Pulmonary arterial hypertension: the key role of echocardiography

Given the nonspecific nature of its early symptoms and signs, pulmonary arterial hypertension (PAH) is often diagnosed in its advanced stages. Although clinical assessment is essential when initially evaluating patients with suspected PAH, echocardiography is a key screening tool in the diagnostic algorithm. It not only provides an estimate of pulmonary pressure at rest and during exercise, but it may also help to exclude any secondary causes of pulmonary hypertension, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease.     

Growth and adult height in atypical coeliac patients, with or without growth hormone deficiency

OBJECTIVE: To evaluate the effect of a gluten-free diet on growth and adult height, when available, in coeliac children without gastrointestinal symptoms. PATIENTS AND METHODS: Sixty-one coeliac children without gastro-intestinal symptoms were included in the study. The age at diagnosis was 9.50 +/- 3.3 years. Thirty-eight had short stature at diagnosis (< 10th percentile) and 23 had normal stature. Thirty-seven reached adult height. RESULTS: After beginning the diet an increase in growth velocity was seen in 30 patients (responders) (20 with initial short stature), while in 31 patients (18 with short stature) there was no catch-up growth (non-responders). Bone age at diagnosis was significantly more delayed in the responders than in the non-responders. Target height was significantly higher in children with normal stature at diagnosis than those with short stature. Growth hormone (GH) deficiency was found and confirmed after 6-12 months of diet in 12 of the 38 patients (32%) with short stature. In the group of the 30 'short' patients who attained final height, target height was attained or improved in 12 patients (40%): in eight of the 16 (50%) responders and in four of the 14 (29%) non-responders; in eight (all responders) out of 22 (36%) without GH deficiency, and in four out of eight (50%) patients with GH deficiency treated with GH (all non-responders). CONCLUSIONS: In children in whom coeliac disease is diagnosed because of short stature, a gluten-free diet will be successful if at diagnosis there is a delay of bone age and in the first year of diet there is an evident catch-up growth. When this does not occur, i.e. in half of the patients (18 out of 38), it may be because of an associated and transient GH deficiency. In these patients a period of GH replacement therapy as well as a gluten-free diet may improve their final height.     

Vessel painting of the microcirculation using fluorescent lipophilic tracers

Flexible approaches to defining microvessel morphometry are useful in the study of both acute and chronic structural changes of the microcirculation. In this report, we examined the utility of the intravascular infusion of lipophilic carbocyanine tracers in the structural assessment of the retina, skin, lung, and colon microcirculation. The microvessel labeling technique, here termed fluorescent vessel painting, involved the intravascular injection of sulfonated lipophilic carbocyanine tracers. The utility of vessel painting in morphometry was assessed using morphometric comparisons with corrosion casting and 2-dimensional and 3-dimensional scanning electron microscopy. The comparisons demonstrated that fluorescent vessel painting modestly overestimated the interbranch angles, interbranch distances, and vessel diameters of the 2D mucosal plexus of the colon. These differences were narrowed with the application of confocal microscopy. The advantages of fluorescence vessel painting included (1) the filling of all tissues including the relatively high resistance microvessels of the mouse skin, (2) the ability to use tissue counterstains such as DAPI, and (3) the prolonged stability of the lipophilic tracer after aldehyde fixation. These studies suggest the utility of fluorescent vessel painting as a complementary technique to corrosion casting in the morphometric study of the microcirculation.     

Newborns' preference for face-relevant stimuli: effects of contrast polarity

There is currently no agreement as to how specific or general are the mechanisms underlying newborns' face preferences. We address this issue by manipulating the contrast polarity of schematic and naturalistic face-related images and assessing the preferences of newborns. We find that for both schematic and naturalistic face images, the contrast polarity is important. Newborns did not show a preference for an upright face-related image unless it was composed of darker areas around the eyes and mouth. This result is consistent with either sensitivity to the shadowed areas of a face with overhead (natural) illumination and/or to the detection of eye contact.     

Preservation of porcine non-heart-beating donor livers by sequential cold storage and warm perfusion

BACKGROUND: Normothermic perfusion has been shown to resuscitate and maintain viability of non-heart-beating donor (NHBD) livers that have undergone significant warm ischemic injury. However, the logistics of clinical organ retrieval are complex, and a period of cold storage before warm preservation would simplify the process. We have investigated the effects of short duration of cold preservation before normothermic preservation on the function of porcine NHBD livers. METHODS: Porcine livers were subjected to 60 minutes of warm ischemia and then assigned to the following groups: group W (n=5), normothermic preservation for 24 hours; and group C (n=4), cold preservation in University of Wisconsin solution for 4 hours followed by normothermic preservation for 20 hours (total preservation time 24 hours). Outcome parameters that were measured included bile production, serum transaminases and hyaluronic acid levels (cellular damage), and base deficit and glucose use (metabolic function). RESULTS: Group W livers had superior bile production, metabolic activity (base deficit and greater glucose use), and less evidence of hepatocellular damage (alanine aminotransferase, aspartate aminotransferase), and sinusoidal endothelial cell dysfunction (hyaluronic acid). Group C livers showed greater necrosis and destruction of architecture on histology. CONCLUSION: Normothermic perfusion failed to resuscitate porcine livers after 60 minutes of warm ischemia and 4 hours of cold preservation. Even a short period of cold ischemia is significantly deleterious to the function of ischemically damaged (NHBD) livers.     

Gene expression of early hypertrophic scar tissue screened by means of cDNA microarrays

BACKGROUND: Hypertrophic scar is an excessive healing response that often follows thermal injury. The most outstanding morphologic change is the overdeposition of collagen, which is caused by imbalance between synthesis and metabolism of collagen. Previous studies also found that transforming growth factor-beta was the key factor controlling scar formation. However, neither anti-transforming growth factor-beta nor other methods could completely control scar formation and contraction. This fact suggests a multifactorial cause. Fortunately, cDNA microarray throws light on the general alteration at the gene level, and thus could allow us to find some new clues for understanding scar formation and contraction. METHODS: In this article, we report the results obtained from the scanning of gene expression of hypertrophic scar by means of cDNA microarray. Five cases of early human postburn hypertrophic scars were selected. Total tissue RNA was extracted from each hypertrophic scar sample and the corresponding uninjured region skin tissue; mRNA was further purified by Oligotex and then was reversely transcribed to cDNAs with the incorporation of fluorescent dUTP to prepare the hybridization probes. The mixed probes were hybridized to the cDNA microarray containing 4,096 genes on a type of chemical material-coated glass slide. After high-stringent washing, the hybridized slides were scanned for fluorescent signal detection. Then, the expression and distribution of cytoskeletal genes such as alpha-smooth muscle actin (alpha-SMA) gene; fibroblast tropomyosin TM30(pl) gene; vimentin gene; profilin gene; and BM40 gene of hypertrophic scar at 3, 6, 9, and 12 months age were further quantitatively studied by in situ hybridization or immunohistochemistry. RESULTS: Our data indicated that there were 94 genes overexpressed and 3 genes down-regulated in early postburn hypertrophic scar. These altered genes were related to proto-oncogenes, apoptosis, immune regulatory genes, cytoskeletal elements, metabolism, and so forth. We also found that the detected cytoskeletal gene expression was much more intense at all time points than the control group. Consistent with clinical observation, cytoskeletal genes reached a peak at an early stage and gradually decreased. CONCLUSION: Our study implied that multiple genes are involved in scar formation and contraction. Interferon is an autosecreted cytokine that might be responsible for self-control of overgrowth of cells in wounds. The early period of hypertrophic scar formation might be a good time for preventing overgrowth and contraction of hypertrophic scar by gene therapy.     

Estimating dermal exposure to jet fuel (naphthalene) using adhesive tape strip samples

A simple, non-invasive dermal sampling technique was developed and tested on 22 human volunteers under laboratory conditions to estimate acute dermal exposure to jet fuel (JP-8). Two sites on the ventral surface of each forearm were exposed to 25 micro l of JP-8 and the non-viable epidermis (stratum corneum) was sequentially tape-stripped using an adhesive tape. Samples were extracted with acetone and analyzed by gas chromatography/mass spectrometry. Analysis of the first tape strips indicated that JP-8 was rapidly removed from the stratum corneum over the 20 min study period. On average, after 5 min of exposure the first two tape strips removed 69.8% of the applied dose. The amount recovered with two tape strips decreased over time to a recovery of 0.9% 20 min after exposure. By fitting a mixed-effects linear regression model to the tape strip data, we were able to estimate accurately the amount of JP-8 initially applied. This study indicates that naphthalene has a short retention time in the human stratum corneum and that the tape stripping method, if used within 20 min of the initial exposure, can be used to measure reliably the amount of naphthalene initially in the stratum corneum due to a single exposure to jet fuel. We are currently investigating the applicability of the developed mixed-effects linear regression model to estimate acute JP-8 exposure levels based upon naphthalene measurements from tape strips collected from occupationally exposed workers.     

Adjuvant, adoptive immunotherapy with tumor infiltrating lymphocytes plus interleukin-2 after radical hepatic resection for colorectal liver metastases: 5-year analysis

BACKGROUND AND OBJECTIVES: Conventional chemotherapy has not proven effective in improving long-term results of surgery for liver metastases from colorectal cancer. We assessed the usefulness of immunotherapy with tumor infiltrating lymphocytes (TIL) plus Interleukin-2 (IL-2) as adjuvant treatment. METHODS: Between 1995 and 1998, 47 patients were enrolled onto a prospective protocol; 25 entered the treatment group (A) and 22 entered the control group (B). All patients had undergone radical liver resection. TIL obtained from surgical specimens from group A patients were cultured and activated in vitro with IL-2, then reinfused into the patients with IL-2. We investigated pre- and post-IL-2 stimulation expression of T cell receptor (TCR) zeta- and epsilon-chains, p56(lck), Fas, and Fas-L by TIL immunostaining. RESULTS: Fourteen patients from group A (56%) received immunotherapy; 14 from group B (60%) underwent conventional chemotherapy, and the remaining 19 patients did not receive any treatment. No significant differences between the two groups were found in the actuarial and disease-free survival (DSF) rates after 1, 3, and 5 years. After IL-2 exposure, TCR zeta-chain expression significantly increased (P = 0.001); An increase in TCR epsilon-chain expression (P = 0.04), and p56(lck) (P = 0.03) was detected; TCR epsilon-chain expression was significantly increased in disease-free patients compared to those who relapsed (P = 0.04). Fas-L expression was correlated with the TCR epsilon-chain and p56(lck) levels (P = 0.05). CONCLUSIONS: Our data suggest that we are still a long way from being able to propose TIL + IL-2 treatment as an effective adjuvant therapy. However, the results confirm that the biological indicators examined could play an important role in modulating immunitary response against tumor cells.