From cholera to burns: a role for oral rehydration therapy.

According to the practice guidelines of the American Bum Association on burn shock resuscitation, intravenous (i.v.) fluid therapy is the standard of care for the replacement of fluid and electrolyte losses in burn injury of > or = 20% of the total body surface area. However, in mass burn casualties, i.v. fluid resuscitation may be delayed or unavailable. Oral rehydration therapy (ORT), which has been shown to be highly effective in the treatment of dehydration in epidemics of cholera, could be an alternate way to replace fluid losses in burns. A prospective case series of three patients was carried out as an initial step to establish whether oral Ceralyte 90 could replace fluid losses requiring i.v. fluid therapy in thermal injury. The requirement of the continuing i.v. fluid therapy was reduced by an average of 58% in the first 24 hours after the injury (range 37-78%). ORT may be a feasible alternative to i.v. fluid therapy in the resuscitation of burns. It could also potentially save many lives in mass casualty situations or in resource-poor settings where i.v. fluid therapy is not immediately available. Further studies are needed to assess the efficacy of this treatment and to determine whether the present formulations of ORT for cholera need modification.

Functional coupling of a mammalian somatostatin receptor to the yeast pheromone response pathway.

A detailed analysis of structural and functional aspects of G-protein-coupled receptors, as well as discovery of novel pharmacophores that exert their effects on members of this class of receptors, will be facilitated by development of a yeast-based bioassay. To that end, yeast strains that functionally express the rat somatostatin receptor subtype 2 (SSTR2) were constructed. High-affinity binding sites for somatostatin ([125I-Tyr-11]S-14) comparable to those in native tissues were detected in yeast membrane extracts at levels equivalent to the alpha-mating pheromone receptor (Ste2p). Somatostatin-dependent growth of strains modified by deletion of genes encoding components of the pheromone response pathway was detected through induction of a pheromone-responsive HIS3 reporter gene, enabling cells to grow on medium lacking histidine. Dose-dependent growth responses to S-14 and related SSTR2 subtype-selective agonists that were proportional to the affinity of the ligands for SSTR2 were observed. The growth response required SSTR2, G alpha proteins, and an intact signal transduction pathway. The sensitivity of the bioassay was affected by intracellular levels of the G alpha protein. A mutation in the SST2 gene, which confers supersensitivity to pheromone, was found to significantly enhance the growth response to S-14. In sst2 delta cells, SSTR2 functionally interacted with both a chimeric yeast/mammalian G alpha protein and the yeast G alpha protein, Gpa1p; to promote growth. These yeast strains should serve as a useful in vivo reconstitution system for examination of molecular interactions of the G-protein-coupled receptors and G proteins.

Superiority of adriamycin-14-octanoate over adriamycin in reducing viability of methotrexate-resistant L5178Y cells: brief communication.

Adriamycin-14-octanoate (ADR-OCT) was superior to adriamycin (ADR) in reducing the viability of L5178Y cells resistant to methotrexate (MTX). This effect was seen in logarithmically growing and plateau-phase cultures and increased both with dose and duration of exposure. Both ADR-OCT and ADR were effective inhibitors of the exogenous Escherichia coli DNA-dependent RNA polymerases in vitro and of the endogenous polymerase in mammalian cultured cells. Drug concentrations required for approximately 50% enzyme inhibition in both systems were comparable for both agents, being of the order of 10(-5) M. These experimental studies suggested that ADR-OCT may be a valuable agent for treating neoplasms resistant to MTX.

Importance of primary site in assessing chemotherapy response and 7-year survival data in advanced squamous-cell carcinomas of the head and neck treated with initial combination chemotherapy without cisplatin.

Two hundred eight patients with advanced head and neck squamous-cell carcinomas were treated between 1975 and 1982 with schedule A chemotherapy containing vincristine, bleomycin, methotrexate, 5-fluorouracil, and hydrocortisone administered over 24 hours followed by a folinic acid rescue. Chemotherapy was administered as initial treatment on days 1 and 14 before "curative" local therapy. Toxicity was minimal and patient compliance was 100%. Chemotherapy response was assessed on day 28 in 200 patients: 132 (66%) had an objective response and 68 (34%) were judged to be nonresponders. The complete remission (CR) rate following local therapy was significantly greater in chemotherapy responders (78%) than nonresponders (49%) (P less than .001). Overall median survival figures were 32 months for all patients, 37 months for all chemotherapy responders, and 69 months for all patients achieving CR. Analysis by tumor site showed that oral cavity or nasopharyngeal tumors responded well to initial chemotherapy (P less than .05 and P less than .01) compared with all other sites. This high response rate was not necessarily associated with increased survival, since the median survival of chemotherapy responders for oral cavity lesions was only 22 months, although in nasopharyngeal tumors, median survival figures were 64 months. Furthermore, the longest median survival duration of 69 months was observed in patients with laryngeal tumors, although these had a lower response rate (61%) to initial chemotherapy. Therefore, response to initial chemotherapy is not automatically a favorable prognostic sign. Survival figures appear markedly influenced by tumor site.

Epidermal aquaporin-3 is increased in the cutaneous burn wound.

INTRODUCTION: Aquaporins (AQP) are a family of transmembrane proteins that transport water and small solutes such as glycerol across cell membranes. It is a mediator of transcellular water flow and plays an important role in maintaining intra/extracellular fluid homeostasis by facilitating water transport in response to changing osmotic gradients. In the skin, AQPs permit rapid, regulated, and selective water permeability and have been demonstrated to play a role in skin hydration, cell proliferation, migration, immunity, and wound healing. However, the expression of AQP-3 in the cutaneous burn wound has never been elucidated. We sought to assess the expression of AQP-3 in patients with burn wounds. METHODS: A fresh full thickness biopsy sample was taken from the center of the burn wound, the burn wound edge, and the graft donor site in 7 patients (n=21), approximately 3-7 days post injury. Fixed, paraffin embedded sections were stained using AQP-3 specific antibody and examined by immunofluorescence. Fresh samples were processed to quantify AQP-3 protein expression with Western blot analysis. RESULTS: The central portion of the burn wound revealed destruction of the epidermis and dermis with no AQP-3 present. Along the burn wound edge where the epidermal architecture was disrupted, there was robust AQP-3 staining. Western blot analysis demonstrated deeper staining along the burn wound edge compared to unburned skin (control). Quantification of the protein shows a significant amount of AQP-3 expression along the burn wound edge (3.6±0.34) compared to unburned skin (2.1±0.28, N=7, *p<0.05). There is no AQP-3 expression in the burn wound center. CONCLUSION: AQP-3 expression is increased in the burn wound following injury. While its role in wound healing has been defined, we report for the first time the effect of cutaneous burns on AQP-3 expression. Our data provides the first step in determining its functional role in burn wounds. We hypothesize that development of AQP3 targeted therapies may improve burn wound healing.

Causes of higher in-hospital mortality in women than in men after acute myocardial infarction.

Clinical, laboratory and cardiac catheterization parameters were reviewed in 355 men and 155 women hospitalized at a tertiary care referral center between February 1987 and December 1991 to analyze why women have a higher in-hospital mortality rate than do men after acute myocardial infarction. Hospital mortality was 21.4% in women and 12.1% in men (p = 0.007). In comparison with men, women were older (63.3 +/- 11.9 vs 60.5 +/- 12.6 years; p = 0.023), had more systemic hypertension (46.5 vs 34.4%; p = 0.001) and higher serum total cholesterol levels (211 +/- 51 vs 197 +/- 49 mg/dl; p = 0.0015), sought medical care later (8.9 vs 5.3 hours; p = 0.026), were referred later (47.7 vs 43.7 hours; p = 0.063) and had more shock (34.8 vs 24.2%; p = 0.013). Logistic regression analysis revealed 5 variables predictive of hospital mortality; age > 65 years, diabetes, shock, non-Q-wave infarction, and not undergoing cardiac catheterization. Gender was of borderline significance in predicting hospital mortality. Cardiac catheterization, performed in 88% of women and 87% of men, showed similar rates of 1-, 2- and 3-vessel disease, and similar characteristics of the infarction-related artery. The differences in hospital mortality between men and women are due to a combination of pre- and in-hospitalization factors in women. The excess mortality is not due to differences in disease severity as evaluated by cardiac catheterization information.

Paraquat and diquat interference in the analysis of creatinine by the Jaffé reaction.

Paraquat and diquat were shown to interfere significantly in the measurement of plasma creatinine by the alkaline picrate (Jaffé) reaction in a young man who ingested a massive dose of a mixture of the 2 herbicides. It is likely that these bipyridylium compounds react in a manner similar but at different rates compared with creatinine in the Jaffé reaction.

Chronic copper toxicosis presenting as liver failure in an Australian child.

A 20 month old Caucasian male child, after a five week illness, developed liver failure which was successfully treated by liver transplantation. The explanted liver had a histology identical to that seen in Indian childhood cirrhosis and its copper content was increased tenfold. Water used to prepare the child's milk feeds came from a bore via copper conduits and at times contained 120 mumol/l of copper, eight times the recommended maximum for human consumption. Because non-Indian cases of Indian childhood cirrhosis associated with excess copper ingestion are increasingly being recognised, and as early treatment can restore normal liver morphology, we support the use of the previously suggested alternative term for this condition, ie; 'copper-associated liver disease in childhood'. Measurement of hepatic copper concentrations in all children less than six years of age who develop hepatic failure of unknown cause will increase its recognition. On diagnosis sources of increased dietary copper should be investigated to ensure that younger siblings are not similarly exposed.

Lack of survival advantage in patients with advanced squamous cell carcinomas of the oral cavity receiving neoadjuvant chemotherapy prior to local therapy, despite achieving an initial high clinical complete remission rate.

Subset analyses have been performed on 50 patients with squamous cell carcinomas of the oral cavity from our earlier series of 208 patients with advanced, previously untreated head and neck tumors (J Clin Oncol 1986;4:1340-7). Forty patients (80%) responded to two initial courses of Schedule A chemotherapy. Side effects were minimal. After definitive local therapy the final complete remission (CR) rate was 76%. Neither chemotherapy response, nor achievement of final CR was significantly affected by stage, T or N status, sex, or histologic grade. With a median follow-up of 11.6 years, the overall 10-year survival rate was 25%. Multivariate analysis indicated that both age, i.e., < 50 years (p = .004) and achievement of a final CR (p = .002) were significant factors for improved survival. Median survival for all patients was only 21 months and for those in final CR 30 months. These survival figures were all significantly lower than those of similarly treated patients with laryngeal or nasopharyngeal tumors, illustrating that all patients with head and neck tumors achieving a final clinical CR do not automatically have improved survival. These results emphasize the need for randomized trials, with sufficient numbers to identify optimal treatment strategies for tumors at specific sites within the head and neck region.

24-hour combination chemotherapy without cisplatin in patients with recurrent or metastatic head and neck cancer.

Sixty-three patients with advanced histologically proven squamous cell carcinomas of the head and neck, considered untreatable other than by chemotherapy, received a combination of vincristine, bleomycin, methotrexate, 5-fluorouracil, and hydrocortisone administered over 24 hours, followed by a folinic acid rescue, every 3 weeks. Fifty-seven patients had received prior radiotherapy and 78% of recurrences were within the radiation field. Sixty-one patients were assessable for response to chemotherapy and 25 (41%) achieved objective responses. Side effects from 167 courses of chemotherapy were minimal and were present only in 38% of patients. There were no cases of bone marrow depression and no drug-induced deaths. Patient compliance was 98%. Chemotherapy responders had a longer median duration of survival of 11.9 months (with four patients still alive at 10, 22, 30, and 90 months) compared with 4.96 months for nonresponders (with two patients alive at 7 and 15 months), p less than 0.001. Ten of 24 chemotherapy responders went on to surgery and eight achieved a complete remission (CR), while only 6/36 nonresponders underwent salvage surgery and all became disease-free. Patients achieving a complete remission had improved survival (median 24.5 months). The presence of metastatic disease was a poor prognostic sign; only 8/30 (27%) responded to chemotherapy and none subsequently achieved complete remission. This safe drug protocol appears to benefit only a small subset of patients, namely those who respond to chemotherapy rendering their tumors operable, but is of no general value in this group of previously irradiated patients since 92% of all patients treated were dead at 2 years.

Treatment of advanced squamous cell carcinomas of the head and neck with initial combination chemotherapy prior to surgery and/or radiotherapy: five-year survival data.

One hundred and thirty-nine patients with advanced head and neck cancer were treated with a combination of vincristine, bleomycin, methotrexate with a folinic acid rescue, 5-fluorouracil and hydrocortisone given over 24 hours, as initial therapy on days one and 14 prior to conventional local therapy on day 28. One hundred and thirty-six patients were assessed for chemotherapy response on day 28. Ninety-one patients (67 per cent) had an objective response and 45 (33 per cent) were classed as non-responders, although 13 had a minimal (20-30 per cent) response. The complete remission rate following local therapy was significantly greater in chemotherapy responders (76 per cent) than in nonresponders (54 per cent) p less than 0.05. Toxicity was minimal, provided standard medical precautions were observed, and 87 patients (63 per cent) reported no side-effects. There was 100 per cent patient compliance. Sex or histological grade did not significantly influence response to chemotherapy. Oral cavity or nasopharyngeal tumours responded better than other sites (p less than 0.05). Patients under 49 were more likely to respond to chemotherapy than older patients (p less than 0.01). Survival data are available for a mean follow-up time of 48 months (range 12-78 months). Chemotherapy responders have a longer median survival than non-responders, 33 versus 20 months (p less than 0.05). Patients who achieve a complete remission after local therapy live significantly longer than those with residual disease, median durations of survival being 52.4 and 7.8 months respectively (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Larynx preservation after initial non-cisplatin containing combination chemotherapy plus radiotherapy, as opposed to surgical intervention with or without radiotherapy in previously untreated advanced head and neck cancer: final analysis after 12 years follow-up.

After a median follow-up of 12 years, median overall survival of 73 patients with advanced squamous cell carcinoma of the larynx was 65 months. The 61 per cent of patients responding to two courses of initial schedule A combination chemotherapy, not including cisplatin, and the 81 per cent of patients achieving a final complete remission after definitive local therapy, had median overall survival figures of 95 and 97 months respectively. Overall survival and relapse-free survival in 51 patients treated with radiotherapy only with larynx preservation, were not significantly different from the 21 patients who completed their surgery with pre- or post-operative radiotherapy; median overall figures were 71 versus 65 months. These data add weight to our proposal that use of initial combination chemotherapy followed by radiotherapy may eliminate the need for radical surgery, so preserving the larynx in patients with advanced disease, and provides evidence of some long-term benefit with 32 per cent of this entire group surviving 12 years.

At second glance: employers and employees with learning disabilities in the Americans with Disabilities Act era.

The impact of the Americans with Disabilities Act (ADA) of 1990 on the American workplace is examined. The findings of a previous study (Gerber, 1992) on employer knowledge about learning disabilities are compared to current findings. Important themes and employer beliefs and practices that were consistent in employer responses are described. Although employers are continuing to make efforts to comply with the regulations of the ADA, they still have relatively little knowledge or experience with it in terms of learning disabilities.

When academic assistance is not enough: addressing the mental health issues of adolescents and adults with learning disabilities.

This article focuses on an answer to a critical question for adolescents and adults with learning disabilities: How can professionals assist students with learning disabilities who have psychosocial issues that appear to be affecting their academic progress and life adjustment? Inherent in this inquiry are other, equally important issues, such as: How do learning disabilities service providers know when to involve other service providers? What are the steps in referring a student for further assistance with different mental health issues? When are team interventions necessary? How are team interventions conducted in either secondary or postsecondary settings? How should learning disabilities service providers establish the boundaries of their professional expertise and/or responsibilities to adequately meet the needs of individuals with learning disabilities? This article illustrates answers to these questions by providing examples of interventions and case studies from two federally funded research/demonstration projects at the University of Minnesota: the Learning Disabilities Transition Project and Project Extra. The authors describe theoretical models for mental health services that address the psychosocial issues frequently encountered in academic or vocational settings. Recommendations are also included that discuss how the models can be personalized to fit the reader's home institution or agency.

Malignant superior vena cava syndrome presenting after trauma.

A 41-year-old man was brought to the ED after a motor vehicle crash. On presentation, he demonstrated symptoms compatible with superior vena cava (SVC) syndrome, including extreme dyspnea, face and neck cyanosis and facial swelling. A chest tube was inserted and drained large amounts of sanguineous fluid. An exploratory thoracotomy revealed an extensive tumour encasing the SVC and the hilum. Biopsy confirmed the diagnosis of T-cell lymphoma. The most common cause of SVC syndrome is malignant disease, with bronchogenic carcinoma and lymphoma being most frequent. Review of the literature uncovered only a few anecdotal reports of traumatic SVC syndrome. There are no previous reported cases of malignant SVC syndrome presenting in association with trauma.

Weak, but complex pulsed magnetic fields may reduce depression following traumatic brain injury.

Many patients who display psychological depression following a traumatic brain injury do not respond completely to antidepressant drugs. We hypothesized that this type of depression is strongly correlated with subclinical, complex partial seizure-activity within the hippocampal-amygdaloid region that continues for months to years after apparent neurological and behavioral "recovery." Four depressed patients who had sustained traumatic brain injuries and who exhibited mild to moderate brain impairment according to standardized tests received 30 min. of weak (1 microT) burst-firing magnetic fields across the temporal lobes once per week for 5 weeks. There was a significant improvement of depression and reduction of phobias while physical symptoms and other complaints were not changed.