Nuclear roundness factor and local failure from definitive radiation therapy for prostatic carcinoma.

Of 375 patients with prostatic carcinoma treated definitively with radiation therapy at this institution with at least a 5 year follow-up, 23 patients failed locally only, 72 failed with distant metastasis only, 60 had both local and distant failure, while 220 showed no evidence of disease. In search for a possible marker for local failure following radiation therapy, we examined several nuclear morphometric parameters which have been shown to correlate with the biologic aggressiveness of this disease. The 23 locally failed only patients were matched with 23 no evidence of disease patients for stage, grade, treatment modality, prior surgery, age at diagnosis and race. Archival hematoxylin and eosin slides were obtained for 22 of the 23 matched pairs, and morphometric features, including nuclear roundness factor and nuclear area, as well as numbers of nucleoli were assessed using computer-assisted image analysis in both tumor cells and normal prostatic epithelium. Tumor nuclei from the locally failed only patients had significantly higher nuclear roundness factor values (p = 0.0089) compared with tumor cells from no evidence of disease patients. Analysis of these data by clinical stage demonstrated no significant differences between the locally failed only and no evidence of disease patients. Likewise, there were no significant differences in nuclear roundness factor values of locally failed only and no evidence of disease patients with poorly or moderately well-differentiated tumors. However, there was a highly significant difference (p = 0.0012) in the nuclear roundness factor values of locally failed only and no evidence of disease patients with well-differentiated tumors. Thus, there appears to be a subset of patients with well-differentiated adenocarcinoma of the prostate who have significantly more irregular tumor nuclei and who fail locally only following definitive radiation therapy.

Are three substages of clinical B prostate carcinoma useful in predicting disease-free survival?

The B1 nodule, a 1.5 cm area of induration surrounded on at least two sides by prostatic tissue of normal consistency, was defined by Jewett in 1968 as the stage of prostatic cancer best suited for treatment and cure by radical prostatectomy (RP). The area of prostatic induration suitable for RP was subsequently extended to less than one lobe (Stage B1); this extension of induration was supported by the study of Walsh and Jewett in 1980 showing a 51 percent survival free-of-disease at fifteen-year follow-up. Subsequently, clinical staging systems evolved which substaged clinical B into three categories of induration: B1N = less than 1.5 cm nodule, B1 = greater than 1.5 cm but less than one lobe, and B2 = one lobe or both lobes. To determine if digital assessment of these progressively greater degrees of induration would translate into different intervals to first progression, whether local or distant, we reviewed prostate diagrams and descriptions of all Stage B patients treated by Iodine-125 interstitial implant and external beam radiation therapy between 1974 and 1985 at our institution. Forty-six patients had B1 nodules, 78 patients B1 (less than one lobe), and 52 patients B2 (one lobe or greater). Mean follow-up was fifty-five months. We found B1N, which was also associated with well-differentiated grade and a normal acid phosphatase, to have the longest interval to progression.

Possible role of pure human follicle-stimulating hormone in the treatment of severe male-factor infertility by assisted reproduction: preliminary report.

OBJECTIVE: Experimental clinical trial assessing the potential of systemic follicle-stimulating hormone (FSH) to improve sperm fertilizing ability in in vitro fertilization (IVF). DESIGN: Retrospective clinical evaluation of severe male factor patients failing fertilization in IVF or showing severe sperm defects. SETTING: Academic tertiary clinical care unit. PATIENTS, PARTICIPANTS: Fourteen patients (41 cycles) who failed IVF, 22 patients (32 cycles) with severe quantitative and qualitative semen abnormalities indicating poor fertilization. TREATMENT: FSH 150 U IM three times a week for 3 months. MAIN OUTCOME MEASURE(S): Pretreatment and post-treatment evaluation of endocrine profile, basic semen analysis, and fertilization and pregnancy rates. HYPOTHESIS: FSH treatment may improve spermatogenesis quality by its multiple actions on the Sertoli-gamete cell compartment without interfering with testicular hormonogenic function. RESULTS: No significant changes were observed in the endocrine profile or in semen parameters; individual cases showed improvements in sperm concentration and motility. Significant increase in fertilization rate of preovulatory oocytes was demonstrated; seven term pregnancies were achieved. CONCLUSIONS: A multicenter randomized, double-blind trial with crossover is needed to demonstrate the benefit of systemic FSH administration and if this effect is FSH exclusive.

Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age.

A study of 1,478 consecutive in vitro fertilization (IVF) cycles was made to determine if basal follicle-stimulating hormone (FSH) levels and age were independent predictors of IVF performance. Regression analyses indicated independent contributions of both basal FSH and age in predicting cancellation rate, peak estradiol, number of oocytes retrieved, fertilized, and transferred, and total and ongoing pregnancy rates. Miscarriage rate was unrelated to both age and basal FSH. Follicle-stimulating hormone level was a better predictor than age for all outcome variables examined and remained a significant predictor after accounting for age, etiology of infertility, and semen quality. The combined use of age and basal FSH in counseling patients improves the accuracy of prognosis, and may provide an index of functional ovarian reserve ("ovarian age").

Relationship between morphology and motion characteristics of human spermatozoa in semen and in the swim-up sperm fractions.

In this study, the authors evaluated the morphology pattern and motion characteristics of human spermatozoa before and after swim-up separation. Samples were divided into two, morphologically different groups according to the percentage of normal sperm forms assessed by the strict criteria of the Norfolk laboratory: "good"(G) and "poor" (P) prognosis patterns. The percentages of normal forms, slightly abnormal forms, and severe head defects were significantly different in the two groups. Motile characteristics were analyzed by a computerized semen analyzer with constant parameter settings. Before swim-up there were no significant differences in semen volume, percentage of neck and tail defects, concentration, or percentage of motility and linearity, but the mean velocity was higher in group G. After swim-up the percentage of motility, total number of motile cells, and recovery rate were higher for group G, and the incidence of severe head defects correlated negatively with the percentage of cells with a velocity of greater than 80 microns/sec. The results suggest that patients with a high incidence of sperm head defects have impaired original velocity, and swim-up selects for velocity as well as normal forms and motility. Although motility and velocity improved substantially after swim-up, the recovery rate and percentage of motility were significantly lower in the P group.

Grief reactions of mothers of adolescents and young adults with traumatic brain injury.

One hundred and two mothers of adolescents and young adults with traumatic brain injury completed a modified Grief Experience Inventory (GEI) (Sanders, Mauger, & Strong, 1985) and rated their child's functioning on a modified Neurobehavioral Rating Scale (NRS) (Levin et al., 1987). More severe grief was reported by mothers who rated their children as having poor neurobehavioral functioning and by mothers of young adult rather than adolescent patients. The guilt component of grief varied significantly across the 3-year post-injury period measured in the study. Historical comparisons of these respondents with other bereaved populations showed that mothers of adolescent and young adults with head injury reported more intense grief than parents who had experienced other significant non-death losses.

Intentional iron overdose in pregnancy--management and outcome.

The objectives of our study were to 1) determine if peak maternal serum iron level or toxicity stage after intentional overdose is associated with adverse maternal-fetal outcome, and 2) describe the use of deferoxamine antidote therapy in obstetric patients. A computer search of the English language literature from 1966-1998 used the key words iron toxicity, iron poisoning, deferoxamine, and pregnancy to identify peer-reviewed papers reporting intentional iron overdoses in pregnancy. Two investigators independently extracted data from articles and their references including stage of toxicity (0 = asymptomatic, 1 = gastrointestinal symptoms, 2 = metabolic disturbance, 3 = organ failure), with differences resolved by consensus. Statistical analysis used the Student t-test, Fisher exact test, or ANOVA, as appropriate. Fourteen publications were identified, describing 61 cases of obstetric iron overdose, including one recent case at our institution. Compared with women who had lower peak levels, women with peak serum iron levels > or =400 mcg/dL were more frequently symptomatic (12/13 vs. 5/10, respectively, p = 0.05). Peak iron level > or =400 mcg/dL was not associated with increased risk of spontaneous abortion, preterm delivery, congenital anomalies, or maternal death. However, patients with stage 3 toxicity were more likely to spontaneously abort (1/3 vs. 1/56, respectively), deliver preterm (2/3 vs. 6/56, respectively), or experience maternal death (3/3 vs. 0/56, respectively). The proportions of patients treated with deferoxamine and total dosages of deferoxamine were similar by peak iron level (> or =400 vs. <400 mcg/dL) and toxicity stage (0-3). Peak iron levels > or =400 mcg/dL are associated with symptomatic iron overdose. Stage 3 toxicity is associated with spontaneous abortion, preterm delivery, and maternal death.

Graviceptor development in jellyfish ephyrae in space and on Earth.

Graviceptor (rhopalium) development in Aurelia aurita ephyrae which developed on Earth and in space during the nine-day NASA SLS-1 mission was compared. The space-developed ephyrae made graviceptors which were morphologically similar to those of their ground-based controls. Rhopalia of both groups developed statocysts with statoliths, ocelli, ciliated mechanoreceptor cells, and immature touch-plates with one type of hair cell. The number of rhopalia formed per arm of ephyrae of both groups revealed no significant differences. The number of statoliths formed per rhopalium was statistically higher in ephyrae which were induced to form in space with iodine than in L(Launch)+8h controls. Statolith numbers were not significantly different between Earth-formed control ephyrae and those formed from polyps induced on Earth and then sent into space 24h and 48h later. Statolith loss from rhopalia was significantly enhanced in the space-maintained ephyrae in ASW as compared to their controls. Ephyrae formed through thyroxine treatment and those maintained in thyroxine in space had statolith numbers comparable to thyroxine-treated controls. Pulsing abnormalities seen in some space-developed ephyrae suggest that some space-formed ephyrae may have developed abnormal rhopalia because normal rhopalia development and function is necessary for normal pulsing.

A military application of a medical self-care program.

The cost of health care is a growing concern to the military. Many military clinic appointments and emergency department visits are unnecessary; they are for minor, self-limiting illnesses and injuries that could be treated at home. Military health care can no longer afford the luxury of treating minor illnesses and injuries in the hospital setting. This paper examines one method for military beneficiaries to obtain health care services appropriately. A selected group of military family members received a medical self-care book and an education session, which resulted in more appropriate decision-making about when to use the health care system. This was a 6-month, experimental study using control and experimental groups, with surveys before and after the study period. The self-care book was used 628 times to help make more informed decisions about when to seek medical care. The mean number of clinic and emergency room visits (p = 0.02) decreased for those using the medical self-care book.

Twin vaginal birth after cesarean.

OBJECTIVE: To determine both success rate and maternal-fetal outcome of vaginal birth after cesarean in twin gestations. METHODS: We identified all women from a single center attempting vaginal birth of twins after cesarean from 1988-98. Twin pairs were excluded for delivery < or = 25 weeks gestation, monoamnionicity, nonvertex twin A, or major anomaly or death of either twin. Cases were matched to the next three consecutive twin gestations attempting vaginal delivery without a prior cesarean. Variables matched were gestational age at delivery (+/- 1 week), presentations of both fetuses, labor onset (spontaneous or induced), and prior vaginal delivery (yes or no). The primary outcome was successful vaginal delivery of both fetuses. Secondary maternal outcomes included chorioamnionitis, hemorrhage requiring transfusion, hysterectomy, uterine rupture, and length of stay. Neonatal outcomes included one and five minute Apgars, NICU admission, and length of NICU stay. RESULTS: Twelve parturients were matched to 36 controls. There were no differences between the groups with respect to maternal demographics, intrapartum variables, fetal genders, birthweights, or chorionicity. Women with a prior cesarean (10/12) delivered both twins vaginally compared to 31/36 parturients without a prior cesarean (P = 1.0). There were no differences between cases and controls with respect to maternal morbidity (1/12 vs 4/36, P = 1.0), or postpartum stay (2.5 +/- 1.0 vs 2.5 +/- 2.3 days, P = .25). Neonatal outcomes were similar by birth order, except that second-born twins of cases had significantly longer NICU stays than controls (22.7 +/- 3.8 vs 10.4 +/- 7.8 days, P = .04). CONCLUSION: Twin trial of labor after cesarean is associated with a high success rate of vaginal delivery but may be associated with a more lengthy NICU stay for the second twin.

Predictors of abnormal cervical cytology: statistical analysis of human papillomavirus and cofactors.

Reported increases in the incidence of human papillomavirus infection have generated speculation that cervical cytological abnormalities may also be increasing. A 10-year retrospective study of cervical cytology in 2,919 college women demonstrated a significant increase in the frequency and severity of cervical-cytological abnormalities (p - 0.0001). The peak year for abnormal cervical cytology coincided with the peak year for overt human papillomavirus infection. Women with papillomarivus, genital herpes and who were also smokers had mean cervical-cytology scores significantly worse than those with none of these risk factors (p - 0.00001). A stepwise regression analysis of abnormal cytology from recorded risk factors accounted for only 10 percent of the variance, with human papillomavirus accounting for 8 percent of the total. If human papillomavirus is indeed responsibile for the majority of abnormalities, this infection is not detected reliably through routine examination and cervical-cytology screening [corrected].

Fetal intracardiac echogenic foci: does it matter which ventricle?

We sought to determine whether an association exists between the location of intracardiac echogenic foci and fetal aneuploidy or structural cardiac lesions. A search of the English language literature since 1980 revealed nine studies reporting location of intracardiac echogenic foci, fetal chromosomal abnormalities, and cardiac anomalies. Aneuploidy was noted in 10 of 217 fetuses with left ventricular and in one of 18 with right ventricular intracardiac echogenic foci. Three of 11 fetuses with biventricular intracardiac echogenic foci were aneuploid, which is significantly more frequently than when intracardiac echogenic foci were present in either ventricle alone (P = 0.02). There were nine cases of trisomy 21, four of trisomy 13, and one of trisomy 18. Structural cardiac lesions were recognized in eight of 217 fetuses with left ventricular foci, two of 18 with right ventricular foci, and one of 11 with biventricular intracardiac echogenic foci (P = 0.16). Biventricular intracardiac echogenic foci are more frequently associated with fetal aneuploidy but not structural lesions, as compared to isolated left or right ventricular intracardiac echogenic foci.

Management of irregular uterine bleeding and spotting associated with Norplant.

Norplant, a systemic contraceptive, has been used extensively throughout the world. A major problem for consumers utilizing Norplant has been irregular, unpredictable uterine bleeding or spotting. This study seeks to determine whether or not an appropriate treatment could be found that will reduce the incidence of spotting and bleeding. Both a pilot study and an interim report of a multi-center trial utilizing ethinyl estradiol 20 micrograms for 10 days, versus Ibuprofen 800 mg three times a day for 5 days, versus placebo is reported. Based on the interim analysis of the multi-center trial, there is a reduction in the mean number of spotting days with one of the three treatments compared to the other two treatments (p = 0.044). There was no difference in the number of bleeding days between treatment regimen. It appears from a review of the literature that both oestrogen, progesterone, and non-steriodal anti-inflammatory agents may reduce the number of bleeding days or inhibit acutely the bleeding in women utilizing Norplant. The completion of this randomized multi-center trial will hopefully give us further insight into an effective treatment for controlling the irregular bleeding and/or spotting that occurs in Norplant users.

PIP: A review of the literature suggests that estrogen, progesterone, and nonsteroidal anti-inflammatory agents have the potential to ameliorate the prolonged bleeding associated with Norplant use. The feasibility of such treatment was investigated in both a pilot study and a multicenter trial. In the pilot study, bleeding episodes were stopped within 5 days (average, 3.1 days) in 8 of the 10 Norplant acceptors with irregular bleeding who received 20 mcg of ethinyl estradiol for 10 days. On the basis of this finding, 44 Norplant users from 5 US sites were administered 20 mcg of ethinyl estradiol for 10 days, 800 mg of ibuprofen 3 times a day for 5 days, or a placebo. Interim analysis of data from the multicenter trial suggests that 1 of these regimens (unknown at this point due to the double-blind nature of the study) produces a reduction in the mean number of spotting days, but there is no difference by treatment group in the number of bleeding days. The mean number of spotting days was reduced (0.23 +or- 0.44) in Group A compared to Group C (1.94 +or- 1.34) during the first 5 days of treatment. The overall mean number of bleeding days was 1.34 days in the first 5 days after treatment initiation and 0.82 during the second 5 days of treatment. Completion of the multicenter trial analysis should provide guidelines on ways to improve the menstrual disturbances that are the major barrier to Norplant use.

Measurement and prediction of hearing loss in a nursing home.

The purpose of this study was to evaluate the abilities of three paper-and-pencil tests to predict pure-tone hearing loss of nursing home residents. The three tests used were the staff version of the Nursing Home Hearing Handicap Index and two tests of mental status, the Mini Mental State and the Short Orientation-Memory-Concentration Test. Testing was done on the residents (n = 122) of a long-term, intermediate-care nursing home. In general, the residents who passed the hearing test (using a 40 dB HL criterion) performed better on all three tests than did the residents who failed the hearing test and the residents who could not be tested. The results of discriminant analyses showed that the factor of age predicted hearing loss with a sensitivity of 93% and a specificity of 35%. The factor of age in combination with question 4 of the SOMCT and question 10 of the NHHI improved specificity to 53%.

Evaluation of dexamethasone for reduction of postsurgical sequelae of third molar removal.

Sixty patients with bilaterally symmetrical impacted third molars participated in this double-blind, within-subject study to quantify the effects of 4 mg of dexamethasone on reducing postsurgical sequelae. Each patient's surgery was staged by mouth side and completed in two appointments 5 to 6 weeks apart. A preoperative dose of dexamethasone given intravenously was randomized to mouth side and surgical appointment; sterile water served as a control. Major areas assessed in this study were facial swelling, pain, and trismus. No difference in swelling and daily pain was noted. However, trismus and global pain were significantly affected by the steroid. Patients had a daily postsurgical increase in incisal opening of 4 to 6 mm over the control side during the examination period. Patients evaluated pain by choosing the least painful side. By a greater than 4:1 margin, patients chose the steroid side as the least painful side. No increase in the rate or type of complications was detected between control and steroid sides.

Use of surgical pass trays to reduce intraoperative glove perforations.

This randomized prospective study evaluated the surgical pass tray to reduce intraoperative glove perforation during cesarean delivery. Surgical team members were assigned to employ normal instrument pass techniques or surgical pass tray during all cesarean deliveries. Surgical team members were asked to record their surgical role and level of training. Gloves were collected and tested using standard hydrosufflation techniques. Additional variables studied were patient weight, surgical indication, estimated blood loss, and length of surgery. A total of 192 cesarean sections were performed during the study period, for which 165 were studied. Data collection was considered adequate in 156 cases. Four hundred forty-four pairs of gloves were collected and tested, including 38 double glove sets. Seventy-eight perforations were noted in 444 pairs of gloves, including 11 in the double glove sets. Among surgeries assigned to use pass trays, 221 pairs of gloves were obtained with 42 (19.0%) perforations noted. Surgeries assigned to the control group contributed 223 glove sets of which 36 (16.1%) perforations were noted (P = .5). There were no complete perforations noted in the total of double glove sets. The frequency of glove perforations is not reduced by using surgical pass trays. While there is no demonstrated benefit in using pass trays there appears to be little adverse impact.

Validation of the hemizona assay (HZA) in a monkey model. II. Kinetics of binding and influence of cryopreserved-thawed spermatozoa.

We compared fresh and frozen-thawed cynomolgus monkey spermatozoa tight binding to the zona pellucida under hemizona assay (HZA) conditions. Monkey oocytes were recovered after superovulation and stored in salt solution. Matching hemizonae were obtained by micromanipulation. Semen, obtained by electroejaculation, was used fresh or was cyropreserved, thawed, and washed by swim-up separation. At the standard initial dilution of 500,000 motile sperm/ml (or 5 x 10(4) motile sperm/hemizona), binding was significantly higher for fresh sperm (P = 0.00004). For frozen-thawed samples, there was a linear increase in the number of tightly bound sperm with increasing sperm concentration (r = 0.95). At 1.5 x 10(6) motile sperm/hemizona, binding of frozen-thawed spermatozoa was similar to that of fresh at a standard concentration. Kinetic studies showed peak binding at 1 hr of gametes coincubation. We conclude that, in this monkey model, the HZA is a valuable bioassay for evaluation of sperm binding to the zona pellucida, the initial requisite for fertilization and embryo development.

Flow cytometric DNA content and clinical outcome in patients with non-small cell lung cancer given postoperative radiation therapy.

DNA content by flow cytometry was assessed in 47 cases from a series of 130 patients with non-small cell lung carcinoma (NSCLC) given radiation therapy postoperatively. This was done in an attempt to identify which patients might benefit, or not benefit, from postoperative radiotherapy. From archival formalin-fixed paraffin-embedded specimens, 16 of the 47 cases (34%) had DNA diploid tumors while 31 cases (66%) were nondiploid. A diploid DNA content was significantly related to improved overall survival (P = 0.0061) and tumor-free survival (P = 0.0167) but not with frequency of tumor recurrence within the irradiated field. Histological grade was not significantly related to overall survival, tumor-free survival, or frequency of in-field tumor recurrence. DNA content was found in this study of NSCLC patients irradiated postoperatively to be a useful marker for predicting survival but not for predicting local recurrence.

Ultrasonographic appearance of the endometrium in natural and stimulated in-vitro fertilization cycles and its correlation with outcome.

Ultrasonographic evaluation of the endometrium in 56 IVF patients was performed prospectively. Endometrial thickness and pattern were analysed in 18 natural-cycle and 38 stimulated-cycle patients. Thickness was measured from the echogenic interface of the endometrium-myometrium junction on a transverse section at the level of the fundus. Patterns were classified as A (homogeneous, hyperechogenic), B (mixed, with an outer hyperechogenic and inner hypoechogenic layer) or C (fluid-filled cavum with ring configuration). The thickness and pattern distributions were similar in natural- and stimulated-cycle patients. There was no correlation between thickness and serum oestradiol levels, the diameter of the largest follicle or the pregnancy outcome in either group. However, the occurrence of endometrial pattern A on the day prior to oocyte retrieval had a predictive value of 100% for a non-conceptional cycle. In contrast, pattern B occurred in a significantly greater proportion of pregnant than non-pregnant patients.

Surgical management of posthemorrhagic hydrocephalus in 22 low-birth-weight infants.

In order to assess the complication rates of cerebrospinal fluid diversion techniques used at our institution, a retrospective study of the surgical management of posthemorrhagic hydrocephalus was conducted from a population of 547 premature infants admitted to the neonatal intensive care unit from 1987 to 1989. The incidences of periventricular-intraventricular hemorrhage in the 3 years studied were 44%, 37%, and 27%, respectively. Thirty-nine of the infants developed posthemorrhagic hydrocephalus as determined by serial cranial ultrasonography; 22 required cerebrospinal fluid diversion. During the study period, we began using subcutaneous ventricular reservoirs and a low-pressure Neonatal Shunt (customized device) in infants weighing less than 1500 g at the time of instrumentation. This change in management was associated with a significant reduction (P < 0.005) in the morbidity and mortality compared to the use of external ventricular drainage devices. On the basis of these findings, the use of external ventricular drainage devices was discontinued.