Allyn W. Kimball

Prostate Specific Antigen in the Preoperative and Postoperative Evaluation of Localized Prostatic Cancer Treated with Radical Prostatectomy

The usefulness of prostate specific antigen to predict final pathological stage was studied in 178 consecutive patients. Prostate specific antigen was determined preoperatively in all patients by a monoclonal immunoradiometric assay. All pathological specimens were examined for capsular penetration, seminal vesicle involvement and lymph node involvement. Prostate specific antigen correlated directly with capsular penetration (p less than 0.002), seminal vesicle involvement (p less than 0.02) and lymph node involvement (p less than 0.05). However the diagnostic accuracy of an elevated serum antigen level on an individual basis was only 55 per cent for capsular penetration and 50 per cent for seminal vesicle involvement and lymph node involvement. With a log-linear regression model, the half-life of prostate specific antigen was calculated to be 3.15 +/- 0.09 days. From the equation PSA (t) equals PSA (2) e[-0.2197(t-2)], prostate specific antigen can be used to detect residual cancer on day t in the immediate postoperative period. With respect to long-term followup, 127 patients have been monitored for longer than 2 months postoperatively with prostate specific antigen (mean followup 2 years, range 2 months to 8.6 years). Of the 101 patients who had favorable pathological findings at operation (organ-confined cancer or capsular penetration only) 92 (91 per cent) had a followup antigen concentration in the female range (0.0 to 0.2 ng. per ml.), whereas only 5 of 26 men (19 per cent) with either seminal vesicle involvement or lymph node involvement had an antigen value that was less than 0.2 ng. per ml. All patients with a documented clinical recurrence (8 of 127, 6 per cent) had an elevated followup serum prostate specific antigen concentration. These findings suggest that preoperative levels of prostate specific antigen are not sufficiently reliable to predict final pathological stage on an individual basis in patients with early prostatic cancer, and that the antigen is a sensitive tumor marker for the detection of residual disease after radical prostatectomy and subsequent recurrence of tumor on long-term followup.

Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia.

To elucidate the multifactorial nature of perioperative changes in body temperature, the influence of several clinical variables, including anesthetic technique, ambient operating room temperature, and age, were evaluated. Perioperative oral sublingual temperatures were measured in 97 patients undergoing lower extremity vascular surgery randomized to receive either general (GA) or epidural (EA) anesthesia. Surgery and anesthesia were performed in operating rooms (OR) with a relatively warm mean ambient temperature (24.5 +/- 0.4 degrees C) (GA, n = 30; EA, n = 33) or relatively cold mean ambient temperature (21.3 +/- 0.3 degrees C) (GA, n = 21; EA, n = 13). Patients were 35-94 yr old, with a mean age of 64.5 +/- 1.1 yr. A regression analysis was performed to determine the variables that correlated with intraoperative decrease in temperature and postoperative rewarming rate. The major correlates of greater intraoperative decrease in temperature were 1) GA (P = 0.003); 2) cold ambient OR temperature (P = 0.07); and 3) advancing patient age (P = 0.03). There was significant interaction between ambient OR temperature and type of anesthesia (P = 0.03): there was a greater intraoperative decrease in temperature with GA compared to EA in a cold OR but a similar decrease with GA and EA in a warm OR. The data also suggest an interaction between type of anesthesia and patient age (P = 0.06), showing a greater decrease in temperature with GA compared to EA in the younger patients, but a similar decrease between GA and EA in older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of Clinical Stage, Serum Prostatic Acid Phosphatase and Preoperative Gleason Grade with Final Pathological Stage in 275 Patients with Clinically Localized Adenocarcinoma of the Prostate

The usefulness of clinical stage, serum prostatic acid phosphatase and preoperative Gleason grade in predicting final pathological stage in patients with adenocarcinoma of the prostate remains controversial. To determine the predictive value of these 3 preoperative variables we reviewed 275 patients with clinically localized disease who were treated between April 1982 and February 1986. All patients were examined preoperatively and subsequently were operated upon by 1 urologist. Serum prostatic acid phosphatase was determined in all patients by the Roy method using thymolphthalein monophosphate as the substrate. The Gleason grade of each prostatic biopsy specimen was determined preoperatively by 1 pathologist, who also examined the final pathological specimen with respect to capsular penetration, and seminal vesicle and pelvic lymph node involvement. Using logistic regression analysis with the likelihood ratio chi-square test, clinical stage and Gleason grade had a direct correlation with capsular penetration (p less than 0.0001 and less than 0.0001, respectively), seminal vesicle involvement (p less than 0.0001 and less than 0.0001, respectively) and positive lymph nodes (p less than 0.0001 and less than 0.0002, respectively). Within the normal range of values (0.0 to 0.8 IU/l.) serum prostatic acid phosphatase correlated directly with capsular penetration (p less than 0.003) and seminal vesicle involvement (p less than 0.01) but not with lymph node involvement (p equals 0.08). Again with logistic regression analysis we determined that the best predictors of final pathological stage are not individual variables but models that use combinations of preoperative variables. The models generated are as follows: capsular penetration--serum prostatic acid phosphatase and Gleason grade (p less than 0.00001), seminal vesicle involvement--clinical stage and Gleason grade (p less than 0.00001), and lymph node involvement--clinical stage and Gleason grade (p less than 0.00001). With these models probability plots have been constructed so that the final pathological stage in patients with clinically localized prostatic cancer can be predicted preoperatively.

Sputum cytopathology: use and potential in monitoring the workplace environment by screening for biological effects of exposure

Sputum cytopathologic monitoring detects squamous cell lung cancers at an extremely early stage (x-ray negative). It holds further potential for preventing disease by detecting epithelial alterations which reflect environmental hazards. The addition of sputum cytology screening to screening by chest x-ray film does not significantly reduce mortality from all types of lung cancer, but preliminary analysis of Johns Hopkins Lung Project data suggests that mortality from squamous cell carcinoma is reduced. Quantitative automated cytopathology systems and biochemical/immunological cell markers enhance understanding of these precursors and offer great promise for increasing capacity, accuracy, and usefulness in cytopathology screening of workers. Cytological specimens collected over years of screening workers considered at risk may be important to eventually understanding development and prevention of major occupational diseases.

Measurement of Benzodiazepine Receptor Number and Affinity in Humans Using Tracer Kinetic Modeling, Positron Emission Tomography, and [11C]Flumazenil

Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration (Bmax) and equilibrium dissociation constant (Kd) from high and low specific activity (SA) [11C]flumazenil ([11C] Ro 15-1788) positron emission tomography studies of five normal volunteers. The high and low SA data were simultaneously fit to linear and nonlinear three-compartment models, respectively. An additional inhibition study (pretreatment with 0.15 mg/kg of flumazenil) was performed on one of the volunteers, which resulted in an average gray matter K1/k2 estimate of 0.68 ± 0.08 ml/ml (linear three-compartment model, nine brain regions). The free fraction of flumazenil in plasma (f1) was determined for each study (high SA f1: 0.50 ± 0.03; low SA f1: 0.48 ± 0.05). The free fraction in brain (f2) was calculated using the inhibition K1/k2 ratio and each volunteers mean f1 value (f2 across volunteers = 0.72 ± 0.03 ml/ml). Three methods (Methods I–III) were examined. Method I determined five kinetic parameters simultaneously [K1, k2, k3 (= konf2Bmax), k4, and konf2/SA] with no a priori constraints. An average kon value of 0.030 ± 0.003 nM−1 min−1 was estimated for receptor-rich regions using Method I. In Methods II and III, the konf2/SA parameter was specifically constrained using the Method I value of kon and the volunteers values of f2 and low SA (Ci/μmol). Four parameters were determined simultaneously using Method II. In Method III, K1/k2 was fixed to the inhibition value and only three parameters were estimated. Method I provided the most variable results and convergence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems. However, the K1/k2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K1/k2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability. The average Bmax values obtained using Method III were 100 ± 25 nM in the occipital cortex, 64 ±18 nM in the cerebellum, and 38 ± 5.5 nM in the thalamus; the average Kd was 8.9 ± 1.0 nM (five brain regions).

Cul-de-sac fluid in women with endometriosis: fluid volume and prostanoid concentration during the proliferative phase of the cycle—days 8 to 12 *

Cul-de-sac fluid from women with histologically confirmed endometriosis (n = 45) or with no evidence of endometriosis (n = 17) was removed during the proliferative phase of the menstrual cycle (days 8 to 12) and analyzed for prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 15-keto-13,14-dihydroprostaglandin F2 alpha (PGFM), and thromboxane B2 (TXB2). The fluid volume was recorded. Peripheral blood was also obtained to determine the concentration of PGFM. Prostanoid concentrations (PGE2, PGF2 alpha, PGFM, TXB2) in women with endometriosis were not significantly different from a comparable group of disease-free women. Furthermore, a meaningful elevation of prostanoid with increasing severity of disease could not be demonstrated. Plasma PGFM was not significantly different from controls. There was, however, an elevation of PGFM with severity of disease, although this increase was not statistically significant (P = 0.11). An increase in fluid volume was not demonstrated in women with endometriosis, as compared with controls.

Cause-Specific Actuarial Survival Analysis: A Useful Method for Reporting Survival Data In Men with Clinically Localized Carcinoma of the Prostate

The primary objective of this retrospective 15-year survival analysis of 57 men with clinical stage B1 carcinoma of the prostate undergoing radical prostatectomy between 1951 and 1963 is to compute the cause-specific curve for these men and argue why it is a useful method to report survival data in men with clinically localized prostatic cancer. Historically, survival following radical prostatectomy and radiotherapy has been reported using all cause survival analysis. Cause-specific survival focuses on the impact of a disease process on survival, since men dying of causes unrelated to carcinoma of the prostate are considered lost to followup as of date of death of such unrelated causes. Cause-specific survival analysis reduces the impact of age, medical condition and other risk factors on survival rates. The cause-specific 15-year actuarial survival rate in our patients was 86 per cent. The 95 per cent confidence interval for this 15-year survival rate was 76.9 to 90.1 per cent. Based upon this series of patients with clinical stage B1 carcinoma of the prostate who undergo radical prostatectomy one may state that the chance of death of carcinoma of the prostate within 15 years of surgery averages 14 +/- 5 per cent. The cause-specific survival curve reached a plateau at 10 years, indicating that most men who survive 10 years are cured of the disease. With the Cox model regression analysis, mortality in this series was related positively to age at operation when the outcome variable was death of all causes (p equals 0.003) but it was unrelated to age when the outcome variable was prostate cancer mortality (p equals 0.85). Cause-specific survival rates are a more precise indicator of the impact of a therapeutic modality on survival and, therefore, they are useful to report survival data in men with localized carcinoma of the prostate and other disease when death from competing causes is an important consideration.

The efficacy of postoperative hydrotubation: a randomized prospective multicenter clinical trial

Term pregnancies following surgery on patients with distal tubal obstruction have been disappointingly few. There has been continuing interest in whether postoperative hydrotubation increases the rate of pregnancy following salpingoneostomy and fimbrioplasty. This hypothesis was tested in a prospective, randomized, multicenter clinical trial. Patients with no infertility factors other than distal fimbrial disease were randomly assigned to either a control group (no hydrotubation, n = 86) or one of two treatment groups (hydrotubation with lactated Ringers solution, n = 60, or lactated Ringers solution containing hydrocortisone, n = 60). The statistical evaluation of differences among treatment groups was based on the Cox Proportional Hazards Model, which allows for covariable adjustment and for the inclusion of all patients regardless of the length of follow-up. A significant difference in the live birth rate could not be demonstrated among the groups studied (P = 0.36). The probability of a successful live birth among women treated by hydrotubation with hydrocortisone was about one-half that of the other groups (P = 0.12). Patients with moderate and severe disease had a substantially lower probability of pregnancy than those with mild disease (P = 0.013 and P = 0.0016, respectively). The probability of pregnancy increased somewhat as the number of previous pregnancies increased (P = 0.12). In this clinical trial, a beneficial effect following postoperative hydrotubation could not be demonstrated.

Exogenous estrogen effect on lipid /lipoprotein cholesterol in transsexual males

Lipid/lipoprotein cholesterol values and sex-hormone-binding globulin levels were determined in 40 transsexual males aged 20–38, 20 castrated and 20 non-castrated, taking conjugated estrogens to induce female characteristics. Variables controlled included dose of estrogen, age, weight, smoking, alcohol intake, exercise and diet history. Transsexual males on estrogens had significantly higher mean (± SE) HDL cholesterol levels (69.0 ± 7.1 mg/dl) respectively, for castrated males and (53.8 ± 6.2 mg/dl) for non-castrated males, respectively compared to normal control males not on hormonal therapy (41.5 ± 5.4) (p < 0.001), regardless of dose of estrogen received. The total cholesterol/HDL ratio was 3.31–4.05 in transsexual males on estrogens compared to 5.03 for normal males (p < 0.001). Transsexual males had mean SHBG levels in the female range (63.4 to 71.8 nmol/ml), significantly higher than controls (26.7 nmol/ml) (p < 0.001). SHBG levels were correlated with estrogen use, dose and HDL cholesterol levels. We conclude that exogenous estrogens administered to transsexual males results in a female pattern of lipid/lipoprotein cholesterol and SHBG concentration. The decreased total cholesterol/HDL ratio may imply a lower atherogenic potential and a lessened cardiovascular risk in males who take estrogens.

Fetal malformations following progesterone therapy during pregnancy: A preliminary report

This report presents the outcome of pregnancies of 93 women who conceived while taking progesterone (P) suppositories (n = 42) or P in oil intramuscularly (n = 51). The dosage and duration of treatment varied according to the indication. The total dose (in milligrams) increased with the duration of treatment and ranged from 75 to 13,500 mg. Two of 75 term pregnancies (2.6%) were noted to have congenital anomalies. Both women had been treated with P in oil. No patient treated with P suppositories gave birth to a malformed infant. An increased spontaneous abortion rate (28.6%) was noted among women treated with P suppositories. The authors recommend that a national registry be created to document fetal outcome after P therapy.