The etiology of pneumonia in malnourished and well-nourished Gambian children

During a 2-year period 159 malnourished children ages 3 months to 5 years with radiologic evidence of pneumonia were investigated to determine the cause of their pneumonia. In addition 119 malnourished children without pneumonia, 119 well-nourished children with pneumonia and 52 well-nourished children without pneumonia were studied as controls. Percutaneous lung aspiration was performed on 35 malnourished and 59 well-nourished children with pneumonia. Bacteria were isolated from the blood, lung or pleural fluid of 28 (18%) malnourished children with pneumonia, 42 (35%) well-nourished children with pneumonia and from the blood of 5 (4%) malnourished children without pneumonia. Streptococcus pneumoniae and Haemophilus influenzae, which were the two organisms isolated most frequently in both groups of children with pneumonia, were found in 17 (11%) malnourished and 39 (33%) well-nourished children with pneumonia. Mycobacterium tuberculosis was detected in 5 malnourished children with pneumonia. A potentially pathogenic virus was identified in 35% of malnourished children with pneumonia and 40% of well-nourished children with pneumonia, and from 25% of children without pneumonia. The viruses identified most frequently were adenovirus and respiratory syncytial virus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrous dysplasia of the spine, costae and hemipelvis with sarcomatous transformation

We describe a patient with polyostotic fibrous dysplasia and secondary malignant fibrous histiocytoma in a spinal lesion.     

Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience

BACKGROUND: The Quebec Neuroblastoma Screening (QNS) Project completed a 5-year program for measuring urinary vanillylmandelic acid (VMA)/homovanillic acid (HVA) levels at age 3 weeks and/or 6 months in 89% of 476,603 Quebec-born infants from 1989-1994; 45 screening positive preclinical cases (S-positive cases) and 20 congenital/neonatal (C/N) cases were identified. As of April 1997, an additional 59 cases in the same birth cohort were diagnosed clinically; these neuroblastomas developed after screening verified normal VMA/HVA levels (S-negative cases). METHODS: Pathology specimens from 45 of 59 S-negative cases were reviewed centrally and classified according to the Shimada system. Results were compared with clinical data and also with S-positive and C/N cases. RESULTS: Of 45 S-negative cases, 27 tumors had favorable histology (FH) and 18 had unfavorable histology (UH). Approximately 52% of FH tumors were diagnosed before age 1 year, whereas UH tumors were nearly exclusively (94%) diagnosed after age 1 year (P < 0.01). Approximately 89% of FH tumors were Stage I, II, or IV-S, whereas 72% UH tumors were Stage III or IV (P < 0.001). All children with FH tumors were alive at last follow-up (range of follow-up period: 9-79 months; median, 35 months), whereas 8 children with UH tumors died of disease even after limited follow-up (range of follow-up period: 0-60 months; median, 20 months). By contrast, S-positive and C/N cases were predominantly (97%) FH tumors, often (76%) Stage I, II, or IV-S, with excellent clinical outcome (survival rate of 98%). CONCLUSIONS: The majority of the UH neuroblastomas that developed in the birth cohort of the QNS Project were included in the group of S-negative cases and could not be detected by the screening at age 3 weeks and/or 6 months.     

Contrasting effects of D- and L-(E)-4-(3-phosphono-2-propenyl)piperazine-2-carboxylic acid as anticonvulsants and as inhibitors of potassium-evoked increases in hippocampal extracellular glutamate and aspartate levels in freely moving rats

Microdialysis experiments performed in the dorsal hippocampus of freely moving rats showed that L-(E)-4-(3-phosphono-2-propenyl)piperazine-2-carboxylic acid (L-CPPene) is 10 times as potent as D-CPPene in inhibiting potassium-induced increases in extracellular levels of aspartate and glutamate. In control experiments, two 100 mM KCl stimuli (S1 and S2) applied for 10 min each (separated by a 40-min recovery period) produced substantial (300-500%) increases in the extracellular levels of aspartate, glutamate, taurine, and GABA and a 50% decrease in the glutamine level. S2/S1 ratios in the control groups were 0.67 (aspartate), 0.78 (glutamate), 0.83 (GABA), and 0.85 (taurine). In the experimental groups, D- or L-CPPene was applied via the probe during the second potassium stimulus (S2). L-CPPene (25 or 250 microM) produced selective suppression of potassium-induced increases of extracellular glutamate (S2/S1 ratio: 0.25) and aspartate (S2/S1 ratio: 0.20) levels, whereas 250 microM D-CPPene was required to inhibit the extracellular aspartate and glutamate increases. Neither enantiomer of CPPene affected the potassium-induced increases of GABA and taurine or the decrease in extracellular glutamine concentration. An additional study comparing the anticonvulsant potencies of D- and L-CPPene was performed using audiogenic DBA/2 mice. The anticonvulsant potency of D-CPPene, as assessed against sound-induced seizures in DBA/2 mice, was an order of magnitude higher than that of L-CPPene [ED50 clonic phase (intraperitoneal, 45 min): 1.64 mumol/kg and 16.8 mumol/kg, respectively]. We attribute the anticonvulsant action of D-CPPene to its antagonist action at the NMDA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cefuroxime axetil in the treatment of acute sinusitis in childhood

A study of the efficacy of cefuroxime axetil was conducted for the treatment of acute sinusitis in childhood. Thirty-nine patients aged 5-14 years were given cefuroxime axetil 20 mg/kg/day divided into two doses for seven days. The diagnosis of acute sinusitis was based on history, physical examination, and radiological findings. The results of throat cultures before treatment were 17 patients with group A beta-haemolytic streptococci, seven patients with pneumococci, and two patients with Staphylococcus aureus; in the remainder of the patients only normal throat flora were isolated. In 36 patients (92%) a satisfactory improvement was reported at the end of the treatment. It was found that cefuroxime axetil was efficaceous for the treatment of sinusitis in childhood.     

The relationship between jaw posture and muscular strength in sports dentistry: a reappraisal

In a previous report, we observed by light microscopy the extracellular matrix in 51 vulvar squamous carcinomas and found that some tumors has a prominent stromal response in the form of a regional or diffuse zone of extracellular myxoid matrix containing immature collagen and fibroblasts at the tumor-stromal junction. These tumors were associated with clitoral involvement, ulcerative nonexophytic growth pattern, older age groups, poorer survival rate, and more extensive lymph node metastases than when prominent fibromyxoid stromal response (PFSR) was absent. This behavior was demonstrated despite the fact that these tumors were not larger, more deeply invasive, or of higher grade than when PFSR was absent. In the current immunohistochemical study, we examined cytokine, cell adhesion receptor, and tumor suppressor gene expression in 50 vulvar squamous carcinomas using a panel of antibodies to identify any potential role of these proteins in the development of a PFSR. Semiquantification of expression into none, focal (< 25% of cells showing expression), regional (25-50%), and diffuse (> 50%) patterns revealed PFSR to be statistically associated with high CD44, transforming growth factor (TGF) beta 3, and p53 protein expression, but not with fibroblast growth factor, epidermal growth factor, epidermal growth factor receptor, or E-cadherin expression. When expression of CD44 and either stromal or tumor TGF-beta 3 expression was high, i.e., regional or diffuse in distribution, 15 (50%) of 30 cases were associated with PFSR. In contrast, only 1 (7%) of 14 cases was associated with PFSR when expression was high for only one of these two proteins and none of 3 cases was associated with response when expression was low for both proteins (p = 0.005). Furthermore, in cases showing high expression for both TGF-beta 3 and CD44, PFSR was found in 13 (72%) of 18 cases when p53 expression was diffuse compared with 2 (17%) of 12 cases when expression was less (p = 0.01). Since TGF-beta acts mitogenically for fibroblasts and has been shown to be an inhibitor of epithelial cell growth, its high expression in a carcinoma with PFSR would suggest loss of effect on the epithelial component but an intact effect on the stroma. Since CD44 is known to act as a receptor for hyaluronic acid, which is a prominent stromal component and known to play an important role in cell mobility and tumor aggressiveness, its high expression in association with PFSR would suggest a role of CD44 overexpression in altered hyaluronate metabolism with accelerated tumor cell migration and subsequent distal spread. The current study demonstrates that alterations in cytokine and cell adhesion receptor status variably occur in vulvar squamous carcinoma and that such alterations may affect tumor morphology and behavior.     

Prothrombotic states associated with retinal venous occlusion in young adults

BACKGROUND: The etiology of retinal venous occlusion in young patients is not well understood although thrombosis does occur histologically. A search for the risk factors that may lead to thrombosis is highly desirable may contribute to our understanding of the pathogenesis of this complication and may improve our therapeutic strategies. METHODS: We studied 17 patients with retinal venous occlusion. All patients were under 45 years of age (mean 37.8 +/- 7.1). Antiphospholipid antibodies (APAs) and certain hemostatic factors were determined. The results obtained in these patients were compared to those of normal controls. RESULTS: We found APAs in 8 out of 17 patients compared to 5 out of 60 controls (p = 0.0002). In patients with major trunk occlusion, there was a trend for the presence of APAs in those with poor visual acuity at presentation. Deficiencies of the coagulation inhibitor proteins C and S and antithrombin III activities were detected in 6 patients, and reduced levels of Factor XII were found in 4 patients. Levels of hematocrit, erythrocyte sedimentation rate. Fibrinogen, alpha 1-globulin, and alpha 2-globulin were significantly higher in patients compared to the controls (p = 0.019; 0.014; 0.0001; 0.011; 0.047), indicating increased blood viscosity in patients with retinal venous occlusion. CONCLUSION: Prothrombotic changes in the form of APAs and/or deficiencies of coagulation inhibitors and Factor XII may contribute to the etiology of retinal venous occlusion in young adults. Young patients with retinal venous occlusion should be evaluated for these prothrombotic states.     

Interorgan signaling between adipose tissue metabolism and skeletal muscle uncoupling protein homologs: is there a role for circulating free fatty acids?

Uncoupling proteins 3 and 2 (UCP3 and UCP2) are two newly cloned genes that have been implicated in the regulation of lipids as fuel substrate in skeletal muscle on the basis that their mRNA expressions are upregulated during starvation (when fat stores are being rapidly mobilized) and downregulated during the early phase of refeeding (when fat stores are being rapidly replenished). To test the hypothesis that circulating free fatty acids (FFAs) may have a physiological role as an interorgan signal linking these dynamic changes in the fat stores to skeletal muscle expression of UCP3 and UCP2, the mRNA levels of these UCP homologs were examined in fed and fasted rats treated with the antilipolytic agent nicotinic acid. In 46-h fasted rats, we observed a threefold increase in serum FFA levels and increases in UCP3 and UCP2 mRNA levels that were more marked in the gastrocnemius and tibialis anterior muscles (predominantly fast-twitch fibers) than in the soleus muscle (predominantly slow-twitch fibers). Treatment with nicotinic acid blunted the fasting-induced increase in serum FFA levels and prevented the increase in mRNA levels of UCP3 and UCP2 in the soleus muscle, but had little or no effect on the elevated mRNA levels of these UCP homologs in the gastrocnemius and tibialis anterior muscles. Furthermore, treatment of ad libitum-fed animals with nicotinic acid resulted in a twofold reduction in serum FFA levels (i.e., by a magnitude similar to that observed during early refeeding) and significant reductions in UCP3 and UCP2 mRNA levels in the soleus muscle, but not in the gastrocnemius or tibialis anterior muscles. These results revealed a muscle-type dependency in the way UCP2 and UCP3 gene expression in skeletal muscle is regulated, and suggest that the hypothesis that circulating FFAs function as an interorgan signal between fat stores and skeletal muscle UCP3 and UCP2 gene expression is adequate only for slow-twitch (oxidative) muscles. Consequently, a signal(s) other than circulating FFAs must be implicated in the link between dynamic changes in body fat stores and UCP expression in predominantly fast-twitch (glycolytic/oxidative-glycolytic) muscles, which constitute the major fiber type of the total skeletal muscle mass and which have high susceptibility to developing insulin resistance and impairment in substrate utilization in metabolic diseases.     

Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine

Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by trombocytopenia, eczema, and progressive decline of the immune function. In addition, lymphocytes and platelets from WAS patients have morphologic abnormalities. Since chemokines may induce morphologic changes and migration of leukocytes, we investigated the monocyte response to chemoattractants in cells from WAS patients with an identified mutation in the WAS protein gene. Here, we report that monocytes derived from four patients with molecularly defined typical WAS have a severely impaired migration in response to FMLP and to the chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha compared with normal donors. Conversely, neither MCP-1 binding to monocytes nor induction of the respiratory burst by MCP-1 and FMLP is significantly different between WAS patients and normal donors. Within a few minutes of stimulation, monocytes respond to chemokines with increased expression of adhesion molecules and with morphologic changes such as cell polarization. Although up-regulation of CD11b/CD18 expression following stimulation with FMLP or MCP-1 is preserved in WAS patients, cell polarization is dramatically decreased. Staining of F-actin by FITC-phalloidin in monocytes stimulated with chemoattractants shows F-actin to have a rounded shape in WAS patients, as opposed to the polymorphic distribution of F-actin in the polarized monocytes from healthy donors. These results suggest that WAS protein is involved in the monocyte response to the chemokines MCP-1 and macrophage inflammatory protein-1alpha.