The villous stromal constituents of complete hydatidiform mole differ histologically in very early pregnancy from the normally developing placenta

Histologic distinction between complete hydatidiform moles and nonmolar abortuses in early pregnancy is often extremely difficult. This study details the chronologic changes that occur in normal placenta, especially in the villous stroma during gestational weeks 4 to 12 and compares the findings in 63 normal placentas and 73 early complete moles. Over time, the chorionic villi in normal placenta showed gradual but recognizable alterations, from basophilic/hypocellular and nonvascular stroma to basophilic/cellular stroma containing angiogenic cell cords (immature blood vessels), and then to loose, edematous/reticular stroma with mature blood vessels containing vascular lumina and hematopoietic components. A basophilic stroma, which was frequently seen in early complete moles, was a constant feature of chorionic villi younger than week 7 in normal placenta, but had disappeared after week 8, except in the newly branched sprouts. Trophoblastic proliferation was virtually unrecognizable in 59% of early complete moles, whereas circumferential trophoblastic sprouts during weeks 4 to 6 of normal placenta can be mistaken as that of complete moles. Few or no mature blood vessels and excessive stromal karyorrhexis are characteristic features of early complete moles, even in the absence of trophoblastic proliferation, but they are occasionally found in normal placenta younger than week 7. Although many features of normal and molar placenta were similar during the earliest weeks (5 to 6) including basophilic stroma, angiogenic cell cords (immature blood vessels), and often circumferential trophoblastic sprouts and proliferation, already by that time early moles showed significantly greater percentages of stromal cells undergoing karyorrhexis and apoptosis compared with normal placenta (37.6% vs. 5.4%). These results indicate the histologic features do exist early on in pregnancy to differentiate normal from molar pregnancy. Further, it points out that complete hydatidiform mole in addition to being disease of trophoblastic proliferation is also associated with defects in vasculogenesis and maturation of villous stromal constituents.     

Acute renal cortical necrosis due to acquired antiprotein S antibodies

Although varicella is a common disease of childhood, renal complications are quite rare. We report here the interesting case of a-22 month-old boy exhibiting renal cortical necrosis related to an acquired protein S deficiency following varicella. Ten days after the vesicle eruption appearance, he presented with ecchymosed heels, oligoanuric kidney failure, anemia [hemoglobin (Hb) 78 g/L], schizocytosis (2.5%), but normal platelet count. Kidney sonography and magnetic resonance imaging evoked renal cortical necrosis. All together, these features suggested acquired protein S deficiency secondary to varicella. Strikingly, it was confirmed by a dramatic decrease in protein S plasma activity and a huge increase in immunoglobulin (Ig)G antibodies against protein S in the plasma. Anticoagulation therapy in addition with plasmapheresis and steroid pulses allowed a dramatic decrease in the antibodies against protein S and recovery of normal protein S activity. Undelayed diagnosis and treatment did not avoid kidney insufficiency but prevented life-threatening complications. In the light of this case report, protein S deficiency due to antibody inhibition should be carefully monitored anytime in the context of varicella when kidney insufficiency or necrosis occurs.     

Clinical implications of quantitative real time-polymerase chain reaction of parvovirus B19 in kidney transplant recipients – a prospective study

This prospective study was designed to investigate the clinically significant level of parvovirus B19 viral load using quantitative real-time (RT) polymerase-chain reaction (PCR) in kidney transplantation (KT) recipients. One hundred forty-three adult recipients who underwent their first KT between November 2003 and October 2005 were enrolled. Six blood samples (the first taken preoperatively, subsequent samples taken every 4 weeks for 20 weeks) were taken from each patient for parvovirus B19 DNA RT-PCR analysis. All recipients were diligently followed for 1 year post-transplant. One hundred sixty-eight of the 715 (23.5%) postoperative samples were positive for parvovirus B19 PCR. Eighty-four of the 143 KT recipients (58.7%) showed at least one positive PCR. Sixteen of the 143 (11.1%) KT recipients had sustained severe anemia (SSA) with hemoglobin lower than 7.0 g/dl, after 4 weeks post-transplant. The incidence of SSA in recipients with a titer higher than 1 × 10⁶ copies/5 μl whole blood was significantly higher than those with a negative or low titer ( P  <   0.001, positive predictive value 84.6%, negative predictive value 96.2%). In conclusion, a high titer of parvovirus B19 DNA higher than 1 × 10⁶ copies/5 μl whole blood in KT recipients was related with SSA after 4 weeks post-transplant.     

The Prevalence and Clinical Characteristics of Reflux Esophagitis in Koreans and Its Possible Relation to Metabolic Syndrome

The prevalence of reflux esophagitis is increasing in Korea. To estimate the prevalence and clinical characteristics of reflux esophagitis in healthy subjects, we retrospectively examined the medical records of healthy subjects undergoing a routine check-up from October 2004 to September 2005. A total of 6,082 (3,590 men, mean age 44±10 yr) subjects were enrolled in this study. The prevalence of reflux esophagitis in healthy subjects was 10.5%. According to the univariate analysis, male sex (odds ratio [OR] 3.49, 95% confidence interval [CI] 2.84-4.30), smoking history (OR 1.91, 95% CI 1.60-2.28), body mass index (BMI) >30 kg/m² (OR 2.13, 95% CI 1.37-3.33), total cholesterol >250 mg/dL (OR 1.50, 95% CI 1.05-2.14), low-density lipoprotein (LDL) cholesterol ≥160 mg/dL (OR 1.52, 95% CI 1.08-2.14), triglyceride ≥150 mg/dL (OR 1.92, 95% CI 1.61-2.30), high blood pressure (BP) (OR 1.46, 95% CI 1.20-1.76), and fasting glucose ≥110 mg/dL (OR 1.45, 95% CI 1.13-1.86) were significantly associated with reflux esophagitis (all p<0.05). However, age, alcohol drinking and Helicobacter pylori infection were not associated with reflux esophagitis. In conclusiosn, significant relationships of reflux esophagitis with obesity, low high-density lipoprotein (HDL) cholesterol, high triglyceride, high BP, and elevated fasting glucose suggested that reflux esophagitis might represent the disease spectrum of the metabolic syndrome.     

Gender Difference in the Prodromal Symptoms of First-episode Schizophrenia

To investigate the gender difference of early symptoms appearing before the onset of the psychotic symptoms in patients with first-episode schizophrenia, we reviewed the medical records of 63 patients (38 males, 25 females), who were hospitalized for first-episode schizophrenia. The frequency and duration of prodromal and psychotic symptoms, Clinical Global Impression scale scores, Global Assessment of Functioning (GAF) scale scores at admission, and other clinical characteristics were recorded for all patients. Overall, the most common prodromal symptoms were attenuated positive symptoms (89%), followed by mood symptoms (86%). Negative symptoms were the most common in male patients (97.4%), whereas attenuated positive symptoms were the most common in female patients (84%). Male patients demonstrated more frequent negative, cognitive, and obsessive-compulsive symptoms than female patients did and also showed a tendency of having negative symptoms for the longer period. Correlational analysis showed a significant negative correlation between the duration of negative symptoms and GAF scores at admission in male patients. Our findings suggest that different patterns of prodromal symptoms between male and female begin before the onset of the psychosis. Further prospective studies should be needed.     

GnRH Agonist Therapy in a Patient with Recurrent Ovarian Granulosa Cell Tumors

A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.     

On-chip testing device for electrochemotherapeutic effects on human breast cells

A microfabricated cell-based testing device for electrochemotherapy (ECT) has been developed by miniaturizing the widely used clinical electroporator with a two-needle array into two-dimensional planar electrodes while keeping the similarity of the electric field strength distribution. In this device, all the biological processes from cell culture to electroporation and final cell-based assays were carried out on a chip using a conventional 2D cell culture method, and the multiple electrochemotherapeutic assays could be realized by exploiting the six electroporation sites in a single device. With the proposed platform, the electroporation rate was evaluated with propidium iodide and cell proliferation after 48 h of electrochemotherapy with bleomycin was determined with T47D human breast ductal carcinoma cell line in various electric field strengths and drug concentrations. This microsystem has several advantages over conventional cuvette type electroporation assay, such as multiple assays on a chip, on-chip based operation from cell culture to final assay, and having similar electric field distribution as that of the clinical electroporator. As the clinical trials of electrochemotherapy are being carried out, this new platform is expected to have valuable applications in basic in vitro ECT studies, drug discovery, and development of clinical ECT equipment.     

Cell encapsulation and oxygenation in nanoporous microcontainers

With strides in stem cell biology, cell engineering and molecular therapy, the transplantation of cells to produce therapeutic molecules endogenously is an attractive and achievable alternative to the use of exogenous drugs. The encapsulation of such cell transplants in semi-permeable, nanoporous constructs is often required to protect them from immune attack and to prevent their proliferation in the host. However, effective graft immunoisolation has been mostly elusive owing to the absence of a high-throughput method to create precisely controlled, high-aspect-ratio nanopores. To address the clinical need for effective cell encapsulation and immunoisolation, we devised a biocompatible cell-encapsulating microcontainer and a method to create highly anisotropic nanopores in the microcontainer’s surface. To evaluate the efficacy of these nanopores in oxygenating the encapsulated cells, we engineered 9L rat glioma cells to bioluminesce under hypoxic conditions. The methods described above should aid in evaluating the long term survival and efficacy of cellular grafts.     

The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer

Background  

Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term “lymphovascular invasion” (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients.