Lymphangiogenesis does not occur in breast cancer

Breast cancer metastasis predominantly occurs via lymphatic vessels. However, the study of lymphatic vessels and lymphangiogenesis has been hampered by lack of specific markers. Recently, antibodies directed against M2A (D2-40), Podoplanin, and Prox-1 that specifically mark lymphatic vessels in paraffin-embedded sections have become available. These were used to study lymphangiogenesis in archival paraffin sections of normal breast (n = 23), fibrocystic disease (n = 7), ductal carcinoma in situ (n = 32), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 5). In addition, endothelial proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and proliferating cell nuclear antigen (PCNA). Expression of D2-40, Prox-1, and Podoplanin was seen in lymphatic vessels but not in blood vessels. Lymphatic vessels were seen in the peritumoral area and as "entrapped" intratumoral vessels adjacent to preexisting normal lobules and ducts. Unlike angiogenesis, there was no increase of lymphatic vessel density in association with neoplastic transformation. On the contrary, a marked reduction in intratumoral lymphatic vessel density was seen in comparison to normal breast tissue, fibrocystic disease, and ductal carcinoma in situ (P = 0.0001). There was an increase in peritumoral lymphatic vessel density as compared with normal breast (P = 0.0001). However, the endothelial cells in the "entrapped" or the peritumoral lymphatic vessels did not show any expression of PCNA indicating minimal or no proliferative activity. This was in contrast to the strong expression seen in adjacent tumor cells and blood vessel endothelial cells. Thus, lymphangiogenesis was not evident when studied by lymphatic vessel density or by lymph vessel endothelial proliferation.     

Review analysis of medullary carcinoma of the thyroid: a 15-year Indian experience

The aim of this study was to emphasize the importance of adequate primary surgery in cases of medullary carcinoma of the thyroid. We retrospectively reviewed 44 cases of medullary carcinoma of the thyroid treated in Government General Hospital, Chennai between 1987 and 2002. Patients who underwent total thyroidectomy with only central compartment dissection were compared with those who had undergone total thyroidectomy with meticulous triple compartment (bilateral lateral and central groups) nodal dissection. The group of total thyroidectomy with only central compartment dissection had a high rate of lymph nodal recurrence and persistent hypercalcitoninemia compared with the group with total thyroidectomy with meticulous triple compartment nodal dissection. (chi square, 4.503; P > 0.05). Primary surgery with total thyroidectomy with meticulous triple compartment dissection is superior to total thyroidectomy with central compartment dissection alone in terms of preventing nodal and local recurrences and achieving normal (basal and stimulated) serum calcitonin levels postoperatively.     

Clinical association: Lyme disease and Guillain-Barre syndrome

Guillain-Barre Syndrome (GBS) is a life-threatening condition in which patients may present to the Emergency Department in respiratory distress leading to death. The early identification and treatment of such a condition is paramount in preventing mortality. While there are many infections associated with GBS, the association with Lyme disease is uncommon. Through our case we aim to highlight Borrelia burgdorferi as an important antecedent infection associated with the development of GBS. In this case we report a 31-year-old male who was diagnosed with Lyme disease and GBS with relevant clinical presentation including progressive numbness and weakness in bilateral hands and feet for the past 1 week along with areflexia. Initiation of medical therapy with intravenous immunoglobulin and parenteral ceftriaxone resulted in resolution of his symptoms. The treatment of both diseases early can help prevent further central nervous complications leading to high morbidity and mortality.     

Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine

OBJECTIVES: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. DESIGN: Two multicenter, open-label, randomized 24-week studies. METHODS: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used. RESULTS: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01). CONCLUSION: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.     

Relation of childhood malnutrition to parental education and mothers’ nutrition related KAP

Severely malnourished children (26), weight for age 55.27±3.17, were identified in a colony of predominantly Muslim urban slum dwellers of low economic status. An equal number of normally nourished children matched for age, sex and per capita income were identified. A strong relation was found between nutritional status of the subjects and educational level of their mothers (P<0.025). Father's education was unrelated to childrens' nutritional status. A thirty seven point questionnaire was administered to the mothers to record their nutritional knowledge, attitudes and practices (KAP). Analysis revealed that better KAP in relation to 16 of these 37 questions was not associated with better nutritional status. Seven questions were found to have only a weak association. The remaining 14 questions were identified as important for a nutrition education programme. Comparison of nutritional KAP score based on these 14 questions in case of mothers of normal and severely malnourished children revealed a significantly higher score in the former. Questions related to growth monitoring and breast feeding were not found to be important. No significant association was found between mothers' KAP and educational level. It is concluded that (i) Maternal education and KAP are significantly and independently associated with childrens' nutritional status. (ii) The content areas of knowledge, attitudes and practices significantly associated with nutritional status pertain to nutritional requirements of children, nutritional value of foods, immunisation, hygiene, oral rehydration and diarrhea.     

Absence of p53 mutation at codon 249 in duck hepatocellular carcinomas from the high incidence area of Qidong (China)

Dietary aflatoxin and hepatitis B virus infection may play arole in generating the p53 tumor suppressor gene codon 249 hotspotmutation found in human hepatocellular carcinomas (HCCs) fromQidong (China) and southern Africa. No data are available onthe HCC site-specific mutation of the p53 gene in hepadnavirus-infectedanimals exposed to AFB₁. We have searched for the presence ofp53 gene codon 249 mutations in both duck hepatitis B virus(DHBV) positive and negative HCCs of domestic ducks from Qidong,where the human p53 hotspot is so prevalent, as well as in duckHCCs experimentally induced by AFB₁. Direct sequencing of DNAamplification products encompassing p53 codon 249 did not revealany mutations in 11 HCCs from Qidongducks, regardless of thestatus of DHBV infection. In addition no mutation was detectedin four HCCs from AFB₁-treated ducks. This contrasts with thehuman data; however, in humans, the mutation and the preferentialbinding of AFB₁ to codon 249 occurs at the third nucleotideG, while in duck, the codon 249 lacks this G residue. The DNAsequence of adjacent codons is also different in the two specieseven though the amino acid sequence is identical. This may explainthe low frequency of mutation we have observed. In addition,species differences in metabolism and DNA repair could influencethe occurrence of codon 249 mutations.