbens opioid receptors but not on dopamine or nicotinic acetylcholine receptors. As observed in naive rats, intra-accumbens microinjection of either the dopamine receptor antagonist flupentixol or the nicotinic receptor antagonist mecamylamine blocked NSIA in rats tolerant to the antinociceptive effects of morphine, but, in contrast to naive rats, intra-accumbens microinjection of either the mu-receptor antagonist Cys2,Tyr3,Orn5,Pen7 amide or the delta-receptor antagonist naltrindole failed to block NSIA. These findings suggest that although NSIA is dependent on nucleus accumbens opioid receptors in the naive state, this dependence disappears in rats tolerant to the antinociceptive effects of morphine, which may account for the lack of NSIA cross-tolerance. In separate experiments, intra-accumbens extracellular dopamine levels were measured using microdialysis. Dopamine levels increased after either capsaicin or systemic morphine administration in naive rats but only after capsaicin administration in morphine pretreated rats. Thus, intra-accumbens dopamine release paralleled antinociceptive responses in naive and morphine pretreated rats