Effects of training in use of executive strategies on a verbal memory problem resulting from closed head injury

This case study reports attempts to improve the recall performance of an adolescent (GC) who had suffered a closed-head injury. GC had a very limited range of ways of processing both spoken and written information and showed significant recall problems. Initial training in the use of strategies for list learning resulted in improvement in paired-associate recall but showed that initiation and use of the newly learned strategies would not occur without prompting. Executive strategy training was provided to improve GC's ability to identify a memory problem and to initiate a general plan for dealing with that problem. This training involved consideration of task analysis, strategy selection and initiation, and monitoring of strategy use. Evidence of long-term maintenance of improvement in level of recall on both paired-associate and free recall tests was noted following the executive strategy training.     

Pulmonary infiltrates associated with noncytotoxic drugs

A wide variety of noncytotoxic drugs, including antibiotics, analgesics, narcotics, and psychotrophic and cardiovascular agents, may cause lung injury accompanied by roentgenographic infiltrates. The clinical manifestations of drug-induced lung disease are protean. Patients may present with acute injury resembling the adult respiratory distress syndrome, which must initially be distinguished from bacterial sepsis. Other drug-associated lung injury is characterized by a more subacute pneumonitis similar to an atypical infectious pneumonia. Finally, some drugs may cause insidiously progressive pulmonary infiltrates that share features with granulomatous infections. The more common drug reactions are discussed in this review, and, although the features of drug-induced lung disease are often relatively nonspecific, those features that either mimic infectious causes or may be helpful in differentiating these processes from infections are given particular emphasis.     

Intraperitoneal mesotheliomas induced in mice by a polycyclic aromatic hydrocarbon

Female mice of 6 strains (C3H/HeN, BALB/c, C57BL/6N, DBA/2, NIH Swiss, and AKR/N) were given the polycyclic aromatic hydrocarbon carcinogen 3-methylcholanthrene (MC) intragastrically in olive oil at a dose of 20 mg/kg, weekly for 12 wk. Half were pretreated 24 h before each MC administration with intraperitoneal beta-naphthoflavone (beta-NF, 150 mg/kg in olive oil), a noncarcinogenic inducer of certain cytochrome P-450 isozymes. Remaining mice were given olive oil prior to MC in the same fashion, or beta-NF in olive oil or olive oil alone without subsequent exposure to MC. All mice were killed when moribund or 13 mo after the start of treatment. Most of the mice, irrespective of treatment, exhibited signs of peritoneal injury, including inflammation, necrosis, granuloma formation, and mineralization. Mice of some of the strains also presented peritoneal mesotheliomas, in addition to a variety of other tumors. The incidence of unequivocal mesothelioma-bearing mice was 12/31 C3H/He and 9/32 BALB/c mice given only MC. Incidence was low in C57BL/6 (1/31) and DBA/2 (1/26), and no definite mesotheliomas were found in Swiss or AKR mice. There were in addition a number of cases of sarcoma (nine total in all strains) and of peritonitis (four total) that resembled mesothelioma to some degree and were initially diagnosed as much. beta-NF pretreatment reduced the frequency of mesotheliomas: there was only one definite mesothelioma in any of the beta-NF-MC groups, in a C3H/He mouse. Most of the mesotheliomas were mixed fibro-mesothelial type, sometimes with papillary epithelial excrescences. They typically grew in a botryoid pattern within the peritoneal cavity, coating the abdominal organs and sometimes actively invading these organs and the diaphragm. Some lesions exhibited pleomorphism, prominent giant cells, and frequent mitoses. In addition, several lesions consisting of severe mesothelial hyperplasia associated with tissue necrosis and inflammation were considered as possible early stages of mesothelioma development. It was postulated that peritoneal injury imposed by repeated intraperitoneal injection of oil acted as an enhancing factor for mesothelioma induction by MC. The pertinence of such a relationship to mechanisms in the etiology of human mesotheliomas is discussed.     

A markedly diminished pleiotropic response to phenobarbital and structurally-related xenobiotics in Zucker rats in comparison with F344/NCr or DA rats.

Phenobarbital (PB) and certain structurally-related compounds induce a variety of hepatic drug-metabolizing enzymes in many strains of rats. Thus, following administration of PB (300, 500 ppm), barbital (BB, 1500 ppm) or 5-ethyl-5-phenylhydantoin (EPH, 500 ppm), CYP2B1-mediated benzyloxyresorufin O-dealkylase activity and epoxide hydrolase activity were profoundly induced in female DA and F344/NCr rats. In contrast, outbred female lean and obese Zucker rats showed markedly reduced CYP2B1 responses (less than 15% and less than 5% of those observed in the female DA or F344/NCr rat) to PB (doses less than or equal to 300 ppm), BB (1500 ppm) or EPH (500 ppm). In parallel studies, profound increases in RNA levels coding for CYP2B1, glutathione S-transferases Ya/Yc (alpha subclass), or epoxide hydrolase were detected in the female F344/NCr rat following treatment with PB (300 ppm), BB (1500 ppm) or EPH (500 ppm). In contrast, lean Zucker rats showed a strong response only to the highest dose of PB (500 ppm), implying that the diminished response in the Zucker rats may occur at some pretranslational level. Similar studies with lower doses of PB, EPH or BB in male lean Zucker rats showed a decreased response, relative to that in male F344/NCr rats. However, this insensitivity was not as profound as that observed in the female Zucker rats. In fact, the response to PB-type inducers in male or female Zucker rats is probably most clearly explained as a shift of the dose-response curve sharply to the right (decreased responsiveness, compared to F344/NCr or DA rats of the same sex). This decreased responsiveness of female lean Zucker rats to induction of CYP2B1, relative to that of F344/NCr rats, was also observed with the structurally-diverse PB-type inducers clonazepam, clotrimazole and 2-hexanone. In contrast, the female Zucker rat (obese or lean) displayed a pronounced response to induction of CYP1A-mediated ethoxyresorufin O-deethylase activity by beta-naphthoflavone, a prototype inducer of CYP1A1 and CYP1A2. The Zucker rat would thus appear to represent a potentially exploitable genetic model for examining the mechanism of enzyme induction by the myriad xenobiotics which induce a PB-type response.     

Symptomatic treatment in the fragile X-associated tremor/ataxia syndrome.

There is no established treatment for the neurological features of the recently discovered fragile X-associated tremor/ataxia syndrome (FXTAS). Fifty-six patients with FXTAS completed a questionnaire to determine whether any medications had been effective for neurological symptoms. Of 11 subjects with definite FXTAS, 8 (70%) were on medications for their neurological symptoms, whereas most subjects with possible or probable FXTAS, 31 (70%) of 45 subjects, were not on medications. Although no therapy was uniformly effective for intention tremor, ataxia, Parkinsonism, memory loss, or anxiety, some subjects with intention tremor or Parkinsonism reported improvement with medications frequently used in other movement disorders. Overall, all 22 subjects on medications reported improvement in one or more symptoms. Lack of insight, recall bias, and cognitive impairment may have resulted in an underestimation of the beneficial effect of medical therapy. This study suggests that patients with FXTAS can derive improvement from medication treatment for some of their symptoms.     

Do shrimp‐allergic individuals tolerate shrimp‐derived glucosamine?

BACKGROUND: There is concern that shrimp-allergic individuals may react to glucosamine-containing products as shrimp shells are a major source of glucosamine used for human consumption. OBJECTIVE: The purpose of this study was to determine whether shrimp-allergic individuals can tolerate therapeutic doses of glucosamine. METHODS: Subjects with a history of shrimp allergy were recruited and tested for both shrimp reactivity via a prick skin test and shrimp-specific IgE by an ImmunoCAP assay. Fifteen subjects with positive skin tests to shrimp and an ImmunoCAP class level of two or greater were selected for a double-blind placebo-controlled food challenge (DBPCFC) using glucosamine-chondroitin tablets containing 1,500 mg of synthetically produced (control) or shrimp-derived glucosamine. Immediate reactions, including changes in peak flow and blood pressure, and delayed reactions (up to 24 h post-challenge) via questionnaire were noted and assessed. RESULTS: All subjects tolerated 1,500 mg of both shrimp-derived or synthetic glucosamine without incident of an immediate hypersensitivity response. Peak flows and blood pressures remained constant, and no subject had symptoms of a delayed reaction 24 h later. CONCLUSION: This study demonstrates that glucosamine supplements from specific manufacturers do not contain clinically relevant levels of shrimp allergen and therefore appear to pose no threat to shrimp-allergic individuals.