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.

Cervical motion after adding a posterior pad to the halo vest.

Investigators have shown that significant segmental motion occurs in patients immobilized in halo vests. One cadaver study showed that this is decreased with a posterior pad added to the construct. To improve nonoperative care of patients with cervical trauma, segmental cervical motion was evaluated in normal volunteers immobilized in a halo vest with and without a posterior pad. Two commonly used methods to measure sagittal angulation were used. Thirty normal volunteers were placed in halo vests by using positioning pins on the cranium. A sphygmomanometer attached to the posterior uprights of the vest inflated to 40 mm Hg was used as a posterior pad at the greatest visible lordosis. Lateral radiographs of the cervical spine were taken with volunteers in the upright and supine positions with and without the posterior pad inflated. Radiographs were randomly sorted and were each read twice by 3 readers. Measurements of the posterior atlantodental interval, sagittal displacement, and sagittal rotation were recorded using 2 different methods: the Buetti-Bauml method, which uses lines drawn along the posterior vertebral bodies, and the method of White and colleagues, which uses lines drawn along the inferior vertebral bodies. Inflation status of the pad showed no statistically significant difference in any of the measured variables. This was true for both methods of measurement. Application of a posterior pad to the halo vest did not show any change in the segmental motion of the cervical spine in normal volunteers.

Surgery versus radiation therapy for patients with aggressive fibromatosis or desmoid tumors: A comparative review of 22 articles.

BACKGROUND: Desmoid tumors (aggressive fibromatoses) are benign neoplasms with high rates of recurrence after surgery. Radiotherapy is sometimes reported to prevent recurrences, but not in all studies. In order to evaluate the effect of radiation, comparative analysis was performed. METHODS: The authors conducted a MEDLINE search and collected all articles in the English language on the treatment of "desmoid tumor" or "aggressive fibromatosis" from the years 1983-1998. They categorized treatment into three groups: surgery alone (S), surgery with radiotherapy (S + RT), or radiotherapy alone (RT). The S and S + RT groups were each subdivided according to whether margins were free (-), positive (+), or unknown. Each subgroup was divided into cases with primary, recurrent, or unknown tumor. RESULTS: The local control rates after treatment for cases in the S group with (-) margins, (+) margins, and overall were 72%, 41%, and 61%, respectively. For the S + RT group the local control results were 94%, 75%, and 75%, respectively, significantly different when compared with the results for the S group. For the RT group, the local control was 78%, significantly superior to that of the S group (61%). Cases with primary and recurrent tumors had significantly superior local control rates with S + RT or RT versus S. Radiotherapy complications noted were fibrosis, paresthesias, edema, and fracture. CONCLUSIONS: RT or S + RT results in significantly better local control than S. Even after dividing the groups into cases with free and positive margins and cases with primary and recurrent tumors, the best local control is achieved with RT or S + RT.

Non-ophthalmologist screening for retinopathy of prematurity.

AIM: To determine if a non-ophthalmologist can accurately screen for retinopathy of prematurity (ROP) by evaluating the posterior pole blood vessels of the retina. ROP is a common ocular disorder of premature infants and may require multiple screening examinations by an ophthalmologist to allow for timely intervention. Since there is a strong correlation between posterior pole vascular abnormalities and vision threatening ROP, screening examinations performed by non-ophthalmologist may yield useful clinical information in high risk infants. METHODS: Infants born at the Medical University of South Carolina who met screening criteria (n = 142) were examined by a single non-ophthalmologist using a direct ophthalmoscope to evaluate the posterior pole blood vessels for abnormalities of the venules and/or arterioles. To determine the accuracy of the non-ophthalmologist's clinical observations, infants were also examined by an ophthalmologist, using an indirect ophthalmoscope, who graded the posterior pole vessels as normal, dilated venules, or dilated and tortuous venules and arterioles (including "plus disease"). RESULTS: There was significant correlation (p <0.001) between the non-ophthalmologist's and ophthalmologist's diagnoses of posterior pole vascular abnormalities. 47 infants had normal posterior pole blood vessels by the non-ophthalmologist examination. Of these, 31 (66%) were considered to have normal vessels and 16 (34%) to have dilated venules by the ophthalmologist. The non-ophthalmologist correctly identified abnormal posterior pole vessels in all 21 infants diagnosed with abnormal arterioles and venules by the ophthalmologist. No infants with clinically important ROP ("prethreshold" or worse) would have failed detection by this screening method. CONCLUSION: Using a direct ophthalmoscope, a non-ophthalmologist can screen premature infants at risk for ROP by evaluating the posterior pole blood vessels of the retina. While not necessarily recommended for routine clinical practice, this technique may nevertheless be of value to those situations where ophthalmological consultation is unavailable or difficult to obtain.

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.

Postdural puncture headache in paediatric oncology patients.

PURPOSE: Previous studies have not determined the correlation between dural puncture and postural headache in paediatric patients. Furthermore, no studies have evaluated the correlation between atypical headache and dural puncture in the paediatric population. Therefore, we prospectively analyzed the incidence of typical postdural puncture headache (PDPHA) and atypical headache in paediatric oncology patients following dural puncture. METHODS: The study population consisted of 66 paediatric patients undergoing 128 consecutive procedures, including 99 lumbar punctures and 29 bone marrow aspirations without concomitant lumbar puncture. Patients were prospectively randomized into four groups: Group I, preteens (< 13 yr) undergoing lumbar puncture, Group II, adolescents (13-21 yr) undergoing lumbar puncture, Group III, preteens undergoing bone marrow aspiration, and Group IV, adolescents undergoing bone marrow aspiration. The presence and description of headache was documented immediately after dural puncture or bone marrow aspiration, and on post-procedure days # 1, 3 and 5 by personnel blinded to the type of procedure. RESULTS: There was an increase in the incidence of headache (9.1%) after lumbar puncture in patients < 21 yr relative to patients undergoing bone marrow aspiration (P < 0.05). No difference was found between the incidence of typical PDPHA after dural puncture in preteens and adolescents. There was also no difference in the incidence of atypical headache after dural puncture or after bone marrow aspiration among preteens and adolescents. CONCLUSIONS: Paediatric patients experience an increased incidence of typical postdural puncture headache after dural puncture compared with age-matched patients undergoing bone marrow aspiration only. Atypical headache is relatively common in the paediatric population after dural puncture or bone marrow aspiration.

Levels of antibodies to transferrin and alpha 2-HS glycoprotein in women with and without endometriosis.

PROBLEM: To establish an enzyme-linked immunosorbent assay (ELISA) for determining the levels of antibodies to transferrin and alpha 2-HS glycoprotein in the serum of women with and without endometriosis. METHOD OF STUDY: Serum samples were obtained from 105 normal women, who were randomly selected for a population-based epidemiologic study, and 123 patients with active endometriosis. An ELISA using transferrin and alpha 2-HS glycoprotein as antigens was established. RESULTS: The levels of antibodies to transferrin and alpha 2-HS glycoprotein in the serum of patients with endometriosis were approximately 21 times higher than those in the serum of control subjects without endometriosis. Only 2% of control subjects had false positive levels of these antibodies, and 5% of patients with endometriosis had false negative levels of these antibodies (specificity, 98.1 and 98.1, respectively, for anti-transferrin and anti-alpha 2-HS glycoprotein; sensitivity, 95 and 96.7, respectively, for anti-transferrin and anti-alpha 2-HS glycoprotein). CONCLUSIONS: Patients with endometriosis have significantly higher levels of antibodies to transferrin and alpha 2-HS glycoprotein than control subjects. Testing women for antibodies to transferrin and alpha 2-HS glycoprotein will provide a specific noninvasive diagnosis of endometriosis.

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.

The body mass index-mortality relationship in white and African American women.

OBJECTIVE: To examine the association of body mass index to all-cause and cardiovascular disease (CVD) mortality in white and African American women. RESEARCH METHODS AND PROCEDURES: Women who were members of the American Cancer Society Prevention Study I were examined in 1959 to 1960 and then followed 12 years for vital status. Data for this analysis were from 8,142 black and 100,000 white women. Body mass index (BMI) was calculated from reported height and weight. Associations were examined using Cox proportional hazards modeling with some analyses stratified by smoking (current or never) and educational status (less than complete high school or high school graduate). RESULTS: There was a significant interaction between ethnicity and BMI for both all-cause (p<0.05) and CVD mortality (p<0.001). BMI (as a continuous variable) was associated with all-cause mortality in white women in all four groups defined by smoking and education. In black women with less than a high school education, there were no significant associations between BMI mortality. For high school-educated black women, there was a significant association between BMI and all-cause mortality. Among never smoking women with at least a high school education, models using the lowest BMI as the reference indicated a 40% higher risk of all-cause mortality at a BMI of 35.9 in black women vs. 27.3 in white women. DISCUSSION: The impact of BMI on mortality was modified by educational level in black women; however, BMI was a less potent risk factor in black women than in white women in the same category of educational status.

Effects of antibodies to transferrin and alpha 2-HS glycoprotein on in vitro sperm motion: implications in infertility associated with endometriosis.

PROBLEM: Women with endometriosis have antibodies to endometrial transferrin and alpha 2-HS glycoprotein in their serum and peritoneal fluid. The objective of this study was to determine whether antibodies to transferrin and alpha 2-HS glycoprotein adversely affect sperm motility and survival. METHOD OF STUDY: Spermatozoa obtained from normal fertile donors and washed free of seminal plasma were incubated with the medium (control), 1:2 and 1:100 dilutions of antitransferrin, 1:4, 1:8 and 1:100 dilutions of anti-alpha 2-HS glycoprotein, and a 1:2 dilution of antialbumin antiserum (negative control). Sperm motion characteristics in 10 microliters aliquots were evaluated at 30 min, 1 hr, 2 hr, 4 hr, and 24 hr using computerized sperm motion analysis. A paired t-test was done to analyze the effects of the various antibodies on sperm motion characteristics. RESULTS: Antibodies to albumin failed to adversely affect sperm motility in general or the several sperm motion characteristics in particular. In contrast, antibodies to transferrin at the dilution of 1:2 adversely affected the percentage of motile and rapid spermatozoa, progressive and path velocities, straightness, linearity, track speed, and anterior-lateral head displacement (P < 0.001) at all the time intervals, whereas a 1:100 dilution of this antiserum adversely affected these parameters only at 24 hr. Elongation and beat cross-frequency were significantly affected at 4 and 24 hr by a 1:2 dilution of antitransferrin antiserum. The effects of anti-alpha 2-HS glycoprotein were more pronounced than those of antitransferrin, but they were similar. Dilutions of 1:4 and 1:8 were effective at all time intervals, whereas a 1:100 dilution was effective in reducing the track speed and the percentage of rapid cells at 24 hr (P < 0.001). CONCLUSION: Antibodies to endometrial transferrin and alpha 2-HS glycoprotein present in the peritoneal fluid, and possibly in the oviductal fluid, of patients with endometriosis may adversely affect postcoital sperm motility and sperm survival.

Interobserver reliability of digital and endovaginal ultrasonographic cervical length measurements.

OBJECTIVE: Our purpose was to prospectively evaluate the interobserver reliability of digital and endovaginal ultrasonographic cervical length measurements. STUDY DESIGN: Forty-three women were recruited from our antepartum clinic to participate in this study. Two independent and blinded digital cervical examinations were performed by the first author and a second examiner. Instructions were given to estimate the cervical length in millimeters. After micturition endovaginal ultrasonographic cervical length measurements were performed by two independent, blinded registered diagnostic medical sonographers. Cervical lengths were compared with the Student t test and Pearson's correlation coefficient. A kappa statistic was calculated for interobserver reliability at three levels of agreement +/- 1 mm, +/- 4 mm, and +/- 10 mm. Data are expressed as means +/- SD. RESULTS: Digital cervical lengths were not different between the two examiners (18.7 +/- 4.8 mm, 20.5 +/- 6.2 mm) nor between the two ultrasonographic measurements (38.6 +/- 6.1 mm, 39.2 +/- 5.4 mm). The digital cervical lengths agreed (+/- 1 mm) 35% of the time (R2 0.10, p = 0.02). The endovaginal ultrasonographic measurements agreed (+/- 1 mm) 74% of the time with a stronger correlation (R2 0.53, p = 0.0001). The kappa statistic for interobserver variability was marginal for both digital and endovaginal cervical length measurements when agreement was defined as +/- 1 mm. Endovaginal ultrasonography was significantly more reliable than digital examination when agreement between examiners was defined as either +/- 4 mm or +/- 10 mm. CONCLUSION: Although both digital and endovaginal ultrasonographic cervical length measurements show correlation between examiners, endovaginal ultrasonography is significantly more reliable when agreement is defined as > or = +/- 4 mm. Serial cervical length measurements to predict preterm labor will be enhanced by the interobserver reliability of endovaginal ultrasonography.

Prediction equations do not eliminate systematic error in self-reported body mass index.

Epidemiological studies of the risks of obesity often use body mass index (BMI) calculated from self-reported height and weight. The purpose of this study was to examine the pattern of reporting error associated with self-reported values of BMI and to evaluate the extent to which linear regression models predict measured BMI from self-reported data and whether these models could compensate for this reporting error. We examined measured and self-reported weight and height on 5079 adults aged 30 years to 64 years from the second National Health and Nutrition Examination Survey. Measured and self-reported BMI (kg/m2) was calculated, and multiple linear regression techniques were used to predict measured BMI from self-reported BMI. The error in self-reported BMI (self-reported BMI minus measured BMI) was not constant but varied systematically with BMI. The correlation between measured BMI and the error in self-reported BMI was -0.37 for men and -0.38 for women. The pattern of reporting error was only weakly associated with self-reported BMI, with the correlation being 0.05 for men and -0.001 for women. Error in predicted BMI (predicted BMI minus measured BMI) also varied systematically with measured BMI, but less consistently with self-reported BMI. More complex models only slightly improved the ability to predict measured BMI compared with self-reported BMI alone. None of the equations were able to eliminate the systematic reporting error in determining measured BMI values from self-reported data. The characteristic pattern of error associated with self-reported BMI is difficult or impossible to correct by the use of linear regression models.

Dimensions of the pediatric crystalline lens: implications for intraocular lenses in children.

As surgeons gain more experience with the implantation of posterior chamber intraocular lenses (IOLs) into the capsular bag in children, the minimum age for which implantation is advised may continue to be lowered. Accurate sizing of an IOL intended for in-the-bag fixation may depend on knowledge of the size of the capsular bag. In order to develop a growth curve for the normal crystalline lens and hence the capsular bag, 50 pediatric autopsy eyes ranging in age from 1 day to 16 years were obtained postmortem and measured within 24 hours after enucleation. Mean crystalline lens diameter was 6.00 mm at birth, 6.80 mm at 2 months, 7.1 mm at 3 months, 7.66 mm at 6 to 9 months, 8.4 mm at 21 months, 8.5 mm at 2 to 5 years, and 9.3 mm at 16 years. The post-lensectomy capsular bag size at each respective age is 1 mm larger. While age was a predictor of crystalline lens size, corneal diameter and globe axial length were better predictors of crystalline lens size. These data and accompanying linear regressions may be helpful in designing appropriate IOLs for pediatric patients.

Intrasubject variability of the pressure-transmission ratio in patients with genuine stress incontinence.

The aim of the study was to determine the intrasubject variability of the pressure-transmission ratio (PTR) with various cough intensities in subjects with genuine stress incontinence. Thirty-six patients with genuine stress incontinence underwent multichannel urodynamics and had a series of pressure-transmission ratios (PTRs) determined with the urethral transducer placed at the point of the maximal closure pressure. Patients were asked to cough with increasing intensities and three to four different cough-induced PTRs were recorded for each subject. The data were analysed using regression analysis, repeated measures analysis of variance and comparison of variance. The PTRs showed a high degree of variability within subjects. The mean within subject standard deviation was 18.5%. The effect of parity, maximal urethral closure pressure and age were insignificant on the variability. Cough intensities of greater than 90 cmH2O have a lesser degree of variability. The mean PTR across all cough intensities was fairly constant in the 82%-87% range. It was concluded that the PTR in an individual has a high degree of variability independent of cough intensity, and cannot be relied upon as a diagnostic measure in subjects with genuine stress incontinence. However, the PTR for the population as a whole was consistent across all cough intensities.

Can non-ophthalmologists screen for retinopathy of prematurity?

BACKGROUND: Dilation and tortuosity of the posterior pole vessels ("plus disease") is a poor prognostic sign and may indicate the presence of threshold or pre-threshold retinopathy of prematurity (ROP). Because stage 3 ROP appears rarely in the absence of posterior pole vascular abnormalities, we prospectively evaluated the ability of non-ophthalmologists (4th-year medical students, pediatric residents, and nurse practitioners) to identify abnormalities in the retinal blood vessels of infants undergoing examinations for ROP. METHODS: Fifty infants weighting less than 1600 g at birth were examined between 32 and 40 weeks after conception. Prior to ophthalmological examination, non-ophthalmologist examiners graded posterior pole vessels as normal or abnormal based on ophthalmoscopic appearance. One hundred twenty-one ocular examinations were performed using the teaching mirror of the indirect ophthalmoscope, 179 using the direct ophthalmoscope. The indirect ophthalmoscopy was performed simultaneously by an ophthalmologist who evaluated the posterior pole vessels for abnormalities prior to conducting a peripheral fundus examination on either eye. RESULTS: Testing sensitivity for the non-ophthalmologist examiners using direct and indirect ophthalmoscopy was 96% and 92%, respectively. Combining the results from direct and indirect ophthalmoscopy, the Clopper-Pearson 95% sensitivity confidence interval for identifying abnormal arterioles and venules was 82% to 99%, with a point estimate of 95%. CONCLUSION: These data suggest that non-ophthalmologist examiners can detect posterior pole vascular abnormalities in premature infants. If properly trained, they could possibly play a role in screening or follow-up examinations for ROP.

Skin color and cancer mortality among black men in the Charleston Heart Study.

The association between skin color and 30-year cancer mortality in a random sample of black men and a peer-nominated group of high socioeconomic status (SES) black men was evaluated in the Charleston Heart Study, a prospective study, begun in 1960, designed to investigate the epidemiology of coronary heart disease in a biracial cohort. Skin color was used as a continuous variable and as a categorical variable, by tertiles, in a Cox proportional hazards regression model. In the high SES group, there was a statistically significant decreasing relationship between skin color and cancer mortality, with those having the lightest skin having the lowest cancer mortality. In the random sample of black men, the relationship between skin color and cancer mortality was not statistically significant; however, the data indicated a slight protective effect among those with the lightest skin color. Because degree of skin reflectance is a measure of black-white admixture, these results may indicate a genetic mechanism underlying the differences in cancer mortality across skin color groups. Skin color is also recognized as a marker for psychosocial factors. Therefore, poor prognosis among those with darker skin color as a result of failure of early detection, inadequate treatment, and a variety of psychosocial stressors represents an alternative explanation of the study findings.

The effect of nicotine on in vitro sperm motion characteristics.

UNLABELLED: PURPOSE AND STUDY PLAN: Men who are habitual smokers tend to have poor semen quality. We studied the effect of nicotine on sperm motility in vitro. Spermatozoa from 13 normal fertile nonsmoking donors, washed free of seminal plasma, were treated with medium alone (control); and, 10 mM, 5 mM, 1 mM and 0.1 mM nicotine (concentrations estimated to approximate residual concentrations of nicotine in the testes of heavy smokers). Computerized sperm motion analysis (CASA) was done at 2, 4, 6 and 24 h after incubation. RESULTS: Sperm motility, beat/cross frequency, linearity and maximum anterior lateral head displacement (ALH max.) were significantly decreased across nominal dosages (P < 0.001 by repeated measures analysis of variance). Of the concentrations tested, 0.1 mM had no effect; 1 mM significantly decreased sperm motility (P = 0.003) and linearity (P = 0.02); 5 mM decreased the beat frequency (P = 0.001) and linearity (0.02); and 10 mM markedly decreased motility (P = 0.0001), beat frequency (P = 0.0002), linearity (P = 0.02) and ALH max. (P = 0.02). The interactions between dose and time were insignificant. CONCLUSION: Nicotine at concentrations of > or = 1 mM significantly decreased sperm motion characteristics after different periods of incubation, whereas 0.1 mM concentration had the least effect.

The predictive value of posterior pole vessels in retinopathy of prematurity.

Dilation and tortuosity of the posterior pole vessels "(plus disease)" is a sign of poor prognosis and may be associated with threshold or prethreshold retinopathy of prematurity (ROP). We have found that normal posterior pole vessels are a reliable marker for the absence of stage 3 ROP. One hundred thirty-two consecutive premature infants weighing less than 1600 g at birth underwent ROP examinations between 32 and 40 weeks' postconceptional age. The status of the posterior pole vessels was compared to peripheral retinal pathology. Vascular findings in the posterior pole were graded 0, 1, 2, or 3, with 0 representing normal arterioles and venules and 3 representing plus disease. The remainder of the fundus examination was recorded using the international Classification of ROP, then converted to a severity scale based on zone and stage of ROP. For each infant, only one examination representing the most severe stage of ROP reached prior to treatment or spontaneous regression was used for data analysis. There was a highly significant Spearman's rank correlation (rs = 0.65) between the posterior pole vascular abnormalities and the severity of ROP in the retinal periphery. Clinically important ROP was not found in any patient with normal posterior pole vessels (grade 0) and stage 3 disease was usually associated with both venous and arterial vascular abnormalities (grades 2 or 3). When ocular examination of premature infants is difficult because of poor dilation of the pupil, hazy media, or medical instability, normal appearance of the posterior pole vessels can be a reassuring finding if it is necessary to postpone complete fundus examination in infants at risk for ROP.

Effects of nicotine on sperm attachment and penetration of zona-free hamster eggs.

A previous study from this laboratory showed that nicotine in vitro has deleterious effects on sperm motion characteristics. This study was conducted to evaluate the effects of nicotine on the ability of human spermatozoa to attach and penetrate zona-free hamster eggs. Spermatozoa from fertile donors, washed free of seminal plasma, were incubated with medium (control) and 0.1, 1, 5, and 10 mM concentrations of nicotine (concentrations estimated to approximate residual concentrations of nicotine in the testes of heavy smokers) for 18 h at 37 degrees C in a humid 5% carbon dioxide incubator. The sperm preparations were then mixed with enzymatically denuded hamster eggs and incubated for 3 h at 37 degrees C. The oocytes were examined by phase-contrast microscopy to enumerate the rates of sperm attachment and penetration. The data were analyzed by a paired t test and repeated measures analysis of variance using the arcsine transformation of the percentages. The percentages of eggs with attached spermatozoa significantly declined in a dose-dependent manner, the highest inhibition being at 10 mM (F = 24). The rate of sperm penetration was even more significantly decreased with the increase in nicotine concentrations in the following order: 10 mM (F = 56) > 5 mM (F = 30) > 1 mM (F = 44) > 0.1 mM (F = 12). Nicotine concentrations of 0.1 mM and above negatively affected sperm penetration of zona-free hamster eggs.

Kinin, a mediator of diabetes-induced glomerular hyperfiltration.

Renal kallikrein is increased in diabetic patients and streptozotocin (STZ)-induced diabetic rats with hyperfiltration. 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 hyperfiltration, renal kallikrein excretion rate was significantly increased (P < or = 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 micrograms.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 < or = 0.001 (means +/- SE). RPF was reduced by 25%, from 6.74 +/- 0.38 to 5.06 +/- 0.17 ml/min, P < or = 0.001. Total renal vascular resistance was significantly increased during BKA infusion, P < or = 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.