Pharmacist intervention in patient selection of nonprescription and self-care products.

OBJECTIVES: To evaluate the potential outcomes of pharmacist intervention on patient selection of nonprescription and self-care products and to evaluate patient confidence and satisfaction with the assistance of the pharmacist. METHODS: A prospective, convenience sample study was conducted at 3 locations of a national supermarket chain pharmacy in the Charlottesville, Virginia, area over 4 months. Patients were recruited for the study if they approached the pharmacy counter and requested assistance with nonprescription and self-care product selection or if the investigating pharmacists approached the patient in the self-care aisles. Men and nonpregnant women age 18 years and older were included in the study. Patients self-selected into the study by agreeing to participate in the study intervention and answering questions relating to their experience with the pharmacist consultation. The study intervention was the pharmacist consultation with the patient to assess the self-care complaint and to make an appropriate recommendation. RESULTS: Forty-two patients participated, the mean (±SD) age was 57 ± 20.8 years, and 62% of patients were female. Sixty percent of patients had used pharmacist help in the past in selecting nonprescription and self-care products. There were 87 total potential outcomes, and a mean of 2.1 potential outcomes per patient. The most potential common outcomes were reduced drug cost, avoided physician visit, corrected product use, and avoided a new prescription. Mean patient confidence (±SD) was 4.38 ± 0.96. Mean patient satisfaction was 4.98. Every patient (100%) stated that they would be more willing to ask for pharmacist help in the future with self-care product selection. The mean encounter time was 6 minutes. CONCLUSION: Pharmacists' active involvement in patient self-care consultation may help patients to select the most effective and safe product and improve patient outcomes. Patients are highly satisfied with pharmacists' help with the selection of nonprescription and self-care products and are more confident with future self-treatment.

State of confusion: sorting out a complex medication regimen for a 79-year-old woman.

Patients with Alzheimer's disease and without caregiver assistance can often have difficulties in managing their medications, which can result in serious consequences. This case study depicts a 79-year-old woman who lives in an assisted living facility and is referred to a geriatric pharmacy specialist in a community pharmacy for a medication review and assistance in medication adherence. During the initial patient visit, the patient was found to have an extremely complex method for managing her medications. She also had multiple medical providers, several duplicate medications, and medications used to treat the adverse effects of other medications. Consequently, this patient had symptoms suggesting she was experiencing medication-induced delirium. This case study illustrates the valuable role of the consultant pharmacist in assisting the patient's medical providers in formulating a simpler and more efficacious medication regimen.

Unraveling multiple complaints in an 82-year-old woman.

With this issue, The Consultant Pharmacist begins a new series, Case Studies in Geriatric Pharmacotherapy. This column will present case studies in which the pharmacist identifies actual or potential patient medication-related problems, presents an evidence-based discussion of options, and develops a patient management plan. As part of this evaluation, the pharmacist consults with both the patient's physicians and family members. Because older individuals generally consume a large number of medications, such a complex, multidisciplinary approach is critical to patient care and one that only pharmacists can provide. The growing consumption of both prescription and over-the-counter drugs by older adults increases the risk of medication-related problems. Pharmacists have an obligation to continually develop skills for identifying, treating, and preventing these medication-related problems.

Study of UltraHigh Performance Supercritical Fluid Chromatography to measure free fatty acids with out fatty acid ester preparation.

Most lipids are best characterized by their fatty acids which may differ in (a) chain length, (b) degree of unsaturation, (c) configuration and position of the double bonds, and (d) the presence of other functionalities. Thus, a fast, simple, and quantitative analytical technique to determine naturally occurring free fatty acids (FFA) in different samples is very important. Just as for saponified acylglycerols, the determination of FFA's has generally been carried out by high resolution gas chromatography (HRGC). The use of an open tubular capillary column coupled with a flame ionization or mass spectrometric detector provides for both high resolution and quantification of FFA's but only after conversion of all free fatty acids to fatty acid methyl esters (FAME) or pentafluorobenzyl esters. Unfortunately, volatilization of labile ester derivatives of mono- and poly-unsaturated FFA's can cause both thermal degradation and isomerization of the fatty acid during HRGC. The employment of a second generation instrument (here referred to as UltraHigh Performance Supercritical Fluid Chromatograph, UHPSFC) with high precision for modified flow and repeated back pressure adjustment in conjunction with sub-2µm various bonded silica particles (coupled with evaporative light scattering, ELSD, and mass spectrometric, MS, detection) for separation and detection of the following mixtures is described: (a) 31 free fatty acids, (b) isomeric FFA's, and (c) lipophilic materials in two real world fish oil samples. Limits of detection for FFA's via UHPSFC/MS and UHPSFC/ELSD versus detection of FAME's via HRGC/MS are quantitatively compared.

Ultrahigh performance supercritical fluid chromatography of lipophilic compounds with application to synthetic and commercial biodiesel.

Ultrahigh performance supercritical fluid chromatography (UHPSFC) in combination with sub-2µm particles and either diode array ultraviolet (UV), evaporative light scattering, (ELSD), or mass spectrometric (MS) detection has been shown to be a valuable technique for the determination of acylglycerols in soybean, corn, sesame, and tobacco seed oils. Excellent resolution on an un-endcapped single C18 column (3.0mm×150mm) with a mobile phase gradient of acetonitrile and carbon dioxide in as little as 10min served greatly as an improvement on first generation packed column SFC instrumentation. Unlike high resolution gas chromatography and high performance liquid chromatography with mass spectrometric detection, UHPSFC/MS was determined to be a superior analytical tool for both separation and detection of mono-, di-, and tri-acylglycerols as well as free glycerol itself in biodiesel without derivatization. Baseline separation of residual tri-, di-, and mono-acylglycerols alongside glycerol at 0.05% (w/w) was easily obtained employing packed column SFC. The new analytical methodology was applied to both commercial B100 biodiesel (i.e. fatty acid methyl esters) derived from vegetable oil and to an "in-house" synthetic biodiesel (i.e. fatty acid ethyl esters) derived from tobacco seed oil and ethanol both before and after purification via column chromatography on bare silica.

Heteroarotinoids inhibit head and neck cancer cell lines in vitro and in vivo through both RAR and RXR retinoic acid receptors.

A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu/nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0. 05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RARalpha, RXRalpha, and RXRbeta were similar in the two cell lines, while RARbeta expression was higher in SCC-2 over SCC-38, and RARgamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.

CH2 (+) transfer to pyridine nucleophiles: a means of producing α-distonic ions.

The distonic radical cation C5H5N(+)-(·)CH2 can be generated by the reactions of neutral pyridine with the radical cations of cyclopropane, ethylene oxide, and ketene, as well as with the [C3H6](+) ion from fragmentation of tetrahydrofuran. The distonic product ion can be distinguished from isomeric methylpyridine radical cations because the former gives characteristic [M-CH2](+), [M - CH2NCH](+), and a doubly charged ion, all of which are produced on collisional activation. Furthermore, the distonic species completely transfers CH2 (+) to more nucleophilic, substituted pyridines. These properties are all consistent with the assigned distonic structure. Another distonic isomer, the (3-methylene) pyridinium ion, can be distinguished from the (1-methylene)pyridinium ion on the basis of their different fragmentation behaviors. The latter ion exhibits higher stability (lower reactivity) than the prototypal [·CH2NH3 (+)], making available a distonic species whose bimolecular reactivity can be readily investigated.

Extreme leukemic leukocytosis (blast crisis) in childhood.

Children with leukemia who have extremely high leukocyte counts (more than 100,000/mm3) when seen initially are at high risk of early sudden death, usually from massive intracerebral hemorrhage. Nine such patients were seen during a 39-month period. Eight had pronounced adenopathy and hepatosplenomegaly without severe anemia or thrombocytopenia. The first six patients died suddenly. Cerebral perivascular infiltration and increased blood viscosity are the probable pathophysiologic mechanisms. A treatment program was developed, the goal being the early elimination of blast cells. Three consecutive patients patients presenting with leukocyte counts greater than 100,000/mm3 were treated with emergency cranial irradiation, and all three survived to receive systemic chemotherapy.

alpha-Effect with Substituted N-Methylbenzohydroxamates and Substituted Phenyldimethylsulfonium Salts: Toward Understanding of an Intrinsic alpha-Effect.

Increasing electron demand in the reactions of G-NMBH anions with substituted phenyldimethylsulfonium ions decreases the alpha-effect for the methyl transfers toward 1.0 (zero effect). An extrapolation shows the possibility of an inverse effect (<1.0). The reactivity of G-NMBH anions correlates with SET parameters and with the known propensity of phenyldimethylsulfonium ions to accept a single electron into a sigma C-S orbital concomitant with expulsion of a CH(3) group. These correlations indicate inclusion of some SET character into the wavefunction of the S(N)2 transition state for these reactions, in agreement with the Shaik and Pross SCD model of the S(N)2 reaction.

The alpha-Effect in Benzyl Transfers from Benzylphenylmethyl Sulfonium Salts to N-Methylbenzohydroxamate Anions.

The investigation of the occurrence of the alpha-effect in group transfers from phenyldialkyl sulfonium ions where one alkyl group is benzyl allows an assay of the effect of changing the nature of the C atom being transferred. The size of the alpha-effect responds to increasing electron demand, as methyl transfers do. Quantitative relationships between the size of the alpha-effect are established from both the nucleophilic side and the leaving group side of the S(N)2 transition state.

Impact of patient history on residents' evaluation on child sexual abuse.

OBJECTIVE: To determine if historical information influences residents' interpretation of physical findings in sexually abused children. METHODOLOGY: In a pediatric residency training program, all residents viewed 15 slides of children's genitalia (8 normal, 7 abnormal) with either a history specific for sexual abuse or one which was nonspecific. Three weeks later the same slides were viewed but with the alternate history scenario. The residents were asked if the physical findings were specific for sexual abuse. RESULTS: Sixty-four percent of residents completed both surveys. Correct response rate did not vary by gender or year of training. Responses were most often correct when the slide and history were normal (87%). Responses were least accurate when normal historical information was presented with abnormal slides (49%). A logistic regression model demonstrated that residents were less accurate when history and physical did not agree (95% CI = .54- .78). Reexamination of the data using areas under the Receiver Operating Characteristic (ROC) curve confirmed that residents performed on a less accurate ROC curve when the slide and history were incongruent (p < .01). CONCLUSION: Incongruency between patient history and physical exam findings negatively affected this group of residents' ability to discriminate between abuse and nonabuse findings.

Sweat gland carcinoma with metastases to the skin: response to 5-fluorouracil chemotherapy.

A 68-year-old white man presented to the inpatient service at Columbia-Presbyterian Hospital with a chief complaint of a progressively enlarging tumor of the right infraorbital region for many years and multiple, pink papulonodules on his head, neck, and trunk. A biopsy specimen of the right infraorbital and back lesions demonstrated an infiltrating adenocarcinoma with prominent signet ring cells, and small lumen formation. Results of an extensive work-up revealed bone marrow metastases and no evidence of a primary malignancy. We present a case of primary sweat gland carcinoma with metastases to the skin based upon history, clinical presentation, results of physical examination, histopathologic examination, immunohistochemical studies, and response to 5-fluorouracil chemotherapy. Due to the rarity of the tumor, the diagnosis is usually not made until the tumor(s) is invasive. An excellent response to systemic chemotherapy with 5-fluorouracil in metastatic sweat gland carcinoma was noted in this case.

On gas phase alpha-effects. 1. The gas-phase manifestation and potential SET character.

The possibility of a gas-phase alpha-effect has been explored for the methyl transfer from methyl formate to hydroxide, hydroperoxide, and ethoxide by computing barrier heights at the HF/6-311++G(2df,2p) level of theory. The alpha-nucleophile (hydroperoxide) is found to have a lower barrier than the gas-phase-acidity-matched normal nucleophile (ethoxide) by 3.6 kcal/mol, offering evidence for a gas phase alpha-effect. A Shi-Boyd analysis for these reactions indicates that there is more single-electron-transfer character in the hydroperoxide transition state than for either hydroxide or ethoxide, further bolstering the existence of a gas-phase alpha-effect and the appropriateness of the Hoz model for the alpha-effect.

Structure-activity studies of hydroxamic acids as direct vasodilators.

A series of beta-hydroxylamine-phenylpropyl hydroxamic acids were prepared. The ability of these compounds to act as hypotensive agents was studied pharmacodynamically. Key structural features for the hypotensive action were identified and correlated to the degree of responses observed. It was ascertained that these compounds do not act through the adrenergic, cholinergic and histaminergic receptor system, but can be classified as direct acting vasodilators.

Radioactive colloidal gold in the treatment of endometrial cancer: Mayo Clinic experience, 1952-1976.

A review of 1670 patients with endometrial cancer who were treated between 1952 and 1976 revealed that 15 patients had received radioactive colloidal gold as an adjunct to surgery. Most of the patients had follow-up more than ten years, and all had microscopic tumor contamination of the peritoneal cavity. Of the 15 patients, 13 had biopsy of peritoneal metastases and underwent resection of gross metastatic lesions that were more than 2 mm in diameter. The other two patients had direct extension of the tumor through the uterus into the peritoneal cavity without visible metastasis. The radiogold was inserted from 4-37 days after the initial surgical procedure. The dosage ranged from 100-140 mCi. At follow-up, from 11 years seven months to 24 years two months after treatment, seven patients were alive without evidence of disease. Three died of intercurrent disease, 16 years, and 14 years, and 14 years two months after treatment. Five patients died of cancer, two with local recurrence and three with distant metastases to lung or bone (or both).

Quantification of the three point receptor hypothesis of Cheng and Zee-Cheng.

The placement of three heteroatoms at the corners of an acute angle triangle was found to correlate roughly with the antineoplastic activity of a wide range of compounds by Cheng & Zee-Cheng (1972, J. Pharm. Sci. 61, 485). Since then the synthetic routes to compounds having a large number of degrees of freedom, as in the 1,4-dihydroxy-5,8-bis([2-(2-hydroethyl)amino]ethyl) amino-9,10-anthracenedione (DHAQ, mitoxantrone) have been discovered. The subsequent high activity of DHAQ vs. numerous cancers has partially verified the worth of the original hypothesis. Quantitative verification of pharmacophoric hypotheses as theories necessitates the use of Popper's risky experiments. These experiences give rise to verification because, unenlightened by the theory undergoing testing, they would predict a result that would refute the theory. Computational chemistry allows such a confirmation through molecular modeling. The molecular force field, MMX, gives confirmation of the theory by showing the riskiness of the synthetic production of DHAQ for the gas phase. The MM+ forcefield in an aqueous medium computation (132 water molecules) shows that the confirmations of DHAQ does not change appreciably from the gas phase. This computation adds a considerable risk. Aquation could significantly change the favorable conformations of the very conformationally free DHAQ molecule. The fact that it does not confirm that the Zee-Cheng and Cheng hypothesis is a strong one. Additionally, a quantitative relationship arises from the new model for the N-O-O atomic placement. This new quantitative relationship further predicts quantitative risky experiments for further verification (falsification).

Chondrosarcoma metastatic to the oral cavity.

Metastases to the oral cavity from nonoral malignant lesions occur rarely. We report the case of a woman with chondrosarcoma of the pelvis in whom gingival metastases, in addition to pulmonary, skin, and brain metastases, developed. Clinical course, x-ray correlation, histopathologic review, and treatment modalities are described. The six previously reported cases of chondrosarcoma metastatic to the oral cavity are tabulated and analyzed. Metastases should be included in the differential diagnosis of gingival lesions in patients with prior or current nonoral malignant tumors.

Carcinoma of the endometrium: stage I.

During the 10-year period ending December, 1972, 577 patients with Stage I endometrial cancer received their primary treatment at the Mayo Clinic. The average age of the group was 60.8 years. The higher-grade lesions were found in older individuals. The data did not show that high grade was related to age at menopause. The initial therapy was total abdominal hysterectomy and bilateral salpingo-oophorectomy. The absolute survival at 5 years was 92.7% for Stage IAG1, 86.5% for IAG2, 68.2% for IAG3, 89.6% for IBG1, 76.4% for IBG2, and 62.9% for IBG3.