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Biomedical subjects

C E Cox

Publications and source records attributed to C E Cox.

178 records · Page 10Linked to original sources

Sentinel node biopsy in ductal carcinoma in situ patients.

BACKGROUND: Sentinel lymph node (SLN) mapping is an effective and accurate method of evaluating the regional lymph nodes in breast cancer patients. The SLN is the first node that receives lymphatic drainage from the primary tumor. Patients with micrometastatic disease, previously undetected by routine hematoxylin and eosin (H&E) stains, are now being detected with the new technology of SLN biopsy, followed by a more detailed examination of the SLN that includes serial sectioning and cytokeratin immunohistochemical (CK IHC) staining of the nodes. METHODS: At Moffitt Cancer Center, 87 patients with newly diagnosed pure ductal carcinoma in situ (DCIS) lesions were evaluated by using CK IHC staining of the SLN. Patients with any focus of microinvasive disease, detected on diagnostic breast biopsy by routine H&E, were excluded from this study. DCIS patients, with biopsy-proven in situ tumor by routine H&E stains, underwent intraoperative lymphatic mapping, using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. All SLNs that had only CK-positive cells were subsequently confirmed malignant by a more detailed histological examination of the nodes. RESULTS: CK IHC staining was performed on 177 SLNs in 87 DCIS breast cancer patients. Five of the 87 DCIS patients (6%) had positive SLNs. Three of these patients were only CK positive and two were both H&E and CK positive. Therefore, routine H&E staining missed microinvasive disease in three of five DCIS patients with positive SLNs. In addition, DCIS patients with occult micrometastatic disease to the SLN underwent a complete axillary lymph node dissection, and the SLNs were the only nodes found to have metastatic disease. Of interest, four of the five node-positive patients had comedo carcinoma associated with the DCIS lesion, and one patient had a large 9.5-cm low grade cribriform and micropapillary type of DCIS. CONCLUSIONS: This study confirms that lymphatic mapping in breast cancer patients with DCIS lesions is a technically feasible and a highly accurate method of staging patients with undetected micrometastatic disease to the regional lymphatic basin. This procedure can be performed with minimal morbidity, because only one or two SLNs, which are at highest risk for containing metastatic disease, are removed. This allows the pathologist to examine the one or two lymph nodes with greater detail by using serial sectioning and CK IHC staining of the SLNs. Because most patients with DCIS lesions detected by routine H&E stains do not have regional lymph node metastases, these patients can safely avoid the complications associated with a complete axillary lymph node dissection and systemic chemotherapy. However, DCIS patients with occult micrometastases of the regional lymphatic basin can be staged with higher accuracy and treated in a more selective fashion.

Axilla↗

Microstaging of breast cancer patients using cytokeratin staining of the sentinel lymph node.

BACKGROUND: Sentinel lymph node (SLN) mapping is an effective and accurate method of axillary nodal evaluation for metastatic disease. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN has found micrometastatic disease previously undetected by routine hematoxylin and eosin (H&E) stains. The purpose of this study is to determine the number of patients who were upstaged or microstaged, i.e., detected to have micrometastatic disease only by combined lymphatic mapping with CK IHC. METHODS: Two hundred and ten patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised sentinel lymph nodes were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed to be malignant by histologic examination. RESULTS: CK IHC staining was performed on 381 SLNs in 210 breast cancer patients. Forty-seven of 210 patients (22.4%) had positive nodes. Thirty of these 47 patients (63.8%) had both H&E- and CK-positive SLNs, and an additional 17 of the 47 positive patients (36.2%) had only CK-positive SLNs. Seventeen of the 180 patients (9.4%) who were negative on H&E staining were upstaged by CK IHC staining of malignant cells in the SLN. Comparison of tumor size with the total number of node-positive patients demonstrated that 16 of 30 node-positive T0 and T1 patients (53.5%) and 22 of 39 nodes (56.4%) were upstaged by CK IHC staining. T2 and T3 patients were less frequently upstaged by cytokeratin analysis of lymph nodes. Only one of 17 node-positive patients (5.9%) and seven of 34 nodes (20.6%) in patients with T2 and T3 tumors were upstaged. CONCLUSION: CK IHC staining of SLNs shifted 9.4% of patients from stage I to stage II. There was a significant upstaging influence noted in patients with tumor sizes under 2 cm. This microstaging shift or upstaging may account for the significant proportion of stage I breast cancer treatment failures. Microstaging of the SLNs using more sensitive assays may help identify a subgroup of patients with invasive breast cancer who would benefit from systemic adjuvant treatment, while sparing a disease-free subset of patients the additional risks of toxic adjuvant chemotherapy.

Biopsy, Needle↗

Pharmaceutical care research and education project: pharmacists' interventions.

OBJECTIVES: To describe the processes of care used by community pharmacists participating in the Pharmaceutical Care Research and Education Project (PREP) in terms of drug-related problems (DRPs), pharmacists' recommendations, and status of DRPs at follow-up, and to determine characteristics associated with DRPs. DESIGN: Descriptive analysis of the treatment group from a larger randomized, controlled cluster design. SETTING: Five independent community pharmacies in Alberta. PARTICIPANTS: One hundred fifty-nine patients who were covered under Alberta Health and Wellness's senior drug benefit plan (i.e., 65 years or older), were taking three or more medications concurrently according to pharmacy records, were able to complete telephone interviews as determined by pharmacists, maintained residence in Alberta for 12 of the 15 study months, agreed to receive their prescription medications only from the study pharmacy during the study period, and provided informed consent. MAIN OUTCOME MEASURES: Frequency of DRPs, recommendations, status of DRPs, and analysis of clinical results as determined during pharmacists' follow-up care. RESULTS: In telephone surveys, patients reported taking 4.7 prescription medications per day, but pharmacists documented 8.7 prescription medications per day in their records. Pharmacists documented 559 DRPs, a mean (+/- SD) of 3.9+/-3.2 problems per patient. Approximately 39% of problems were actual DRPs, while 60% were potential DRPs. Medical conditions associated most frequently with a DRP involved the respiratory, cardiovascular, and musculoskeletal systems. The most common DRP categories were "patient requires drug therapy" or "patient requires influenza or pneumococcal vaccination." Pharmacists wrote 551 initial clinical notes using the subjective, objective, assessment, plan (SOAP) format, and they recorded 346 follow-up interventions, also using SOAP notes. Counseling, preventive consultations, and clinical monitoring represented 40% of their recommendations. In 80% of situations, the pharmacist made the recommendation directly to the patient. On follow-up, 40% of the 559 DRPs identified were resolved, controlled, or improved. Patients accepted 76% of pharmacists' recommendations, and physicians accepted 72% of pharmacists' suggested resolutions of DRPs. Pharmacists were more likely to follow up about actual DRPs, as compared with potential ones; overall, they followed up on 62% of identified DRPs. CONCLUSION: Pharmacists identified more DRPs for study patients than previous community-based, observational studies have reported. Undertreatment appears to be a prevalent DRP. Community pharmacists' recommendations to prevent and resolve DRPs were made primarily to patients and were well accepted. More follow-up was needed for all DRPs. When follow-up occurred, the DRP results generally showed improvement.

Aged↗

Pharmaceutical care research and education project: patient outcomes.

OBJECTIVE: To compare patients' adherence to therapy, expectations, satisfaction with pharmacy services, and health-related quality of life (HRQOL) after the provision of pharmaceutical care with those of patients who received traditional pharmacy care. DESIGN: Randomized controlled cluster design. SETTING: Sixteen community pharmacies in Alberta, Canada. PATIENTS AND OTHER PARTICIPANTS: Ambulatory elderly (> or = 65 years of age) patients covered under Alberta Health & Wellness's senior drug benefit plan and who were concurrently using three or more medications according to pharmacy profiles. INTERVENTION: Pharmacies were randomly assigned to either treatment (intervention) or control (traditional pharmacy care) groups. Patients at treatment pharmacies were recruited into the study, and pharmacists provided comprehensive pharmaceutical care services. Pharmacists at control pharmacies continued to provide traditional pharmacy care. MAIN OUTCOME MEASURES: Study participants' opinions, adherence to therapy, and scores on the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS: Compared with those of patients receiving traditional care, treatment patients' expectations that their pharmacist would perform activities congruent with pharmaceutical care changed over the study period. Treatment patients' satisfaction with the constructs "trust," "evaluation and goal setting," and "communicates with doctor" were also positively affected. HRQOL and patient adherence were not significantly affected by pharmaceutical care interventions. CONCLUSION: Successful implementation of a pharmaceutical care practice model has the potential to increase patients' satisfaction with their pharmacists' activities and may increase patients' expectations that pharmacists will work on their behalf to assist them with their health care needs. If pharmaceutical care affects patients' HRQOL, instruments more specific than the SF-36 may be needed to detect the differences.

Aged↗

Importance of missed axillary micrometastases in breast cancer patients.

Axillary lymph node metastases dramatically worsen the prognosis of patients with breast cancer. Despite this prognostic significance, routine histologic examination of axillary lymph nodes examines less than 1% of the submitted material. It is therefore obvious that micrometastatic disease is missed with this rather cursory examination, and the question arises as to the significance of this missed disease. Most lines of evidence suggest that missed axillary micrometastases exist and contribute to patient mortality. Most large studies of breast cancer micrometastases have suggested that undetected axillary micrometastases can be identified with more detailed examinations of the regional lymph nodes and that this group of patients has a poorer prognosis than those with no metastases identified. In addition, small-volume nodal disease, too small to be detected by traditional hematoxylin and eosin staining, has been shown to be capable of producing tumors in animal models. Finally, micrometastases have been shown to be of significance in other diseases. This article reviews the lines of evidence and the ongoing studies that are attempting to clarify the significance of micrometastatic disease in patients with breast cancer.

Breast Neoplasms↗

Treatment of urinary tract infections in hospitalized patients: a double-blind comparison of cefonicid and cefamandole.

In a randomized double-blind comparison of cefonicid (dose, 1.0 g every 24 hr) and cefmandole (dose, 1.0 g iv every 6 hr), 147 hospitalized patients (105 men, 42 women) with urinary tract infections (UTIs) were assessed. Ninety-one of the men had complicated UTIs. For the 62 cefonicid-treated men, 61 of 62 etiologic pathogens were eliminated. For 17 patients, reinfection with the pretherapy pathogen occurred in the five- to nine-day posttherapy follow-up. Overall cure rate for cefonicid in the treatment of complicated UTIs was 71%. For the 29 cefamandole-treated men, 28 of 29 etiologic pathogens were eliminated. Reinfection occurred in nine patients. Overall cure rate for cefamandole in the treatment of complicated UTIs was 66%. All 14 men (nine receiving cefonicid; five, cefamandole) with uncomplicated infection were cured. For 25 cefonicid-treated women, cure rate was 84%; one of the failures was due to persistence of the pathogen; three were reinfections during follow-up. For 17 cefamandole-treated women, the cure rate was 82%; two of the failures were due to persistence of the pathogen, and one was a reinfection. Similar, minimal adverse reactions occurred with both drugs. Cefonicid is as effective as cefamandole in curing complicated UTIs in men and uncomplicated infections in both sexes. Cefonicid, however, offers the advantage of once-daily therapy.

Adult↗

Aztreonam therapy for complicated urinary tract infections caused by multidrug-resistant bacteria.

Aztreonam was administered to 145 consecutive patients with complicated urinary tract infections caused by multidrug-resistant, aztreonam-sensitive bacteria. Multidrug resistance was defined by disk diffusion testing as resistance to aminopenicillins and to first- and second-generation cephalosporins, with or without resistance to aminoglycosides. The first 40 assessable patients received 1 g of aztreonam intravenously three times daily for a median period of eight days; the remaining 95 assessable patients received 0.5 g twice daily for a median period of nine days. Fifty-five patients were infected with Pseudomonas aeruginosa, 24 with Escherichia coli, 18 with Serratia marcescens, 13 with Morganella morganii, 12 with Providencia rettgeri, and 10 with Enterobacter species. Bacteriologic cure rates were 98% for the group given 3 g daily and 96% for that given 1 g daily. Minimal and transient adverse reactions occurred with both dosages.

Adolescent↗

Localization of I-131-labeled goat and primate anti-carcinoembryonic antigen(CEA) antibodies in patients with cancer.

Thirty patients with anti-carcinoembryonic antigen (CEA)-producing cancers of the colon, breast, or thyroid were injected with 1 to 2 mCi of Iodine-131 (131I)-labeled, affinity-purified, goat or baboon anti-CEA antibodies. Images were obtained daily for four days. Computerized background subtraction using technetium 99m (99mTC)-labeled compounds was used. Images obtained with and without background subtraction were correlated with other evidence of disease. Activity levels in plasma, urine, and thyroid gland were monitored. Significant deiodination of antibody occurred within the first 24 hours. The mean plasma half-disappearance-time of baboon antibody was significantly longer than the mean half-disappearance-time of goat antibody. With exogenous blockade, total thyroid uptake was less than 0.1% of the injected dose. Without background subtraction, scintigraphic localization of known tumor was possible in one of two patients with colon carcinoma, in three of 20 patients with breast cancer, and in one of five patients with medullary carcinoma of the thyroid. With background subtraction, potential false-positive results could be generated for every patients, depending on the normalization site chosen and the degree of subtraction used. In contrast to results of previous reports, CEA-producing tumor was found to be infrequently localized using highly purified goat or primate radiolabeled anti-CEA. Furthermore, the subtraction technique described by previous investigators may lead to a high false-positive rate.

Adolescent↗

The effect of sentinel node selective axillary lymphadenectomy on the incidence of postmastectomy pain syndrome.

BACKGROUND: Postmastectomy pain syndrome (PMPS) has been reported following procedures involving complete lymph node dissection (CLND). Since the triggering event is probably related to nerve injury, sentinel lymph node dissection (SLND) should decrease the incidence of PMPS. The purpose of this report is to determine the impact of SLND on the number of patients referred to the pain clinic for PMPS treatment. METHODS: The records of all breast surgical patients with a diagnosis of PMPS referred to the Moffitt Cancer Center pain clinic were reviewed. The criterion for diagnosis of PMPS was a history of postoperative pain in the upper anterior chest wall, upper extremity, axilla, and/or shoulder in the absence of recurrent disease. RESULTS: A total of 55 patients with a diagnosis of PMPS were seen in the pain clinic since 1991. Treatments included local anesthetics/corticosteroid injection, stellate ganglion block, and tricyclic antidepressants. A decrease from 15 patients in 1991 to 3 in 1998 was observed. All but one of the 55 patients with PMPS had CLND, and none referred to the pain clinic had undergone SLND. CONCLUSIONS: PMPS is a complication of CLND. The increased use of SLND in our center has reduced the number of referrals to the pain clinic for treatment of PMPS. This benefit of SLND reduces suffering in the postoperative breast patient.

Axilla↗

Cost-effective management of complicated urinary tract infections.

Complicated urinary tract infection (UTI), which often requires hospitalization or prolongs a hospital stay, presents numerous diagnostic and therapeutic challenges. Implementation of effective antimicrobial treatment is vital because of the risk of adverse sequelae due to persistence of infection, relapse, or reinfection. Further, the increasing resistance of common uropathogens, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter species, can complicate the therapeutic outcome. Economic factors also mandate cost-effective therapy. The costs of managing adverse sequelae have placed a significant liability on an already overburdened health care system. Estimates for prolonged hospitalization due to nosocomial UTI are reported as high as $2 billion a year in the United States. When parenteral rather than oral antimicrobial therapy is used, additional health care costs approximate $1000 per day per patient. Given the resistance to commonly used medications and the risk of serious adverse sequelae, clinicians are seeking more appropriate therapy. New oral antimicrobial agents now permit outpatient management of complicated UTIs that formerly required hospitalization for prolonged treatment. Currently, quinolones are recommended as first-line agents for complicated UTI. Reviews of pharmacokinetics, antimicrobial activity, efficacy, and safety of these drugs have noted equipotence or superiority to other antimicrobials, including trimethoprim/sulfamethoxazole. When used appropriately, quinolones provide effective and safe therapy for complicated UTI and offer in vitro efficacy against a broad range of pathogens.

4-Quinolones↗

Tools used to help community pharmacists implement comprehensive pharmaceutical care.

OBJECTIVE: To describe the tools and processes used in the practice enhancement program (PEP) of the Pharmaceutical Care Research and Education Project to enable community pharmacists to acquire the necessary skills, knowledge, and attitudes to deliver comprehensive pharmaceutical care to elderly ambulatory patients. SETTING: Independent community pharmacies in Alberta. PRACTICE DESCRIPTION: The PEP was designed to allow self-directed learning in a problem-based environment. The intent was for pharmacists to apply the knowledge they gained to improve drug therapy outcomes. PRACTICE INNOVATION: As a systematic approach to providing care, several tools were adapted to help pharmacists execute tasks required by the nine steps of the pharmaceutical care process proposed by Helper and Strand. These tools and processes facilitated (1) self-directed learning about diseases and drugs, (2) acquisition of relevant patient data, (3) a consistent and stepwise approach to the identification and resolution of drug-related problems, (4) documentation of care provided, and (5) continuity of care. RESULTS: To help pharmacists in the PEP acquire the necessary competency to provide pharmaceutical care, they were required to use the tools and processes described herein to work up and resolve patient problems. Initially, patient problems were presented as paper cases covering a range of acute and chronic problems, including topics applicable to geriatric patients. This was followed by a practicum phase wherein patient problems represented individuals from among their clientele. CONCLUSION: The tools and processes used in the project increased community pharmacists' competency for providing pharmaceutical care, by helping them develop the needed skills, knowledge, and attitudes.

Aged↗

Ofloxacin versus trimethoprim/sulfamethoxazole in the treatment of uncomplicated urinary tract infection.

A multicenter randomized study was conducted to compare the efficacy and safety of ofloxacin with that of trimethoprim/sulfamethoxazole (TMP/SMX) in the treatment of uncomplicated urinary tract infection in adults. Patients were randomized to receive either oral ofloxacin 200 mg daily for three days (102 patients), or oral TMP/SMX 160 mg/800 mg twice daily for seven days (100 patients). The pathogen was eradicated in 73 (97.3%) of the 75 evaluable patients receiving ofloxacin and in 66 (97.1%) of the 68 evaluable patients receiving TMP/SMX. The most frequently isolated pathogens were Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. More urinary pathogens were susceptible to ofloxacin than to TMP/SMX, although this difference was not statistically significant. The clinical cure rate for patients receiving ofloxacin was 93.3%, with 4% improved and 2.7% failed. For patients receiving TMP/SMX, the clinical cure rate was 86.4%, with 12.1% improved and 1.5% failed. Side effects were reported by 29.7% of the patients receiving ofloxacin and by 40.4% of the patients receiving TMP/SMX. Drug-related adverse experiences, as determined by the investigators, occurred in 5% of the ofloxacin patients and in 15.2% of the TMP/SMX patients, a statistically significant difference. No patients receiving ofloxacin, compared with three patients receiving TMP/SMX, discontinued therapy because of an adverse reaction. These results indicate that short-course ofloxacin is as effective as TMP/SMX in the treatment of uncomplicated urinary tract infection. Ofloxacin therapy is also better tolerated than TMP/SMX.

Adolescent↗

Cytology of lumpectomy specimens.

Residual microscopic disease after lumpectomy may cause significant local recurrence. This study evaluated the use of touch preparation cytology to assess lumpectomy margins. For 90 specimens, the findings on Diff-Quik-stained touch preparations (rendered intraoperatively within 15 minutes after the lumpectomy) were correlated with the gross findings, frozen-section results and, later, the findings in the permanent histologic sections. Three specimens were cytologically unsatisfactory, 68 yielded benign findings, and 19 were suspicious or diagnostic for malignancy. The margins showed tumor involvement in 5 lumpectomy samples by gross examination, in 13 by frozen-section evaluation and in 17 by the study of permanent sections. Touch preparation cytology was putatively falsely positive in two cases while frozen-section evaluation was falsely negative in four cases. Cytology had a sensitivity of 100%, a specificity of 97.1% and a diagnostic accuracy of 97.7%. These results demonstrate that touch preparation cytology rapidly and reliably evaluates lumpectomy margins and can overcome some sampling errors and artifacts related to frozen-section analysis. Touch preparation cytology is now being used to complement frozen-section evaluation of lumpectomy margins as part of a protocol aimed at reducing the local recurrence rate.

Biopsy↗

Role of fine needle aspiration cytology after lumpectomy.

Lumpectomy with axillary dissection followed by radiotherapy is a frequently utilized technique for the treatment of selected breast carcinomas. Following this procedure, patients often present within a variable period of time with either clinical or mammographic abnormalities at the lumpectomy site suggesting recurrent cancer. In order to evaluate the utility of fine needle aspiration biopsy (FNAB) in the follow-up of such patients, aspirates were obtained 1-73 months after lumpectomy from 72 patients. A spectrum of cytologic changes was seen as a consequence of surgery and irradiation at the site of the lumpectomy as well as in the axilla and lumpectomy scar. The majority of these changes (94%) were benign and generally resolved during follow-up visits. Recurrent malignancy was detected in 4 of 72 patients. These results show that FNAB can reliably differentiate benign from neoplastic changes in postlumpectomy patients and indicate that FNAB may play an important role in the nonsurgical management of clinically alarming but benign postlumpectomy lesions.

Biopsy, Needle↗

Imprint cytology of needle-localized breast lesions.

Intraoperative evaluation of nonpalpable breast lesions by frozen section frequently is not performed because of potential tissue loss, sampling errors and frozen section artifacts. In a retrospective review we found that only 50 of 503 needle-localized breast biopsies (NLBBs) were evaluated at our institution by frozen section (FS), with a sensitivity of 88%. However, intraoperative evaluation of such lesions may be essential to single-stage and cost-effective management. To this end, this study evaluated the diagnostic accuracy and potential clinical role of intraoperative imprint cytology (IIC) in NLBB. A total of 88 lesions were evaluated by IIC and permanent histology. Fifteen of them were also concomitantly evaluated by FS. All but one deferred cytologic diagnoses were correct. Twelve of 15 FS diagnoses were correct, 2 were deferred, and 1 was false negative. The data suggest that IIC may circumvent some of the difficulties associated with FS, thereby allowing immediate clinical management and later definitive histologic typing and evaluation of prognostic parameters in nonpalpable breast lesions.

Adenoma↗