Comparison of cytological features of myxopapillary ependymomas on crush preparations

Myxopapillary ependymoma (ME) is a rare neoplasm found predominantly in the sacro‐coccygeal region in adults and is characterized by its distinct epithelial and stromal components. From 1990 to April 2008, a total of 10 ME cases were recorded at our institution. Six out of 10 cases underwent frozen section examination with concomitant crush preparations, which forms the basis of this study. The clinical and cytologic findings in all six cases were reviewed. There were four males and two females. The age ranges from 15 to 36 years with a mean age of 27 years. The epithelial component of ME is strikingly similar for all six cases showing tumor cells appearing singly or in loose clusters, most with papillary branching. There was also presence of indistinct cell boundaries, tapered cytoplasmic prolongations, wispy/fragile cytoplasm, and uniform oval‐to‐fusiform shaped nuclei with an evenly distributed chromatin pattern. The stromal component was composed mainly of thick, metachromatic material and adenoid cystic‐like areas. One case showed rosette‐like structures. These aforementioned characteristics can be utilized to distinguish ME from other primary and metastatic tumors such as meningioma, adenoid cystic carcinoma, chordoma, mucinous adenocarcinoma, chondrosarcoma, and germ cell tumors. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Initiation of a pharmacovigilance programme at a tertiary care hospital in South India

Objective India is a country with the availability of a large number of pharmaceutical preparations as branded generics. At the time of this study there was no established pharmacovigilance system at the national level except a co‐ordinating centre at the national capital. The study site was a tertiary care teaching hospital with a bed capacity of 500 and with an average of 200 outpatient visits and 50 inpatient admissions per day. The hospital did not have any system of monitoring and documenting adverse drug reactions. The objective of the study was to introduce an adverse drug reaction (ADR) monitoring programme at a tertiary care teaching hospital and assess ADR‐related issues in both inpatient and outpatient departments. Method All departments willing to report ADRs were included in the study, which was carried out for one year. Physicians and nurses filled in the notification forms when they encountered suspected ADR cases. These cases were then assessed by a panel of four judges. According to Naranjo's algorithm, the ADRs were assessed and classified based on World Health Organization (WHO) classification. Key findings A total of 288 suspected cases were reported and 264 ADRs were confirmed by the panel. According to Naranjo's probability scale, 83 cases were categorized as ‘probable’, 181 cases were classified as ‘possible’, and none were classified as ‘unlikely’ or ‘definite’. The most common classes of drugs involved were antibiotics (25%), psychotropics (20%), analgesic and cardiovascular agents (14% each). Generalised itch and rash, tremors, urticarial drug reaction, oral ulcer, gastritis and akathesia and extrapyramidal symptoms were found to be the most common ADRs observed; 2.1% of the patients in the studied departments had ADRs. Conclusion The ADR reporting system was initiated at the hospital and was well received by the physicians. Appreciable participation of physicians was noted during the study in reporting ADRs. The study also gave an insight into the awareness of physicians about ADR‐related issues. The number of ADRs reported was reasonably comparable with the findings of other authors from India.     

Infrequent p53 mutations in 7,12-dimethylbenz[a]anthracene–induced mammary tumors in BALB/c and p53 hemizygous mice

We conducted experiments to determine if p53 alterations, which are frequent in human breast cancers, were also common in murine mammary tumors. In 13 mammary tumors from 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/c mice were immunohistochemically analyzed for overexpression of p53; p53 protein was not detectable. Three of the tumors were established as cell lines in vitro. p53 protein was rarely detected at passage 4 in these lines but was overexpressed by passage 8 in two of them. The p53 nucleotide sequence was shown to be wild type in one primary mammary tumor and in the two p53-overexpressing cell lines. One cell line that overexpressed p53 in vitro was implanted into BALB/c mice. The resulting tumors retained the wild-type p53 nucleotide sequence but no longer expressed detectable levels of p53 protein, suggesting that the overexpression of wild-type p53 was related to in vitro culture conditions. The effect of DMBA on mammary-tumor development was also tested in mice rendered hemizygous for p53. These mice and wild-type littermate controls had no differences in susceptibility to induction of mammary tumors by oral administration of DMBA. Furthermore, Southern blot hybridizations detected no gross alterations in the wild-type p53 allele in mammary tumors from the p53-deficient mice. Point mutation of the wild-type p53 allele was also infrequent in the DMBA-induced mammary tumors from hemizygous p53 mice; it occured in only one of seven tumors. Thus, the p53 gene is apparently not a primary target for genetic alterations in DMBA-induced mammary tumors. Next, we examined mammary tumors derived from D1 and D2 transplantable hyperplastic alveolar nodule (HAN) outgrowths, which rapidly form tumors containing Ha-ras mutations after DMBA treatment. As ras and p53 mutants can cooperate in transformation, we examined whether D1 and D2 HAN outgrowths have p53 mutations. Unlike in the DMBA-induced primary mammary tumors, nuclear p53 accumulation was observed frequently (10 of 14) in tumors that arose from D1 and D2 HAN outgrowths. Direct sequencing of the entire coding region of the p53 cDNA from six D1 and D2 tumors confirmed that the sequence was wild type. Although wild-type p53 was retained in both DMBA-induced mammary tumors and mammary tumors derived from D1 and D2 preneoplastic outgrowths, wild-type p53 overexpression was detected only in D1 and D2 tumors. Therefore, D1 and D2 tumors appear to arise by a pathway in which p53 expression is altered, whereas DMBA induction affects a different pathway that does not require such alteration. © 1994 Wiley-Liss, Inc.     

Chylous ascites in infants and children: a case report and literature review

Successful treatment of an infant with chylous ascites secondary to "congenital leaky lymphatics" is described, followed by a literature review of cases of pediatric chylous ascites. The infant was placed on home total parenteral nutrition for 10 weeks, during which time the chylous ascites resolved and did not recur with the introduction of a normal diet. Forty cases of pediatric chylous ascites have been reported since 1960, with an age range from birth to 18 years. The presenting signs and symptoms were secondary to abdominal distension in over 80% of cases. The chylous ascites was secondary to trauma, which included child abuse (19%), obstruction (27%), or lymphatic abnormalities (54%). Most studies described were not helpful in making the diagnosis, except for lymphangiography and exploratory laparotomy. Many patients were treated with a high-protein, low-fat diet, with or without medium-chain triglycerides, with variable success. Total parenteral nutrition (TPN) was the primary therapeutic modality in five patients, and in all but one of the cases there was complete resolution of the chylous ascites over 3 to 10 weeks with no significant side effects. Total parenteral nutrition, including home TPN, is a safe and effective therapeutic modality for some cases of chylous ascites.     

Induction of differential patterns of local cerebral glucose metabolism and immediate-early genes by acute clozapine and haloperidol

Atypical antipsychotic drugs, such as clozapine, show many differences in their actions as compared to typical antipsychotic drugs, such as haloperidol. In particular, the neuroanatomical substrates responsible for the superior therapeutic profile of clozapine are unknown. In order to identify regions of the CNS which are affected either differentially or in parallel by clozapine and haloperidol, we have used 2-deoxyglucose autoradiography to monitor local cerebral glucose utilisation (LCGU), in parallel with in situ hybridisation to monitor the expression of five immediate-early genes (c-fos, fos B, fra 1, fra 2 and zif 268). Clozapine (20 mg/kg i.p.) caused a reduction in LCGU in many areas of the psychosis-related corticolimbothalamic and Papez circuits, such as the anterior cingulate and retrosplenial cortices and the mammillary body. Haloperidol (1 mg/kg i.p.) showed less ability to modulate LCGU in these regions. Clozapine also increased immediate-early gene expression in these limbic circuits, although the pattern of induction was different for each gene, and also differed from the pattern of effects on LCGU. The only region which displayed similar effects with both antipsychotics was the anteroventral thalamus, with LCGU and c-fos mRNA expression being altered similarly by both drugs. This further supports the hypothesis of the thalamus being a common site of antipsychotic action. Since the Papez circuit has been implicated in emotive learning, and to be involved in mediating the negative symptoms associated with schizophrenia, the greater action of clozapine on regions within this circuit may also provide clues to the atypical antipsychotic's superior efficacy against negative symptoms.This is one of the first studies which provides a direct comparison of regional activity as assessed by LCGU and by a panel of IEGs. The results emphasise the necessity of monitoring a number of different parameters of regional activity in order to identity the neuroanatomical substrate for actions of a drug in the CNS.     

The effect of enamel matrix proteins on periodontal regeneration as determined by histological analyses

BACKGROUND: Therapeutic approaches to periodontal regeneration in the past have utilized bone replacement grafts, growth factors, barrier membranes, or combinations of these approaches. More recently, enamel extracellular matrix proteins have been introduced to stimulate periodontal regeneration. One factor thought to have an impact on the outcome of the regenerative process is the initial size of the periodontal defect. This is particularly the case when using proteins to stimulate regeneration, because the concepts of guided tissue regeneration emphasize the need for space maintenance to allow for selected cell repopulation. The goal of this study was to evaluate periodontal regeneration in intrabony defects of various sizes treated with enamel matrix proteins. METHODS: Periodontal defects ranging in size from 1 to 6 mm were created bilaterally around 3 teeth in the mandibles of baboons. Plaque was allowed to accumulate around ligatures placed into the defects. After 2 months, the ligatures were removed, the teeth were scaled and root planed, and a notch was placed at the base of the defect. On one side of the mandible, neutral ethylene diamine tetracetic acid and enamel matrix proteins were used to treat the defects. The other side served as a control, with neutral ethylene diamine tetracetic acid treatment alone after scaling and root planing. Flaps were sutured and the animals were allowed to heal without oral hygiene procedures. After 5 months, the animals were sacrificed and the teeth were processed for histological evaluation. RESULTS: Periodontal regeneration occurred in all sizes of the periodontal defects. Qualitatively, new cementum, periodontal ligament with Sharpey's fibers, and new bone tissue were observed. In general, enamel matrix protein treatment resulted in greater tissue formation than controls. In many instances, dramatic tissue formation occurred far coronal to the base of the defects. In addition, horizontal bone fill occurred in defects that were initially 4 or 6 mm wide. The resultant width of the periodontal ligament was similar in all defects regardless of the original defect width. The cementum width was slightly greater in the wider (4 and 6 mm) defects compared to the more narrow (1 and 2 mm) defects. When evaluating the combined 1 and 2 mm defects, the height of new cementum with enamel matrix protein treatment was 45% greater than the control, with 31% greater new bone height versus the control. In the combined wider defects (4 and 6 mm), new tissue height was more similar between enamel matrix protein-treated defects and control defects. The results from the wider defects must be interpreted cautiously, because the interproximal bone heights were resorbed more adjacent to the wider defects during the plaque accumulation period and likely limited the potential for regeneration. CONCLUSIONS: The treatment of various sized periodontal defects with enamel matrix proteins stimulated substantial periodontal regeneration. In many cases, dramatic amounts of new cementum, Sharpey's fibers, periodontal ligament, and bone tissue were formed far coronal to the notch at the base of the defect, especially considering the width of the original defects. This periodontal regeneration occurred in the absence of exogenous growth factors, bone replacement grafts, barrier membranes, or their combination.     

Osteoblast-mediated mineral deposition in culture is dependent on surface microtopography

Osteoblast phenotypic expression in monolayer culture depends on surface microtopography. Here we tested the hypothesis that mineralized bone nodule formation in response to osteotropic agents such as bone morphogenetic protein-2 (BMP-2) and dexamethasone is also influenced by surface microtopography. Fetal rat calvarial (FRC) cells were cultured on Ti implant materials (PT [pretreated], Ra = 0.6 microm; SLA [course grit blasted and acid etched], Ra = 4.0 microm; TPS [Ti plasma sprayed], Ra = 5.2 microm) in the presence of either BMP-2 (20 ng/ml) or 10(-8) M dexamethasone (Dex). At 14 days post-confluence, a homogenous layer of cells covered the surfaces, and stacks of cells that appeared to be nodules emerging from the culture surface were present in some areas on all three Ti surfaces. Cell proliferation decreased while alkaline phosphatase specific activity (ALPase) and nodule number generally increased with increasing surface roughness in both control and treated cultures. There was no difference in cell number between the control and Dex-treated cultures for a particular surface, but BMP-2 significantly reduced cell number compared with control or Dex-treated cultures. Treatment with Dex or BMP-2 further increased ALPase on all surfaces except for PT cultures with Dex. Dex had no effect on nodule area in cultures grown on PT or SLA disks, yet increased nodule number by more than 100% in cultures on PT disks. Though the effect of BMP-2 on nodule number was the same as Dex, BMP-2 increased nodule area on all surfaces except TPS, where area was decreased. Ca and P content of the cell layers in control cultures did not vary with surface roughness. However, cultures treated with Dex had increased Ca content on all surfaces, but the greatest increase was seen on SLA and TPS. BMP-2 increased Ca content in cultures on all surfaces, with the greatest increase on the PT surface. BMP-2 treatment increased P content on all surfaces, whereas Dex only increased P on rough surfaces. Of all cultures examined, the Ca/P weight ratio was 2:1 only on rough surfaces with BMP-2, indicating the presence of bone-like apatite. This was further validated by Fourier transform infrared (FTIR) imaging showing a close association between mineral and matrix on TPS and SLA surfaces with BMP-2-treated cells, and individual spectra indicated the presence of an apatitic mineral phase comparable to bone. In contrast, mineral on the smooth surface of BMP-2-treated cultures and on all surfaces where cultures were treated with Dex was not associated with the matrix and the spectra, not typical of bone apatite, implying dystrophic mineralization. This demonstrates that interactions between growth factor or hormone and surface microtopography can modulate bone cell differentiation and mineralization.     

HIV prevalence among foreign- and US-born clients of public STD clinics

OBJECTIVES: We examined differences in HIV seroprevalence and the likely timing of HIV infection by birth region. METHODS: We analyzed unlinked HIV antibody data on 61 120 specimens from 7 public health centers in Los Angeles County from 1993 to 1999. RESULTS: Most (87%) immigrant clients were Central American/Mexican-born. HIV prevalence was similar for US- and foreign-born clients (1.8% [95% confidence interval (CI) = 1.7%, 1.9%] and 1.6% [95% CI = 1.5%, 1.8%], respectively). Seroprevalence was high among sub-Saharan African females and low among Asian/Pacific Islander males and females. For HIV-positive immigrants, the average age at and time since immigration were 20.6 years and 12.3 years, respectively. CONCLUSIONS: The relatively young age at arrival and long time since arrival for HIV-positive foreign-born clients suggest that most were infected after immigration.