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Two cases of neuropathic arthropathy of the hip are reported. One was the first manifestation of tabes dorsalis in a 74-year-old man, whereas the second occurred in a 47-year-old woman with a history of spina bifida and L2-L5 epidural lipoma. Radiographic joint destruction occurred within five and three months, respectively. The main clinical and radiological features of neuropathic arthropathy are reviewed, and diagnostic pitfalls are discussed. There are no specific laboratory tests or histologic findings. This now rare condition should be routinely considered in patients with severe joint destruction contrasting with minimal pain. The reasons for the decision to use trochanteric-iliac coaptation in one of our patients and a wait-and-see approach in the other are explained. The literature is reviewed. Ten cases treated by joint replacement have been reported. However, neither joint replacement nor arthrodesis seem capable of restoring satisfactory hip function.

A novel method using the nonparametric bootstrap is proposed for testing whether a quantitative trait locus (QTL) at one chromosomal position could explain effects on two separate traits. If the single-QTL hypothesis is accepted, pleiotropy could explain the effect on two traits. If it is rejected, then the effects on two traits are due to linked QTLs. The method can be used in conjunction with several QTL mapping methods as long as they provide a straightforward estimate of the number of QTLs detectable from the data set. A selection step was introduced in the bootstrap procedure to reduce the conservativeness of the test of close linkage vs. pleiotropy, so that the erroneous rejection of the null hypothesis of pleiotropy only happens at a frequency equal to the nominal type I error risk specified by the user. The approach was assessed using computer simulations and proved to be relatively unbiased and robust over the range of genetic situations tested. An example of its application on a real data set from a saline stress experiment performed on a recombinant population of wheat (Triticum aestivum L. ) doubled haploid lines is also provided.

The sun is the most important and universal source of non-ionizing radiation shed on human populations. Life evolved on Earth bathed by this radiation. Solar UV damages cells, leading to deleterious conditions such as photoaging and carcinogenesis in human skin. During the process of evolution, the cells selected dark- and light-dependent repair mechanisms as a defence against these hazardous effects. This study describes the induction by non-coherent infrared radiation (700-2000 nm), in the absence of rising temperature, of a strong cellular defense against solar UV cytotoxicity as well as induction of cell mitosis. Blocking mitoses with arabinoside-cytosine or protein synthesis with cycloheximide did not abolish the protection, leading to the conclusion that this protection is independent of cell division and of protein neosynthesis. The protection provided by infrared radiation against solar UV radiation is shown to be a long-lasting (at least 24 h) and cumulatif phenomenon. Infrared radiation does not protect the lipids in cellular membranes against UVA induced peroxidation. The protection is not mediated by heat shock proteins. Living organisms on the Earth's surface are bathed by infrared radiation every day, before being submitted to solar UV. Thus, we propose that this as yet undescribed natural process of cell protection against solar UV, acquired and preserved through evolutional selection, plays an important role in life maintenance. Understanding and controlling this mechanism could provide important keys to the prevention of solar UV damage of human skin.

Intramedullary metastases are uncommon. We report two cases in patients with small cell bronchogenic cancer. The clinical diagnosis was supported by T1 magnetic resonance imaging after gadolinium injection. A unique medullary metastasis associated with other metastatic localizations was observed in the first patient and multiple intramedullary metastases alone in the second. These secondary intramedullary localizations were highly sensitive to chemotherapy after the first monthly cure in the first patient and after the third in the second patient. We emphasize the importance of chemotherapy in such cases, usually associated with focal radiotherapy.

Several nonparametric bootstrap methods are tested to obtain better confidence intervals for the quantitative trait loci (QTL) positions, i.e., with minimal width and unbiased coverage probability. Two selective resampling schemes are proposed as a means of conditioning the bootstrap on the number of genetic factors in our model inferred from the original data. The selection is based on criteria related to the estimated number of genetic factors, and only the retained bootstrapped samples will contribute a value to the empirically estimated distribution of the QTL position estimate. These schemes are compared with a nonselective scheme across a range of simple configurations of one QTL on a one-chromosome genome. In particular, the effect of the chromosome length and the relative position of the QTL are examined for a given experimental power, which determines the confidence interval size. With the test protocol used, it appears that the selective resampling schemes are either unbiased or least biased when the QTL is situated near the middle of the chromosome. When the QTL is closer to one end, the likelihood curve of its position along the chromosome becomes truncated, and the nonselective scheme then performs better inasmuch as the percentage of estimated confidence intervals that actually contain the real QTL's position is closer to expectation. The nonselective method, however, produces larger confidence intervals. Hence, we advocate use of the selective methods, regardless of the QTL position along the chromosome (to reduce confidence interval sizes), but we leave the problem open as to how the method should be altered to take into account the bias of the original estimate of the QTL's position.

Plants accumulate abscisic acid (ABA) under droughted conditions. Genetic variation in the accumulation of ABA in deteched and partially dehydrated leaves of rice has previously been reported, and this was found to be associated with variation in leaf size (smaller leaves made more ABA). Correlation analysis failed to distinguish clearly between a causal relationship between the two traits and close genetic between loci controlling the traits. Here we present a detailed genetic analysis of ABA accumulation in detached and partially dehydrated rice leaves. using a population of F2 plants generated from the lowland x upland cross IR20 (high-ABA) x 63-83 (low-ABA) which was mapped with RFLP and AFLP markers. Several highly significant quantitative trait loci (QTLs) for ABA accumulation and leaf weight were identified. Only one of the minor QTLs for ABA accumulation (accounting for only 4% of the phenotypic variance) was coincident with any QTLs for leaf size such that the high-ABA allele was associated with smaller leaves. This analysis, therefore, showed that the association previously found between ABA accumulation and leaf size was probably largely due to genetic linkage and not to a direct effect of leaf size on ABA accumulation or vice versa. Because of the importance of ABA accumulation in regulating responses of plants to drought stress and the effects of plant size on the rate of development of stress, QTLs for drought-induced ABA accumulation, leaf size and tiller number were compared between rice and wheat. In particular, a possible location in rice was sought for a homoeologue of the major wheat vernalization responsive gene, Vrn1, as this gene is also associated with major effects on leaf size, tiller number and ABA accumulation in wheat. The likelihood of homoeologous loci regulating ABA accumulation, leaf size and tiller number in the two crops is discussed.

In this study, we analysed the modulation of keratinocyte growth factor (KGF) mRNA expression in human dermal fibroblasts cultured either in monolayer or within a collagen matrix (dermal equivalent). In monolayer cultures, KGF expression by quiescent fibroblasts was stimulated by different growth substances such as serum, epidermal growth factor and basic fibroblast growth factor. Moreover, we demonstrated that the induction of this gene was mediated by at least 2 different signalling pathways involving protein kinase C (PKC) and cAMP. In dermal equivalents, we observed that the collagen matrix negatively modulated KGF mRNA expression. Indeed, among the growth substances used, only the serum slightly stimulated KGF expression. Nevertheless, as in monolayers, this induction involved at least PKC and cAMP signalling pathways. As the collagen matrix can modulate fibroblast growth, we also studied KGF expression in growing fibroblasts from either monolayer cultures or dermal equivalents. We then showed that this collagen matrix negatively influenced KGF expression independently of the proliferative state of fibroblasts. All these results underline the fact that KGF mRNA expression by human dermal fibroblasts is induced by different substances; however this expression can be modulated by fibroblast-matrix interactions.

In this study, epidermal growth factor (EGF), 20 ng/ml, and keratinocyte growth factor (KGF), 10 ng/ml, were able to stimulate human keratinocyte growth only in presence of GF 109203X 1 microM, a selective PKC inhibitor. This suggests that PKC negatively controls keratinocyte growth in response to EGF and KGF. On the other hand, EGF and KGF have no significant effect on PKC activity. In contrast, in human fibroblasts, EGF stimulated fibroblast growth in the presence or not of GF 109203X. Thus, EGF seems to stimulate fibroblast growth in a PKC independent manner. Moreover, EGF didn't modify significantly PKC activity in fibroblasts. KGF had no effect on fibroblasts. These results show differences in the interconnections between PKC and EGF transduction pathway in the modulation of human keratinocyte and fibroblast growth. Moreover, they especially demonstrate that PKC would negatively control human keratinocyte growth in response to EGF and also to KGF.

We report an unusual observation of peritoneal localisation in a non-Hodgkin lymphoma, the only sign of digestive injury. This peritoneal injury may be more frequent with AIDS patients, as in our observation. Tomodensitometry was the best exam to visual this injury.

Osteocondensation of the spine and stress fractures of the appendicular bones are observed under treatment with sodium fluoride or after long-term drinking of Vichy Saint-Yorre spring water. Five patients with a mean total dose of fluoride intake of 24.7 g (9-66) were studied with MR imaging. Two of them had a diffuse osteocondensation; MRI showed a low signal intensity in the vertebrae on T1 and T2-weighted images. MRI was performed in an asymptomatic patient who was being treated with sodium fluoride for 16 months; it revealed a heterogenous low signal intensity in the pelvis and femoral metaphysis. Two patients experienced stress fractures; MRI demonstrated a linear area of very low signal intensity surrounded by an area of decreased signal intensity on T1-weighted images and high signal intensity on T2-weighted images. MRI of fluorosis shows a non specific low signal intensity linked to a densifying image on the standard radiograph or an area of high technetium-99m intake on bone scan.

We report the pharmacologic effects of retinoids in a human skin-equivalent model. This sophisticated culture system is composed, as in vivo, of a dermis and epidermis, and provides a unique in vitro system for studying dermal-epidermal interactions and thus, whether normal dermal fibroblasts influence the effects of retinoids on epidermal growth. Epidermalization was initiated on collagen substrates in which fibroblasts were either viable or lysed by osmotic shock. Retinoic acid, isotretinoin, and acitretin at 10(-6) M or 10(-7) M were added to the cultures just after epidermalization, then every two days. Epidermal growth was determined after 2 weeks in terms of the surface area, DNA content, and tritiated thymidine incorporation during the last 24 h of culture. In the absence of viable fibroblasts, retinoic acid and isotretinoin increased epidermal growth, whereas etretin inhibited it. In contrast, in the presence of viable fibroblasts, retinoic acid and isotretinoin inhibited epidermal growth, whereas etretin had no effect. Thus, retinoic acid and isotretinoin had a similar effect on keratinocyte proliferation that contrasted with that of etretin. Taken as a whole, these results show that fibroblasts, present within a collagen substrate, can modulate the pharmacologic effects of retinoids on epidermal growth.

Tissue inhibitor of metalloproteases (TIMP) is a major regulator of extracellular matrix synthesis and degradation. Moreover elevated tissue inhibitor of metalloproteases levels are found in the blister fluid of many diseases, suggesting that tissue inhibitor of metalloproteases plays a role in epidermal and dermal wound healing. The aim of this work was to study the effects of human recombinant tissue inhibitor of metalloproteases in a skin equivalent model used to evaluate the effects of drugs on epidermal and dermal components. Planimetry, DNA assays, and histologic studies showed that tissue inhibitor of metalloproteases enhanced the growth of normal human keratinocytes on dermal equivalent. Thus, the extracellular matrix regulator tissue inhibitor of metalloproteases also stimulates the growth of keratinocytes. Identity of the gene encoding tissue inhibitor of metalloproteases and Erythroid Potentiating Activity (EPA) has been reported. The effects of tissue inhibitor of metalloproteases on keratinocytes described herein are reminiscent of the stimulating effect of erythroid potentiating activity on the growth of erythroid precursors.

Pulmonary aspergillosis invading the thoracic wall is rare and of sombre prognosis. We report the case of a 49-year old man who developed a pulmonary aspergilloma some time after lung resection and radiotherapy for bronchial adenocarcinoma. Surgical excision of the aspergilloma was followed by sternal, then costal aspergillosis. Conventional surgery and antifungal therapy failed, and the lesion stubbornly followed a chronic course until itraconazole therapy was instituted, resulting in a complete cure which still persists nearly 4 years after withdrawal of any chemotherapy.

A prospective study in 60 consecutive patients evaluated gain in quality of image using ECG servo-assistance during pulmonary digital subtraction angiography (PDSA). Two groups of 30 comparable patients were randomly allocated to examination with ECG servo-assistance or three images per second technique. Criteria for assessment of quality of image were defined and used to compare results. No significant difference were noted and ECG servo-assistance failed to improve images during PDSA.

3 cases of desmoid tumours of the mesentery occurring as part of Gardner's syndrome are reported. In 2 cases, CAT scanning was carried out. We underline the value of this examination compared to other imaging methods. It allows the establishment of a diagnosis, investigation for complications, the operability to be assessed and is useful for monitoring patients. Its major value is in avoiding an unnecessary laparotomy, a factor certain to produce recurrence, in certain patients. Other alternative therapy may then be proposed.

A case of sarcoidosis with lesions also localized to the cranial region is reported, and 21 similar cases published in the literature reviewed. Lesions are usually seen as small lacunae in the cranial vault, and are commonly associated with neurologic and cutaneous manifestations of the disease. They appear to be very rare but their frequency is probably underestimated. Their detection is facilitated by the use of technetium scintigraphy.

13 cases of sclero (dermato)myositis are reported with cutaneous signs specific of dermatomyositis in 6 cases. Scleroderma was rather benign, without any visceral involvement. In contrast, myositis was much more severe that usually encountered in systemic sclerosis, threatening the vital prognosis and requiring aggressive therapeutic measures to be controlled. In 6 cases, the axial musculature was involved. Occurrence of each component was not simultaneous. No case was paraneoplastic. Antinuclear antibodies were present in all cases. Antibodies against soluble nuclear antigens, specifically found by others in sclerodermatomyositis, were absent. The very peculiar clinical spectrum of this syndrome associated with immunologic abnormalities, elsewhere described, confirm the individualization of sclerodermatomyositis.

A 23 year old man, expert in karate, complained of sudden movements of right hip during "circular kicks", followed by persistent pain. Arthrography showed synovial plication in joint at upper border femoral neck, with a tongue-like projection from upper recess extending to head/neck junction and provoking bone erosion visible on standard images. Recovery followed resection of the fold. This is probably the first case of this type to be published. The lesion recalls the internal synovial plica of knee but differs from "frenula capsulae" and does not appear to have been described by anatomists. As in the knee it is probably an embryonic relic.

A reproducible method for sequential study of migration out of human skin, phagocytosis and bactericidal activity of neutrophils is described. Untreated psoriatics exhibit an early increase of chemotactic activity (0-8 h, p less than 0.02) and subsequently a strong inhibition of chemotaxis (8-24 h, p less than 0.01), a slight decrease of phagocytosis and a decrease in bactericidal activity (20 mn, p less than 0.02; 30 mn, p less than 0.003); 60 mn, p less than 0.001; 120 mn, p less than 0.001) as compared with controls. After clearing of skin lesions, the early increased chemotactic activity returned to normal values but the subsequent chemotactic inhibition remains as strong as before treatment. Phagocytosis increased to normal values (p less than 0.02) and bactericidal activity also increased but remained significantly low. The abnormalities were more evident in migrating than in circulating neutrophils, underlining the sensitivity of the described method. Using the same method we have shown that the aromatic retinoid etretinate (Ro 10-9359) and its main metabolite (Ro 10-1670) significantly inhibit the migration of neutrophils from the blood to tissues when applied into skin chambers (0.1 mg/ml) or when given orally (1 mg/kg/day) for 8 days to normal volunteers. This pharmacological property could be closely linked to the antipsoriatic properties of these drugs.

Using a method that allowed the reconstruction of simplified living human skin in vitro, we investigated the effects of collagen texture and dermal fibroblasts on epidermal growth. Like in vivo skin, our in vitro model comprised two tissues: a dermal equivalent and an overlying epidermis. It permitted measurement of epidermal growth and therefore evaluation of the effect of the dermal equivalent on this growth. Epidermal growth was enhanced when the collagen matrix had previously been reorganized by fibroblasts, and was greatest when living fibroblasts persisted in this matrix. On cell-free collagen gel and on collagen matrices containing dead fibroblasts, epidermal growth increased when the medium was conditioned by fibroblasts grown in monolayers. We conclude that the function of the fibroblasts is not only to synthesize and degrade the extracellular matrix, but also to regulate epidermalization; on the one hand by remodeling the collagen fibers, and on the other by secreting diffusible factors that promote epidermal growth. These results underline the importance of fibroblasts in dermo-epidermal interactions, and show that the skin equivalent culture model provides a way to quantitatively study these interactions.