Temporally Distinct Roles for the Zinc Finger Transcription Factor Sp8 in the Generation and Migration of Dorsal Lateral Ganglionic Eminence (dLGE)-Derived Neuronal Subtypes in the Mouse.

Progenitors in the dorsal lateral ganglionic eminence (dLGE) are known to give rise to olfactory bulb (OB) interneurons and intercalated cells (ITCs) of the amygdala. The dLGE enriched transcription factor Sp8 is required for the normal generation of ITCs as well as OB interneurons, particularly the calretinin (CR)-expressing subtype. In this study, we used a genetic gain-of-function approach in mice to examine the roles Sp8 plays in controlling the development of dLGE-derived neuronal subtypes. Misexpression of Sp8 throughout the ventral telencephalic subventricular zone (SVZ) from early embryonic stages, led to an increased generation of ITCs which was dependent on Tshz1 gene dosage. Additionally, Sp8 misexpression impaired rostral migration of OB interneurons with clusters of CR interneurons seen in the SVZ along with decreased differentiation of calbindin OB interneurons. Sp8 misexpression throughout the ventral telencephalon also reduced ventral LGE neuronal subtypes including striatal projection neurons. Delaying Sp8 misexpression until E14-15 rescued the striatal and amygdala phenotypes but only partially rescued OB interneuron reductions, consistent with an early window of striatal and amygdala neurogenesis and ongoing OB interneuron generation at this late stage. Our results demonstrate critical roles for the timing and neuronal cell-type specificity of Sp8 expression in mouse LGE neurogenesis.

Hematological changes following early ligation of splenic artery during splenectomy in shunt surgery for portal hypertension.

OBJECTIVE AND BACKGROUND DATA: Reduction in cellular elements of blood, secondary to hypersplenism is an established component of non-cirrhotic portal hypertension. Prior transfusion of blood or blood components is frequently required for safe surgical intervention. Due to thrombocytopenia, epidural catheter insertion for effective and durable analgesia is not possible. The aim of the present study was to objectively demonstrate the gain in blood components following early ligation of splenic artery for splenectomy in shunt surgery. METHODS: From Jan 2008 to July 2010, 30 patients underwent elective proximal spleno renal shunt for portal hypertension, for various indications and were analyzed prospectively. We followed the standard protocol of ligating the splenic artery in situ, first in the lesser sac. Proximal spleno shunt was done. After the surgical procedure and before extubation, an epidural catheter was placed for effective and durable analgesia. 5ml of venous blood was drawn in the following order of sequence: prior to induction of anesthesia, immediately after the ligation of splenic artery, 30 minutes after ligation of splenic artery and 30 minutes after splenectomy. Samples were sent for complete hemogram and values were analyzed in respective order. Patients requiring transfusion of blood or blood components during surgery were excluded from the study. RESULTS: 30 patients (M - 9, F- 21) with mean age of 29.4 years (11-60 years) were analyzed (NCPF- 20, EHPVO- 9, cirrhosis- 1). We objectively demonstrated a significant gain in RBCs (p = 0.016) and platelets (p = 0.000) using this standard protocol. As there were no intrinsic abnormalities in RBCs, red blood cell indices (MCV, MCH, MCHC) showed no changes as expected (p-0.9). CONCLUSION: By following this standard protocol, in addition to reduction in blood loss there was a significant gain in RBCs and platelets. This gain allows the surgeon to perform the surgical procedure safely and the anesthetist to secure an epidural catheter immediately after surgery for effective and durable analgesia without prior transfusion.

Proposed Mayo Clinic criteria for the diagnosis of Tako-Tsubo cardiomyopathy and long-term prognosis.

Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy with a clinical presentation indistinguishable from myocardial infarction. TTC is estimated to represent 1%-2% of patients presenting with acute myocardial infarction. It most commonly occurs in postmenopausal women and is frequently precipitated by a stressful event. Chest pain and dyspnea are the typical presenting symptoms. Transient ST-segment elevation on ECG and a small rise in cardiac biomarkers are common. Characteristic wall motion abnormalities extend beyond the territory of a single epicardial coronary artery in the absence of obstructive coronary lesions. Supportive treatment leads to spontaneous rapid recovery in nearly all patients. The prognosis is excellent, and recurrence occurs in < 10% of patients. In this article, we review the clinical features of TTC that form the basis of the Mayo Clinic diagnostic criteria, as well as the long-term prognosis for this type of cardiomyopathy.

Isolated mesenteric fibromatosis.

Fibromatosis is a rare, locally aggressive but non-metastasising fibrous mass often associated with familial adenomatous polyposis in Gardner's Syndrome (GS). Although sporadic cases occur, unlike in GS, they are predominantly extra-abdominal. We report the case of a 40-year-old lady who underwent laparotomy for a large isolated abdominal mass three years after a Whipple's procedure for adenocarcinoma of the distal common bile duct. A spherical, football sized tumour was found in the jejunal mesentery. Resection of the tumour with jejunum was carried out. No metastasis was detected. This case is peculiar in that mesenteric fibromatosis occurred in a patient with prior history of periampullary carcinoma and without history of familial adenomatous polyposis.

Intra-cranial metastatic lacrimal gland tumour.

We report a case of an adult who presented with progressive swelling in the right eye with suggestive of intracranial lesion on imaging. Histopathological revealed a lacrimal gland malignant mixed tumour.

Epilepsy surgery on dysembryoplastic neuroepithelial tumours.

Two rare cases of intractable epilepsy caused by Dysembryoplastic Neuroepithelial Tumours (DNET) are reported and their different management discussed. The first case required vagal nerve stimulation and radiosurgery while the later was operated with the help of neuronavigation. Both had good outcome according to Engel classification after a one year follow up.

Extradural spinal cord and intraabdominal ganglioneuroblastoma.

We report a rare case of a giant extradural and intraabdominal ganglioneuroblastoma in a young Malay girl who presented to a paediatrician initially at 5 days of life with a palpable abdominal mass. Unfortunately, the parents refused any form of surgical intervention until the child was 3 years old. She subsequently underwent vascular embolisation followed by the removal of this large tumour both via the abdomen and through a laminectomy approach and subsequently refused chemotherapy. The c-myc amplication in this patient was absent and there were no chromosomal aberrations, During the 2 year folow-up the patient remained well, and ambulatory with no tumour recurrence.

Serum bilirubin distribution and its relation to cardiovascular risk in children and young adults.

There is evidence that bilirubin functions as an endogenous tissue protector by its antioxidant and anti-complement actions, properties that are relevant to atherogenesis. Serum bilirubin distribution and its relation to cardiovascular risk were examined in 4156 individuals aged 5-30 years from a biracial (black white) community. Bilirubin levels showed significant differences related to race (whites > blacks) and sex (males > females, except in 5-10 year olds). In males the levels increased with age up to 24 years, while in females the changes were less conspicuous. Both adiposity and cigarette smoking associated independently and inversely with bilirubin. In addition, serum bilirubin correlated positively with HDL cholesterol and inversely with triglycerides, VLDL cholesterol, LDL cholesterol, insulin, glucose and systolic blood pressure although these correlations were significant only in certain age-race-sex groups. Offspring with a parental history of heart attack or hypertension had consistently lower bilirubin levels than those without such parental history. Thus, bilirubin may be an inverse risk factor for cardiovascular disease.

Ocular changes in epidermolysis bullosa letalis.

Ocular changes in a rare case of epidermolysis bullosa letalis included edema of the trabecular meshwork, ciliary body, lens, optic nerve, and formation of edema cysts in the iris. The retinal was completely detached and focally necrotic. Foci of necrosis and detachment of the retinal pigment epithelium were also observed with occasional breach in the Bruch's membrane. The choroid showed focal edema and congestion.

Genetics of anesthetic response: autosomal mutations that render Drosophila resistant to halothane.

Molecular mechanisms of anesthetic action are poorly understood. Genetic approaches to investigate mechanisms of anesthesia, although sparse and rather new, are turning out to be informative and add a new perspective. Before beginning a systematic investigation of anesthesia by this approach, it is necessary to have at hand a large collection of mutations in different loci that alter anesthetic response. We report here the isolation and characterization of six mutant autosomal lines that show a decreased sensitivity to the inhalation of anesthetic halothane. Two of these mutations, Omar(82) and Qajjem(211) are shown to map to separate loci on the third chromosome.

Nm23H1 and p53 proteins are differentially correlated to metastasis in breast carcinoma.

The prognostic significance of nm23H1 and p53 proteins as predictors of nodal involvement and distant recurrence was evaluated in 63 cancer and 47 benign lesions of the breast. Assessment was carried out by immunohistochemical staining using nm23H1 and p53 antibodies. Results show no relation of nm23H1 either to the malignant nature when compared to benign lesions or to the nodal status. P53 protein, on the other hand, showed significantly increased expression in malignant lesions (p=0.001) and correlated well with nodal positivity (p=0.03). A follow-up study of 5 years showed that among the cases showing recurrence, those with positive mn23H1 showed a shorter distant recurrence free survival (DRFS, p=0.01), while p53 expression had no effect. This result did not agree with the previous reports showing nm23H1 as an antimetastatic gene. This is the first report of positive correlation between nm231-11 and distant recurrence in breast cancers, though such a correlation was reported earlier in certain other cancers. Since nm23H1 is an NDP kinase, having more involvement in signal transduction of cell proliferation, it is not difficult to comprehend such a role for nm23H1 during recurrence. Combining the expression of both proteins, lesions positive for both p53 and nm23H1 had significantly reduced distant recurrence free survival (DRFS), when compared to those negative for both proteins (p=0.0006). It can be concluded that nni23H1 alteration has a potential in predicting DRFS, while p53 alteration has the potential to predict lymph node involvement.

Apoptotic index: use in predicting recurrence in breast cancer patients.

Apoptosis maintains tissue homeostasis through its ability to control cell population and has been extensively studied in human cancers. Relation of apoptosis to prognosis is still controversial. In this study, we analyzed the prognostic significance of apoptotic and mitotic indices (AI & MI) using hematoxylin and eosin stained slides by light microscopy in breast cancer patients. In our study, apoptotic index was significantly associated with predicting relapse free survival (RFS), distant recurrence free survival (DRFS) and overall survival (OS) with lesions having higher apoptotic index showing poor prognosis. Our results also point out that quantitation of apoptotic index by simple light microscopy as a routine practice along with histological diagnosis, could provide additional prognostic information in patients who are at high risk of developing recurrence with breast cancers.

Primary pulmonary adenoid cystic carcinoma: report of a case diagnosed by fine-needle aspiration cytology.

Adenoid cystic carcinoma of the lower respiratory tract is an uncommon tumor that can arise in the mainstem bronchus and often presents as an endobronchial mass lesion causing bronchial obstruction with post obstructive atelectasis and pneumonia. Exfoliative cytology is seldom useful in the diagnosis of primary bronchial adenoid cystic carcinoma, because these neoplasms usually have a submucosal location with often intact mucosa. Since most endobronchial adenoid cystic carcinomas are endoscopically visible, bronchoscope-guided fine-needle aspiration constitutes an excellent approach to establish a pathologic diagnosis. The fine-needle aspiration cytology of primary pulmonary adenoid cystic carcinoma has been rarely described. We report a case of primary adenoid cystic carcinoma of the lung having characteristic cytologic features and correlate with computed tomography, bronchoscopic, and histological findings. Bronchoscope-guided aspiration cytology provided a conclusive diagnosis of adenoid cystic carcinoma, which was further corroborated by histology in the pneumonectomy specimen. Diagn. Cytopathol. 2004;30:51-56.

Serum lipid and lipoprotein fractions in bengal gram and biochanin A induced alterations in atherosclerosis.

Serum lipids and lipoproteins were studied in rabbits fed on egg yolk supplemented diet to induce hypercholesterolemia. Bengal gram and synthetically pure isoflavone Biochanin A have been used as lipodiatic agents in this study. Rabbits were divided into four groups: Group A were fed on egg yolk supplement alone to form the positive control group, Group B were fed with 40 gms of overnight soaked bengal gram (Cicer arietinum), Group C were fed with 50 mgs of Biochanin A fortnightly, Group D was negative control group fed on pelleted laboratory feed. Serum samples were taken every month and total cholesterol, triglycerides and HDL cholesterol were estimated. The other lipoproteins like LDL cholesterol and VLDL cholesterol were obtained by calculations. The Group B and C showed a significant decrease of their lipids and lipoprotein in comparison to Group A thereby indicating the lipodiatic effect of these two substances. However, HDL cholesterol showed an increase in these two groups thereby proving that an increased HDL cholesterol has a protective effect on the atherosclerotic process.

Studies on serum and tissue lipid fractions in Bengal gram induced retardation of experimental atherosclerosis.

Serum and tissue lipid levels were studied in rabbits in whom egg yolk was used to induce atherosclerosis and Bengal gram was supplemented in the diet as a lipodiatic agent. Monthly serological and tissue studies were done to assess the levels of total cholesterol, triglycerides and phospholipids and it was found that egg yolk feeding leads to statistically significant increases in all these fractions in the serum, liver, adrenals, heart and aorta. Bengal gram supplementation of the diet led to flattening of the atherosclerotic plaques and showed statistically significant decline in the organs with the exception of the kidney. This study confirms the lipodiatic effect of the bengal gram and its beneficial effect on the atherosclerotic plaque.

Protein C levels in ischaemic heart disease.

Protein C is a circulating glycoprotein with anticoagulant properties. Functional and immunological levels of protein C were determined in 34 cases of ischaemic heart disease and 12 healthy age-matched controls. The sensitive colorimetric assay was used to determine the functional levels and ELISA for antigenic levels. Mean protein C activity and antigenic levels were found to be elevated in these patients as compared to controls. Protein C levels in the three individual subgroups-acute myocardial infarction, previous myocardial infarction and chronic stable angina pectoris-were also raised as compared to controls. The elevation was significant in the case of the acute myocardial infarction group. These results further support the hypothesis that the body synthesises increased amounts of protein C in ischaemic heart disease to compensate for the hypercoagulable state that exists in this disorder, thus playing a protective role.

Malignant paraganglioma of frontoethmoidal region.

Nonchromaffin paragangliomas are unusual tumours arising from widely distributed paraganglionic tissues probably of neural crest origin. In the head and neck region they are usually seen as carotid body or jugulotympanic tumours. Other rarely reported sites in the head and neck region are the orbit, nose and larynx. This report deals with a case of sinonasal paraganglioma which was initially treated with surgery and radiotherapy. Twenty two years later the tumour recurred and showed a rapid growth due to malignant transformation which we believe is late effect of radiotherapy. The clinical features, histopathology and role of radiotherapy in sinonasal paragangliomas together with a review of the medical literature have been discussed.

Diagnostic parameters of vascular neoplasms by immunohistochemistry.

Immunohistochemical identification of Factor VIII-related antigen and Ulex Europaeus A-I lectin as endothelial markers were studied in a series of 103 cases, comprising of benign and malignant vascular tumours, and few undifferentiated sarcomas. The results are correlated with that of others in this area and emphasizes the utility of these markers in surgical pathological diagnosis, especially to confirm the difficult diagnosis of angiosarcoma from other poorly differentiated sarcomas.

Cell marker studies in undifferentiated soft tissue sarcoma.

100 cases of undifferentiated soft tissue sarcomas were studied using cell markers by immunoperoxidase technique with DAB as substrate. Vimentin, Desmin, Myoglobin, Actin, Keratin, Epithelial Membrane Antigen, S-100 protein, F VIII R Ag, A1 Antitrypsin, A1 Antichymotrypsin, Collagen-IV and UEA-1 lectin were used as markers. Fibrosarcoma was consistently positive for Vimentin and Collagen-IV. The undifferentiated Rhabdomyosarcoma showed strong and consistent positivity for Vimentin Actin and Myoglobin. Desmin positivity was the hallmark of leiomyosarcoma, whereas the malignant schwannomas were identified by their S-100 positivity. This marker along with A1AT and A1ACT reactivity was of great use in the identification of malignant fibrous histiocytoma. Angiosarcoma/malignant haemangioendothelioma could be identified with great accuracy by their strong positivity for F VIII RAg and UEA-1 lectin. Other miscellaneous sarcomas also could be identified by their specific reactivity to the markers used. We consider immunohistochemistry to be an important and essential adjunct to routine stains in the diagnosis of undifferentiated soft tissue sarcomas.