Management of chylothorax

BACKGROUND: Chylothorax is a rare primary or secondary condition the optimum management of which remains uncertain. METHODS: Twenty cases of chylothorax, including ten of primary chylothorax and ten secondary to either malignancy, subclavian vein thrombosis or lymphangioma treated between 1956 and 1986 have been reviewed. RESULTS: Open pleurectomy was the most successful treatment in preventing reaccumulation of the effusion. Three patients had thoracic duct-azygous vein anastomoses, but all anastomoses were probably occluded within a year of surgery. Three patients have been lost to follow-up and five died within 2 years of their treatment, but 12 patients were alive and free from an effusion 3-22 years after treatment. CONCLUSION: Patients with chylothorax should undergo lymphangiography to identify the cause and site of the lymphatic abnormality. Conservative treatment is successful in some patients but should be abandoned if the fluid loss exceeds 1.5 l/day for more than 5-7 days in an adult or more than 100 ml/day in a child. Parietal pleurectomy is the most successful treatment when no distinct chylous leak can be identified. Less commonly, an isolated chylous leak either in the chest or in the abdomen may be identified and this should be treated by direct ligation.     

Role of diameter differences among follicles in selection of a future dominant follicle in mares

Follicles > or = 5 mm were ablated in pony mares by a transvaginal ultrasound-guided technique on Day 10 (ovulation = Day 0). Follicle emergence (at 15 mm, experiment 1; at 6 mm, experiment 2) and development of the new wave was monitored by transrectal ultrasound. Deviation was defined as the beginning of a marked difference in growth rates between the two largest follicles. In experiment 1, mares were grouped (n = 4 per group) into controls, ablation-controls (ablations at Day 10 only), and a two-follicle model (periodic ablation sessions so that only the two largest follicles developed). There were no significant indications that the two-follicle model altered follicle diameters, growth rates, or time intervals of the two retained follicles at or between events (follicle emergence, deviation, and ovulation). In experiment 2, the two-follicle model (n = 14) was used for follicle and hormonal characterization and hypothesis testing, without the tedious and error-prone necessity for tracking many (e.g., 20) individual follicles. The future dominant follicle emerged a mean of 1 day earlier (p < 0.008) than the future subordinate follicle, the growth rates for the two follicles between emergence and deviation (6 days later) did not differ, and the dominant follicle was larger at the beginning of deviation (23.1 +/- 0.8 mm versus 19.6 +/- 0.9 mm; p < 0.0001). Mean FSH and LH concentrations increased (p < 0.05) concomitantly from emergence of the future dominant follicle and peaked 3 days later when the follicle was a mean of 13 mm. Thereafter, the two hormones disassociated until ovulation: FSH decreased and LH increased. Results supported the hypothesis that the future dominant follicle has an early size advantage over future subordinate follicles and indicated that the advantage was present as early as 6 days before deviation.     

Activation of protein kinase C modulates cell-cell and cell-substratum adhesion of a human colorectal carcinoma cell line and restores 'normal' epithelial morphology

Abnormal cell adhesion is an important contributing factor in invasion and metastasis. Here, we show that morphologically 'normal' cell-cell and cell-substratum adhesion can be restored to a poorly differentiated carcinoma cell line by activation of protein kinase C (PKC). This cell line, VACO 10MS, grows as multicellular aggregates loosely attached to the substratum. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, 7.5 nM) induces rapid adhesive changes with 2 components. First, within 15 min of TPA the cells become closely apposed, an event resembling the 'compaction' seen in the mouse early embryo. Next, over 2 hr, the cells spread, forming a monolayer. We show that compaction depends on extracellular calcium, E-cadherin-mediated adhesion and F-actin but not on protein synthesis, microtubules or substratum adhesion. By contrast, cell spreading is independent of cadherin and extracellular Ca2+ but involves the formation of focal contacts containing alpkha(v) integrin. TPA treatment causes rapid translocation of PKC-alpha to the insoluble fraction. During compaction, actin- and PKC-alpha-containing lamellae form over the entire aggregate surface, those adjacent to the substratum appearing to initiate spreading. Compaction does not involve increased phosphorylation of the cadherin/catenin complex. We conclude that activation of PKC-alpha restores 'normal' morphology to these poorly differentiated cells. Our results are of general interest in relation to the regulation of cell adhesion and, through further investigation, may lead to identification of novel targets for therapeutic suppression of invasion and metastasis.     

Fusion-competent vaccines: broad neutralization of primary isolates of HIV

Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.     

The crying infant

The crying infant is a common presenting complaint and a difficult diagnostic dilemma that may represent the primary manifestation of a serious or even life-threatening condition. Although many children experience an exacerbation of the normal crying tendencies or minor ailments typical of the early months of life, a significant number of infants have underlying pathologic conditions requiring immediate intervention. This article briefly reviews current and past research on this phenomenon and presents differential diagnoses and recommendations for the evaluation and management of the acute crying episode.     

Isolation and characterization of the Saccharomyces cerevisiae DPP1 gene encoding diacylglycerol pyrophosphate phosphatase

Diacylglycerol pyrophosphate (DGPP) is involved in a putative novel lipid signaling pathway. DGPP phosphatase (DGPP phosphohydrolase) is a membrane-associated 34-kDa enzyme from Saccharomyces cerevisiae which catalyzes the dephosphorylation of DGPP to yield phosphatidate (PA) and then catalyzes the dephosphorylation of PA to yield diacylglycerol. Amino acid sequence information derived from DGPP phosphatase was used to identify and isolate the DPP1 (diacylglycerol pyrophosphate phosphatase) gene encoding the enzyme. Multicopy plasmids containing the DPP1 gene directed a 10-fold overexpression of DGPP phosphatase activity in S. cerevisiae. The heterologous expression of the S. cerevisiae DPP1 gene in Sf-9 insect cells resulted in a 500-fold overexpression of DGPP phosphatase activity over that expressed in wild-type S. cerevisiae. DGPP phosphatase possesses a Mg2+-independent PA phosphatase activity, and its expression correlated with the overexpression of DGPP phosphatase activity in S. cerevisiae and in insect cells. DGPP phosphatase was predicted to be an integral membrane protein with six transmembrane-spanning domains. The enzyme contains a novel phosphatase sequence motif found in a superfamily of phosphatases. A dpp1Delta mutant was constructed by deletion of the chromosomal copy of the DPP1 gene. The dpp1Delta mutant was viable and did not exhibit any obvious growth defects. The mutant was devoid of DGPP phosphatase activity and accumulated (4-fold) DGPP. Analysis of the mutant showed that the DPP1 gene was not responsible for all of the Mg2+-independent PA phosphatase activity in S. cerevisiae.