The fate of free flaps used to reconstruct defects in recurrent head and neck cancers.

The purpose of this study was to assess free-flap viability in patients treated for recurrent head and neck cancers. A 10-year retrospective review identified 121 patients who had had prior head and neck cancers extirpated for cure, who subsequently presented with documented recurrent cancers that were removed, and who then underwent reconstruction with free flaps. The charts of these patients were reviewed for patient demographics, tumor types, location, flaps used for reconstruction, size of area requiring reconstruction, length of operation, previous radiation, and all postoperative morbidity and mortality. The time to recurrence ranged from 21/2 months to 21 years. The majority of tumors treated were squamous cell carcinomas (n = 82). Most of them were located intraorally (n = 75). Radiation therapy had been delivered to 88 patients before their free-flap reconstructions. In this series, 31 percent of all patients required additional surgery for complications, 14 percent of free flaps were lost, and 4 percent of patients died within 30 days of their operation. The significant findings were that a flap that was >4 cm in diameter was related to flap loss (p = 0.03 by the chi2 method) and that flap loss was related to operative times greater than 11 hours (p = 0.03 by the chi2 method). It was concluded that recurrent head and neck cancers with large postextirpation defects that required prolonged operative times yielded a significantly high tendency toward flap failure.

Testicular cytotoxicity of intravenous procarbazine in rats.

Although the testicular cytotoxicity of procarbazine has been evaluated in the rat, previous models have utilized routes other than the intravenous one, and have generally employed multiple-dose regimens. In this report, we describe testicular toxicity in the Sprague-Dawley rat following a single intravenous bolus of procarbazine (0-700 mg kg body weight), with necropsy 59 +/- 2 days later. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulation index and epididymal index. Effects of procarbazine on heart, lung, liver and kidney histology were evaluated qualitatively. Progressive dose-dependent testicular atrophy and oligospermia occurred at low and intermediate dosages of procarbazine. Marked testicular atrophy, oligospermia and germinal hypoplasia were observed at high dosages (500 and 700 mg kg-1 body weight). LD50 at day 59 for procarbazine appears to be approximately 600 mg kg-1 body weight using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage.

Distribution and metabolism of doxorubicin in rats undergoing testicular circulatory isolation.

Several hundred thousand men receive chemotherapy each year; many are sterilized by this treatment. Temporary testicular circulatory isolation (TCI), a regional drug delivery approach to circumvent this, decreases doxorubicin-induced testicular injury in the rat and provides partial protection from doxorubicin-related infertility. We evaluated the distribution of doxorubicin and its metabolites (doxorubicinol and doxorubicin aglycone) in rats treated with TCI. In each of 56 male Sprague-Dawley rats, the left spermatic cord and gubernaculum were mechanically clamped for 45 minutes. Immediately after clamp application, these rats received doxorubicin (6 mg/kg, intravenous bolus) and were killed at seven time points after doxorubicin administration, ranging from 30 minutes to 48 hours. Twenty-one control rats were treated identically but did not receive TCI. Doxorubicin and its metabolites were extracted from tissue (left testis, right testis, left kidney, heart, left lung, liver) and serum and analyzed by high-performance liquid chromatography. In the TCI group, the distribution of the parent drug and doxorubicinol in tissue and serum closely approximated levels from doxorubicin-treated controls not receiving TCI in all organs except left testis. No anthracycline was detected at any time point in the left testis of the TCI group. These results indicate that TCI completely protects the testis from doxorubicin exposure in this model and that TCI does not affect distribution of doxorubicin in other organs.

The use of carbamazepine to treat benzodiazepine withdrawal in a geriatric population.

Rapid withdrawal of short to intermediate half-life benzodiazepines may be hazardous, particularly in the elderly. The use of carbamazepine to facilitate withdrawal has been reported in younger patients. We describe four elderly patients (average age, 72.5 years) who had each experienced at least one unsuccessful attempt at alprazolam withdrawal and who were subsequently successfully withdrawn via the use of carbamazepine over a period ranging from 2 to 6 days. These geriatric patients experienced no major withdrawal symptoms, but mild symptoms were common. There was no correlation between dose or duration of alprazolam use and extent of withdrawal symptoms. We recommend use of this treatment regimen in a hospital setting only, where close monitoring can occur.

Calcium transport by basal lateral membrane vesicles from rat small intestine decreases with age.

There is a marked decrease in active Ca2+ transport by the rat small intestine with age, particularly between 2 and 12 months. Much evidence suggests that the active component of Ca2+ transport resides in the energy-dependent pumping of Ca2+ across the intestinal basal lateral membrane. Therefore, we have characterized Ca2+ uptake by basal lateral membrane vesicles isolated from young (2-3 month old) and adult (12-14 month old) rats. In vesicles from the proximal duodenum, ATP-dependent Ca2+ uptake was about 4-times greater in the young animal than in the adult. There were no age differences in Ca2+ uptake in the absence of ATP. In vesicles from the ileum, Ca2+ uptake was much less than in the duodenum. The age differences in the ileum were smaller, and ATP-dependent Ca2+ uptake in the young was only twice that seen in the adult. Osmotic lysis of duodenal vesicles reduced Ca2+ uptake to low levels in both age groups, indicating that most of the Ca2+ was being taken up into an osmotically active space. Kinetic studies of Ca2+ uptake showed that there was no change in the apparent affinity but a 5-fold decrease in the Vmax of the adult Ca2+ transport system compared to that of the young animal. This marked decrease in the capacity of basal lateral membrane vesicles to actively transport Ca2+ may contribute to the decline in intestinal Ca2+ absorption with age.

Changes in intestinal glucose transport over the lifespan of the rat.

Age-related changes in intestinal glucose absorption were studied using everted intestinal sacs and brush border membrane vesicles prepared from male F344 rats. Glucose uptake by everted intestinal sacs was greatest in young (2-3-month-old) as compared with adult (12-14-month-old) and old (24-month-old) rats. The greatest decrease in glucose uptake occurred between 2 and 12 months. The addition of phloridzin reduced glucose uptake to similar levels in all age groups, suggesting that the age-related change was in the carrier-mediated component of glucose transport. In order to localize the site of decreased carrier-mediated glucose transport, experiments were performed using brush border membrane vesicles. Vesicular glucose uptake in the presence of Na was significantly greater in vesicles prepared from 2-month-old rats (133 +/- 18 pmol/mg/s), compared with those prepared from 12-month-old rats (82 +/- 13 pmol/mg/s). Kinetic studies performed under non-equilibrium conditions demonstrated that the major effect of age was on the Na-dependent component of the brush border transport system. There was a reduction in the Vmax from 335 +/- 37 pmol/mg/s in the young to 217 +/- 22 pmol/mg/s in the adult, but there was no change in the Km. Isotope exchange studies performed under equilibrium conditions confirmed a decrease in the activity of the glucose transporter with age. No age-related changes in Na uptake by brush border membrane vesicles were observed. These findings suggest that a decrease in the number and/or activity of Na-linked glucose carriers may account for the decrease in intestinal glucose transport with age.

Projection systems and terminal localization of dorsal column afferents: an autoradiographic and horseradish peroxidase study in the rat.

Projection systems from the gracile nucleus and the cuneate nuclear complex to their terminal sites in the mesencephalon, diencephalon, and cerebellum were examined by means of anterograde autoradiography and retrograde horseradish peroxidase methods. Three projection systems emerge from the dorsal column nuclei, decussate via internal arcuate fibers, and form the contralateral medial lemniscus (ML). At the obex, some fibers split off the ML and course dorsolaterally, forming an ascending lateral system which fits the "lemniscal adjunct channel" (LAC) concept of Graybiel ('72). The ML continues rostrally as the "main lemniscal line channel" (MLLC). At the inferior colliculus, some LAC fibers terminate in the pontine nuclei, parabrachial, dorsal reticular nuclei, and the external and ventral medial part of the central nucleus of the inferior colliculus. More rostrally at the level of the superior colliculus, terminal fields are found in the medial nucleus of the medial geniculate body, the suprageniculate, pretectal, and mesencephalic reticular nuclei, marking the end of the LAC. In the diencephalon, gracile fibers leave the MLLC and form a crescentlike terminal field along the extreme lateral border of the ventral posterior lateral nucleus (VPL) of the thalamus. Cuneate MLLC fibers terminate in a bandlike formation in the VPL medial to the gracile termination. The third fiber system, the cuneocerebellar projection, emerges from the cuneate, the external cuneate nuclei, and the "cellular bridge" and immediately enters the ipsilateral inferior cerebellar peduncle. Upon entering the cerebellum, the major fiber component remains ipsilateral and terminates as vertical bands in vermal and paravermal lobules, and lobules I through IVa. The posterior cerebellar lobe contains terminal bands in lobules VII-IX, the copula pyramidis, and the paramedian lobule. It is concluded that the dorsolateral fiber system conforms to Graybiel's LAC. It is more divergent and probably less modality specific, whereas the medial lemniscal system conforms to the MLLC, which is said to be modality specific, less divergent, and locked to specific sensory-motor response characteristics. The topography of cerebellar terminal bands indicates that there is sensory-motor representation from all parts of the body to all parts of the cerebellum, at least in the rat.