Culture and characterization of sinusoidal endothelial cells isolated from human liver

BACKGROUND: Epidemiologic data concerning skin diseases in many rural areas in sub-Saharan Africa are not available. Little is known about the effect of regular treatment schedules by paramedical staff (especially community health workers) in the primary healthcare system on the severity and prevalence of dermatoses. METHODS: 5780 school and pre-school children from 13 primary schools in four sublocations in rural western Kenya (Kisumu District) were examined for dermatoses by the author, together with community health workers in 1993. On-the-spot training and weekend seminars about important and common dermatoses were also given. In 1994 a dermatology program was started within the primary healthcare system. Twelve trained community health workers carried out regular school visits once a week and diagnosed and treated pupils with dermatoses. Treatment was performed with gentian violet 1% solution for bacterial skin infections, Whitfield's ointment for dermatophytoses, benzylbenzoate emulsion 25% for scabies, and hydrocortisone acetate 1% cream for eczemas. All schools were visited again in 1995 to evaluate the long-term effects of the program. RESULTS: In 1993, the prevalence rate for dermatoses was 32.4%. Most of the skin diseases found were of infective origin (27.1% were caused by bacteria, 21.6% by fungi, and 17.6% by arthropods, mainly scabies mites). Dermatitis accounted for 3.5%. In 1995, the prevalence of dermatoses declined to 29.6% (p<0.05), and this reduction was most strongly observed for tropical ulcers and tinea capitis. Additionally, there was an improvement in the extent and severity of skin diseases. CONCLUSIONS: This study defines, for the first time, the number and extent of skin diseases in children in rural Kisumu District; most dermatoses were of infective origin. The study demonstrates that community health workers in the primary healthcare system are capable of dealing successfully with the most common dermatoses in children following a short training period.     

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q

The degree and nature of patient involvement in consultations with health professionals influences problem and needs recognition and management, and public accountability. This paper suggests a framework for understanding the scope for patient involvement in such consultations. Patients are defined as co-producers of formal health services, whose potential for involvement in consultations depends on their personal rights, responsibilities and preferences. Patients' rights in consultations are poorly defined and, in the National Health Service (NHS), not legally enforceable. The responsibilities of patients are also undefined. I suggest that these are not to deny, of their own volition, the rights of others, which in consultations necessitate mutuality of involvement through information-exchange and shared decision-making. Preferences should be met insofar as they do not militate against responsibilities and rights.     

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.     

Efficacy of arthroscopic lysis and lavage in patients with temporomandibular joint symptoms associated with generalized osteoarthritis or rheumatoid arthritis

PURPOSE: This study evaluated the efficacy of arthroscopic lysis and lavage in patients with temporomandibular joint (TMJ) symptoms and generalized osteoarthritis (GOA) or rheumatoid arthritis (RA). PATIENTS AND METHODS: Twenty-three GOA patients and 23 RA patients were evaluated after 1 year. RESULTS: Seventeen of 23 patients (74%) in the RA group improved after arthroscopic lysis and lavages compared with 10 of 23 (43%) of the GOA patients. Lateral joint tenderness, crepitation, maximal opening, and maximal protrusion showed most improvement in the RA group. CONCLUSIONS: On the basis of this short-term follow-up study, arthroscopic lysis and lavage seem to provide an effective treatment for TMJ pain and dysfunction in RA patients but not in GOA patients.     

DSM-IV field trials for oppositional defiant disorder and conduct disorder in children and adolescents

OBJECTIVE: The purpose of the field trials for oppositional defiant disorder and conduct disorder was to select valid diagnostic thresholds for these disorders and to compare the psychometric properties of DSM-IV criteria for oppositional defiant disorder and conduct disorder with previous DSM diagnostic formulations. METHOD: Structured diagnostic interviews, standardized clinician's validation diagnoses, and multiple measures of impairment were obtained for 440 clinic-referred children and adolescents aged 4-17 years. RESULTS: A diagnostic threshold of four symptoms of oppositional defiant disorder optimized identification of impaired children, improved agreement somewhat with the clinician's validation diagnosis, and had somewhat better test-retest agreement than DSM-III-R. In the case of conduct disorder, the optimal time window for ascertainment of symptoms was clarified. A diagnostic threshold of three symptoms of conduct disorder maximized accurate identification of impaired children and agreement with the clinician's validation diagnosis and resulted in slightly better test-retest agreement than DSM-III-R. Compared with the DSM-III-R definition, the DSM-IV definition of oppositional defiant disorder was somewhat more prevalent, but the prevalence of conduct disorder was essentially unchanged. CONCLUSIONS: DSM-IV definitions of oppositional defiant disorder and conduct disorder are somewhat better than DSM-III-R definitions in terms of internal consistency and test-retest agreement, and the validity of the DSM-IV definition of oppositional defiant disorder is slightly better than that of DSM-III-R.     

Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis

Farmers lung disease is a common form of hypersensitivity pneumonitis (HP) and is characterized by inflammation and granuloma formation in the lung. Interferon-gamma is important for the expression of granulomatous diseases caused by infectious agents; however, the role this mediator in regulating expression of the granulomatous response to inhaled antigen is not known. To evaluate this, we compared the response to inhaled antigen of mice that do not express the gene coding for interferon-gamma (GKO) with that of their normal littermates (WT). GKO and WT mice on a BALB/c background were exposed to 150 microg of the thermophilic bacteria Saccharopolyspora rectivirgula or saline alone, for three consecutive days a week, for 3 wk. After exposure to antigen, WT mice developed a marked granulomatous inflammation associated with an increase in lung weight and numbers of cells in bronchoalveolar lavage fluid (BAL). Although GKO mice also exhibited an increase in lung weight and numbers of cells in BAL fluid, they developed minimal inflammation and no granulomas after a similar exposure to antigen. To further evaluate if the lack of a response to antigen in GKO mice was due to lack of IFN-gamma, we replaced this mediator via intraperitoneal injections. When given replacement IFN-gamma, the GKO mice developed granulomatous inflammation in the lung. These studies show that IFN-gamma is essential for the expression of hypersensitivity pneumonitis.     

Leukoregulin induction of protein expression in human orbital fibroblasts: evidence for anatomical site-restricted cytokine-target cell interactions

The molecular basis for the profound inflammatory response and the accumulation of hyaluronan in orbital connective tissues seen in thyroid-associated ophthalmopathy is unknown. Moreover, the link between the orbital manifestations of Graves' disease and those in the pretibial skin, localized dermopathy, has yet to be established. We have reported recently that leukoregulin, an activated T lymphocyte-derived cytokine, dramatically induces hyaluronan synthesis and prostaglandin-endoperoxide H synthase 2 in human orbital fibroblasts in culture. In the current studies, utilizing giant two-dimensional gel electrophoresis, we find that orbital fibroblasts express constitutively a protein profile that distinguishes them from skin fibroblasts derived from the abdominal wall and from the pretibium. We further demonstrate that leukoregulin, when present in culture medium for 16 hr, up-regulates a set of orbital fibroblast proteins not present in untreated cultures or in fibroblasts from the abdominal wall. However, some of the same protein inductions are present in the pretibial fibroblasts. These leukoregulin-induced changes in protein expression are completely blocked by dexamethasone (10 nM). Our findings are the first to identify proteins that appear to be expressed and differentially regulated in an anatomical site-restricted manner in orbital and pretibial fibroblasts and seem to establish a molecular link between fibroblasts from the orbit and those in pretibial skin.     

Regional 5-hydroxyindoleacetic acid production in humans

Veno-arterial plasma concentration differences and regional organ plasma flows were used to quantify the relative amounts of 5-hydroxyindoleacetic acid (5-HIAA) contributed by various sites into the peripheral circulation. Positive venoarterial concentration gradients were found in the hepatosplanchnic, forearm, cardiac and jugular vessels in the healthy subjects. The renal circulation was determined to be the principal site of 5-HIAA clearance, extracting 18 +/- 2 nmol/min. The gut was the greatest contributor to the total 5-HIAA plasma pool with the relative contributions of the various organs being as follows: hepatosplanchnic organs 58%, skeletal muscle 26%, brain 6% and the heart 3%. The source of 5-HIAA stemming from these regional beds remains unknown, it may derive from serotonin taken up by and deaminated in ubiquitous endothelial cells, enterochromaffin cells of the gut, peripheral serotonergic nerves, serotonin turnover in platelets or perhaps the metabolism of serotonin taken up by sympathetic nerves. To test the latter hypothesis we examined 23 patients with chronic congestive heart failure and 9 patients with pure autonomic failure to investigate the possible effects of sympathetic nervous system overactivity and underactivity on peripheral 5-HIAA production and plasma 5-HIAA concentration. The resting arterial plasma 5-HIAA concentration in the heart failure patients was increased three-fold. This elevated plasma 5-HIAA concentration was attributable to an increased rate of whole body 5-HIAA production. The arterial 5-HIAA plasma concentration in the autonomic failure patients was paradoxically elevated, being 70% greater than that of the healthy subjects. The increased 5-HIAA plasma concentration in these patients was accounted for by a reduction in 5-HIAA plasma clearance. In all subjects studied there was a weak relationship only between total body norepinephrine spillover to plasma and the arterial 5-HIAA plasma concentration. We found that in healthy subjects the overflow of 5-HIAA into the hepatic vein was significantly related to the underlying degree of sympathetic activity. It can be concluded that 5-HIAA is produced at a number of sites throughout the body with the arterial plasma concentration being dependent on both the level of production and plasma clearance. By far the majority of 5-HIAA in plasma is derived from the gut with only minimal contribution from the brain.