Calcium dynamics in bovine adrenal medulla chromaffin cell secretory granules

The secretory granules constitute one of the less well-known compartments in terms of Ca2+ dynamics. They contain large amounts of total Ca2+, but the free intragranular [Ca2+] ([Ca2+]SG), the mechanisms for Ca2+ uptake and release from the granules and their physiological significance regarding exocytosis are still matters of debate. We used in the present work an aequorin chimera targeted to the granules to investigate [Ca2+]SG homeostasis in bovine adrenal chromaffin cells. We found that most of the intracellular aequorin chimera is present in a compartment with 50-100 microM Ca2+. Ca2+ accumulation into this compartment takes place mainly through an ATP-dependent mechanism, namely, a thapsigargin-sensitive Ca2+-ATPase. In addition, fast Ca2+ release was observed in permeabilized cells after addition of inositol 1,4,5-trisphosphate (InsP3) or caffeine, suggesting the presence of InsP3 and ryanodine receptors in the vesicular membrane. Stimulation of intact cells with the InsP3-producing agonist histamine or with caffeine also induced Ca2+ release from the vesicles, whereas acetylcholine or high-[K+] depolarization induced biphasic changes in vesicular[Ca2+], suggesting heterogeneous responses of different vesicle populations, some of them releasing and some taking up Ca2+during stimulation. In conclusion, our data show that chromaffin cell secretory granules have the machinery required for rapid uptake and release of Ca2+, and this strongly supports the hypothesis that granular Ca2+ may contribute to its own secretion.     

Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia

We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-function with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin. Received: 15 December 2000, Received in revised form: 29 May 2001, Accepted: 18 June 2001     

Citrobacter koseri in scalp folliculitis

Gram-negative folliculitis, an uncommon condition, is most often seen in older patients who have acne and who either have received prolonged courses of antibiotic therapy or have used antibacterial cleansers that selectively inhibit gram-positive organisms. Citrobacter infections are uncommon, and dermatologists seldom encounter them. In the past, these infections occurred in hospitals, particularly in neonatal intensive care units. Bacteremias also occur in elderly or immunocompromised patients. In this article, we present a case of Citrobacter koseri scalp folliculitis in an otherwise healthy patient.     

Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia

Elderly patients are more prone than younger patients to develop cerebral desaturation because of the reduced physiologic reserve that accompanies aging. To evaluate whether monitoring cerebral oxygen saturation (rSO(2)) minimizes intraoperative cerebral desaturation, we prospectively monitored rSO(2) in 122 elderly patients undergoing major abdominal surgery with general anesthesia. Patients were randomly allocated to an intervention group (the monitor was visible and rSO(2) was maintained at > or =75% of preinduction values; n = 56) or a control group (the monitor was blinded and anesthesia was managed routinely; n = 66). Cerebral desaturation (rSO(2) reduction <75% of baseline) was observed in 11 patients of the treatment group (20%) and 15 patients of the control group (23%) (P = 0.82). Mean (95% confidence intervals) values of mean rSO(2) were higher (66% [64%-68%]) and the area under the curve below 75% of baseline (AUCrSO2(2)< 75% of baseline) was lower (0.4 min% [0.1-0.8 min%]) in patients of the treatment group than in patients of the control group (61% [59%-63%] and 80 min% [2-144 min%], respectively; P = 0.002 and P = 0.017). When considering only patients developing intraoperative cerebral desaturation, a lower Mini Mental State Elimination (MMSE) score was observed at the seventh postoperative day in the control group (26 [25-30]) than in the treatment group (28 [26-30]) (P = 0.02), with a significant correlation between the AUCrSO(2) < 75% of baseline and postoperative decrease in MMSE score from preoperative values (r(2)= 0.25, P = 0.01). Patients of the control group with intraoperative cerebral desaturation also experienced a longer time to postanesthesia care unit (PACU) discharge (47 min [13-56 min]) and longer hospital stay (24 days [7-53] days) compared with patients of the treatment group (25 min [15-35 min] and 10 days [7-23 days], respectively; P = 0.01 and P = 0.007). Using rSO(2) monitoring to manage anesthesia in elderly patients undergoing major abdominal surgery reduces the potential exposure of the brain to hypoxia; this might be associated with decreased effects on cognitive function and shorter PACU and hospital stay.     

Epidemiology of type 2 diabetes in Mexico

The epidemiology of diabetes in Mexico is reviewed. In less than four decades, diabetes has become the main health problem in Mexico. It is the principal cause of death in women and the second among men since the year 2000. It is the primary cause of premature retirement, blindness, and kidney failure. By the year 2025, close to 11.7 million Mexicans are expected to be diagnosed with diabetes. In the year 2000, diabetes was the 11th most frequent cause of hospitalization but the second most common cause of hospital mortality. The number of cases reported in children has also increased since 1995. The results of population-based, nationwide surveys have detected a 25% increment over a 7-year period. Fourteen percent of people with diabetes are <40 years of age, and a large proportion of patients have other conditions that determine the appearance of macrovascular complications and kidney failure. In addition, many cases do not reach treatment goals. In conclusion, the growing number of cases and the significant health burden imposed on affected subjects makes diabetes a disease that needs to be prevented. Well-planned strategies are urgently needed to modify the lifestyle of the population and to increase their physical activity. In addition, an enormous effort will be required to educate the population and physicians to improve the diagnosis and treatment of patients with diabetes.     

Persistent B-cell lymphopenia, multiorgan disease, and erythema multiforme caused by Mycoplasma pneumoniae infection

We report a 6-year-old girl in whom Mycoplasma pneumoniae infection presenting with erythema multiforme, multiorgan, and hematologic dysfunctions induced a long-standing, marked B-cell lymphopenia. An increase of CD8+ lymphocytes was also detected. We suggest that a selective cytotoxic T lymphocyte-dependent B cell lysis and the expansion of super-antigen activated CD8+ T cells may account for the multiorgan and hematologic disturbances triggered by M. pneumoniae.     

The upper inflection point of the pressure-volume curve. Influence of methodology and of different modes of ventilation

OBJECTIVE: The pressure-volume (P/V) curve has been proposed as a tool to adjust the ventilatory settings in cases of acute respiratory distress syndrome (ARDS). The aim of this study was to test the influence of P/V tracing methodology on the presence and value of the upper inflection point (UIP). METHODS: In 13 medical ARDS patients, the interruption and the automated low flow inflation methods were compared while the patients were ventilated at conventional (10-12 ml/kg) and at low (5-6 ml/kg) tidal volume (Vt). Two levels of inspiratory flow and insufflation time were used (3 and 6 s). RESULTS: No significant difference in UIP was found between the static and the dynamic methods, whatever the flow used. At Vt 10-12 ml/kg, the static and dynamic UIPs were 22.4 +/- 4.4 cmH(2)O and 22.1 +/- 4.5 cmH(2)O ( p = 0.86), respectively; at Vt of 5-6 ml/kg, the static and dynamic UIPs were 26.6 +/- 4.1 cmH(2)O and 25.5 +/- 5 cmH(2)O ( p = 0.34), respectively. Significant differences in UIP were found, in the static and dynamic conditions, between the two levels of Vt ( p < 0.005): it was lower with the higher Vt, suggesting that UIP is dependent on previous tidal alveolar recruitment. CONCLUSION: Interruption and continuous flow techniques gave similar results, but the previous Vt influences the pressure value of the UIP.     

beta-Catenin regulates vascular endothelial growth factor expression in colon cancer

To evaluate whether beta-catenin signaling has a role in the regulation of angiogenesis in colon cancer, a series of angiogenesis-related gene promoters was analyzed for beta-catenin/TCF binding sites. Strikingly, the gene promoter of human vascular endothelial growth factor (VEGF, or VEGF-A) contains seven consensus binding sites for beta-catenin/TCF. Analysis of laser capture microdissected human colon cancer tissue indicated a direct correlation between up-regulation of VEGF-A expression and adenomatous polyposis coli (APC) mutational status (activation of beta-catenin signaling) in primary tumors. In metastases, this correlation was not observed. Analysis by immunohistochemistry of intestinal polyps in mice heterozygous for the multiple intestinal neoplasia gene (Min/+) at 5 months revealed an increase and redistribution of VEGF-A in proximity to those cells expressing nuclear beta-catenin with a corresponding increase in vessel density. Transfection of normal colon epithelial cells with activated beta-catenin up-regulated levels of VEGF-A mRNA and protein by 250-300%. When colon cancer cells with elevated beta-catenin levels were treated with beta-catenin antisense oligodeoxynucleotides, VEGF-A expression was reduced by more than 50%. Taken together, our observations indicate a close link between beta-catenin signaling and the regulation of VEGF-A expression in colon cancer.     

Three informants' reports of child behavior: parents, teachers, and foster parents

OBJECTIVE: To evaluate whether disagreements in reporting child behavior problems between biological parents and foster parents and teachers are related to depressive symptoms in the biological parent. METHOD: Child Behavior Checklists and Teacher's Report Forms were completed by parents, foster parents, and teachers on 95 foster children between ages 5 and 16 during 1990-1991. Depressive symptoms in biological parents were assessed using the Center for Epidemiologic Studies Depression Scale. Structural equation modeling was used to estimate the relation between parental depressive symptoms and the discrepancies between their reports and those of two other informants. RESULTS: In both the internalizing and externalizing behavior models, a significant relation was found between parents' depressive symptoms and their discrepancies in reporting, but not with child behavior. This relation was stronger for internalizing than externalizing models. CONCLUSIONS: Using foster parents (and teachers) as informants offered a unique opportunity to view the reports of biological parents in comparison to two independent reports. Foster parents have a similar observational situation as biological parents but bring a less emotionally invested perspective to behavior observation, even when they are relatives. It is likely that depressive symptoms in parents distort their reports of their children's behavior. Clinicians would be wise to supplement parental with other informant reports.