Thrombin Inhibits the Migration of Human Liver Myofibroblasts

Scarring of the cornea, the transparent tissue at the front of the eyeball, is an important cause of visual impairment. A major chemokine upregulated in tear fluid after corneal injury is platelet‐derived growth factor (PDGF), which induces the stromal cells of the cornea (keratocytes) to assume a fibroblastic phenotype. We have investigated the role of PDGF in matrix contraction by human corneal fibroblasts (HCF) using the standard three‐dimensional (3D) fibroblast‐populated collagen matrix model (FPCM).
When stimulated with PDGF, HCF in monolayer (2D) display circular ruffles (CR) on their dorsal surface. Using immunolabeling, we found that CR contain proteins of the Arp2/3 complex, which is required for the assembly of filamentous actin during protrusive activity. This PDGF‐mediated ruffling ability is altered by antibodies or blocking peptides that specifically interfere with the Arp2/3‐mediated pathway of actin polymerization, as well as by the myosin light chain kinase inhibitor, ML9. Preincubation with anti‐PDGF‐BB antibody or with the tyrosine kinase inhibitor, AG1295, also inhibits CR. While PDGF efficiently stimulates HCF‐mediated cell protrusive activity and macroscopic collagen gel contraction in the 3D model, this effect is directly inhibited by all the substances which inhibit CR in 2D, demonstrating a direct involvement of the PDGF‐mediated CR pathway in tissue contraction. Thus, 3D PDGF‐induced matrix contraction by HCF involves the same players as CR, a phenomenon observed in 2D cell cultures: PDGF‐BB receptor, receptor tyrosine kinase, the machinery for filamentous actin assembly (Arp 2/3 complex, Scar and Wasp proteins), and myosin. The functional role of circular ruffling or its equivalent in three‐dimensional fibroblast‐populated collagen matrices seems to be a rapid reorganization of the actin cytoskeleton in preparation for cell‐matrix interaction.     

Necrotizing pneumonia and arthritis due to Staphylococcus aureus producing Panton and Valentine leukocidin in a 10-year-old boy]

Staphylococcal necrotizing pneumonia producing the Panton Valentine leukotoxin (PVL) has been described for many years. The french reference center for staphylococcal toxaemia defined it with precision in 1999. A 10-year-old child, died in 36 hours from respiratory distress and shock. Staphylococcal pneumonia was suspected then confirmed: S. Aureus producing PVL was isolated in lung, blood and articulations.     

A study of the interaction of alcohol drinking and tobacco smoking among French cases of laryngeal cancer.

Laryngeal cancer represents an important cause of cancer in France, and the individual effects of alcohol and tobacco on this cancer site are well known. However the problem of the interaction between these agents is less extensively documented, and the role of the high consumptions of alcohol has not been studied frequently. A case-control analysis was undertaken to investigate the joint effect of alcohol and tobacco by comparing 197 glottic and 214 supraglottic cancer cases to 4135 controls representative of the French general population. Heavy drinkers were available from the two groups of cases, the highest alcohol category being equivalent to a consumption of more than 2 litres of wine per day. The relative risks estimated for heavy drinkers and smokers were high, and the results indicated an even stronger effect of alcohol drinking and tobacco smoking on the upper part of the laryngeal region. Additive and multiplicative models were fitted to the data. The multiplicative hypothesis was found to be the most appropriate, implying that the risks associated with alcohol and tobacco multiply when the exposures occur simultaneously. The public health implications of this result and the contribution of heavy drinkers and smokers to the frequency of upper respiratory and digestive tract cancers are discussed.     

From laparoscopic training on an animal model to retroperitoneoscopic or coelioscopic adrenal and renal surgery in human

So far, laparoscopic approaches to kidney and adrenal have been limited because of their retroperitoneal location. We here report eight renal and adrenal endoscopic procedures performed in seven patients: two adrenalectomies for hyperaldosteronism, one adrenalectomy for isolated metastasis from an adenocarcinoma of the lung; two nephrectomies for end-stage infected hydronephrosis, two partial nephrectomies for small circumscribed lesions of the kidney, and one endoscopic resection for pain relief of a voluminous cyst at the kidney. The approach was transperitoneal in two cases and retroperitoneal in five cases using the retropneumoperitoneum insufflation technique. One patient was operated by a combined approach using the retro- and transperitoneal routes. All procedures were successfully completed endoscopically. The retroperitoneoscopic approach of the kidney is safe and does not interfere with the peritoneal organs. Its working space is tenuous, but allows a direct access on the kidney with good exposure of its pedicle. For adrenal surgery, the retroperitoneoscopic dissection is more difficult, because movements of instruments are often impaired by the closeness of the costal margin and the iliac crest. However, in case of difficulties we found it very convenient to switch from a retroperitoneal endoscopic approach to a combined coelioscopic and retroperitoneoscopic operation. Far from excluding each other, both approaches are complementary, particularly for difficult situations (i.e., previous peritoneal or retroperitoneal surgery).     

Prenatal screening in utero of urinary abnormalities. Management]

The major benefit of antenatal ultrasonography is to allow early diagnosis of urinary tract malformations before postnatal infection worsens the prognosis. In the majority of cases, there is a unilateral and moderate dilatation requiring a check-up only during the second week of life; treatment subsequently depends on the etiology of the uropathy and the consequences on the kidney. Unilateral severe dilatations and bilateral, but moderate, dilatations must be managed immediately after birth in a pediatric surgical center. In the rare cases of severe bilateral obstructive uropathy, in utero decompression by catheterisation or surgery is now considered to be uselessly invasive, considering that renal dysplasia is already present when the malformation is detected.     

Secretogranin I (chromogranin B) mRNA accumulation is hormonally regulated in GH3B6 rat pituitary tumor cells

Secretogranin I (SgI; chromogranin B) belongs to a class of acidic tyrosine-sulfated secretory proteins believed to play a role in the secretory process of endocrine cells. Our aim here was to compare the levels of SgI mRNA to that of prolactin (PRL) and growth hormone (GH), using rat pituitary cell lines. As far as the constitutive expression is concerned, we found a positive correlation between SgI mRNA and PRL mRNA levels. However, the neuropeptide TRH (50 nM) inhibited the accumulation of SgI mRNA in GH3B6 cells whereas, as expected, it induced a rapid and sustained increase in PRL mRNA accumulation. By contrast, 17β-estradiol (1 nM) stimulated the accumulation of both SgI and PRL mRNAs, with the same EC₅₀ (18–59 pM). Reciprocally, treatment with dexamethasone (100 nM) reduced the level of SgI and PRL mRNAs to 23% and 29% of control, respectively, but led to a 2.1-fold increase in the GH mRNA level. Altogether, the present work shows that SgI gene expression is subject to multiple hormonal regulations and occasionally parallels the regulation of the PRL gene but never that of the GH gene, under the conditions tested.     

Pain in sciatica depresses lower limb nociceptive reflexes to sural nerve stimulation.

The inhibitory effects of acute pain produced by the Lasègue's manoeuvre on the lower limb nociceptive flexion reflexes induced by electrical sural nerve stimulation were explored in patients complaining of sciatica as a result of an identified unilateral disc protrusion. Lassègue's manoeuvre on the affected side produced a typical radicular pain and resulted in a powerful depression of nociceptive reflexes elicited either in the normal or in the affected lower limb. Simultaneously, patients reported relief of the electrically-induced pain. In contrast, painless Lasègue's manoeuvre on the normal side had no effect on these parameters.     

Group A Streptococcus invasive infections: a review

The incidence of group A Streptococcus (GAS) invasive infections has been increasing worldwide, and there is no obvious explanation for this phenomenon. In 1993, a working group on severe GAS infections was established to define accurately what constitutes an invasive infection. Three types of infection are particularly feared: necrotizing fasciitis, myositis and a newly defined entity, named streptococcal toxic shock syndrome (STSS) because of a certain analogy with its staphylococcal counterpart. GAS produces many toxins responsible for its clinical manifestations. Some of them, labelled streptococcal pyrogenic exotoxins, have been characterized as superantigens. These proteins play a key role in initiating the immune response to GAS and are mostly responsible for the precipitous course of invasive infections. Death rates are high in streptococcal invasive infections, ranging from about 20% for necrotizing fasciitis to almost 100% for myositis. Therapy consists mainly of high doses of antibiotic combinations, aggressive surgery, and intravenous administration of immunoglobulins for STSS.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

A survey of postoperative nausea and vomiting

A prospective interview-based survey on the incidence of postoperative nausea and vomiting in 1107 in-patients aged 4–86 years was conducted during a 3-month period. Nausea, emetic episodes and the need for anti-emetic medication were recorded for 24 h postoperatively. In the recovery room, the incidence of nausea and vomiting was 18% and 5%, respectively. Over the whole 24-h period, these figures were 52% and 25%, respectively; severe nausea was experienced by 8%. The highest incidence of emetic sequelae was observed in gynaecological patients; 52% of the 822 patients who received general anaesthesia and 38% of the 285 patients who received regional anaesthesia reported nausea. The most important predictive factors associated with an increased risk for nausea and vomiting were female gender, a previous history of postoperative sickness, a longer duration of surgery, nonsmoking and a history of motion sickness. Based on these five items, a simple score predicting the risk of nausea and vomiting was constructed with a moderately good discriminating power.