A Zukowski | PubMed Health

PubMed1998

Modulation of platinum-induced toxicities and therapeutic index: mechanistic insights and first- and second-generation protecting agents.

Platinum-type drugs have proven to be valuable in the treatment of a variety of solid tumors, beginning with the commercial approval of cisplatin 18 years ago. There are several clinically important toxicities commonly associated with the administration of these drugs. Despite the extensive use of cisplatin and carboplatin, the fundamental chemical transformations and mechanisms that underlie their antitumor and toxic effects have not been fully characterized. Several first-generation protective thiols have been clinically studied in an attempt to reduce the toxicity of platinum-type drugs; while some of these agents appear to protect against certain toxicities, nearly all platinum-protecting drugs have their own intrinsic toxicities, which can be additive to the toxicity of platinum-type drugs. Tumor protection by platinum-protecting drugs is an additional untoward effect that is associated with certain types of agents and must be addressed with care. Recent advances in theoretical and laboratory methods and the use of supercomputers have extended our understanding of the possible major mechanisms underlying platinum drug antitumor activity and toxicity; we present strong evidence that there are two classes of chemical species of platinum drug. One class appears to predominantly account for the antitumor activity, and the other class of chemical species produces many of the toxic effects of platinum drugs. We have discovered a new nontoxic, second-generation platinum-protecting agent, known as BNP7787, which appears to selectively inactivate and eliminate toxic platinum species. BNP7787 has recently entered phase I clinical testing in cancer patients.

Amifostine↗

PubMed1996

Children's sensitivity to syllables, onsets, rimes, and phonemes.

It has been argued that children's performance on phonological awareness tasks varies with the linguistic level that is tapped by the task. For example, tasks that involve syllables are thought to be easier than tasks that involve lower-level linguistic units, and tasks that tap the level of onsets are thought to be easier than tasks that require access to single phonemes. In previous research, however, the linguistic status of a unit has often been confounded with its size. Five experiments were carried out in an attempt to disentangle these variables and so to provide a better test of the linguistic status hypothesis. In the first study, preschoolers and kindergartners more readily judged that two stimuli shared a beginning sound when that sound was an onset on its own than when it was part of a cluster onset. In two additional experiments, there was an advantage for syllables over rimes in kindergarten and first-grade children when the shared units occurred in the middle syllables of trisyllabic stimuli. The superiority for syllables was largely masked in two other studies in which the stimuli that shared a unit rhymed. This latter result suggests that children's familiarity with rhyme can override the syllable advantage. Overall, the results support the linguistic status hypothesis by indicating that effects of linguistic level on phonological sensitivity cannot always be reduced to effects of unit size.

Child↗

PubMed1996

Children's sensitivity to syllables, onsets, rimes, and phonemes.

It has been argued that children's performance on phonological awareness tasks varies with the linguistic level that is tapped by the task. For example, tasks that involve syllables are thought to be easier than tasks that involve lower-level linguistic units, and tasks that tap the level of onsets are thought to be easier than tasks that require access to single phonemes. In previous research, however, the linguistic status of a unit has often been confounded with its size. Five experiments were carried out in an attempt to disentangle these variables and so to provide a better test of the linguistic status hypothesis. In the first study, preschoolers and kindergartners more readily judged that two stimuli shared a beginning sound when that sound was an onset on its own than when it was part of a cluster onset. In two additional experiments, there was an advantage for syllables over rimes in kindergarten and first-grade children when the shared units occurred in the middle syllables of trisyllabic stimuli. The superiority for syllables was largely masked in two other studies in which the stimuli that shared a unit rhymed. This latter result suggests that children's familiarity with rhyme can override the syllable advantage. Overall, the results support the linguistic status hypothesis by indicating that effects of linguistic level on phonological sensitivity cannot always be reduced to effects of unit size.

Child↗

PubMed1995

What happened to the "n" of sink? Children's spellings of final consonant clusters.

Children's spellings provide a window on their representations of spoken words. These representations may not always match those assumed by the conventional orthography. We examined one specific case in which this may be true, that of CVCC (consonant-vowel-consonant-consonant) syllables. In three experiments, first graders often produced spellings such as "sach" for the nonword [symbol: see text] and "pit" for the nonword /pIlt/. We suggest that many children consider these syllables to contain three phonemes instead of four phonemes. Rather than treating the postvocalic nasal or liquid as a separate phoneme, children consider it an attribute of the vowel. This suggestion was supported by the results of a phoneme counting test in which children often used three tokens for syllables such as [symbol: see text] and /pIlt/. The results suggest that, in addition to difficulties in gaining access to phonemes, nonstandard phonemic representations may be a stumbling block in the acquisition of alphabetic literacy.

Attention↗

PubMed1994

What types of linguistic information do children use in spelling? The case of flaps.

We sought to determine what types of linguistic information children represent in their spelling by examining their performance on the flaps of words such as city and lady. In 4 experiments, children often misspelled flaps as d. This d bias was common until at least second grade, with few children showing a bias toward t. We found no evidence that children have an underlying representation of city as containing /t/, for children said such words with /d/ when speaking very slowly. Even kindergartners were more accurate at spelling the flaps of words such as dirty, which have a stem ending with /t/, than the flaps of words such as city. Thus, children use meaning relations among words to aid their spelling before they have formally been taught to do so. The results show that young children are not purely phonetic spellers as they are often portrayed. The results further suggest that phonology and orthography are closely related systems that interact during development.

Age Factors↗

PubMed1988

Noninvasive imaging for deep venous thrombosis.

In 96 patients, 127 extremities were identified by duplex ultrasonography as having acute deep venous thrombosis. The majority of these patients were found to have factors that predisposed them to thrombi formation. Doppler examination correlated with the duplex results in 77 extremities (61 percent). Two factors were identified that led to discrepancies between the results of these two modalities: (1) Thrombi that were more proximally located and totally occlusive were more likely to result in abnormal Doppler results than those that were not. (2) Doppler examination of the deep venous system of the lower extremities, although more accurate than clinical evaluation, was of insufficient accuracy to make correct decisions regarding the need for anticoagulation.

Acute Disease↗

PubMed1982