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.

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.

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.

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.

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.

The alpha-effect in methyl transfers from S-methyldibenzothiophenium fluoroborate to substituted N-methylbenzohydroxamates.

Studies of the alpha-effect show increased reactivity of nucleophiles having lone pairs of electrons on atoms neighboring the lone pair involved in reactivity when compared to the basicity of the nucleophiles. Hammett-type plots and Brönsted-type plots of substituted methylphenyl sulfates vs hydrogen peroxide anions and substituted N-methylbenzohydroxanates (NMBH) with substituted methylarenesulfonates or substituted arenedimethylsulfonium ions have large rho or beta(nuc) values, indicating a putative tightening of the usual S(N)2 transition states (anti-Hammond effect). Electrochemical studies of S(N)2-SET or reactivity indicate that SET character occurs in looser transition states, whereas S(N)2 transition states are associated with greater tightness. The alpha-effects for the series of sulfonium salts in completion reactions for 3-ClNMBH anions and 3-nitrophenolate anions are (log k(alpha)/k(normal)) 1.124 for dimethylphenyl sulfonium, 1.512 for dimethyl-1-naphthyl sulfonium, 1.835 for dimethyl-9-anthracenyl sulfonium, and 1.137 for S-methyldibenzylthiophenium. Correlations of the sizes of alpha-effects with typical SET (or ET) experimental parameters and the inverse dependence of the size of the alpha-effect on electron demand indicate inclusion of SET character in these S(N)2 transition states, vs no (or at least diminished) SET character in normal transition states. This dichotomy of tighter S(N)2 transition states, but looser SET transition states indicated in the alpha-effect, is examined in the present work.

Peritoneal mesothelioma.

Malignant peritoneal mesothelioma is an aggressive neoplasm that rapidly spreads within the confines of the abdominal cavity to involve most accessible peritoneal and omental surfaces. Current treatments are unsatisfactory, and new approaches are needed. We have noted prolonged survival in selected patients after intensive multimodality treatment. Our current experimental regimen includes initial laparotomy with omentectomy, resection of peritoneal implants, and placement of bilateral peritoneal Port-a-Caths (Sims Deltec, Inc., St. Paul, MN); repeated courses of intraperitoneal chemotherapy with doxorubicin, cisplatin, and interferon gamma; second-look laparotomy and intraoperative hyperthermic perfusion with mitomycin and cisplatin; and whole abdominal radiation. Patients with peritoneal mesothelioma who are not candidates for this approach can sometimes be palliated with systemic (intravenous) chemotherapy using doxorubicin or mitomycin, alone or in combination with cisplatin or carboplatin. Newer agents such as gemcitabine and multitargeted antifolate (pemetrexed disodium, LY231514) show promise of greater effectiveness.

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.

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.

Multiple myeloma involving the orbit.

Multiple myeloma is a plasma cell malignancy often associated with destructive skeletal lesions. Orbital involvement in multiple myeloma is rare. Risk factors for orbital involvement have not been established, although risk may vary with immunoglobulin subtype. Early detection of orbital plasmacytoma may affect treatment and clinical course. A case is reported of multiple myeloma without elevated serum immunoglobulins that involves the orbit, and the implications of early detection are discussed. The patient was first examined by an ophthalmologist 13 months after multiple myeloma was diagnosed and 5 months after the external appearance of an orbital tumor. Urine protein electrophoresis demonstrated kappa light chains. Hypergammaglobulinemia was not detected. Plain-film roentgenography showed orbital involvement at the time of initial diagnosis. An impressive clinical response to external beam radiation therapy was seen. Attention to immunoprotein characteristics in multiple myeloma may help to identify risk factors for orbital involvement. Early detection may permit safer and equally effective treatment. All patients with multiple myeloma should undergo thorough ophthalmic examination at the time of initial diagnosis.

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.

Efficacy of pelvic floor muscle exercises in women with stress, urge, and mixed urinary incontinence.

OBJECTIVES: Our purpose was (1) to evaluate the efficacy on an intent-to-treat basis of a 3-month course of pelvic floor muscle exercises as first-line therapy for urinary incontinence in consecutive women seen in a tertiary care center with stress, urge, and mixed urinary incontinence and (2) to evaluate whether a specially designed audiotape improves compliance and efficacy of the exercises. STUDY DESIGN: A prospective randomized trial wa conducted with 71 women seen for treatment of urinary incontinence in two tertiary care center referral clinics (in the departments of gynecology and urology). The primary outcome measure was the number of incontinent episodes, as documented with a 3-day voiding diary. Statistical analysis included t tests and Wilcoxon signed-ranks test, as appropriate. A value of p < or = 0.05 was considered significant. RESULTS: Forty-four percent of all enrollees had a > or = 50% improvement in the number of incontinent episodes per day. This increased to 56% of enrolles who completed the treatment course. For all enrollees the mean number of incontinent episodes per day decreased from 2.6 to 1.7 for genuine stress incontinence, from 3.5 to 2.3 for detrusor instability, and from 3.9 to 3.2 for mixed incontinence. For enrollees who completed the 3-month course the mean number of incontinent episodes per day decreased from 2.5 to 1.4 for genuine stress incontinence, from 2.8 to 0.5 for detrusor instability, and from 3.0 to 1.7 for mixed incontinence. Six months after completing the course of exercises approximately one third of all enrollees reported that they continued to note good or excellent improvement and desired no further treatment. There was no difference in outcome measures and no difference in compliance between the women who exercised with the aid of the audiotape and those who exercised according to our usual office routine (p > 0.05). CONCLUSIONS: One third of all participants remained improved to the patient's satisfaction 6 months after completion of a risk-free, inexpensive, simply provided therapy. Our audiotape did not improve our success rate or decrease the dropout rate. In this study the exercises were equally effective for all three urodynamic diagnoses. Inexpensive methods that could be used by primary care providers to improve the success rate of this therapy merits further attention.

Response of small cell carcinoma of pancreas to a small cell lung cancer regimen: a case report.

Small cell carcinoma of the pancreas is a very rare malignancy with 18 cases reported in the literature, of which only 3 were treated with chemotherapy. A 52-year-old man was diagnosed with small cell carcinoma originating in the head of the pancreas and invading the duodenum. He was treated with a similar approach as for localized small cell lung cancer, with six cycles of combination chemotherapy and local radiotherapy, and went into complete remission. After 3 months, he developed liver metastases along with an enlarged left supraclavicular lymph node. He was treated with two cycles of CVA, but developed lung metastases and was treated with ifosfamide/mesna. However, his overall condition deteriorated and hospice care was instituted until the patient's demise. The patient survived 14 months following diagnosis, significantly longer than the 15 reported patients with small cell pancreatic carcinomas not treated with chemotherapy. Combination chemotherapy and radiation therapy as it is utilized for small cell lung cancer appear to be beneficial for small cell carcinoma of the pancreas.

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.

Soft-tissue sarcomas: MR imaging findings after treatment in three pediatric patients.

PURPOSE: To characterize the skeletal and bone marrow magnetic resonance (MR) imaging changes during and after treatment of childhood soft-tissue tumors. MATERIALS AND METHODS: Three boys with soft-tissue sarcomas of the popliteal fossa underwent surgery, radiation therapy, and chemotherapy. Plain radiographic and MR imaging findings were correlated with the effect of treatment. RESULTS: After radiation therapy, MR images revealed findings that resembled those of rickets at sites of irradiation in the three patients. These findings included metaphyseal sclerosis, metaphyseal fraying, and epiphyseal plate widening. Bone marrow imaging changes were temporally related to therapy. During chemotherapy, reconversion to hematopoietic marrow was noted in nonirradiated areas in two patients, but after cessation of all treatment, these areas converted back to fatty marrow. Irradiated areas of bone marrow remained fatty throughout therapy in the three patients. CONCLUSION: Awareness of the MR imaging findings related to antineoplastic treatment of soft-tissue tumors is important to distinguish these changes from progression of primary disease.

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.

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).

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.