Philip F. Rust

Predictors of physical disability in elderly blacks and whites of the Charleston heart study

During the 1984/85 recall of the Charleston Heart Study Cohort, physical function data were obtained for 247 white males, 376 white females, 123 black males, 247 black females and 71 high socioeconomic status (SES) black males over 60 years of age. Black females had the highest prevalence of physical disability (55.8%), followed by white females (43.2%), black males (39.0%) and white males (25.8%) and high SES black males (22.3%). Physical disability was 1.5-2.5 times as prevalent among individuals with a history of cardiovascular disease (CVD) than those without such a history. Among individuals without a current history of CVD univariate analyses showed the following as significant (lower 95% CI greater than 1.0) predictors of physical disability: elevated systolic blood pressure in white females, black males, and black females; elevated cholesterol in black females; obesity in black females; and low educational level in white females. Regression analyses indicated that obesity in 1960 accounted for 10.9 and 2.9% respectively of the variability in physical disability scores in 1985 for black females and white females.

Anti-sperm antibodies, detected by agglutination, immobilization, microcytotoxicity and immunobead-binding assays

To determine the reliability of tests currently utilized in the detection of sperm-reactive antibodies, sera were provided as unknowns and studied without knowledge of the clinical histories. Four laboratories performed tray agglutination tests (TAT), three complement-dependent immobilization (SIT), and single laboratories sperm cytotoxicity (SCT), passive haemagglutination (PHA) and immunobead binding (IBB). Most investigators demonstrated an excellent correlation between duplicate sample results. Nearly all of the female sera were free of anti-sperm antibodies and positive results did not appear in greater frequency in women with unexplained infertility as compared with other categories. For the male sera, the highest incidence of anti-sperm antibodies in the infertile group (21% positive for sperm-reactive IgGs) was obtained by immunobead binding. The GAT and TAT results gave 7 and 12% positives, except for lower results in one laboratory. Sperm-reactive antibodies were detected most commonly in vasectomized men, with all assays except SCT and PHA. Of the newer techniques studied, IBB results correlated well with TAT, GAT and SIT, while SCT and PHA did not, suggesting that a different group of antibodies, perhaps directed against other sperm-associated antigens, was being detected by the latter procedures. In this light, emphasis was placed on the need to validate whether results of particular methodologies correlated with impaired sperm function and to develop methods that provided evidence for this premise, either on the basis of clinical criteria or altered gamete interaction in vitro.

Endometrial antigens involved in the autoimmunity of endometriosis.

Serum and peritoneal fluid from five fertile women without endometriosis and serum (n = 23) and peritoneal fluid (n = 12) from infertile women with endometriosis were tested for the presence of antibodies against endometrial tissue antigens by a Western blot analysis. Antigens with molecular weights (MW) of 19, 31, 38, and 42 kd reacted with antibodies in the serum and peritoneal fluid from both fertile and infertile women. Antibodies in 20 of 23 (87%) sera and all 12 (100%) peritoneal fluid samples from endometriosis patients reacted against endometrial antigens with molecular weights (MW) of 26 kd and/or 34 kd. Serum from 10 patients (43%) and peritoneal fluid from 6 patients (50%) also had antibodies to an endometrial antigen with MW of 21.5 kd. Reactivity to other endometrial antigens with MW 16, 24, 48, and 75 kd was also noted in patients with endometriosis. Antibodies in the serum and peritoneal fluid from fertile women failed to react against these antigens. It is concluded that the humoral and local endometrial autoimmunity detected in patients with endometriosis is primarily directed against antigens with MW of 26 and 34 kd.

Dose-volume relationship for acute side effects during high dose conformal radiotherapy for prostate cancer

PURPOSE To determine acute and late complications for bladder and rectum and to determine dose-volume correlations. METHODS AND MATERIALS Sixty-four patients received definitive treatment for prostate cancer between January 1995 and December 1998 using conformal three-dimensional radiotherapy. Doses ranged from 72 to 80Gy. The acute and late side effects were gathered retrospectively, and graded according to Radiotherapy and Oncology Group criteria (RTOG). The patients were divided into two groups: <or=72Gy (Group A) and >or=76Gy (Group B) and had a mean follow-up of 32 and 22 months, respectively. RESULTS No grades 3-4 acute, urinary or rectal toxicity was reported. Acute grade 2 rectal complications were seen in 10 and 18% of the patients in Groups A and B, respectively. They were observed at a mean dose of 38Gy. Acute grade 2 urinary symptoms were 33 and 47% for Groups A and B, respectively. They were seen at a mean dose of 43Gy. Acute rectal symptoms were dose-volume related. Patients without diarrhea had a mean rectal volume receiving a dose of 70Gy or more of 8.5 cm(3). However, patients with RTOG 2 diarrhea had a volume of 16.5 cm(3) (P=0.042). No dose-volume relationship for acute bladder symptoms or late complications were seen. Grades 1-2 late rectal and bladder complications were seen in 11 and 8% of the patients, respectively. None required hospital admission or transfusion. CONCLUSION Radiotherapy to the prostate can be given at 80Gy. No grades 3-4 acute, urinary or rectal toxicity was reported. Acute rectal symptoms are dose-volume related.

Intrafamilial Phenotypic Expression of Autosomal Dominant Polycystic Kidney Disease

It has been suggested that the clinical expression of autosomal dominant polycystic kidney disease (ADPKD) is uniform among individuals of a given family. To test this hypothesis, intrafamilial variations in ages at onset of first symptoms, types of first symptoms, serum creatinine concentrations, and renal sizes were evaluated in 131 patients with ADPKD from 36 unrelated families. These parameters were compared in younger and older affected relatives in the same family at a single time, due to difficulties of following them longitudinally. Because the natural course of the disease is to progress with age, it was presumed that disease progression in a given family was nonuniform if older individuals had lower serum creatinine concentrations, and/or smaller kidneys than their affected younger relatives, or if relatives of similar ages had different serum creatinine concentrations and/or kidney sizes. Nonuniform progression was suggested in 38% of affected relatives by serum creatinine concentrations and in 53% by kidney sizes. Ages at onset of first symptoms and types of first symptoms were also different in patients from the same families. These data indicate that phenotypic expression of ADPKD may differ considerably among patients who belong to the same families.

Kinin, a mediator of diabetes-induced glomerular hyperfiltration.

Renal kallikrein is increased in diabetic patients and streptozotocin (STZ)-induced diabetic rats with hyperflltration. Chronic inhibition of renal kallikrein reduces glomerular filtration rate (GFR) and renal plasma flow (RPF) in hyperfiltering STZ-induced diabetic rats. To investigate whether these actions of kallikrein and its inhibition are kinin-mediated, we used a B2-kinin receptor antagonist (BKA). In STZ-induced diabetic rats with hyperflltration, renal kallikrein excretion rate was significantly increased (P < 0.01), and kinin excretion rate was increased 57%, as compared with control rats. Left kidney GFR and RPF were measured before and during a 40-min infusion of BKA (0.5 μg · kg−1 · min−1) or vehicle. Infusion of the kinin receptor antagonist reduced the GFR and RPF significantly. GFR was reduced by 18%, from an average baseline value of 2.07 ± 0.11 to 1.70 ± 0.06 ml/min, P < 0.001 (means ± SE). RPF was reduced by 25%, from 6.74 ± 0.38 to 5.06 ± 0.17 ml/min, P < 0.001. Total renal vascular resistance was significantly increased during BKA infusion, P < 0.001. Vehicle infusion for the same period had no significant effect on GFR, RPF, or renal vascular resistance. These findings further support the hypothesis that increased renal production of kinins contributes to the renal vasodilation of diabetes.

Sperm motility on postcoital testing correlates with male autoimmunity to sperm

To assess whether or not immunologic factors in husbands, wives, or both, influence the motility of sperm in the female reproductive tract, hemagglutination and cytotoxicity sperm antibody (Ab) assays and postcoital tests (PCTs) were performed in 293 infertile couples. More couples without male autoimmunity to sperm (64% of 66; P less than 0.001) had greater than or equal to 10 motile sperm per high power field (adequate PCT), as compared with 26% of 122 couples with untreated male autoimmunity, 19% of 77 couples with corticosteroid-treated male autoimmunity without a pregnancy, and 36% of 28 couples with successfully treated male autoimmunity to sperm. Good correlation was obtained among pregnancy achievement, lack of sperm antibodies, and adequate sperm motility in the PCT (P less than 0.0001). Sperm motility in the PCT correlated positively with sperm motility in the semen and inversely with cytotoxic sperm Ab in the serum and seminal plasma of men and women and hemagglutinating sperm Ab in the cervical mucus samples. Sperm motility in the PCT has a predictive value of 72% for male autoimmunity and 57% for female isoimmunity to sperm in the presence of normal cervical mucus and in the absence of infections.

Human Papilloma Virus (HPV)-E6/E7 and Epidermal Growth Factor Receptor (EGF-R) Protein Levels in Cervical Cancer and Cervical Intraepithelial Neoplasia (CIN)

BACKGROUND: About 90% of cervical cancers and advanced cervical intraepithelial neoplasia (CIN II/III) are squamous epithelial cells with mRNA for human papillomavirus (HPV)16 and 18 and up‐regulated epidermal growth factor receptor (EGF‐R). Since presence of proteins rather than mRNA may be truly indicative of active infection or disease progression, establishing reliable methods for quantifying these proteins in cervical biopsies is important.
 METHOD: We have established an objective semi‐quantitative immunofluorescent antibody assay to reliably assess the levels of HPV‐E6/E7 and EGF‐R proteins in the cervical biopsies from 12 normal women, five women with CIN I, 15 with CIN II/III and ten with cervical cancer.
 RESULTS: HPV‐E6/E7 and EGF‐R, when present, were specific to para‐basal, basal and squamous epithelial cells (negative in stromal cells). Nine of ten women with cervical cancer and 15 (14 CIN II/III; 1 CIN I) of 20 women with CIN were positive for HPV‐E6/E7. All 12 controls were HPV‐negative. The controls and six women with CIN (four with CIN I) negative for HPV had low levels of EGF‐R. The only exception was one woman with cervical cancer negative for HPV, with high levels of EGF‐R. Levels of HPV‐E6/E7 and EGF‐R were significantly higher (P<0.001 vs. controls) in women with advanced CIN II and III (P<0.05 vs. controls in CIN I) and cervical cancer. The HPV‐E6/E7 and EGF‐R levels correlated significantly (r=18.98; P<0.001, by linear regression analysis).
 CONCLUSION: We have established a highly specific and sensitive semi‐quantitative immunofluorescent antibody assay for measuring levels of HPV‐E6/E7 proteins and EGF‐R in archival cervical biopsies. Our data suggest an association between HPV‐E6/E7 and EGF‐R.

Morphometric discrimination of melanoma in situ of sun-damaged skin from chronically sun-damaged skin

BACKGROUND The histologic discrimination of melanoma in situ of sun-damaged skin (MIS) from chronically sun-damaged skin (SDS) can sometimes be difficult using accepted criteria. OBJECTIVE We evaluated these entities by means of morphometry and multifactorial analysis. METHODS We measured the number and area of melanocyte nuclei, melanocyte nucleoli, stratum spinosum keratinocyte nuclei, and papillary dermal lymphocyte nuclei from hematoxylin-eosin-stained slides representing 38 cases of MIS and 18 cases of SDS matched for age, sex, and site with a high-resolution digital imaging and analysis system. RESULTS Multiple logistic regression analysis correctly classified 100% of the cases using the number of melanocytes per 0.5 mm and the maximum melanocyte nuclear area divided by the maximum keratinocyte nuclear area. The strongest results were achieved measuring approximately 1 mm of epidermis. CONCLUSION Morphometry and multifactorial analysis can distinguish MIS from SDS. Morphometric analysis of melanocytic proliferations may be useful at the margins of surgical resections.

Levels of Transferrin and Alpha 2-HS Glycoprotein in Women with and without Endometriosis

The study objective was to test the hypothesis that elevated levels of transferrin and alpha 2-HS glycoprotein occur in the peritoneal environment of patients with endometriosis that may lead to the observed autoimmunity to these proteins. We set up a double sandwich enzyme-linked immunosorbent assay (ELISA) for measuring levels of transferrin and alpha 2-HS glycoprotein in the serum and peritoneal fluid samples from women with (n = 24-60) and without endometriosis (n = 35-49). Serum and peritoneal fluid levels of alpha 2-HS glycoprotein and peritoneal fluid levels of transferrin were significantly elevated in patients with endometriosis, in contrast to the controls. Serum levels of transferrin in patients, however, were significantly less in the patients than in controls. We conclude that transferrin and alpha 2-HS glycoprotein are present at high concentrations in the peritoneal fluids of patients with endometriosis. This may play a significant role in the autoimmune pathophysiology of endometriosis.