Impact of physiologically relevant temperatures on dermal absorption of active substances - an ex-vivo study in human skin.

Skin temperature plays a certain role in the dermal absorption of substances, but the extent and mechanisms of skin temperatures-induced modulation in ranges caused by physiological thermoregulation or environmental conditions are largely unknown. The influence of dermal temperature on the absorption of the model lipophilic compound (anisole) and the model hydrophilic compounds (1,4-dioxane, ethanol) through human skin was investigated at three dermal temperatures (25, 32 and 39 °C) in an ex-vivo diffusion cell model. The substances were applied to the skin and transdermal penetration was monitored. All substances showed temperature dependent variations in their penetration behavior (3 h: 25-39 °C: 202-275% increase in cumulative, transdermally penetrated amounts). The relative differences in absorption in relation to temperature were greatest within 45 min after exposure (25-39 °C: 347-653% rise in cumulated penetration), although absolute amounts absorbed were small (45 min vs. 3 h: 4.5-14.5%). Regardless of blood circulation, skin temperature significantly influences the amount and kinetics of dermal absorption. Substance-dependent, temperature-related changes of the lipid layer order or the porous pathway may facilitate penetration. The early-stage modulation of transdermal penetration indicates transappendageal absorption, which may be relevant for short-term exposures. For both, toxicological evaluation and perfusion cell studies, it is important to consider the thermal influence on absorption or to perform the latter at a standardized temperature (32±1 °C).

Synergy between methionine stress and chemotherapy in the treatment of brain tumor xenografts in athymic mice.

This study describes a novel approach to the treatment of brain tumors with the combination of recombinant L-methionine-alpha-deamino-gamma-lyase and chemotherapeutic regimens that are currently used against such tumors. The growth of Daoy, SWB77, and D-54 xenografts in athymic mice was arrested after the depletion of mouse plasma methionine (MET) with a combination of a MET- and choline-free diet and recombinant L-methionine-alpha-deamino-gamma-lyase. The treated tumor-bearing mice were rescued from the toxic effects of MET withdrawal with daily i.p. homocystine. This regimen suppressed plasma MET to levels below 5 microM for several days, with no treatment-related deaths. MET depletion for 10-12 days induced mitotic and cell cycle arrest, apoptotic death, and widespread necrosis in tumors but did not prevent tumor regrowth after cessation of the regimen. However, when a single dose of 35 mg/m(2) of N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), which was otherwise ineffective as a single therapy in any of the tumors tested, was given at the end of the MET depletion regimen, a more than 80-day growth delay was observed for Daoy and D-54, whereas the growth of SWB77 was delayed by 20 days. MET-depleting regimens also trebled the efficacy of temozolomide (TMZ) against SWB77 when TMZ was given to animals as a single dose of 180 mg/m(2) at the end of a 10-day period of MET depletion. The enhanced responses of both Daoy and SWB77 to DNA alkylating agents such as BCNU and TMZ could be attributed to the down-regulation of O(6)-methylguanine-DNA methyltransferase activity. However, the synergy of MET depletion and BCNU observed with D-54 tumors, which do not express measurable O(6)-methylguanine-DNA methyltransferase protein, is probably mediated by a different mechanism. MET depletion specifically sensitizes tumors to alkylating agents and does not significantly lower the toxicity of either BCNU or TMZ for the host. In this regard, the combination approach of MET depletion and genotoxic chemotherapy demonstrates significant promise for clinical evaluation.

The role of ergonomics in the elimination and prevention of work-related musculoskeletal problems.

Ergonomics, the study of the relationship between the human and the environment, can be effectively applied to identify those aspects of a job that lead to the injuries and to the design or redesign of a job to prevent injury. This article addresses the importance of ergonomics in the prevention of work-related musculoskeletal injuries and the questions the orthopaedic nurse should ask to assist in the design of safer workplaces.

"Don't destroy the evidence!".

As nurses, we interact with both victims and perpetrators of violence. Our goal is to save the patient; however, we also play a role in the legal outcome of that violence. What we do in caring for these patients is important. Means of preserving and documenting evidence while caring for the victims of violence are discussed and guidelines for the nurses legal role are given.

Mobile surgical transport team.

The "golden hour" of trauma is based on the principle that severely injured patients are more likely to survive with rapid, appropriate resuscitation and treatment. An inequality exists between sophisticated urban trauma centers and rural/community hospitals in their efforts and abilities to treat severely injured patients. A level I trauma center developed a unique program in an attempt to equalize this inequality--a mobile surgical transport team (MSTT). This article explains the origin of the MSTT, how and why the MSTT is activated, and the roles and responsibility of MSTT members. To further explain the MSTT, two contrasting case studies on trauma patients are presented.

Use of decompressive craniectomy after severe head trauma.

Ten percent of head injuries quality as "severe," requiring prompt diagnosis and treatment. This level I trauma center uses an aggressive approach to treatment of severe head injuries and, when indicated, intervenes with decompressive craniectomy. This article explains decompressive craniectomy, including indications, procedures, and protocols. The case studies presented highlight two patients with profound head injuries. Additionally, cranioplasty replacement of autograft flap is explained and discussed.

Second-trimester diagnosis of triploidy: a series of four cases.

Triploidy occurs in 2 to 3% of conceptuses and accounts for approximately 20% of chromosomally abnormal first-trimester miscarriages. As such, triploidy is estimated to occur in 1 of 3,500 pregnancies at 12 weeks', 1 in 30,000 at 16 weeks', and 1 in 250,000 at 20 weeks' gestation. We present a series of four cases of second-trimester triploidy diagnosed at our center within a 1-year timeframe. This is remarkable, as the delivery volume at our institution is roughly 2,500/y. All patients were at least 19 weeks' gestation, with multiple abnormalities identified on prenatal ultrasound at 18 to 20 weeks' gestation; all fetuses had lethal anomalies, but anomalies were not consistent between cases. All patients elected for induction of labor before 24 weeks' gestational age. Two of the four cases had amniocentesis and chromosome analysis prior to delivery, and two cases had chromosome analysis performed on fetal tissue after delivery. All fetuses were examined following delivery. This case series demonstrates that the diagnosis of triploidy may not be obvious based on ultrasound and physical examination findings and highlights the importance of routine chromosome analysis on all prenatal diagnoses of multiple congenital anomalies prior to consideration of more complex genetic testing.

Drug administration through feeding tubes; an integrated qualification program.

INTRODUCTION: The literature documents numerous inconveniences of drug administration through feeding tubes. Actions to improve the quality of this practice are of great importance. OBJECTIVE: The objective of this study is to describe the implementation process and results of an Integrated Program to improve drug administration through feeding tubes in a Brazilian general hospital. METHODS: This is a descriptive study of a clinic quality improvement program which proceeded in four steps: (1) design of a data base with technical characteristics of oral drugs; (2) application of an identification label on non-crushable tablets; (3) evaluation, through focal groups, of nursing technicians' knowledge of drug administration through feeding tubes, and formal training; (4) prescription review of patients prescribed enteral nutrition and subsequent pharmaceutical intervention. RESULTS: A list with 131 oral drugs used within the hospital was compiled with recommendations for their administration through feeding tubes. Seven non-crushable drugs were identified with "do not crush" labels. Formal training regarding drug administration through feeding tubes was elaborated incorporating findings from the focal groups and applied to the nursing team. Over eight months, we analyzed 888 prescriptions written for 185 patients and addressed 263 pharmaceutical interventions to the medical team (which they accepted in 100% of the cases), and 105 interventions to the nursing team. CONCLUSIONS: Qualification programs with multiple strategies, as the one described here, may directly improve drug administration through feeding tubes and help to solve and prevent problems related to this practice.

Supervision of pharmacy personnel.

OBJECTIVE: To review legal, acceptable, and optimal personnel practices. DATA SOURCES: A general literature search was conducted to identify appropriate material. In addition, the personnel manuals of several organizations (large and small) were reviewed for alternative ways to address similar problems. DATA SYNTHESIS: The cost of personnel is often the largest single non-drug expense in a pharmacy's operating budget. Pharmacists rarely receive comprehensive training during their professional training to address the unique issues of supervision. A review of the basics of supervision, and some topics unique to pharmacy, is presented. CONCLUSION: Familiarity with appropriate supervisory practices can enhance productivity, improve morale, and create a better practice environment.

Case report: survival of a type I transthoracic impalement.

The care of a patient who became impaled on a large aluminum pipe is presented. A review of the literature reveals that most patients with a type I injury either do not survive or present with an unpredictable pattern of injury. Preoperative care requires rapid stabilization, assessment, and interventions based on the pattern of injury. Perioperative management may involve multiple surgeons performing simultaneous surgical procedures.

The ventilatory response to intravenous and ventriculo-cisternal theophylline.

The stimulatory effect of theophylline on ventilation was studied in nine anesthetized dogs. Theophylline infused intravenously (10 mg/kg bolus, then 1.00 mg/kg/hr) for 210 minutes significantly increased the minute volume of ventilation (P less than 0.05 at 210 minutes). After a recovery period of seven to fourteen days, ventriculo-cisternal perfusion was performed with mock cerebrospinal fluid (CSF). Theophylline added to the mock CSF did not significantly change the minute ventilation. ventriculo-cisternal perfusion utilizing mock CSF not containing theophylline combined with intravenous theophylline infusion stimulated ventilation similarly to the previous intravenous theophylline infusion. Therefore, stimulation of ventilation by theophylline appears to relate to the serum theophylline concentration and not the ventricular CSF theophylline concentration.