Optimal histopathologic examination of the sentinel lymph node for breast carcinoma staging

Sentinel lymph node dissection is a minimally invasive surgical technique for staging of breast carcinoma. The optimal pathologic examination of the sentinel node (SN) has not yet been determined. Our standard protocol for evaluation of the SN in patients with breast cancer included frozen section at one level, plus paraffin sections at two levels, separated by 40 microm, and stained with hematoxylin and eosin and cytokeratin immunohistochemistry (IHC) at each paraffin section level. In the current study, we evaluated the use of step sections and cytokeratin IHC in 60 SNs (42 consecutive patients) that were tumor-negative on frozen section and hematoxylin and eosin staining at permanent section levels 1 and 2. The SN were reexamined with cytokeratin IHC at eight additional levels (levels 3-10) of the paraffin block, each separated by 40 microm. Previous IHC sections from levels 1 and 2 had shown micrometastases in nine SNs (eight patients) and no tumor cells in the remaining 51 SNs (34 patients). Of the 51 previously negative SNs, only two (4%) SNs from one (3%) patient had metastatic carcinoma cells in levels 3-10. Thus, the additional step sections with cytokeratin IHC did not significantly increase the number of patients with tumor-positive SNs. We currently recommend that the SN be examined with cytokeratin IHC at two levels of the paraffin block. This should optimize sentinel lymph node dissection as a staging technique and minimize the labor and financial burden associated with multiple step sections and IHC stains.     

Development of a brief questionnaire for screening for multiple chemical sensitivity syndrome

The objective of this study was to identify a parsimonious set of questions that has high sensitivity and specificity for screening for individuals with multiple chemical sensitivity (MCS) syndrome. We performed a cross-sectional survey using a case-control design. Subjects were derived from patients seen at an academically based Occupational and Environmental Medicine Clinic. Cases consisted of patients who fulfilled the Cullen definition for MCS. Controls were patients who had diagnoses excluding MCS and asthma and who were matched to cases by age and sex. Cases and controls filled out a screening questionnaire that, among things, elicited responses as to whether and how subjects reacted to 122 different types of environmental exposures. Data from 44 pairs of cases and controls were available for analysis. The average age of cases was 50.2 years, and 91% was female. Among cases, the most common exposure that was purported to incite MCS was 'indoor air quality contaminants (unspecified)' (59%), followed by solvents (27.3%). After randomly excluding five cases and controls, a stepwise selection procedure for two-group discriminant analysis revealed that the main contributors to the discrimination of the remaining cases and controls were self-reported reactions to copy machine emissions, marking pens, aftershave, window cleaner, nylon fabric, pine-scented products, and rayon material. When a positive response to these factors was used as the sole method for discriminating cases from controls, only one of 41 cases was misclassified as a control while none of the controls was misclassified as a case. When the same method was applied to the five excluded cases and five excluded controls, only one of the five cases was misclassified while none of the five controls was misclassified as a case. Among patients with MCS defined by the Cullen criteria in this clinical setting, having a reaction to these seven common potential exposures comprised a parsimonious set of factors that discriminated between MCS patients and age- and sex-matched normal controls. These questions may have utility in screening for individuals with MCS in general population survey studies.     

Erythromycin coadministration increases plasma atorvastatin concentrations

The effect of erythromycin on the pharmacokinetics of atorvastatin, an inhibitor of HMG-CoA reductase, was investigated in 12 healthy volunteers. Each subject received a single 10 mg dose of atorvastatin on two separate occasions, separated by 2 weeks. Erythromycin (500 mg qid) was given from 7 days before through 4 days after the second atorvastatin dose. Atorvastatin concentrations were determined by an enzyme inhibition assay, which measured both atorvastatin and active metabolites. When erythromycin was coadministered with atorvastatin, mean Cmax and AUC(0-infinity) increased by 37.7% and 32.5%, respectively. Mean terminal half-life was similar following each atorvastatin dose. Possible mechanisms for this interaction include erythromycin inhibition of first-pass conversion of atorvastatin to inactive metabolites and erythromycin inhibition of P-glycoprotein-mediated intestinal or biliary secretion.     

The effect of l-dopa and propranolol on human CSF cyclic nucleotides

Human CSF cyclic AMP and cyclic GMP have been measured as possible indicators of activity of central neurotransmitter-sensitive adenylate or guanylate cyclase. In an attempt to help to identify the specific neurotransmitter systems of origin of human CSF cyclic AMP and GMP, we studied Parkinson patients with and without l-dopa therapy and schizophrenic patients before and after propranolol therapy. No effect of l-dopa or propranolol was found on CSF cyclic nucleotides. However, Parkinson patients had a 40–50% reduction of CSF cyclic AMP and a 80–90% reduction of CSF cyclic GMP compared with the schizophrenic patients. Implications of this finding are discussed.     

Utilization of physician services for dermatologic complaints. The United States, 1974.

The National Ambulatory Medical Care Survey provides data on the "who," "for what complaint," and "to whom" for office visits to office-based physicians. In 1974, complaints referable to the skin accounted for 44 million physicians visits. This represents 7% of the 634 million visits to physician offices made during this period. Dermatologists accounted for 34% of all visits for skin complaints. General and family practitioners accounted for 40% of such encounters. Office visits prompted by dermatologic complaints were frequently less than 16 minutes long. Each office-based dermatologist accounted for an average of 5,600 patient visit per year. According to the dermatologist's diagnosis, 31% of these visits were prompted by acne; warts accounted for an additional 8%.     

Use of photodynamic therapy in the palliation of massive advanced rectal cancer

Photodynamic therapy (PDT) is a relatively new form of cancer therapy utilizing a photosensitizer such as hematoporphyrin derivative. We conducted a pilot study to determine the efficacy of its use in palliating advanced rectal cancer, to determine toxicity, and to establish objective outcome criteria. Six patients with very advanced, usually recurrent rectal cancer were treated with PDT after being photosensitized with Photofrin II^®. A protocol was established to measure clinical and radiologic response to therapy. A new intraluminal delivery system was incorporated. Five patients had both clinical and radiologic responses to therapy. In two patients we observed such significant responses that they cannot be accounted for on a photobiologic basis alone. One patient developed a significant sunburn after discharge. There was no major toxicity of bleeding or sepsis even at maximum doses (200 J/cm²). We are confident that PDT has a role to play in rectal cancer and speculate as to future applications.     

The epidemiology of Parkinson's disease. A case-control study of young-onset and old-onset patients

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests that certain external factors, ie, environmental agents, may act as neurotoxins, initiating the chain of oxidative reactions that ultimately destroy neurons in the substantia nigra. Young-onset PD might result from greater exposure to a putative neurotoxin. This hypothesis has rekindled interest in the epidemiology of PD. We therefore conducted a detailed analysis of various environmental exposures and early life experiences in 80 patients with old-onset PD (at an age older than 60 years), 69 young-onset patients (younger than 40 years), and 149 age- and sex-matched control subjects. Contrary to previous reports, we were unable to implicate well water or exposure to herbicides, pesticides, or industrial toxins as significant PD risk factors. A residential history of rural living was reported by more patient cases than control subjects and was marginally significant. On the other hand, at least one episode of head trauma "severe enough to cause vertigo, dizziness, blurred or double vision, seizures or convulsions, transient memory loss, personality changes, or paralysis" occurred significantly more often prior to disease onset in patients with both young-onset and old-onset PD than in control subjects (odds ratio = 2.7). When adjusted for head trauma and rural living, smoking was inversely associated with PD, as has been previously reported (odds ratio = 0.5). There were no significant differences in early life experiences or environmental exposures between young-onset and old-onset patients. We suggest that the risk of developing PD is influenced by a variety of factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phenylacetic acid in human body fluids: high correlation between plasma and cerebrospinal fluid concentration values.

In a group of six Parkinsonian patients and 13 "controls" with non-Parkinsonian neurological disease, there was a high correlation between both free and conjugated phenylacetic acid concentrations in plasma and cerebrospinal fluid taken at about the same time. This compound is the major metabolite of phenylethylamine, the production of which may be disturbed in a number of neuropsychiatric illnesses. Thus plasma measurements might be employed clinically to provide an estimate of central changes in phenylethylamine economy. A small but significantly higher proportion of conjugated phenylacetic acid was present in the plasma (but not cerebrospinal fluid) of Parkinsonians compared with controls.