Ectopic pregnancy early diagnosis markers.

Ectopic pregnancy (EP) is a high-risk medical condition with an incidence of 1.9% in reported pregnancies, and has proven to be the most common cause of pregnancy-related deaths in the first trimester. The clinical symptoms can mimic non-EP conditions, thus creating a challenge for developing diagnostic criteria and new diagnostic tools. Early diagnosis of ectopic pregnancy is essential in order to minimize the morbidity and to assess the need for urgent surgical intervention. Currently, ultrasound and serum biomarkers are used by clinicians for early detection and diagnosis. This review summarizes and comments on the available literature on the various markers including their utility and their statistical parameters.

Impaired access of lymphocytes to neoplastic prostate tissue is associated with neoangiogenesis in the tumour site.

Recent reports demonstrated that neovasculature of certain murine tumours inhibits migration of lymphocytes to malignant tissues. We examined the possible existence of this phenomenon in human prostate adenocarcinoma by relating extent, patterns and composition of leucocyte infiltrates in adenocarcinoma specimens (N=28) to microvessel density and percentages of these vessels expressing adhesion molecules CD54, CD106 and CD62E. Specimens of nodular hyperplasia (N=30) were used as a control for nonmalignant prostate. Increased microvessel density was detected in foci of adenocarcinoma, as compared with adjacent benign areas (P=0.004) or hyperplastic specimens (P=0.001). Only CD54 was detected on prostate vasculature; percentages of CD54-expressing vessels in adenocarcinoma lesions and adjacent areas were higher than in hyperplasia (P=0.041 and P=0.014, respectively). Infiltrating leucocytes were either scattered diffusely in tissue or organised into clusters mainly composed of CD4-positive lymphocytes; smaller percentage of tissue was occupied by clustered infiltrates in adenocarcinoma foci (mean=0.7; median=0; range=0-5) than in adjacent tissue (mean=2.5; median=1; range=0-15; P=.021) and hyperplasia (mean=1.9; median=2; range=0-5; P=.006). In adenocarcinoma foci, microvessel density tended to negatively correlate with percentage of tissue occupied by an overall leucocyte infiltrate (mean=8.6; median=7.5; range=30) and negatively correlated with percentage of tissue occupied by clustered infiltrate (P=0.045). Percentage of CD54-expressing vessels positively correlated with percentage of tissue occupied by an overall (mean=12; median=10; range=30; P=0.01) and clustered (P=0.023) infiltrate in hyperplasia, whereas in carcinoma-adjacent benign areas, correlation was detected only for clustered infiltrates (P=0.02). The results indicate that impaired access of lymphocytes to malignant lesions is associated with increased numbers of newly formed blood vessels, whereas vascular CD54 likely contributes to extravasation of lymphocytes only in benign prostate tissue.

The endoscopic Draf II frontal sinusotomy: non-navigated approach.

OBJECTIVE: Endoscopic endonasal Draf II frontal sinusotomy is indicated for a variety of pathologies such as mucocele and non-responsive chronic frontal sinusitis. However, this approach is challenged and controversial. The objectives were to evaluate the advantages, disadvantages, indications, and rate of complications of this approach, without the use of a navigation system. METHODS: The files and computed tomography (CT) scans of 25 patients who underwent endoscopic endonasal Draf II sinusotomy at Assaf Harofeh Medical Center between 1999 and 2002 were reviewed. RESULTS: Thirty-one frontal sinuses were operated on and follow-up was between 18 and 62 months (average 30.3). Twenty-two sinuses (71%) had previous surgery. The Draf II procedure was used in 3.7% of all cases during the survey period. The most frequent indication for surgery was inflammation (48%) followed by mucocele (28%). In all but 2 sinuses (93%), the frontal floor between the lamina papyracea and the middle concha was drilled out. Twenty-four patients (96%) were successfully ventilated. No major complications were noted. CONCLUSIONS: The Draf II approach can be used safely and successfully without a navigation system, including cases of revision endoscopic sinus surgery. Correct interpretation of the surgical field and a CT scan are crucial for success. Careful patient selection is essential for this procedure.

Treatment policies among Israeli specialists in paediatric dentistry.

AIM: This was to evaluate some suggested diagnostic procedures, treatment policies and professional attitudes of specialists in paediatric dentistry, in light of the periodically published guidelines by The American Academy of Pediatric Dentistry, The European Academy of Paediatric Dentistry and The British Society of Paediatric Dentistry. METHODS: Using a structured questionnaire, 67% of the Israeli specialists in paediatric dentistry, who agreed to participate in this study, were personally interviewed. RESULTS: Only 7.5% of the participants reported that they carry out pulp capping of primary teeth in cases of pulp exposure. Over 50% reported restoring teeth after pulpotomy with preformed crowns. Most indicated sealing pit and fissures after considering depth and morphology of the fissures and correlation with the patient's risk to caries. Cleaning teeth after eruption of the first tooth was suggested by 75.5% of the participants. A striking majority (96%) claimed that they restored permanent anterior teeth with composite resins and most used these materials for occlusal restoration in both primary and permanent posterior teeth. Most specialists advocated the use of amalgam in proximal posterior restorations. The presence of a parent in the operatory/surgery was preferred by 85% of the dentists. CONCLUSIONS: Israeli specialists in paediatric dentistry mostly comply with the mentioned guidelines. Further studies of this nature should also be encouraged in other countries to emphasize the importance of monitoring compliance with established and evidence based guidelines.

The integrity of cholesterol-enriched microdomains is essential for the constitutive high activity of protein kinase B in tumour cells.

A deregulated activity of PKB/Akt (where PKB stands for protein kinase B) renders tumour cells resistant to a variety of apoptosis-inducing stimuli. Elucidation of the mechanisms responsible for this deregulation is of prime importance for the development of novel anti-cancer drugs. Results of the present study demonstrate that the constitutive activity of PKB/Akt in B16BL6 melanoma cells depends on the integrity of cholesterol-enriched membrane microdomains, since the exposure of cells to cholesterol-depleting agents decreases the phosphorylation of this enzyme, with no change in its total protein level. Inhibitors of Hsp90 (heat-shock protein 90) decreased phosphorylation of PKB/Akt with a similar pattern. Dephosphorylation of the enzyme, as a consequence of raft disintegration, could be precluded by inhibition of serine/threonine (but not tyrosine) phosphatases. Our results imply that destabilization of lipid rafts seemingly affects the association of Hsp90 with the respective serine/threonine phosphatases, thereby increasing the accessibility to PKB/Akt to deactivating phosphatases. We have found recently that reconstituted expression of H-2K class I glycoproteins in class I-deficient B16BL6 cells also decreases the phosphorylation of PKB/Akt. Therefore it is possible that raft-associated regulation of this important enzyme involves both H-2K glycoproteins and Hsp90.

Non-immune functions of MHC class I glycoproteins in normal and malignant cells.

MHC class I glycoproteins play a pivotal role in the regulation of immune responses by presenting antigenic peptides to cytotoxic T lymphocytes and by regulating cytolytic activities of natural killer cells. Cells originating in malignant tumours are often characterized by a profound immune escape phenotype. This phenotype is frequently associated with alterations in MHC class I-related antigen processing and presentation that enable tumours to escape immune surveillance. However, it now becomes clear that MHC class I molecules do not only provide a mechanistic framework for the presentation of antigenic peptides but, rather, possess broader biological functions due to their ability to regulate cell-to-cell communication and receptor-mediated trans-membrane signal transduction. In the present review we made an attempt to reevaluate the significance of an altered MHC class I phenotype for tumour progression in view of the current state of knowledge concerning the aforementioned non-immune functions performed by these membrane glycoproteins.

The significance of the degree of myometrial invasion in patients with stage IB endometrial cancer.

OBJECTIVE: To study the validity of the FIGO staging classification of endometrial cancer Stage IB by correlating degree of myometrial invasion depth with outcome measures. STUDY DESIGN: Fifty patients with endometrial adenocarcinoma FIGO Stage IB who underwent hysterectomy between 1989 and 2001 were divided into two groups according to depth of myometrial invasion. The first group comprised of 31 patients with myometrial invasion of less than or equal to one-third. The second group included 19 patients with invasion greater than one-third but less than one-half. The two groups were compared with regard to prognostic factors and outcome measures. RESULTS: The overall 5-year recurrence-free survival, disease specific survival and overall survival rates were 87%, 94% and 77%, respectively. These outcome measures did not vary significantly between the two groups. There were no statistically significant differences between the two groups with regard to the following parameters: duration of follow-up, age, proportion of patients who underwent complete surgical staging and postoperative adjuvant radiotherapy. Histologic parameters of the two groups, such as histological type, grade and proportion of patients with capillary space-like involvement and lower uterine segment involvement were not significantly different. CONCLUSIONS: In patients with Stage IB endometrial cancer the amount of myometrial invasion defined as less than one third compared with invasion greater than one third does not appear to correlate with their outcome, thus validating the FIGO staging system.

Single dermatome analgesia sparing in an obstetric patient following previous radiation to that region.

We present a case of an obstetric patient with prior radiation therapy for Hodgkins lymphoma to the right hip, right flank region and lumbar spine, who suffered persistent right sided L1 dermatone distribution sensory and analgesia sparing after routine epidural placement despite additional boluses of local anesthetic. We postulate that the previous radiation therapy received by our patient left sufficient epidural fibrosis as a barrier to prevent spread of local anesthetic to cover the L1 dermatome. Subsequent replacement, using a combined spinal-epidural technique at a higher lumbar space, overcame this obstruction. In patients who have received substantial radiation therapy to the lumbosacral region in the past, awareness of this potential problem may assist in clinical management.

Adrenocortical oncocytoma in pregnancy.

BACKGROUND: Adrenal oncocytomas are uncommon, nonfunctioning tumors occurring most often in endocrine organs. CASE: A 32-year-old woman presented at 25 weeks' gestation complaining of right flank pain. Abdominal ultrasonography and computed tomography revealed a 9 x 10-cm solid right-sided adrenal mass. Endocrine evaluation was normal. At 36 weeks' gestation, she underwent cesarean followed by resection of the adrenal mass. Histopathologic and ultrastructural studies revealed a benign adrenocortical oncocytoma. CONCLUSION: Although rare, adrenocortical oncocytomas should be included in the differential diagnosis of solid, nonfunctioning, adrenal tumors in pregnancy.

Oxidation of galactose by galactose-1-phosphate uridyltransferase-deficient lymphoblasts.

The ability of EB virus-transformed lymphoblasts with undetectable galactose-1-phosphate uridyltransferase (GALT) from 15 galactosaemic patients to oxidize [1-(14)C]galactose to 14CO2 was compared to that of cells from 7 normal subjects. The oxidation of galactose but not of glucose was markedly diminished by cells from Q188R homozygous galactosaemic patients but was not absent. After 2.5 h these cells liberated 14CO2 at nearly 3% and at 5 h up to 9% of normal. Cells from patients homozygous for the S135L mutation produced much larger amounts of 14CO2 (15-17% of normal) and were distinguishable from the Q188R homozygous cells. A cell line with a homozygous deletion of the GALT gene oxidized galactose at 7% of the normal rate, suggesting that pathways(s) other than GALT exist in these cells as well as Q188R homozygous cells for oxidation of galactose to CO2. Concentration dependence studies are consistent with the presence of a pathway that is unsaturable or has a very high Km The ability of 10(7) lymphoblasts with the S135L genotype to oxidize more than 7% of the sugar to 14CO2 in 5 h suggests the presence of residual GALT despite the inability to detect the activity by enzymatic analysis.

Intraoperative sonographic localization of breast masses: success with specimen sonography and surgical bed sonography to confirm excision.

OBJECTIVE: To assess the use of intraoperative sonography for localization of breast masses at excisional biopsy, with specimen and surgical bed sonography to confirm excision. METHODS: A computer search of the 5-year period from January 1993 through January 1998 revealed 138 consecutive women referred for sonographically guided excisional biopsy of 148 masses; 35 masses were excluded because they had no postoperative mammograms. One hundred thirteen masses constituted the study group. Specimen sonography (n = 60) or surgical bed sonography (n = 53) was performed as the initial evaluation to confirm excision, but ultimately, surgical bed sonography may have been necessary after specimen sonography, and specimen sonography may have been necessary after surgical bed sonography. The miss rates determined by postoperative imaging were calculated for each group and compared with those of mammographically guided needle localization series from the literature. RESULTS: Follow-up physical examination and mammography showed no residual mass in the region of surgery in any patient. However, follow-up sonography had 1 miss in the initial specimen sonogram group (1 [1.7%] of 60) and 1 miss in the initial surgical bed group (1 [1.9%] of 53). As shown by the Fisher exact test, there was no significant difference between the miss rates of the 2 initial methods of confirming lesion excision or between the miss rates of these initial methods, both groups combined, and 6 mammographic localization series from the literature. CONCLUSION: Intraoperative breast sonography, using specimen sonography and scanning the surgical bed, has miss rates comparable with those of mammographic needle localization. Follow-up sonography must be performed if there is any doubt of complete excision.

[Prenatal Down's syndrome screening at 10-14 weeks gestation using the combined nuchal translucency and maternal serum biochemistry: preliminary results of the first 358 cases].

We report our preliminary experience of prenatal screening for Down's syndrome (DS) using nuchal translucency (NT) measurement combined with the serum biochemistry analysis of Free beta-human chorionic gonadotropin (F beta hCG) and pregnancy associated plasma protein A (PAPP-A) all measurement at 10-14 weeks of gestation. Of the 358 parturient women which enrolled in the study, 9 cases were not included because of fetal anomalies or miscarriages. Thus the study group included 349 singleton pregnancies in which complete prenatal and infant follow-up was available. Forty-four pregnant women were found to be screen positive (12.6%) and in 13 cases (27%) of them fetal chromosomal aneuploidies were diagnosed. Looking into the markers profile we found that the NT was a sensitive marker which was abnormally increased in all the fetal aneuploidies. Serum F beta hCG was found to be a promising marker as well, being significantly elevated (2.26 +/- 0.86 multiple of the medians, MoM) in DS cases, and decreased (< 0.5 MoM) in two cases of Edward's syndrome. On the contrary, PAPP-A was found less sensitive, and its mean MoM values were not significantly different between DS versus euploid fetuses. Our preliminary results support the promising success of DS screening using NT and F beta hCG.

Thyroglossal duct cyst: is thyroid scanning necessary in the preoperative evaluation?

BACKGROUND: Evaluation of thyroglossal duct cysts before surgical excision traditionally includes hormonal evaluation, ultrasound of the neck, and thyroid scanning. OBJECTIVE: To evaluate the need for thyroid scanning in cases of thyroglossal duct cysts scheduled for operation. METHODS: A retrospective chart review of 100 cases of thyroglossal duct cyst between 1988 and 1995 was carried out. RESULTS: No cases of ectopic thyroid were detected. CONCLUSION: Our goal was to document the presence of normal thyroid tissue by non-invasive tools such as ultrasound, rather than to rule out the existence of ectopic thyroid tissue by radionuclide scanning. Radionuclide scanning is justified in cases of lingual thyroid and where a normally located thyroid gland cannot be detected.

Sonographically guided renal mass biopsy: indications and efficacy.

PURPOSE: To review the clinical indications, pathologic results, and success rate of all our sonographically guided solid renal mass biopsies over a 5-year period. METHODS: Between 1993 and 1998, 44 consecutive patients underwent sonographically guided percutaneous biopsy of a solid renal mass. Indications included prior history of nonrenal malignancy, metastatic disease of unknown primary origin, previous contralateral nephrectomy for a renal cell neoplasm, a renal transplant mass, suspected renal lymphoma, history of tuberous sclerosis, and poor surgical candidacy. Aspiration biopsies were initially performed with 22- to 18-gauge spinal needles. If the initial cytologic evaluation findings were nondiagnostic, core biopsies were then performed with 20- to 18-gauge core biopsy guns. Dictated sonographic reports of the biopsies were reviewed to determine the following: indication for biopsy, location and size of the renal mass, needle gauge and type, number of needle passes, and complications. Final cytologic and surgical pathologic records were reviewed. RESULTS: Thirty-six (82%) of the 44 biopsy specimens were diagnostic. Aspirated smears were diagnostic in 24 (67%) of these cases, with the diagnosis made on the basis of cell block alone in an additional 2 (6%). A definitive diagnosis came from core biopsy alone in 10 cases (28%). The 18-gauge core needle yielded diagnostic results more reliably than the 20-gauge core needle, and a significant correlation was seen between core biopsy needle size and the rate of diagnostic core samples (P = .017). Pathologic diagnoses included renal cell carcinoma (n = 18), lymphoma (n = 4), oncocytic neoplasm (n = 4), transitional cell carcinoma (n = 2), angiomyolipoma (n = 1), papillary cortical neoplasm (n = 1), and metastatic carcinoma (n = 6). Complications were seen in 4 (9%) of 44 cases; all were treated conservatively. CONCLUSIONS: For specific clinical indications, sonographically guided fine-needle aspiration and core biopsy of a solid renal mass can be performed safely. In many cases, a definitive diagnosis can be made on the basis of fine-needle aspiration alone. However, diagnosis may ultimately require core biopsy, for which 18-gauge core needles would be more reliably diagnostic than 20-gauge needles.

Preoperative CA-125 level as a predictor of non optimal cytoreduction of advanced epithelial ovarian cancer.

BACKGROUND: Suboptimal cytoreduction of advanced ovarian cancer is related to initial tumor bulk which correlates with CA125 level. METHODS: Retrospective record study of 40 patients with stage III ovarian cancer. The ability of a CA125 threshold level of 500 U/mL to predict suboptimal cytoreduction was determined. RESULTS: Twenty-four (60%) of the patients were optimally cytoreduced. At the CA125 cut off level of 500 U/mL the sensitivity for predicting suboptimal debulking was 62% and specificity was 83%. Above a CA 125 level of 1500 U/mL none of the patients were optimally cytoreduced. CONCLUSIONS: More data are needed to determine the CA125 cut off level at which the standard approach of initial laparotomy and cytoreduction may be modified.

The role of MHC class I glycoproteins in the regulation of induction of cell death in immunocytes by malignant melanoma cells.

A deranged expression of MHC class I glycoproteins, characteristic of a variety of malignancies, contributes to the ability of cancer to avoid destruction by T cell-mediated immunity. An abrogation of the metastatic capacity of B16 melanoma cells has been achieved by transfecting an MHC class I-encoding vector into class I-deficient B16 melanoma clones [Gorelik, E., Kim, M., Duty, L. & Galili, U. (1993) Clin. Exp. Metastasis 11, 439-452]. We report here that the deranged expression of class I molecules by B16 melanoma cells is more than a mere acquisition of the capacity to escape immune recognition. Namely, cells of the B16 melanoma prompted splenic lymphocytes to commit death after coculture. However, a class I-expressing and nonmetastatic CL8-2 clone was found to be less potent as an inducer of apoptosis than class I-deficient and metastatic BL9 and BL12 clones. Both Thy1.2(+) and Thy1.2(-) splenocytes underwent cell death when exposed to the class I-deficient BL9 clone. A proportion of CD4(+) and CD8(+) cells among splenocytes exposed to the BL9 clone was lower than that observed in a coculture with cells of the CL8-2 clone. Consistently, none of the melanoma clones studied produced a ligand to the FAS receptor (FAS-L). Thus, our results provide evidence that (i) the production of FAS-L may not be the sole mechanism by which malignant cells induce apoptosis in immunocytes, and (ii) absence of MHC class I glycoproteins plays an important role in preventing the elimination of potential effector immunocytes by tumor cells.

Plasma galactose and galactitol concentration in patients with galactose-1-phosphate uridyltransferase deficiency galactosemia: determination by gas chromatography/mass spectrometry.

The plasma concentration of galactose and galactitol was measured in 27 patients with galactose-1-phosphate uridyltransferase (GALT) deficiency galactosemia on a lactose-restricted diet, 17 infants on lactose-free formula, and 21 infants and children on a normal diet, by a newly devised isotope dilution gas chromatograph/mass spectrometry (GC/MS) method. The method was linear in the range of 0.1 to 10 micromol/L for galactose and 1 to 20 micromol/L for galactitol with good reproducibility and a coefficient of variation less than 3%. The mean plasma galactose in 15 patients who were homozygous for the most common Q188R mutation of the GALT gene was 2.72 +/- 0.70 micromol/L (mean +/- SE) with a range of 0.58 to 3.98 in specimens obtained at regular clinic visits. In 12 patients with other GALT mutations, it was 2.45 +/- 0.75 micromol/L. The mean value in nongalactosemic subjects on lactose-free formula was 0.52 +/- 0.08 micromol/L, with a range of 0.12 to 1.25. The range in 21 normal subjects without diet restriction was 0.11 to 6.33 micromol/L, with a mean of 1.48 +/- 0.32. The plasma galactitol level was 11.63 +/- 0.46 and 10.85 +/- 1.38 micromol/L in the 2 galactosemic groups. There was no relationship between plasma galactose and galactitol levels, with variable ratios of the two substances in the galactosemic patients. Galactitol was not detectable in the plasma of normal subjects. The red blood cell galactose-1-phosphate level was also measured in the galactosemic patients, and no relationship between plasma galactose and red blood cell galactose-1-phosphate was found. The galactose-1-phosphate concentration was 28 to 54 times higher than the ambient galactose. The low galactose concentration in the plasma of galactosemics on galactose-restricted diets in relation to the higher plasma galactitol and red blood cell galactose-1-phosphate is a metabolic enigma. The ability to measure plasma galactose accurately presents a new way of characterizing the galactosemic patient and the levels monitored over time may provide insight into the development of long-term complications associated with the disorder.

The effect of a rapid change in availability of epidural analgesia on the cesarean delivery rate: a meta-analysis.

OBJECTIVE: This study was undertaken to quantitatively estimate the effect of a rapid introduction or withdrawal of on-demand epidural analgesia on the cesarean delivery rate. STUDY DESIGN: MEDLINE and meeting abstracts were searched for studies reporting the cesarean delivery rate immediately before and after a rapid change in the availability of epidural analgesia. Nine studies reporting data on 37,753 patients were selected. Meta-analysis was performed to estimate the means and 95% confidence intervals for the changes in rates of total cesarean deliveries, cesarean deliveries among nulliparous women, cesarean deliveries for dystocia, and operative vaginal deliveries. RESULTS: There was no significant change in the overall cesarean delivery rate with an increase in the availability of epidural analgesia. Similarly, the rates of cesarean deliveries among nulliparous patients, of cesarean deliveries for dystocia, and of operative vaginal deliveries did not significantly differ between periods of high and low epidural analgesia availability. CONCLUSION: A rapid change in the availability of epidural analgesia is not associated with any increase in the cesarean delivery rate.

Cleft lip in the Talmud.

The authors address the problem of why the cleft lip anomalad is not mentioned even once in the Talmud, which contains detailed reports of numerous other forms of pathology and congenital anomalies. It also attempts to define the Sandal deformity, one of the most common congenital anomalies mentioned in the Talmud. It is assumed that cleft lip, the most common major facial defect, existed at the time of the Talmud. It is proposed that the Sandal deformity was actually made up of a number of entities grouped together because of a theorized common etiology, and that the cleft lip entity is included in the Sandal anomalad. This deformity, in its various forms, included, besides cleft lip, aborted tissue and products of gestation. They are all related to the common etiology of a twin gestation during which one fetus presses against the other causing the deformity. The Sandal was noted to look like the Sandal fish or sole, for which it is named. When photos of the Sandal fish and the cleft lip deformity are compared, a similarity is seen. In addition, this deformity apparently was thought to be fatal, and none of these babies survived. It is theorized that cleft lip babies were allowed to die because they were considered nonviable in the eyes of Jewish law. Supporting evidence for the ideas presented by the authors is derived from the talmudic texts and commentaries. If the Sandal does indeed include the cleft lip entity, the citation in the Mishnah (70-200 AD) makes it the earliest historical reference to the cleft lip deformity.

The current clinical presentation of complete molar pregnancy.

OBJECTIVE: To study the current clinical presentation of complete molar pregnancy. METHOD: Retrospective study of the clinical and ultrasonographic records of 41 patients with complete hydatidiform mole. RESULTS: 17 (41%) patients were asymptomatic. 24 patients (58%) presented with vaginal bleeding, 6 (15%) had excessive uterine size, 1 (2%) had anemia and 1 (2%) had hyperemesis. Non of the patients had any other systemic manifestation. Pre-evacuation ultrasound was performed in all cases and molar pregnancy was diagnosed in 36 (88%). CONCLUSIONS: Currently with routine first trimester ultrasonography a significant proportion of patients with molar pregnancy are asymptomatic at the time of diagnosis.