Enlarged fetal bladder: Differential diagnosis and outcomes

The sonographic finding of an enlarged fetal bladder may simply be a transitory normal variant, but it may also be secondary to reflux or to obstructive, neurogenic, or myopathic causes. In this report, we describe the cases of 3 fetuses with an enlarged bladder, each of which had a different cause. The first fetus had posterior urethral valve obstruction, the second, a ruptured neurogenic bladder, and the third, megacystic-microcolon-intestinal hypoperistalsis syndrome. When sonographic examination reveals an enlarged fetal bladder, the ureter, kidneys, genitalia, and spine should be evaluated carefully. Although sonography is good at identifying urinary tract abnormalities, it often cannot provide the specific diagnosis or cause. We recommend frequent sonographic monitoring to evaluate such fetuses for persistence of or changes in bladder enlargement and for changes in the volume of amniotic fluid because these signs may be indicators of abnormalities of renal function and risk factors for a poor prognosis. Analysis of fetal electrolyte levels can also aid in determining the prognosis and whether the condition is amenable to therapeutic intervention.     

Functional properties of ryanodine receptors in hippocampal neurons change during early differentiation in culture

6-((4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl)amino)hexanoic acid ryanodine (BODIPY-ryanodine) binding and Ca(2+) imaging were used to study the properties of ryanodine receptors (RyRs) and cytoplasmic Ca(2+) (Ca) changes in neurons cultured from the embryonic rat hippocampus during the earliest stages of differentiation. Baseline Ca levels declined from 164 +/- 5 (SD) nM at early stages to 70 +/- 4 nM in differentiated neurons. Fluorescent BODIPY-ryanodine binding signals identified activated RyRs in somata, which were eliminated by removal of external Ca(2+) or by blockage of Ca(2+) entry through L-type but not N-type Ca(2+) channels. The GABA synthesis inhibitor 3-mercaptopropionic acid completely abolished ryanodine binding. Caffeine or K(+)-depolarization inhibited the activity of RyRs at very early stages of differentiation but had stimulatory effects at later stages after a network of processes had formed. BayK-8644 stimulated RyRs throughout all regions of all differentiating cells. The results suggest that in differentiating embryonic hippocampal neurons the activity of RyRs is maintained via Ca(2+) entering through L-type Ca(2+) channels. The mode of activation of L-type voltage-gated Ca(2+) channels with either membrane depolarization or specific pharmacological agents affects the coupled activity of RyRs differently as neurons differentiate processes and networks.     

Adverse effects from inappropriate medication administration via a jejunostomy feeding tube.

Numerous complications can arise when administering medications to patients receiving continuous enteral feeding. We report a case of a patient who could not be fed by mouth and was receiving continuous jejunal enteral feeding who had an adverse event associated with inappropriate administration of a medication via his jejunostomy tube. He had taken an extended-release niacin product before hospitalization for type IIb hyperlipidemia. The patient was inappropriately given a single dose of 750 mg of niacin as the short-acting tablets that were crushed and administered via the jejunostomy tube. He experienced severe cutaneous flushing, a feeling of warmth, itching, nausea, and emesis. He was noted to have "prickly heat" to the forehead, according to the nursing notes. A discussion of problems and guidelines for medication administration in adult patients receiving continuous tube feeding is provided.     

Di-alkyl phosphate biomonitoring data: assessing cumulative exposure to organophosphate pesticides

The 1996 Food Quality Protection Act (FQPA) requires the evaluation of both aggregate and cumulative health risks from pesticides (FFDCA 408(b)(2)(D)(v) and (vi).) Organophosphate (OP) pesticides are the first class of chemicals to undergo FQPA mandated aggregate and cumulative assessments. In this report, summary data on biomonitoring for urinary levels of six alkyl phosphate (AP) metabolites of OPs, as reported in the initial, March 2001, U.S. Centers for Disease Control and Prevention's (CDC) "National Report on Human Exposure to Environmental Chemicals," are compared to EPA modeled estimates of OP exposure reported in Registration Eligibility Decision documents (REDs), Interim REDs and to currently reported cumulative exposure estimates in the EPA's Cumulative Risk Assessment of the Organophosphate Pesticides. This comparison indicates that EPA's aggregate exposure estimates (dietary, drinking water, and non-dietary residential exposures) for many individual OPs were greater than the cumulative estimate for all OPs combined based on the CDC AP biomonitoring data. The results also suggest that EPA's screening level assessments of OPs, while being qualitative indicators of the relative importance of various exposure sources, are not good quantitative indicators of actual exposures. However, the mean biomonitoring estimate of cumulative OP exposure appears to exceed the EPA's subsequent preliminary estimate of cumulative OP exposure by as much as the REDs appear to overestimate the biomonitoring results. While the conservatism, tendency to overestimate exposure, in the individual REDs is readily acknowledged, the conservatism and limitations of applying currently available CDC AP biomonitoring data to evaluate human exposure to OPs are not as readily apparent. We postulate that oral absorption of non-anti cholinergic, pre-hydrolyzed OPs, sources of APs other than pesticides, and the conservative result of summing exposure from each AP at the geometric mean contribute to non-quantified overestimates of absorbed dosage from the CDC biomonitoring data reported in March 2001. CDC AP biomonitoring data may serve a useful purpose in providing an upper bound estimate of absorbed dosage for "ground truthing" aggregate exposure estimated from first tier models used in REDs, but at best may provide only a credible "target" for the complex cumulative exposure assessment models currently under development. The reliability of quantitative estimates of OP exposure levels will improve as cumulative risk exposure models are validated over time and under use conditions prevalent at the time the AP biomonitoring samples are collected. Analyses contained herein should be revisited and compared to the CDC Second National Report on Human Exposure to Environmental Chemicals ( http://www.cdc.gov/exposurereport), released to the public on January 31, 2003, and the final EPA OP Cumulative Risk Assessment.     

Transitions and transversions in Ki-ras gene in colorectal cancers in Mexican patients

AIMS & BACKGROUND: An important increase in the incidence of colorectal cancers has been detected in the last 15 years in Mexico. This fact has been attributed to several causes, including the change in diet acquired from industrialized countries. Various groups have studied the mutational pattern of oncogenes, including Ki-ras gene, in colorectal cancers from different human populations. The aim of this work was to study the prevalence of mutations at codons 12, 13 and 61 of the Ki-ras gene in 37 colorectal tumors from Mexican patients and to correlate them with clinical data. METHODS: Point mutations were studied in 37 colorectal cancers at codons 12 and 13 of the Ki-ras gene, using PCR followed by RFLP. We also performed PCR-SSCP to identify mutations at codon 61. We confirmed mutations by sequence analysis in all the altered codons. RESULTS: Our results indicated that 24.3% of the tumors presented mutations at codon 12, 5.4% at codon 13, and 2.7% at codon 61 of the Ki-ras gene. We found that 75% of these mutations were transitions and 25% transversions. The overall results indicated that the frequency of Ki-ras mutations in colorectal cancers in a sample of a Mexican population (Mexico City) was 32.4%, which is similar to that reported in other populations. We did not find a correlation between the Ki-ras mutations and gender, location of the tumor, or Dukes' stage, but survival of the patient without recurrence was statistically significant. CONCLUSIONS: The study of colorectal cancer indicated that in a Mexican population Ki-ras mutations were present in tumors of patients who survived without tumor recurrence. Most of them were transitions in the first and second base of codon 12.     

Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans

In this study, we have examined the correlation between the histological and histochemical changes of articular cartilage and bone parameters of the underlying subchondral bone. The aim was to elucidate patterns of bone parameter changes within different depths of subchondral bone in the joints with macroscopically normal cartilage and in joints with osteoarthritis (OA). Ten tibial plateaus were taken from patients during total knee replacement surgery due to severe OA. They were compared with 10 sets of tibial condyles obtained from autopsy subjects with no history of bone or joint disease. The cylindrical cartilage-bone samples were taken out from the anterior, posterior, external, and internal areas of the condyles for cartilage assessment (Mankin score) and subchondral bone histomorphometry. Four histomorphometric parameters were measured: bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.S). Our study showed that subchondral bone from the OA group had significantly higher bone volume (54.1 +/- 10.6%) than control group (37.8 +/- 8.1%) (P < 0.01). In addition, trabecular parameters from the OA subchondral bone showed a smaller number of sparsely distributed and thicker trabecules than in control group (P < 0.05). Medial and lateral condyle from the control group did not differ significantly, while medial condyle from OA group showed a high increase of bone volume (62.8 +/- 13.3) and consecutively different trabecular parameters when compared with the lateral condyle from the same group. Also, it was shown that there are regional differences (anterior, posterior, internal, and external) in bone parameters between both condyles within both, control and OA groups. Comparison of bone parameters from three different stage of articular cartilage degeneration (Mankin score) showed that higher degree of cartilage degeneration is followed by significant changes in subchondral bone architecture. Furthermore, we have found that progression of cartilage degeneration leads to changes in bone parameters which affected deeper levels of subchondral bone. According to these results, it can be suggested that changes in histomorphometric parameters of subchondral bone are secondary to cartilage damage and proceed deeper into subchondral bone with increasing cartilage degeneration.     

RBC transfusion requirements after allogeneic marrow transplantation: impact of the before-transplant Hb level on transfusion and early survival

BACKGROUND: Most patients undergoing allogeneic marrow transplantation (alloBMT) require transfusions of RBCs. A retrospective analysis was performed to evaluate the utilization and risk factors for RBC transfusions including age and sex of recipient, HLA matching between donor and recipient, disease status at time of BMT, the occurrence of GVHD, ABO blood group compatibility, the source of progenitor cells and the Hb level before BMT (PT-Hb). STUDY DESIGN AND METHODS: Data from 519 consecutive patients receiving transplants between January 1995 and March 2000 were reviewed. The number of RBC transfusions was determined for the following periods: 0 to 60, 61 to 120, and 121 to 180 days after BMT. RESULTS: The transfusion requirements were greatest during the first 60 days after BMT and decreased with time. The total number of units transfused to this cohort of patients was 5398, of which 3505 units were utilized within the first 2 months. The mean number +/- SD of units transfused per patient from 0 to 60 days was 6.8 +/- 6.4; 61 to 120 days, 3.2 +/- 5.5; and 121 to 180 days, 2.0 +/- 4.6. An increased transfusion requirement was associated with lower PT-Hb, major ABO mismatch between donor and recipient, BMT in patients with more advanced disease, use of unrelated donors, older age, and female sex by Spearman's correlation analysis. The source of progenitor cells and the development of GVHD did not influence transfusion requirements. Increased mortality during the 6-month period after transplant was associated with lower PT-Hb, use of unrelated donors, advanced disease status at BMT, and sex by Cox regression analysis. In a multivariate model, PT-Hb remained significant when controlling for the other risk factors. CONCLUSION: The PT-Hb was identified as an independent risk factor for RBC transfusions during alloBMT. As well, a lower PT-Hb was found to be an independent risk factor for increased mortality during the 6-month study period.     

Examining the secretor status in the saliva of patients with oral pre-cancerous lesions

It has been demonstrated in a number of earlier studies on the aetiology and pathogenesis of certain diseases that the patients' secretor status (ABO (H) blood group antigens) may possibly be a factor influencing the development of systemic oral diseases. This likelihood has prompted the present study, to examine the differences in the saliva secretor status by comparing patients with oral pre-cancerous lesions on the one hand, and the healthy population on the other; (i) in relation to the intensity of the clinical manifestation of diseases and (ii) in relation to the intensity of epithelial dysplasia of patients with oral pre-cancerous lesions. In total 122 subjects were examined, half of whom suffered from oral pre-cancerous lesions (excluding Candida albicans in oral smears), while the other half were the healthy control group. All were subjected to clinical oral examinations and standard evaluation tests in order to establish the secretor status of their saliva. In the group of patients with oral pre-cancerous lesions (experimental group), a pathohistological examination of the oral mucosa was performed. The results have demonstrated that the large majority of the people examined in both groups were secretors and no significant difference between secretors and non-secretors was found in the comparison between the experimental group and the healthy control group. However, (i) we found a higher intensity of oral disease in the non-secretor group, and (ii) the occurrence of epithelial dysplasia was found exclusively in the non-secretor group.