Ericoside, a new antibacterial biflavonoid from Erica mannii (Ericaceae).

A new dihydroflavonol-flavonol biflavonoid derivative, named ericoside was isolated from the ethanol extract of the whole plant of Erica mannii along with the known flavonoid, taxifolin 3-O-α-L-rhamnopyranoside; and two readily available sterols (sitosterol, sitosterol 3-O-ß-D-glucopyranoside). The isolation was performed using chromatographic methods and the structure of purified molecules were elucidated using spectroscopic techniques (e.g. MS, NMR) and by comparison with literature data. The crude ethanol extract, ericoside, and taxifolin 3-O-α-L-rhamnopyranoside were tested against ten Gram-negative bacteria including multidrug resistant clinical isolates using a broth microdilution method. The crude ethanol extract showed no noteworthy activity. Of the purified compounds, ericoside displayed moderate activity against the resistant Escherichia coli AG100 with a MIC of 64 µg/mL.

Quantitation of minimal residual disease in multiple myeloma using an allele-specific real-time PCR assay.

OBJECTIVE: To develop a real-time PCR method, based on the 5'nuclease TaqMan technology, for quantitation of clonal cells in multiple myeloma (MM). MATERIALS AND METHODS: The real-time quantitative PCR method incorporates both an allele-specific oligonucleotides (ASO) primer and an ASO dual-labeled fluorogenic probe (ASO TaqMan probe). The ASO primer and probe corresponded to the complementary determining region 3 (CDR3) of the rearranged immunoglobulin heavy chain gene (IgH). With the use of a sequence detector, PCR product accumulation was measured through the ASO TaqMan probe. The real-time PCR method was compared with flow cytometric quantitation of myeloma plasma cells. RESULTS: The application of the real-time quantitative ASO IgH PCR method is illustrated by a sequential analysis of minimal residual disease (MRD) in bone marrow (BM) samples from myeloma patients undergoing peripheral blood stem cell (PBSC) transplantation. The real-time PCR method was able to quantitate residual malignant cells in BM samples from patients who were considered to be in complete remission. Further, it was illustrated that a potential problem in determining tumor cell content in myeloma BM samples is the heterogeneous infiltration of the marrow. CONCLUSION: The application of the real-time PCR method provides a sensitive, highly specific, and reproducible quantitation of myeloma cells.

Amplification of the gene encoding the alpha-subunit of the mitochondrial ATP synthase complex in a human retinoblastoma cell line.

A cDNA clone encoding the precursor of the alpha-subunit of the human mitochondrial ATP synthase (F1-ATPS) complex was isolated from a library prepared from the poly(A)+ RNA present in a retinoblastoma (RB) cell line. Northern blot analysis of RNAs derived from a variety of transformed cell lines as well as from normal human fetal tissues indicated that RNA expression was significantly higher in two of the four RB cell lines analysed, Y79 (10- to 30-fold) and RB522A (3- to 8-fold), than in other cell lines or tissues. The increased mRNA level was apparently the result of gene amplification in Y79, but not in RB522A.

An analysis of the impact of pathology review in gynecologic cancer.

PURPOSE: To analyze the impact of pathology review in gynecologic malignancies. METHODS AND MATERIALS: For all new gynecologic patients seen between December 2, 1993 and January 4, 1996, we conducted a retrospective chart review to determine if a pathology review by the institute's consultant pathologist changed the diagnosis, and if so whether the change altered patient management. A total of 514 patients were seen, of whom 120 had cervical cancer, 226 had endometrial cancer, 122 had a primary ovarian or peritoneal malignancy, 9 had a vaginal malignancy, 28 had vulvar cancer, and 9 had a miscellaneous gynecologic malignancy. RESULTS: On pathology review the diagnosis changed for 200 of 599 specimens (33%). This altered management for 63 of 514 patients (12%). For patients with cervical cancer, the grade of tumor was the main change in pathologic diagnosis, with occasional change in the presence of lymph vascular invasion. These did not translate into patient management alterations. Eight patients (1.5%) had management alterations. The changes in depth of invasion and vascular invasion altered management for 3 patients. Changes in pap smears resulted in two management alterations, and changes in histologic diagnoses altered management for 3 cases. For endometrial primaries the changes in pathologic diagnosis included grade, depth of invasion, and the presence of cervical involvement. This did alter management in 40 cases (8%). For the ovarian malignancies, the main changes were grade, extent of disease, or histologic classification, some of which (10 patients, 2%) resulted in altered management. One patient with a vaginal lesion had the diagnosis changed, which did alter management. Of the patients diagnosed with vulvar cancer, the pathologic diagnosis changed for 11 patients. This included changes in grade and depth of invasion. This altered management of 2 patients. The remaining miscellaneous gynecologic malignancies had only two diagnosis changes that altered management. CONCLUSIONS: Pathologic review of gynecologic malignancies is justified as it can alter patient management. In addition, the process facilitates cooperation of the multidisciplinary team and provides a valuable educational forum to enhance patient care.

Inherent radiosensitivity testing of tumor biopsies obtained from patients with carcinoma of the cervix or endometrium.

The inherent radiosensitivity of tumor biopsies obtained from a series of patients with carcinoma of the uterine cervix or endometrium has been characterized. Early passage cell lines were irradiated and assayed for cell survival using a clonogenic assay system. Survival curves were generated using the alpha/beta model and the surviving fraction at 2 Gy (SF2) was estimated. A wide range of SF2 values was observed among histologically similar tumors. The mean (+/- SD) SF2 value was 0.29 +/- 0.12 (range = 0.11-0.59) for the cervical biopsies and 0.30 +/- 0.13 (range = 0.11-0.67) for the endometrial biopsies. No correlation between inherent radiosensitivity and tumor DNA index or histopathology was observed. Patient accrual continues with the expectation that these results may help to determine whether SF2 values are of clinical value in predicting the response of individual patients to treatment with radiotherapy.

Possible association between the hernia of Morgagni and trisomy 21.

Of the 5 liveborn infants with the hernia of Morgagni recorded in the California Birth Defects Monitoring Program, 3 had trisomy 21. This significant association (P < 10(-6)) between the hernia of Morgagni and trisomy 21 may reflect defective dorsoventral migration of rhabdomyoblasts from the paraxial myotomes, caused by increased cellular adhesiveness in trisomy 21.

Poland anomaly with a limb body wall disruption defect: case report and review.

We describe a female infant with apparent Poland anomaly (PA) and limb body wall defect. Analysis of the defects suggest that a disruption of the lateral embryonic plate mesoderm may have been responsible for the observed lesions. Because of the overlap of this case with PA, we re-examined previous reports of this syndrome. We think that the lesions could be equally well explained as a mesodermal disruption, and point out a previously unrecognised discrepancy between sex and affected side in sporadic PA and inherited PA which supports this view.

Microscopic study of holoprosencephalic facial anomalies in trisomy 13 fetuses.

The cerebral and facial anatomy of four trisomy 13 fetuses was studied in order to delineate the varying degrees of expression of severity of holoprosencephaly. Fetal heads were serially sectioned and analyzed microscopically in the horizontal plane. Examples of cyclopia, cebocephaly, and a proposed new category, premaxillary dysgenesis, were studied. The last category represents the least severe end of the facial spectrum of holoprosencephaly in this series. In this condition, there are deficiencies or clefts within the premaxilla, in contrast to the usual site of clefting between the maxilla and the premaxilla. There is asymmetry of the defects in the anterior midface of all four cases.

Is there an association of Down syndrome and omphalocele?

The possible association of Down syndrome (DS) with omphalocele is controversial. We reviewed the 2,979 live births and stillbirths with DS born from 1983 to 1993 in the catchment area of the California Birth Defects Monitoring Program (CBDMP). We observed one infant with both defects, a number that did not differ significantly from what was expected (P < 0.40). We also reviewed the pathological reports of one of us (L.H.H.) from a series of 36 DS fetuses and neonatal deaths; none had an omphalocele. We then reviewed the literature for epidemiological studies of DS and for epidemiological, surgical, prenatal, and familial studies of omphalocele. Possible biases inherent in each type of study were evaluated. The majority of epidemiological studies showed no association of DS with omphalocele. In surgical series, the occasional infant with both defects was more likely to undergo surgery than infants with omphalocele and trisomies 13 and 18 or other severe birth defects. Inclusion of both omphalocele and umbilical hernia in the same ICD-9 code may explain some of the correlations with DS noticed in a few epidemiological studies. In conclusion, our data suggest that trisomy 21 does not predispose the fetus to an increased risk for an omphalocele.

Ovarian hilus cell heterotopia.

A systematic pathologic study was done of the paratubal and parametrial tissues, submitted along with distal tubal segments excised for sterilization and with uteri (with or without attached adnexa) removed for common gynecologic conditions. Heterotopic ovarian hilus cell rests were noted in 12 cases, giving an overall incidence of 0.52% (12/2299). These cell rests, confined exclusively to the endosalpinx and perisalpinx, were easily differentiated from pregnancy-related decidual nodules, Walthard rests, foci of paratubal endometriosis, and ectopic adrenal rests.

Invasive squamous cell carcinoma of the vagina during pregnancy.

BACKGROUND: Squamous cell carcinoma of the vagina in pregnancy is rare. CASE: A 28-year-old primigravida with antepartum bleeding at 20 weeks' gestation was diagnosed with squamous cell carcinoma after biopsy of a vaginal mass. The histology revealed an invasive grade 3 squamous cell carcinoma of large-cell, nonkeratinizing type. The patient declined pregnancy termination and immediate radiation treatment. She continued to have episodes of vaginal bleeding and was admitted at 30 weeks' gestation. A decision was made in consultation with the neonatal unit to deliver her at 32 weeks' gestation. After corticosteroid treatment, she was delivered by cesarean delivery. Positive pelvic lymph nodes were noted at surgery. Postoperatively, she received external beam radiation and brachytherapy and concurrent cisplatin chemotherapy. She is disease free 3 years from her original diagnosis. CONCLUSION: This case emphasizes the importance of a thorough pelvic examination to assess the vaginal walls and cervix at the first prenatal visit and with any antepartum bleeding episode.

Nonspecific peritesticular fibrosis manifested as testicular enlargement.

Nine cases of peritesticular fibrosis initially appeared to be enlargement of the testes. Seven patients under went orchiectomy and two had biopsy specimens taken of the grossly thickened tunica albuginea. In six patients, a hydrocele was present with intramural fibrosis and minimal chronic inflammation. Active epididymitis and chronic interstitial orchitis were present in two patients, with some spread of the inflammation into the fibrotic peritesticular tissues. One case, without associated hydrocele or epididymitis, showed dense fibrosis of the peritesticular tissues with focal edema, lymphangiectasis, and minimal perivascular round cell infiltration. This clinicopathological entity of diffuse peritesticular fibrosis is an unrecognized cause of benign testicular enlargement. The hypothesis is advanced that the primary process is a congenital hypoplasia of the peritesticular lymphatics progressing at various speeds into a state of chronic lymphedema and end stage noninflammatory fibrosis.

Cholesterol cholelithiasis in adolescent females: its connection with obestiy, parity, and oral contraceptive use--a retrospective study of 31 cases.

Thirty-one adolescent females, aged 14 to 20 years, underwent cholecystectomy for pathologically documented cholesterol gallstones. A retrospective study, using the Mantel-Haenzel method of statistical analysis, showed a strong association between cholesterol cholelithiasis and obesity and parity. The patients with gallstones had a higher rate of oral contraceptive use, which just failed to attain statistical significance. These findings indicate that adolescent cholelithiasis is largely preventable. Dietary obesity can be controlled by balanced diets and physical exercise. Early pregnancy should be discourgaed, espeically if there is a strong family history of cholelithiasis and if weight control is unsuccessful. Oral contraceptives should be used cautiously in the presence of other predisposing factors.

Unilateral anorchism. Report of 11 cases with discussion of etiology and pathogenesis.

Eleven cases of unilateral anorchism are presented. The patients, aged two to thirty-nine years, were explored for cryptorchism but, though ducts could be identified operatively in most cases, there was doubt regarding the presence of the testis. These tissues, including the putative testes, were excised and pathologically the excurrent ducts, consisting of vas deferens with or without epididymis, were seen in all cases. No tunica albuginea or testicular parenchyma was identified and the structures, submitted as possibly testicular, were nonencapsulated, well-circumscribed, subserosal foci of highly vascularized fibrous tissue with few small nerves and smooth muscle bundles. Dystrophic calcific deposits were seen in 2 cases and microfoci of poorly developed Leydig cells in 2 cases. A vascular hypothesis is proposed for the etiology and pathogenesis of unilateral anorchism.

Hypernephroma with perirenal hemorrhage.

Two cases of hypernephroma with rupture of the renal capsule and localized perirenal hemorrhage are reported. This unusual complication of hypernephroma exhibited a subacute clinical presentation with pain as the major presenting symptom.

The influence of anatomical site and hormonal status on the copper and zinc levels of human uterine smooth muscle.

Copper and zinc levels were measured in smooth muscle from 47 uteri. Results were obtained for myocervix, isthmus and corpus in the secretory and proliferative phases and also from post-menopausal subjects. The levels were found to vary both with site sampled and the physiological state of the uterus.

A significant association between spontaneous abortion and tubal ectopic pregnancy.

A retrospective study of 83 patients with pathologically documented tubal ectopic pregnancy demonstrated a statistically significant association (P less than 0.005) between prior spontaneous abortion and ectopic pregnancy. In this population with a low incidence of chronic salpingitis, it is suggested that delayed (post-midcycle) ovulation, causing preovulatory over-ripeness of the ovum, may be the common underlying etiologic factor. The clinical significance of this finding is also briefly discussed.

Salpingitis isthmica nodosa in female infertility and ectopic tubal pregnancy.

Salpingitis isthmica nodosa has been studied in relation to female infertility and tubal ectopic pregnancy. The incidence of this lesion in a control Caucasian population was 0.6%, as compared with incidences of 2.86% in an ectopic group and 50% in a small infertility group undergoing tuboplasty. It is suggested that salpingitis isthmica nodosa should be considered as an etiologic factor in these reproductive disorders. Chronic tubal spasm is suggested as the underlying process.

Failed tubal sterilization as an etiologic factor in ectopic tubal pregnancy.

An indirect statistical method was used to demonstrate that failed tubal sterilization must be considered as a significant etiologic factor in tubal ectopic pregnancy. Since the exact incidence of poststerilization pregnancies was unknown in our population, a "theoretical" incidence of a 0.71% failure rate was used as the most realistic estimate on the basis of published reports of failed tubal sterilizations. From this figure the "expected" number of poststerilization conceptions, both total and tubal, was computed. The observed incidence of poststerilization ectopic tubal pregnancy was found to be 20 times the "expected" incidence in our population.

The late luteal phase in infertile women: comparison of simultaneous endometrial biopsy and progesterone levels.

Endometrial biopsy specimens were obtained from 107 normally menstruating infertile women 2 to 3 days before the anticipated onset of menses and were day-dated according to histologic criteria. A simultaneous blood sample was obtained for measurement of progesterone (P) and beta-subunit of human chorionic gonadotropin. Of 98 biopsies which could be accurately dated, 56 were in-phase (IP) and 42 were out-of-phase (OOP). Mean serum P levels were significantly lower in women with OOP biopsies undertaken more than 4 days before the onset of menses. A sharp decline in serum P levels was observed in women with IP but not OOP biopsies, so that on the final premenstrual day serum P levels were significantly higher than normal in women with OOP biopsies. Pregnancy continued without interruption in two of six patients who underwent biopsy in the cycle of conception. One patient had an ectopic pregnancy; and the three remaining pregnant patients, all with subnormal P values, aborted. The study suggests that there is a high frequency of minor abnormalities in luteal function in normally menstruating, infertile women for whom tubal and male factors were normal. The frequency of subclinical pregnancy (2 of 107) was lower than anticipated from earlier studies.