Search

For centuries in Europe, population movements have contributed to ethnic groups, cultures, and consequently, inheritance mixing. There are certain genetic diseases such as hereditary hemochromatosis whose distribution is directly related to the population movements. The objective of the present investigation was to determine the C282Y and H63D mutation frequency of the HFE gene in a cohort study of 1,000 neonates in the Community of Madrid (Spain), thus contributing to the HFE gene mutations distribution research in Europe and establishing the origin of the mutations in Spain. The allelic frequency of C282Y mutation was 1.7% (CI 95% 1.1-2.3) and the H63D allele was present in 16.4% of chromosomes (CI 95% 14.8-18). In Spain, the presence of C282Y mutation and its distribution could be due more to Celtic than to Viking legacy, whereas it is assumed that the one in relation to the H63D variant occurred in the Basque Country during the Paleolithic Period.

Context: The study and treatment of psychiatric disorders is made difficult by the fact that patients with identical symptoms often differ markedly in their clinical features and presumably in their etiology. A principal aim of genetic research is to provide new information that can resolve such clinical heterogeneity and that can be incorporated into diagnostic practice., Objective: To test the hypothesis that the DRD4 seven-repeat allele and DAT1 ten-repeat allele would prove useful in identifying a subset of children with attention-deficit/hyperactivity disorder (ADHD) who have compromised intellectual functions., Design: Longitudinal epidemiologic investigation of 2 independent birth cohorts., Setting: Britain and New Zealand., Participants: The first cohort was born in Britain in 1994-1995 and includes 2232 children; the second cohort was born in New Zealand in 1972-1973 and includes 1037 children., Main Outcome Measures: Evaluation of ADHD, IQ, and adult psychosocial adjustment., Results: We present replicated evidence that polymorphisms in the DRD4 and DAT1 genes were associated with variation in intellectual functioning among children diagnosed as having ADHD, apart from severity of their symptoms. We further show longitudinal evidence that these polymorphisms predicted which children with ADHD were at greatest risk for poor adult prognosis., Conclusion: The findings indicate that genetic information of this nature may prove useful for etiology-based psychiatric nosologies.

Hb La Coruña [beta38(C4)Thr --> Ile] is a new hemoglobin (Hb) variant that has an increased oxygen affinity. Clinically, this Hb leads to erythrocytosis. Hb La Coruña is an electrophoretically silent variant that can be detected by reversed phase high performance liquid chromatography (HPLC) and characterized by DNA sequencing. The patient was a 22-year-old Spanish male whose family lived in La Coruña, in the northwest of Spain. His mother was also a carrier.

This report describes the first case in Spain of a severe form of beta-thalassemia (thal) due to a compound heterozygosity for the IVS-II-848 (C --> A) and the nonsense codon 39 (C --> T) mutations. Five members of a family from Cadiz (southern Spain) were studied. The proband was an 8-year-old girl diagnosed as anemic at the age of 13 months. Her father had the codon 39 (C --> T) mutation and her mother the C --> A change at nucleotide (nt) 848 of IVS-II. Haplotype analysis showed that the proband was a compound heterozygote for haplotypes I [+ --> + +] and VII [+ --> +]. This is the first description in Spain of the IVS-II-848 (C --> A) mutation. It appears, from restriction fragment length polymorphism (RFLP) analysis, that this mutation has a different origin in the various populations, where it was found. This observation shows that in this case the association of a beta(0)- and a beta(+)-thal mutation does not lead to a thalassemia intermedia but to a severe thalassemia with very low hemoglobin (Hb) levels. From a therapeutic point of view, early introduction of a transfusion regimen may improve the clinical picture of these children, allowing for better development and growth.

Background and Objective: Hemoglobin S (HbS) alpha-thalassemia together with ss-thalassemia and hemoglobins C, E and D are named common hemoglobinopathies. In this study, we analyzed the frequency of the association between alpha-thalassemia and HbS and its phenotypic expression., Patients and Method: Since January 1995 to March 2003 we studied 83 cases of HbS, which were diagnosed by electrophoretic and chromatographic criteria. The molecular study was carried out by Southern blot with the restriction enzymes Bam HI and Bgl II and a (1.5 Kb Pst) and z (1.8 Kb Sac Y) probes., Results: 45 cases (54.2%) had a-thalassemia (36 -alpha3,7/aa; 1-alpha4,2/alphaalpha; 6 -alpha3,7/-alpha3,7; 1-alpha4,2/-alpha4,2); 36 had not alpha-thalassemia and in two cases there were a triplication of a genes. The patients with HbS heterozygote associated with alpha-thalassemia showed a percentage of HbS (p < 0.0001), CMV (p = 0.004), MCH (p = 0.002) and MCHC (p = 0.02) significantly lower than the cases of HbS without this association. However, no differences between both groups were found with regard to the rest of parameters analyzed (Hb p = 0.56; PVC p = 0.84; RDW p = 0.06; Reticulocytes p = 0.26; HbF p = 0.76; HbA2 p = 0.13). In the cases with a severe form of disease (HbS homozygote; HbS/Hb C; HbS/beta-thalassemia), patients with alpha-thalassemia had a number of leukocytes that was significantly lower than that of patients without alpha-thalassemia (p = 0.034)., Conclusion: An association between HbS and alpha-thalassemia was common (> 50%). Screening for this association is of great interest because the clinical expression in the cases of HbS homozigote will be modulated. This association must be suspected in cases of homozygous HbS in which levels of HbS are lower than expected.

A solid-phase microextraction method (SPME) coupled to gas chromatography-mass spectrometry (GC-MS) has been developed for the determination of the six phthalate esters included in the US Environmental Protection Agency (EPA) Priority Pollutants list in water samples. These compounds are dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP) and di-n-octyl phthalate (DOP). Detailed discussion of the different parameters, which could affect the extraction process, is presented. Main factors have been studied and optimized by means of a multifactor categorical design. Different commercial fibers, polydimethylsiloxane (PDMS), polydimethylsiloxane-divinylbenzene (PDMS-DVB), polyacrylate (PA), Carboxen-polydimethylsiloxane (CAR-PDMS) and Carbowax-divinylbenzene (CW-DVB), have been investigated, as well as the extraction mode, exposing the fiber directly into the sample (DSPME) or into the headspace over the sample (HS-SPME), and different extraction temperatures. The use of this experimental design allowed for the evaluation of interactions between factors. Extraction kinetics has also been studied. The optimized microextraction method showed linear response and good precision for all target analytes. Detection limits were estimated considering the contamination problems associated to phthalate analysis. They were in the low pg mL(-1), excluding DEHP (100 pg mL(-1)). The applicability of the developed SPME method was demonstrated for several real water samples including mineral, river, industrial port and sewage water samples. All the target analytes were found in real samples. Levels of DEP and DEHP were over 1 ng mL(-1) in some of the samples.

Purpose: One cause of excessive gingival display is the muscular capacity to raise the upper lip higher than average. Several surgical procedures have been reported to improve the condition, but surgery always involves risk and is costly. Botulinum toxin type A (BTX-A) (Botox; Allergan, Irvine, Calif) has been studied since the late 1970s for the treatment of several conditions associated with excessive muscle contraction or pain. This clinical pilot study was performed to determine whether BTX-A injections would reduce excessive gingival display., Material: Five subjects with excessive gingival display due to hyperfunctional upper lip elevator muscles were treated with BTX-A injections., Results: This treatment modality was effective, producing esthetically acceptable smiles in these patients. The improvements lasted 3 to 6 months., Conclusions: Injection with BTX-A at preselected sites is a novel, cosmetically effective, minimally invasive alternative for the temporary improvement of gummy smiles caused by hyperfunctional upper lip elevator muscles.

We describe, in a Spanish family with moderate microcytosis and hypochromia, a novel nondeletional alpha-thalassemia (thal) mutation localized on the alpha2-globin gene. DNA sequencing revealed a point mutation at codon 125 (CTG --> CGG) in the heterozygous state, that was confirmed by restriction analysis. The resulting variant, which causes a nondeletional alpha-thal, was named Hb Plasencia [alpha125(H8)Leu --> Arg (alpha2)] after the place of residence of the affected family.

Hb E-Saskatoon [beta22(B4)Glu-->Lys] does not cause any clinical symptoms in the heterozygous state. The homozygous state shows moderate phenotype expression. It has also been detected in association with beta-thalassemia. We present the first case of Hb E-Saskatoon associated with Hb Lepore-Baltimore. This unusual combination of mutations does not aggravate the clinical picture, as only microcytosis and hypochromia have been observed. Hb E-Saskatoon can only be correctly characterized by ion exchange high performance liquid chromatography (HPLC) or by DNA sequencing.

Research on child effects has demonstrated that children's difficult and coercive behavior provokes harsh discipline from adults. Using a genetically sensitive design, the authors tested the limits of child effects on adult behavior that ranged from the normative (corporal punishment) to the nonnormative (physical maltreatment). The sample was a 1994-1995 nationally representative birth cohort of 1,116 twins and their families who participated in the Environmental Risk Longitudinal Study. Results showed that environmental factors accounted for most of the variation in corporal punishment and physical maltreatment. However, corporal punishment was genetically mediated in part, and the genetic factors that influenced corporal punishment were largely the same as those that influenced children's antisocial behavior, suggesting a child effect. The authors conclude that risk factors for maltreatment are less likely to reside within the child and more likely to reside in characteristics that differ between families., ((c) 2004 APA, all rights reserved)

We evaluate the efficacy of the oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 71 refractory/relapsed multiple myeloma patients, including a prognostic analysis to predict both response and survival. Patients received thalidomide at escalating doses (200-800 mg/day), daily cyclophosphamide (50 mg/day) and pulsed dexamethasone (40 mg/day, 4 days every 3 weeks). On an intention-to-treat basis and using the EBMT response criteria, 2% patients reached complete response (CR), 55% partial response (PR) and 26% minor response (MR) yielding a total response (CR+PR+MR) rate of 83% after 3 months of therapy. After 6 months of therapy, responses were maintained including a 10% CR. The 2-year progression free and overall survival were 57 and 66%, respectively. A favorable response was associated with beta2 microglobulin < or =4 mg/dl, platelets >80 x 10(9)/l and nonrefractory disease. Regarding survival, low beta2 microglobulin (< or =4 mg/dl), age (< or =65 years) and absence of extramedullary myelomatous lesion were associated with a longer survival. Major adverse effects included constipation (24%), somnolence (18%), fatigue (17%) and infection (13%). Only 7% of patients developed a thrombo-embolic event. ThaCyDex is an oral regimen that induces a high response rate and long remissions, particularly in relapsing patients with beta2 microglobulin < or =4 mg/dl and < or =65 years.

If maternal expressed emotion is an environmental risk factor for children's antisocial behavior problems, it should account for behavioral differences between siblings growing up in the same family even after genetic influences on children's behavior problems are taken into account. This hypothesis was tested in the Environmental Risk Longitudinal Twin Study with a nationally representative 1994-1995 birth cohort of twins. The authors interviewed the mothers of 565 five-year-old monozygotic (MZ) twin pairs and established which twin in each family received more negative emotional expression and which twin received more warmth. Within MZ pairs, the twin receiving more maternal negativity and less warmth had more antisocial behavior problems. Qualitative interviews were used to generate hypotheses about why mothers treat their children differently. The results suggest that maternal emotional attitudes toward children may play a causal role in the development of antisocial behavior and illustrate how genetically informative research can inform tests of socialization hypotheses., (((c) 2004 APA, all rights reserved))

Solid-phase microextraction has been applied for the first time to the determination of trace concentrations of some brominated flame-retardant compounds (BFRs) in water samples. For the development of the method, six polybrominated diphenyl ethers and two polybrominated biphenyls were considered as target analytes. The factors expected to influence the extraction process are fully discussed. Quantification has been performed by gas chromatography/tandem mass spectrometry using an ion trap mass analyzer. This is also the first time that tandem mass spectrometry is applied with these analytes. Unlike conventional methods for BFR analysis, which involve solvent extraction and several cleanup steps before gas chromatography, the proposed method uses headspace extraction and hard contamination of the chromatographic system is prevented. In addition, tandem mass spectrometry provides selectivity and sensitivity in the detection process. The method performs well achieving good linearity (R(2) > 0.997), precision, and detection limits (S/N = 3) ranging from 7.5 to 190 pg/L. The method has been applied to a variety of water samples.

Headspace solid-phase microextraction, followed by GC-MS analysis is presented as a suitable technique for the determination of musk compounds in sewage treatment plant sludge. Five polycyclic musks (celestolide, phantolide, traseolide, galaxolide and tonalide) and four nitro musks (musk xylene, musk moskene, musk tibetene and musk ketone) were considered in the optimisation of the analytical method. The influence of extraction temperature, fibre coating, agitation, pH and salting out on the efficiency of the extraction along with the extraction kinetics were studied. An extraction temperature of 100 degrees C and sampling the headspace over the stirred sludge sample using polydimethylsiloxane -divinylbenzene as fibre coating lead to effective extraction. The method proposed is very simple and yields high sensitivity, good linearity and repeatability for all the analytes with limits of detection at the sub-ng/g level. The total analysis time, including extraction and GC analysis, was only 40 min, and no manipulation of the sample was required.

A solid-phase microextraction method (SPME) for determining trace levels of synthetic musk fragrances in residual waters has been developed. Six polycyclic musks (cashmeran, phantolide, celestolide, traseolide, galaxolide and tonalide), and a macrocyclic musk (ambrettolide) have been analysed. A detailed study of the different parameters affecting the extraction process is presented. The main important factors affecting the microextraction process have been studied and optimised by means of a categorical factorial design. Two extraction modes (direct SPME and headspace SPME) were tried at different extraction temperatures using four different fiber coatings [polydimethylsiloxane (PDMS), Carboxen (CAR)-PDMS, PDMS-divinylbenzene (DVB) and Carbowax (CW)-DVB]. An extraction temperature of 100 degrees C sampling the headspace over the sample using CAR-PDMS or PDMS-DVB as fiber coatings were found to be the experimental conditions that lead to a more effective extraction. The method proposed is very simple and yields high sensitivity, with detection limits in the low pg/ml, good linearity and repeatability for all the target compounds. The total analysis time, including extraction and GC analysis, was only 45 min. The optimised method performed well when it was applied to waste water from an urban treatment plant.

Objective: To describe the clinical and histological findings of a case of renal cell carcinoma metastatic to the testes, an uncommon site of metastasis of this tumor type that can cause difficulty in making the differential diagnosis and consequently, in the staging and treatment of the disease., Methods/results: A 65-year-old patient diagnosed of renal cell carcinoma presented a paratesticular mass. Histopathological examination of the orchidectomy specimen showed proliferation of clear cells arranged in a diffuse pattern, with intimate intertwining with vascular structures. Tumor cells were strongly positive for vimentin, CAM5.2 and EMA., Conclusions: Although renal cell carcinoma rarely metastasizes to the testes, it should be considered in the differential diagnosis of testicular masses. Histological examination is essential to diagnosis and correct management.

In order to investigate the effect of a competitive inhibitor of the HMG-CoA reductase on tumor growth and cholesterol homeostasis of host and non-host mice, we maintained a human lung mucoepidermoid carcinoma (HLMC) in nude mice, treating these animals with Simvastatin for 33 days. The drug increased the total activity of hepatic HMG-CoA reductase without affecting the cholesterolemia. Non-treated host animals presented lower serum, tissue and microsomal hepatic cholesterol than non-host animals. These differences disappeared when animals were treated with Simvastatin, though the induction of the reductase activity at mid-dark was higher in non-host than in host animals. Simvastatin produced no significant effects on both final tumor volume and body weight. Synthesis and cholesterol homeostasis restoration induced by liver and tumoral reductase would account for no effect on the HLMC growth after a long treatment with Simvastatin.

The t(9;22)(q34;q11) produces the BCR/ABL fusion gene which codifies a 210 kb protein with a strong tyrosine kinase activity and is involved in cellular development and growth. Because this translocation is a reciprocal event, it could give rise to a second fusion gene, ABL-BCR, on the derivative 9q+. We analyzed the influence of the 3' M-BCR deletion on the clinical picture at diagnosis and disease outcome in 57 patients with a clinical diagnosis of CML. Molecular studies were done on DNA from peripheral blood leukocytes or bone marrow with the restrictions enzymes BglII, EcoRI, HindIII, and BamHI, and the BCR 3' probe (transprobe 1) (Oncogene Science Inc.), which encompasses almost all of the 5.8 Kb of the M-BCR gene area. In 18 patients Southern blot analysis showed deletion of the 3' end of BCR gene (32.7%). There were no significant differences between patients with or without deletion, either in the clinical and laboratory data at the disease diagnosis or at the disease outcome. The absence of differences between the patients with and without 3' BCR deletion supports the hypothesis that the hybrid gene ABL-BCR does not have an important role in leukemogenesis in CML cases.

Intubating laryngeal mask airway (ILMA) is a very useful device for difficult airway management. The use of this device has not yet been studied in otorhinolaryngology surgery. The case of a 52-year-old man, weighing 104 kg, anesthetized for microlaryngoscopy due to aphonia occurred 6 months before, is reported. Traditional intubation was impossible. ILMA was easily positioned and the patient was ventilated. Intubation using ILMA was difficult and the operation postponed. Later, a bilateral false vocal chords hypertrophy was found. Impossible intubation using ILMA is a rare occurrence, less than 10% of cases. From previous evidence failed intubations are caused by anatomical anomalous formations, often predictables by clinical history. Blind intubation with ILMA is not, probably, the first alternative in these cases. Fiberoptic equipment intubation or use of ILMA with fiberoptic bronchoscope must be considered in these situations for possible better RESULTS. The use of ILMA in otorhinolarynogology surgery must be investigated with a specific study because there are only few experiences on this subject.

Two studies tested hypotheses on the content and structure of autobiographical memories and the affect linked to them. In Study 1, agentic- and communal-motivated individuals recorded their most memorable experiences and completed the PANAS each day for 6 weeks. Memories were coded for content and structure. Agentics and communals reported more motive congruent memories, and their congruent memories were structured using more differentiation and integration, respectively. In addition, agentics had slightly higher PA and lower NA scores. In Study 2, agentics and communals recalled an event pertaining to either social separation or connection and then completed an affect measure of agentic and communal items. Agentics recalled more agentic memories in the separation condition and communals recalled more communal memories in the connection condition. Complexity analyses showed that agentics and communals used differentiation and integration respectively to recall their motive-congruent memories. The affect data showed a modestpredicted pattern. Results suggest that implicit motives have an impact on autobiographical memory but are not as clearly related to self-report affect measures, possibly due to method variance.

Meshed split-thickness skin grafts, especially when required to be widely spread, do not obtain immediate biologic wound closure. In cases of patients with burns that cover a large percentage of the body surface area, this leaves the patient at risk for metabolic problems and life-threatening infection. Several cytokines and growth factors could theoretically affect the rate of epithelialization and, therefore, the rate of meshed graft interstitial closure. With the use of human meshed skin grafts explanted onto athymic "nude" rats, the epithelialization kinetics of interleukin-4 (IL-4), macrophage colony-stimulating factor (MCSF), keratinocyte growth factor-1 (KGF-1), keratinocyte growth factor-2 (KGF-2), basic fibroblast growth factor (bFGF), and transforming growth factor beta-2 (TGF(B2)) were investigated; the results were compared with the rates of epithelialization of grafts treated with a vehicle control. On postoperative day 3, wounds treated with IL-4, KGF-2, bFGF, and TGF(B2) showed a significantly increased rate of interstitial closure (P < .05). On postoperative days 5 and 7, wounds treated with KGF-2, bFGF, and TGF(B2) all exhibited a significantly higher rate of interstitial closure than the grafts in the control group (P < .05). These data suggest that epithelialization kinetics can be accelerated with the use of several topical growth factors, and they provide support for a future clinical trial.

Keloids, hypertrophic scars, and burn hypertrophic scars are all forms of proliferative scarring characterized by overabundant matrix formation. Recently these dermal proliferative disorders have been linked clinically to the cytokine transforming growth factor beta (TGF-beta), and in vitro tests have shown it to be responsible for the activation of fibroblasts and their production and deposition of collagen. Using an established in vivo animal model of proliferative scarring, the effects of this cytokine, specifically the isoform TGF-beta2, on these scars were examined. Proliferative scar specimens were implanted into athymic, asplenic nude rats and isolated in sandwich island flaps based on the superficial inferior epigastric pedicle. After establishment of the transferred flap, the scars were injected with varying doses of TGF-beta2 or vehicle for 5 consecutive days and then again on days 10, 15, and 20. The specimens were measured weekly during the period of dosing, and a biopsy was acquired on days 30 and 60. Fibroblasts from the explanted biopsies and the original scars were grown in cell culture, and cell proliferation studies were performed and the results compared. There was a dose response to TGF-beta2, with 200 ng showing the greatest effect. From the original scar specimens, keloid scars demonstrated the greatest cell proliferation kinetics--significantly faster than nonburn and burn hypertrophic scars. After treatment with TGF-beta2, both keloids and burn hypertrophic scars showed an increase in their cell proliferation kinetics compared with vehicle alone. This was not demonstrated with the nonburn hypertrophic scars. Elevated levels of TGF-beta2 are a major contributing factor to the process of proliferative scars, but because nonburn hypertrophic scars do not result in an equally increased response to this cytokine, a truly causative role for this cytokine cannot be promulgated. Rather, it is the combination of the proliferative scar fibroblasts' abnormal response to TGF-beta2 stimulation and elevated levels of this cytokine that controls more accurately the process of keloid and burn hypertrophic scar formation.

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activities and cholesterol content in the liver of athymic mice either bearing or not an implanted human lung mucoepidormoid carcinoma (HLMC) and in the neoplasic tissue, were analyzed. The properties of the HMG-CoA reductase of HLMC grown in nude mice and those ones found in the liver of these animals, sacrificed either at mid-light or mid-dark, were similar. The hepatic reductase activity was found to be four- to five-fold greater at mid-dark than at mid-light (462 +/- 141 vs. 123 +/- 22 pmol min-1 mg protein-1). Since the Km value was not modified, the mid-dark activity could be due to an increase in the amount of enzyme. In contrast, HLMC reductase activity and cholesterol content showed similar values at mid-light and mid-dark points. HLMC reductase does not appear to have any diurnal variation and the cholesterol synthesis and content seems to be independent of food intake. HLMC-bearing nude mice undergo several alterations in the biosynthesis and homeostasis of cholesterol. Hypocholesterolemia, lower hepatic cholesterol content and higher HMG-CoA reductase activity are characteristic of host mice.

Findings from 4 studies suggest that differentiation and integration are used by individuals high in agency and communion to structure motive-related information in episodic memory. Studies 1 and 2 demonstrated that agentic and communal individuals recalled more emotional experiences related to their motives, and that agentic individuals used more differentiation whereas communal individuals used more integration to structure these memories. Study 3 showed that agentic and communal individuals used more differentiation and integration to structure memories about social separation and connection, respectively. Study 4 demonstrated a similar pattern of recall in an experimentally controlled retrieval task. For a motive-congruent topic, agentic individuals recognized more differentiated information and had fewer differentiation recognition errors, and communal individuals freely recalled more integration.

Background: The biochemical and cellular pathways resulting in the production of proliferative scar in the thermally injured patient remain incompletely elucidated. A promising area of investigation is the phenomenon of programmed cell death and its modulation. The following study was designed to quantify differential levels of the bcl-2 protooncogene and the Fas cell surface receptor, two apoptosis-modulating proteins, in the peripheral blood mononuclear cell (PBMC) fractions of burn patients with hypertrophic scar versus those considered to have healed normally. The study also encompassed an immunohistochemical examination of fibroblasts in vitro, to identify differential levels of Fas, bcl-2, and interleukin converting enzyme (ICE)., Methods: PBMC fractions were isolated from two matched burn patient cohorts of 10 patients each, the experimental group carrying the clinical and histopathologic diagnosis of hypertrophic burn scar. The supernatant from each mitogenically stimulated specimen was halved and subjected to the Fas/APO-1 enzyme-linked immunosorbent assay (ELISA) and the bcl-2 ELISA. Results for each assay were compared between groups by unpaired t tests. Further biopsy specimens of isolated proliferative scar were used in vitro to analyze the role of these apoptosis-modulating proteins and ICE. This immunoperoxidase technique was analyzed qualitatively., Results: The expression of the bcl-2 protein in the PBMC fractions of the burn patients with hypertrophic scar is significantly elevated in comparison to the control cohort (307.72 +/- 72.29 u/ml vs 31.55 +/- 6.73 u/ml; P = 0.0042). The quantitative levels of the Fas receptor did not differ significantly between the groups, respectively (0.3988 +/- 0.179 u/ml vs 0.2899 +/- 0.066 u/ml; P = 0.5787). Immunoperoxidase staining of proliferative scar fibroblasts and those from surrounding skin revealed relatively decreased levels of membrane-bound Fas and ICE. bcl-2 was not detectable in these specimens., Conclusions: Differential expression of the bcl-2 protooncogene and the Fas cell surface receptor in the PBMC fraction of patients with burn injuries may suggest a disequilibrium in a complex biochemical signaling mechanism mediating programmed cell death. The increased levels of bcl-2 could be responsible for delayed fibroblast apoptosis, resulting in the disruption of normal healing and subsequent hypertrophic scarring. This is confirmed by an in vitro examination of wound fibroblasts versus those from surrounding uninjured skin. This immunoperoxidase technique reveals a localized relative decrease in Fas and ICE, two apoptosis-inducing proteins, at the level of the fibroblast in the proliferative scar specimen.

Background: Many aspects related to the biology and the effective therapy of proliferative scars have remained undefined, in part due to a lack of an accurate and reproducible animal model with which to systematically study them. This report describes a new model for investigating the pathophysiology and manipulation of human proliferative scars., Materials and Methods: Human proliferative scars (n = 86) were explanted into flaps based on isolated vascular pedicles in congenitally athymic rats. Serial analysis of the structural and functional integrity of the explanted scars was performed by microscopy and by measurement of human procollagen type III peptide (PIIIP) production, human factor VIII immunostaining, and in vitro cellular proliferation., Results: By these methods, both fibroblastic and epithelial components of explanted scar specimens retained the histologic characteristics of original human scar specimens, for up to 12 months. Over the same duration, scar explants continued to have high levels of human PIIIP, comparable to those found in original surgical specimens. The microvasculature of scar explants demonstrated a double basement membrane, with no staining of human factor VIII in the inner capillary endothelial layer, suggesting that host vessels were growing into ghost vessels of the human donor scar. Human factor VIII staining decreased over time. Fibroblasts cultured from explanted scar demonstrated less aggressive growth characteristics than those from original surgical specimens., Conclusions: This new model is the first to allow such long-term maintenance and serial evaluation of human proliferative scar on an accessible, isolated vasculature. It may prove useful in further defining the biology and therapy of this widespread pathologic process.

Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) reductase is a highly regulated enzyme which shows a marked circadian rhythmicity. We studied the impact of aging on this rhythm as well as the degree of correlation between age changes in circulating pituitary hormone levels and liver reductase activity in young (4 months) and old (33 months) Sprague-Dawley female rats. Lipid composition was also assessed in plasma and liver microsomes. The maximal activity (midnight) of HMG-CoA reductase fell from 864 +/- 28 pmol mevalonate/min/mg protein in the young rats to 552 +/- 45 pmol/min/mg protein in the old animals, whereas significant change was not observed in the basal (noon) activity levels of the enzyme. Noon serum cholesterol, but not midnight values, was significantly higher in the old rats. Liver cholesterol levels were similar in young and old rats. In old rats, fatty acid composition of liver microsomes revealed an increase in linoleic acid concurrently with a significant decrease in arachidonic acid (AA). A significant correlation was not detected between the age changes in pituitary hormone (GH, PRL, TSH, FSH) serum levels and those in reductase activity. On the other hand, a significant positive correlation was found in the old rats between hepatic reductase activity and the severity of mammary pathology. We conclude that, like most biological rhythms, HMG-CoA reductase circadian fluctuation decreases in amplitude with age. This change does not seem to be linked to the alterations of neuroendocrine function associated with the aging process. The presence of growing mammary tumors seems to stimulate liver reductase activity, which may constitute an adaptive response of the enzyme to cholesterol demand by the growing neoplastic tissue.

To clarify the significance of the role of the immune system in the formation of proliferative burn scars, this study attempted to identify differential production of cytokines between patients with burn injuries with and without hypertrophic scars. Mononuclear cell fractions were isolated from the peripheral blood (PBMC) of each patient and incubated with and without antigenic or mitogenic stimulation. The resultant supernatants were then assayed by ELISA techniques for production of various cytokines. The production of IL-1, IL-6, TNF-alpha, and TGF-beta2 by unstimulated PBMC was elevated significantly in patients with proliferative scar compared to control patients. Production of TGF-beta2 by stimulated PBMC also was elevated significantly in patients with proliferative scar. This study suggests that an increase in the production of TGF-beta and of proinflammatory cytokines by mononuclear cells may play a significant role in the processes that lead to excessive scar formation after burn injury.

Objective: To model the variability of medical visits by children for respiratory reasons as a consequence of the daily changes in environmental pollution observed in the emergency and family medicine departments of a hospital of the Instituto Mexicano del Seguro Social located in the southwest of Mexico City during 1993., Materials and Methods: The correlation between the presence of upper and lower respiratory tract infections and exposure to ozone and nitrogen dioxide was studied. To model this association, the authors used multivariate Poisson regression models with linear and non-linear risk, with lag periods between the environmental measurements and the medical visits of one, two and three days, as well as the average of the measurements of three, five and seven days previous to the visit., Results: The model estimates that an increment of 50 ppb in the daily average of ozone would cause an increase of 9.9% in emergency visits due to high respiratory tract infections during the winter, which could rise to 30% if the increment would last five consecutive days in average., Conclusions: Results suggest that exposure of children younger than 15 years of age to ozone and nitrogen dioxide significantly affect the number of medical visits for respiratory causes in this part of Mexico City.

Minoxidil has been proposed as a potential topical inhibitor of wound contraction and proliferative scarring. Suggestions for this application are derived from in vitro investigations demonstrating inhibition of various fibroblastic functions. The purpose of this study was to attempt to establish in vivo support of these effects using an established animal model of wound contraction. Standardized cutaneous wounds were created on the dorsum of Sprague-Dawley rats, which were divided equally into six treatment groups. Wounds were treated daily after tracing their unhealed areas. On complete closure of the wounds, analyses of the contraction rates and tensile strength were performed for comparison among groups. Minoxidil did not demonstrate significant inhibition of wound contraction rates relative to either an inert vehicle, an active vehicle, or no treatment. Contrarily, as previously demonstrated in this animal model, silver sulfadiazine did demonstrate significant inhibition of wound contraction rates relative to both vehicles. No significant difference in tensile strength was demonstrated among groups. These observations do not support the proposed use of minoxidil as an "antifibrotic" agent.

The effect of lovastatin, a hypocholesterolemic drug, on tumor growth and desaturase activity was studied in a human lung mucoepidermoid carcinoma (HLMC) grown in nude mice. After administration of a diet supplemented with 25 mg% (w/w) lovastatin for 30 days the growth of HLMC was not inhibited. Liver and tumor phospholipid/cholesterol ratio was increased in lovastatin group but serum cholesterol was unaffected. Treatment with lovastatin increased delta 5 and delta 9 desaturation in tumor microsomes, whereas delta 6 desaturation did not change in tumors of treated mice. The changes were not reflected in the fatty acid composition of total tumor lipids.

The authors report their 12 years of experience of intra arterial chemotherapy in pelvic recurrences and inoperable advanced stages of uterine carcinoma, rectal cancer and anal cancer. In squamous cell cancers the drug associations were mitomycin C, bleomycin, fluorouracil and folinic acid and cisplatin. In adenocarcinoma the same protocol contained no bleomycin. Drugs were infused for a 48 hours period in continuous infusion. The dosages were the same than in the intravenous regimens. Twenty patients with pelvic recurrences were included in this retrospective study: six were uterine cancers, fourteen were colo rectal cancers and two had advanced stage uterine cancer. Pain decreased in 10/14 patients with ano-rectal cancer pre sacral recurrence. Partial response was observed in 12 patients. Complete secondary surgical resection was possible in 4/14 rectal cancers and 6/6 uterine cancer recurrences. Chemotherapy induced a pathological complete response in 4/6 uterine cervix carcinoma recurrences. These observations led to perform pelvic intra arterial chemotherapy as first line treatment of locally-advanced inoperable pelvic tumors: 11 uterine cancers and five ano-rectal cancers. The objective were: tumor reduction before radiotherapy or surgery, tumor sterilization, decrease tumor volume for better radiation dosimetry, increase the chance of organ-preservation. The observation of tumor reduction in this small number of patients does not allow to draw definite conclusions. However the introduction of intra arterial pelvic chemotherapy as first line treatment of inoperable pelvic cancer warrants further studies.

Biphotonic absorptiometry has begun to demonstrate its usefulness in the field of osteoporosis. In algodystrophy, the radiology and the degree of isotopic fixation suggest a bone disorder, although both techniques are unable to objectively quantify it. Biphotonic absorption is an scanning technique which allows the quantification of bone demineralization in the segment affected by algodystrophy and its evolutive follow-up.

The authors report the case of a girl with achondroplasia suffering from a progressively worsening hypotonic quadriparesis. CT scan showed slight dilatation of ventricular and subarachnoid spaces, with well-defined evidence of cortical sulci and gyri. This aspect was compatible with the diagnosis of macrocrania and megalencephaly (CP being 51 cm). The foramen magnum was narrowed, the transverse diameter measuring 15 mm and the 50th percentile being, for age, 26 mm. Somatosensory evoked potentials (SEPs) revealed bilaterally prolonged interpeak latencies Erb-N13, slowing of central conduction time N13-N20 from right median nerve stimulation, and block from left median nerve. The suspicion of cervicomedullary compression was confirmed by MRI, showing a very marked stenosis with compression exerted by the odontoid process. Further, a stenotic cervical canal and optic nerves verticalization were manifest. The patient underwent neurosurgical decompression by suboccipital craniectomy and cervical-C1 laminectomy. In spite of treatment, both neurologic and respiratory problems (rapid, shallow and almost abdominal breathing) were unchanged. The girl died 4 1/2 months later. The authors emphasize the important role of SEPs in detection of cervicomedullary compression in achondroplastic children and also stress the necessity of an early surgical treatment as the only condition for possible clinical improvement and/or full recovery.

The neurilemoma (benign schwannoma) is a benign tumor which arises from the Schwann cells of the peripheral nerves. In an intraosseous localization it is a very rare lesion, only forty cases being reported in the literature, and only two of these with the tumor located in the femur. This paper reports on a patient with a large neurilemoma in the lower part of the left femur.

The association of urethral stenosis and stones is not frequent. The urethral stenosis, particularly common in males, recognizes, as predisposing causes, urethritis, IPB, perineal trauma, neurogenic bladder and, last, but not the least important, endoscopic treatments or repeated catheterism. The authors report a case of a 42 year old man who underwent, for urolithiasis, several endoscopic examinations, which became urethral-stenosis with stones within four years. With responsible and critical behaviour, etiology, the diagnostic procedures and the therapy (invasive or not) of the urethral-stenosis are examined and evaluated. Diagnosis must be based on a non painful approach (clinical, bacteriological, ultrasonography, uro-dynamic studies); the invasive procedures must be limited as much is possible. Whatever treatment is used, which may always give sequences or complications, a prolonged follow-up is mandatory to have an objective evaluation of the results.

We present the case of a female patient with tuberculosis of the gallbladder, the adipose tissue and lymph nodes surrounding the common bile duct; the patient presented with obstructive jaundice. We discuss the diagnostic criteria, approach to the biliary tract and treatment of this type of patients.

The authors make a review of the correlation between the clinical and pathological data in Ewing's sarcoma. The morphological lesions are generally wider than those given by the radiographic record. The microscopic picture is the same for both osseous and extraosseous cases. The different cell types of Ewing's sarcoma are indicated, all of them giving rise to a similar clinical picture. The histogenesis of the disease is still discussed, the most favored hypothesis being that it originates in the non-differentiated mesenchyma of the primitive bone marrow.