Frozen section diagnosis of metastatic prostate adenocarcinoma in pelvic lymphadenectomy compared with nomogram prediction of metastasis.

OBJECTIVES: To compare the sensitivity and negative predictive values of frozen section analysis of pelvic lymphadenectomy in patients undergoing radical retropubic prostatectomy for prostate adenocarcinoma with the predictive power of published nomograms for metastasis to lymph nodes. METHODS: A retrospective review was performed on all patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for prostate adenocarcinoma between 1991 and early 1997. The sensitivity and negative predictive values were computed comparing frozen section analysis, and patients were grouped by risk stratification. Comparison was made using the McNemar text. RESULTS: The sensitivity for detecting lymph node metastasis on frozen section analysis for all risk groups was 33% (9 of 27). The sensitivity for identifying patients at high risk of having nodal metastasis by published nomograms alone was 67% (18 of 27) (P = 0.04). The overall negative predictive value for frozen section analysis was 96.5% (503 of 521). The negative predictive value for uninvolved lymph nodes, using low and intermediate-risk groups stratified by published nomograms, was 97.9% (436 of 445). CONCLUSIONS: Frozen section analysis of pelvic lymph nodes to detect metastatic prostate adenocarcinoma is less sensitive in determining which patients will have lymph nodes involved by metastatic adenocarcinoma than using risk stratification by published nomograms. The negative predictive value of frozen section analysis in all risk groups was very high, up to 97.9%.

The clinical value of commonly used spinal fluid diagnostic studies in the evaluation of patients with suspected multiple sclerosis.

OBJECTIVE: This study was designed to evaluate the diagnostic value of cerebrospinal fluid (CSF) oligoclonal banding and immunoglobulin G (IgG) production in the diagnosis of multiple sclerosis. STUDY DESIGN: Spinal fluid changes in patients with suspected multiple sclerosis were compared with clinical data to determine sensitivity, specificity, and predictive value of the procedures. The results were evaluated in terms of cost compared with clinical utility in the managed care environment. PATIENTS AND METHODS: The CSF oligoclonal banding and CSF IgG index were measured in 50 patients being evaluated for possible multiple sclerosis at a multispecialty group practice clinic. RESULTS: CSF oligoclonal banding had a sensitivity of 75% and a specificity of 92% in the diagnosis of multiple sclerosis. The CSF IgG index had a sensitivity of 75% and a specificity of 95% in the diagnosis of multiple sclerosis. CONCLUSIONS: Although neither test would identify 100% of patients with multiple sclerosis, the combination of CSF oligoclonal banding and an elevated CSF IgG index correctly identified most patients with multiple sclerosis and excluded all patients without the disease in this patient population.

Use of age-specific normal ranges for serum prostate-specific antigen.

BACKGROUND: The traditional normal range for prostate-specific antigen has been 0.0 to 4.0 ng/mL. Two different age-specific normal ranges have been proposed, one by Oesterling et al and the other generated by the Prostate Cancer Awareness Week experience. METHODS: We studied 213 consecutive cases of biopsy-proven prostate adenocarcinoma to evaluate age-specific normal ranges for prostate-specific antigen. We examined each patient's age, stage of disease, and serum concentration of prostate-specific antigen at the time of diagnosis. The three normal ranges were applied to each case. RESULTS: The patients ranged in age from 45 to 87 years. At all stages of disease, more patients had elevated serum prostate-specific antigen values using the traditional normal range as opposed to either age-specific normal range. These discrepancies were most obvious for stage II disease, in which 93 of 119 cases (78%) were elevated according to the traditional normal range versus 78 of 119 cases (66%) according to the Oesterling et al range and 80 of 119 cases (67%) according to the range defined during Prostate Cancer Awareness Week. For patients aged 40 to 59 years, all three normal ranges provided identical results (18 of 22 [82%] cancers detected). CONCLUSIONS: Use of either age-specific normal range would have missed more than 10% of stage II prostate adenocarcinomas in patients over the age of 60 years. This indicates that caution should be exercised when applying age-adjusted normal ranges for serum concentrations of prostate-specific antigen in patients of that age group.

Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris.

Troponin-T was measured in patients with chest pain and negative creatine phosphokinase-MB isoenzymes. Patients with elevated troponin-T had a significantly greater risk of cardiac events over the next 6 months than patients with normal troponin-T.

Development of a lipoprotein profile using capillary electrophoresis and mass spectrometry.

A new program for lipoprotein characterization is outlined where capillary electrophoresis (CE) plays a central role in the analysis of intact lipoprotein serum components and the apoprotein domains. The first characterization step involves separation and particle density analysis of very low-, low-, and high-density lipoprotein fractions (VLDL, LDL, HDL) by ultracentrifugation and image analysis. VLDL, HDL, and LDL fractions are analyzed by capillary electrophoresis. Sodium dodecyl sulfate (SDS) at low concentrations in the background electrolyte used in the CE analysis is incorporated into the lipoprotein particle without appreciable delipidation, as determined by ultracentrifuge particle density analysis. Increasing the concentration of SDS results in extensive delipidation, resulting in the release of apoproteins (apo) which are detected as components of the electropherogram. Apo B-100 is detected in the delipidated VLDL and LDL fractions along with micelles of the lipids. Micelles from LDL delipidation have uniform charge densities. Apo A-I and A-II are detected in the HDL fraction. A new method for lipoprotein delipidation is introduced where the lipoprotein fraction is adsorbed on a reversed-phase hydrophobic cartridge. Delipidation and recovery of the apoprotein fractions is made by serial elutions with acetonitrile. CE of the lipid-free apoprotein mixture shows the presence of apoC-I,II,III and apoE in the VLDL fraction, and apoA-I,II apoC-I and apoE in the HDL fraction. Electrospray ionization mass spectrometry analysis gives the isoform distribution for each apoprotein. The identification of the apoproteins in the electropherograms is the first step in developing a CE-based quantitation method for measuring serum levels of these apoproteins and their distribution between the lipoprotein fractions. The assay described in this paper is being used as a level 2 and 3 cardiac risk profile analysis for individuals with normal lipid profiles who have a documented or family history of cardiovascular disease.

Effective resource management using a clinical and laboratory algorithm for chest pain triage.

BACKGROUND: Bridgeport Hospital recently compared the use of a clinical algorithm with unaided physicians for the triage of 200 emergency department (ED) patients with chest pain for coronary care unit (CCU) admission. HYPOTHESIS: Cardiac troponin-T may be an effective adjunct to an established clinical algorithm for accurate selection of patients who are admitted to the CCU for suspected acute myocardial infarction (AMI). It is elevated 6 hours earlier than lactate dehydrogenase fraction 1 (LD1) and may be the most effective test for confirming non Q-wave AMI (usually with ST-T changes and LD1/lactase dehydrogenase > 35%). It is elevated in class 3 angina with a high risk of fatal arrhythmia. STUDY DESIGN: Clinical and electrocardiogram criteria for triage are as defined by Goldman et al. (see references 6 and 11). The exclusion of non-AMI within 4 hours of ED visit using troponin-T (or an alternative test) should allow more rapid treatment of non-AMI patients at a lower intensity of hospital service (e.g., telemetry versus ICU). This should translate into shorter length of stay for non-AMI patients and facilitate thrombolytic therapy with significant resultant medical and cost benefits. LABORATORY DATA: Creatine kinase and its MB isoenzyme (CK-MB) are measured at the time of clinical triage and 4, 8, and 12 hours later. LD1 and total lactase dehydrogenase are measured 12 hours after initial sampling. Cardiac troponin-T is measured at the time of ED arrival and 4 hours later. ANALYSIS OF BENEFIT: The first thing to consider is reducing the cost from stress thalliums for low risk evaluation. The second is the evaluation of active ischemia--unstable angina and diagnosis of missed AMI. The Goldman algorithm eliminates unnecessary admissions to the CCU for chest pain, including unstable angina. There is a difference between AMI and triage for CCU admission (200 patients). CK-MBs allowed for the elimination of 37 non-AMIs. However, we missed eight cases of AMI that would have been LD1 positive (troponin positive) and gained 10 cases of unstable angina that should have been assigned to CCU or a monitored bed. Troponin found six more cases of unstable angina that were CK-MB negative but should have been class 3 unstable angina that could be assigned to at least a telemetry bed. This makes 14 cases of AMI or unstable angina unaccounted for by CK-MB (5.6%). All of the cases were at risk of ventricular arrhythmia within 36 hours. The only question was whether to assign them to CCU or to monitored beds. The third point in the analysis is to examine the savings in operating costs by substitution. The cost model, in selecting a strategy, takes test costs, clinical outcomes, and the cost of clinical algorithms into consideration.

Corticosteroid alteration of carboplatin-induced hematopoietic toxicity in a murine model.

Corticosteroids exhibit extensive hematopoietic effects both in vitro and in vivo. Some of the previously studied effects suggested that corticosteroids may alter hematopoietic toxicity of chemotherapeutic agents. In this study, we examined (1) the optimum dose and schedule of cortisone acetate (CA) to reduce hematopoietic toxicity of carboplatin (CB) and (2) possible mechanisms involved in this protective effect. CA given subcutaneously at 0.5 mg/d per mouse for 7 days before CB reduced CB-induced mortality due to neutropenia from 88% in controls to 14% in CA-treated mice (P < .05). Lower CA doses were not effective. Three days of pretreatment (but not 1 day) was as effective as 7 days. CA given after CB had no effect on mortality. Pharmacokinetic studies of CA at 0.5 mg per mouse demonstrated blood levels of cortisol achievable in patients (peak level, 82 micrograms/dL). CA treatment markedly reduced spleen cell number and colony-forming units-granulocyte/macrophage (CFU-GM) as well as bone marrow CFU-GM. Bone marrow CFU-GM removed from CA-treated mice demonstrated increased resistance to platinum and increased resistance to high specific activity 3H-thymidine. These findings suggest that treatment of mice with CA induces cellular resistance of hematopoietic precursors to platinum and, thus, reduces CB hematotoxicity. CA or other corticosteroids may be useful in reducing clinical toxicity of CB.

Evaluation of age-specific normal ranges for prostate-specific antigen.

OBJECTIVES: To compare the traditional normal range (TNR) of 0.0 to 4.0 ng/mL for serum prostate-specific antigen (PSA) to age-specific normal ranges (ASNRs). METHODS: An autopsy series of completely sectioned, clinically benign prostates from 171 consecutive Caucasian men over the age of 40 years was selected. These patients were divided into those having no prostate cancer at autopsy, prostate cancer less than 1 cc in volume, and prostate cancer at least 1 cc in volume. The PSA values of each group were compared using both the TNR and the ASNR. RESULTS: Twenty-three of 105 (21.9%) patients with no cancer had elevated PSA values by the TNR, whereas only 18 (17.1%) were elevated using the ASNR. Nine of 54 (16.7%) with cancer less than 1 cc were elevated using the TNR, and 7 of 54 (13.0%) using the ASNR. Of 12 patients with cancer at least 1 cc, all had elevated PSA levels using the TNR and 11 (91.7%) were elevated using the ASNR. All discrepancies between the TNR and ASNR occurred in the 60- to 79-year age range. CONCLUSIONS: Use of ASNRs appears helpful in increasing the specificity of PSA by eliminating some elevated values in patients in their 60s and 70s.

Serum prostate-specific antigen levels in stage A1 prostatic cancer.

Quantitation of serum prostate-specific antigen (PSA) has recently come into widespread use. Controversy exists regarding its usage in screening for carcinoma of the prostate (CAP), based partly on concern that it may detect small foci of CAP that will not cause any significant morbidity or mortality. This study was conducted to evaluate serum PSA levels in stage A1 CAP. The authors identified 143 consecutive men who had PSA levels drawn within 8 weeks of transurethral resection performed for presumed benign prostatic hyperplasia. One hundred twenty-four of these (86.7%) had no cancer, 11 (7.7%) were found to have stage A1 CAP, and eight (5.6%) were found to have CAP beyond stage A1. The mean PSA level in patients with stage A1 CAP was 2.3 ng/mL, and the benign (no cancer) group had a mean PSA level of 3.8 ng/mL. Ten of the 11 patients in the stage A1 group had PSA values less than 4.0 ng/mL. Therefore, it was found that most patients with stage A1 CAP did not have elevated PSA levels. In the authors' experience, elevation of PSA levels caused by CAP is indicative of a tumor burden greater than that found in stage A1 CAP.

Proteins used in nutritional assessment.

The importance of maintaining or restoring the size of the protein pool remains the primary objective of nutrition therapy for the hospitalized patient. Also, newer nutritional markers are needed that identify malnourished patients and effectively monitor nutritional intervention on the patient's nutritional status. To do this, one must assess protein pools in an effective manner. Newer protein markers must have a short biologic half-life and reflect protein deficiency with decreasing serum concentrations. The proteins discussed offer unique opportunities for investigating malnutrition in the hospital and clinic setting. More studies to elucidate the effects that diseases and drugs have on these proteins in particular patient subpopulations are needed. Additional methods also need to be developed to make assays for SMC and interleukin cost effective in hospital or clinic settings. In the next decade, certainly more research will be undertaken on these promising new nutritional markers.

Determination of malnutrition in hospitalized patients with the use of a group-based reference.

We clustered a selected population of patients at Bridgeport (Conn) Hospital into distinct nutritional classes using critical decisions points for the serum concentrations of aspartate aminotransferase activity, cholesterol, total protein, albumin, and prealbumin. The decision points that divided the populations with the highest efficiency were delineated by the information in the data set. At these decision values the hospital population adjusted malnutrition rate was just more than 30%. This was lower than the reported prevalence of malnutrition in the hospital population and was better in agreement with global estimates of malnutrition. The study identified a problem in the assignment of decision values that are used for nutritional support which has implications for nutritional interventions.

Testosterone deficiency as a risk factor for hip fractures in men: a case-control study.

The objective of this study was to determine whether decreased gonadal function is a risk factor for hip fracture in elderly men. The study was a matched case-control study performed at an in-hospital orthopedic service at a semi-rural and academic tertiary care center. The patients were seventeen men who presented with hip fractures after simple falls over a 10-month period, 11 men with a history of hip fractures in the preceding 25 months, and 28 randomly selected age-, race-, and living status-matched control subjects (mean age 73 years). Serum pooled total testosterone (9.2 +/- 5.5 nmol/L vs. 12.8 +/- 5.4 nmol/L; p less than 0.02) and free testosterone (37.9 +/- 18.8 pmol/L vs. 48.4 +/- 20.6 pmol/L; p less than 0.03) were significantly lower in hip fracture vs. control patients. Testosterone deficiency was found in 20 (71%) hip fracture men vs. 9 (32%) of the controls (p = 0.003; odds ratio 5.3). Analysis of testosterone values within the stratum of absence of any chronic disorder revealed similar results. Serum 25-hydroxyvitamin D levels were significantly lower in the hip fracture group than in control men (p less than 0.001). The conclusion is that gonadal deficiency appears to be an important and heretofore understudied risk factor for hip fractures in men. Prevention of hip fractures in men may involve early recognition and treatment of testosterone deficiency.

Prostate-specific antigen levels from completely sectioned, clinically benign, whole prostates.

Clinically benign whole, untrimmed prostates and pelvic lymph nodes were obtained from 105 patients at autopsy. All 105 patients had premortem serum from which prostate-specific antigen (PSA) levels were obtained. Sixty-eight did not have carcinoma of the prostate (CAP), 28 had CAP less than 1 ml and 9 had CAP larger than 1 ml. Eleven untrimmed prostates weighed 80 g or more and eight had elevated PSA levels (more than 4.0 ng/ml): five of eight without CAP, two of two with CAP less than 1 ml, and one of one with CAP larger than 1 ml. Ninety-four whole untrimmed prostates weighed less than 80 g and 20 had elevated PSA levels: ten of 60 without CAP, two of 26 with CAP less than 1 ml, and eight of eight with CAP larger than 1 ml. This study suggests that PSA levels from patients with untrimmed prostates weighing 80 g or more (equivalent to a 60-g trimmed prostate) are usually elevated regardless whether CAP is present. However, CAP less than 1 ml, in untrimmed prostates less than 80 g, usually does not elevate PSA levels whereas CAP larger than 1 ml usually does (P less than 0.0001). The likelihood that elevated PSA levels, from patients with untrimmed prostates less than 80 g, are due to CAP larger than 1 ml increases as the PSA level increases.

Long-term inhibition of cellular proliferation by immunotoxins.

The proliferation and fibrous metaplasia of retinal glial and pigment epithelial cells cause proliferative vitreoretinopathy. The immunotoxin 454A12 MAB-rRA is composed of a murine monoclonal antibody, specific for the human transferrin receptor, and is chemically linked to recombinant ricin A chain, a cellular toxin. The rapidly proliferating cells take up the immunotoxin, but non-proliferating cells do not. Using a collagen-gel medium to simulate the vitreous, we have studied the effect of the immunotoxin on fibroblast proliferation in vitro. Exposure of the fibroblasts to 1000 ng of immunotoxin per milliliter of the collagen gel medium for 10 minutes kills 96% or more of the cells for 20 days. These in vitro data indicate that the immunotoxin is effective in an environment similar to the vitreous; however, in vivo studies will be necessary to prove if it is a suitable agent for the long-term prevention of cell proliferation in the human eye.

Prostatic complications of testosterone replacement therapy.

The prostatic complications of testosterone replacement therapy have received little clinical attention. We describe three hypogonadal men who had prostatic disease (adenocarcinoma in two) detected in relation to such therapy. Literature review suggests that surveillance for early prostate cancer is appropriate during replacement therapy in men over the age of 50 years. We discuss the selective use of digital rectal examination, transrectal sonography, directed prostate biopsy, and prostate-specific antigen determinations before therapy and in subsequent follow-up in this age group of men during androgen replacement.

Euthyroid hyperthyroxinemia and inappropriate secretion of thyrotropin. Recognition and diagnosis.

Various disease states associated with euthyroid hyperthyroxinemia and inappropriate thyrotropin secretion are becoming increasingly recognized. These diagnoses were established in six (11%) of 57 patients referred for evaluation of elevated free thyroxine index over an 11-month period. Failure to separate these entities from primary thyrotoxicosis may result in unnecessary thyroid ablative therapy and subsequent clinical confusion. Several illustrative patient summaries are presented to outline an approach to this clinical challenge.

Effects of eight weeks of physical conditioning on atherosclerotic plaque in swine.

Effects of individually prescribed exercise on the regression or interference with deposition of atherosclerotic plaque were studied. Twenty miniature swine allotted, by litter, to a control-diet group (groups CE and CS) and an atherogenic diet group (groups AE and AS). All pigs were subjected to injury (balloon catheter) of the aortic endothelium. They were fed for 8 weeks and after an initial graded exercise test was done, then each group was suballotted to an exercising group (groups CE and AE) or a sedentary group (groups CS and AS). Groups CE and AE (exercised) were given 8 weeks of training. Groups CS and AS (sedentary) were sham exercised during this period. A second graded exercise test was administered to the swine (all groups) before they were euthanatized. Aortas were analyzed for the percentage of area involved and for atherosclerotic plaque density. Samples of blood from the swine after they were fasted were obtained before the start of the project (base line) and once every 2 weeks thereafter. These were analyzed for triglycerides, high- and low-density lipoprotein, and total cholesterol concentration. Comparison of results of blood lipid analyses from weeks 1, 9, and 15 did not show significant differences within diet groups between exercise and sedentary. Significant differences at weeks 9 and 15 were observed between diet groups (ie, the pigs fed the atherosclerotic diet had higher blood lipids). Plaque formation was not found in the pigs fed the control diet (groups CE and CS). Plaque formation was evident in all pigs fed the atherosclerotic diet (groups AE and AS) with no significant differences between exercised and sedentary groups.(ABSTRACT TRUNCATED AT 250 WORDS)