Aftermath of failed diagnosis of late-presenting congenital diaphragmatic hernias

A congenital posterolateral diaphragmatic (Bochdalek) hernia generally presents with symptoms within a day after birth. This article reports on 3 children whose hernias produced symptoms for the first time beyond a week of age. One 3-year-old child died acutely with symptoms resembling that of a tension pneumothorax. In 2 children symptoms only developed at 12 and 23 days of age. They were initially thought to have lower lobe pneumonias and delayed diagnosis led to the death of one. Although the late presentation of a congenital posterolateral diaphragmatic hernia is rare, it is important to recognise it because with appropriate therapy all such children should have a normal life expectancy, whereas unsuspected hernias in older children carry a mortality that is even worse than that of neonatal cases. The first requisite for the diagnosis of a congenital diaphragmatic hernia (CDH) is a high index of suspicion. Cystic lesions or masses in the lower lung fields should suggest the possibility of a CDH with herniated abdominal content at any age. Congenital diaphragmatic hernias should be included in the differential diagnosis of apparent lower lobe pneumonias in all children below a month of age.     

Outcome of hip and knee arthroplasty in persons aged 80 years and older

Recent studies have established the cost effectiveness and safety of total joint arthroplasties. As the population ages, it is important to determine whether these procedures are equally beneficial in the elderly. The short term safety and efficacy of total hip and knee arthroplasties in subjects 80 years of age and older was evaluated. Between 1988 and 1993, preoperative and postoperative physical and functional information was collected on 99 consecutive elective hip and knee arthroplasties in subjects 80 years of age or older. These data were compared with those derived from a younger otherwise matched control group. Data collected included subject demographics and characteristics, information concerning the acute and postacute hospital stay, comorbid conditions, postoperative complications, discharge disposition, Hospital for Special Surgery knee and Harris hip scores, pain scores, and functional capacity. The average age of the subjects was 83 years; osteoarthritis was the most common diagnosis; and the average followup was 25 months. Complication rates and length of stay in acute care facilities were not significantly different than for the control group. Mean preoperative Hospital for Special Surgery knee and Harris hip scores were 58 and 60, respectively, with postoperative scores of 77 and 88, respectively. Pain dramatically improved with 98% of total knee arthroplasty and 100% of total hip arthroplasty subjects reporting mild or no pain at followup. Preoperatively, none of the knee or hip subjects could walk unlimited distances. Postoperatively 51% of the total knee arthroplasty and 54% of the total hip arthroplasty subjects could walk more than five blocks; 71% of the total knee arthroplasty and 86% of the total hip arthroplasty subjects walked with a cane or no assistive device. The most dramatic postoperative functional gains were seen in the most disabled subjects. Total charges of care for patients 80 years of age and older was slightly greater than for a younger group. It was established that total joint arthroplasty can be performed safely in patients 80 years of age and older, promising excellent pain relief and improved functional outcome.     

Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel

The epothilones are naturally occurring, cytotoxic macrolides that function through a paclitaxel (Taxol)-like mechanism. Although structurally dissimilar, both classes of molecules lead to the arrest of cell division and eventual cell death by stabilizing cellular microtubule assemblies. The epothilones differ in their ability to retain activity against multidrug-resistant (MDR) cell lines and tumors where paclitaxel fails. In the current account, we focus on the relationship between epothilone and paclitaxel in the context of tumors with multiple drug resistance. The epothilone analogue Z-12,13-desoxyepothilone B (dEpoB) is >35,000-fold more potent than paclitaxel in inhibiting cell growth in the MDR DC-3F/ADX cell line. Various formulations, routes, and schedules of i.v. administration of dEpoB have been tested in nude mice. Slow infusion with a Cremophor-ethanol vehicle proved to be the most beneficial in increasing efficacy and decreasing toxicity. Although dEpoB performed similarly to paclitaxel in sensitive tumors xenografts (MX-1 human mammary and HT-29 colon tumor), its effects were clearly superior against MDR tumors. When dEpoB was administered to nude mice bearing our MDR human lymphoblastic T cell leukemia (CCRF-CEM/paclitaxel), dEpoB demonstrated a full curative effect. For human mammary adenocarcinoma MCF-7/Adr cells refractory to paclitaxel, dEpoB reduced the established tumors, markedly suppressed tumor growth, and surpassed other commonly used chemotherapy drugs such as adriamycin, vinblastine, and etoposide in beneficial effects.     

Staining of cell surface human CD4 with 2'-F-pyrimidine-containing RNA aptamers for flow cytometry

We have used recombinant human CD4 presented on beads as an affinity matrix to screen a 2'-F-pyrimidine-containing RNA library with a complexity of approximately 10(14) molecules. Affinity-selected aptamers bind recombinant CD4 with low nanomolar equilibrium dissociation constants. These high-affinity aptamers conjugated to different fluorophores such as fluorescein and phycoerythrin were used to stain cells, expressing human CD4 on cell surface, for analysis by flow cytometry. Aptamers, conjugated to fluorophores, stained mouse T cells that express human CD4 on the surface, but not the control mouse T cells lacking human CD4. The control cells, however, do express mouse CD4 whose extracellular domain has 55% sequence identity to the human form. These human CD4-specific aptamers selectively stained CD4(+) T cells in a preparation of human peripheral blood mononuclear cells. These results and others suggest that aptamers are emerging as a versatile class of molecules that can be used for various diagnostic applications performed under different formats or platforms.     

Localized mucosal involvement and severe pulmonary involvement in a young patient with paraneoplastic pemphigus associated with Castleman''s tumour

OBJECTIVES: This study examined the impact of state legislation on mammography quality and access in Michigan. METHODS: The impact of state legislation was analyzed with respect to utilization, numbers of machines and facilities, and image quality. RESULTS: The legislation had a positive effect on image quality improvement, had no impact on utilization by women aged 50 years and above, and resulted in few facility closures. CONCLUSIONS: Michigan's legislative intervention appears to have had a positive effect on efforts to improve mammography quality assurance with implications for other federal and state efforts to achieve quality assurance in health care delivery.     

Selective cytotoxicity of topoisomerase-directed protoberberines against glioblastoma cells

Protoberberines are a new class of organic cations that are dual poisons of topoisomerases I and II. Certain protoberberines exhibit greater in vitro cytotoxicity against cell lines derived from solid tumors than from leukemias. Using a group of seventeen different protoberberine analogs, the structural basis for selective cytotoxicity toward sensitive SF-268 glioblastoma cells as compared with resistant RPMI 8402 lymphoblast cells was explored. The selective cytotoxicity is associated with the presence of an imminium ion and other structural features of protoberberines, and is not shared by drugs such as camptothecin, doxorubicin, vinblastine, and etoposide, which are either equally or more cytotoxic against RPMI 8402 cells than SF-268 cells. The selective cytotoxicity of protoberberines against SF-268 over RPMI 8402 cells is not due to differences in topoisomerase levels or known drug efflux systems such as multidrug resistance (MDR1) and multidrug-resistance protein (MRP). Comparative in vitro studies of the accumulation of coralyne, a fluorescent protoberberine, into sensitive and resistant cells demonstrated a correlation between drug accumulation and selective cytotoxicity. Inhibitors of coralyne uptake included several protoberberine-related compounds. Of these, palmatine, a minimally cytotoxic protoberberine, both inhibited coralyne accumulation and reduced cytotoxicity against SF-268 cells, but not against RPMI 8402 cells. Despite the structural resemblance of protoberberines to catecholamines, our experiments using inhibitors and cells expressing biogenic amine uptake systems have ruled out the involvement of biogenic amine uptake1, uptake2, and vesicular monoamine transport systems. Uptake systems remaining as candidates, supported by preliminary data, include transport via vesicles derived from specialized membrane invaginations and selected carrier-mediated organic amine transport systems.     

cagA-positive Helicobacter pylori populations in China and The Netherlands are distinct

The aim of this research was to study whether and to what extent Chinese cagA-positive Helicobacter pylori isolates differ from those in The Netherlands. Analysis of random amplified polymorphic DNA (RAPD)-PCR-assessed DNA fingerprints of chromosomal DNA of 24 cagA-positive H. pylori isolates from Dutch (n = 12) and Chinese (n = 10) patients yielded the absence of clustering. Based on comparison of the sequence of a 243-nucleotide part of cagA, the Dutch (group I) and Chinese (group II) H. pylori isolates formed two separate branches with high confidence limits in the phylogenetic tree. These two clusters were not observed when the sequence of a 240-bp part of glmM was used in the comparison. The number of nonsynonymous substitutions was much higher in cagA than in glmM, indicating positive selection. The average levels of divergence of cagA at the nucleotide and protein levels between group I and II isolates were found to be high, 13.3 and 17.9%, respectively. Possibly, the pathogenicity island (PAI) that has been integrated into the chromosome of the ancestor of H. pylori now circulating in China contained a different cagA than the PAI that has been integrated into the chromosome of the ancestor of H. pylori now circulating in The Netherlands. We conclude that in China and The Netherlands, two distinct cagA-positive H. pylori populations are circulating.     

Primary biliary cirrhosis associated with mixed type autoimmune hemolytic anemia and sicca syndrome: a case report and review of literature

A case presenting with an unusual association of primary biliary cirrhosis and mixed type autoimmune hemolytic anemia plus sicca syndrome is described. The 49-yr-old female primary biliary cirrhosis patient had a confirmed sicca syndrome and presented with jaundice and life-threatening anemia. Laboratory tests revealed positive Coombs' test with coexisting cold and warm autoantibodies. She was successfully treated by blood transfusion with packed red cells lacking any red cell antigens corresponding to serum alloantibodies and pulse methylprednisolone therapy. The patient remained stable under maintenance treatment using oral steroids and ursodeoxycholic acid. This case is probably the first reported showing an association between primary biliary cirrhosis and mixed type autoimmune hemolytic anemia plus sicca syndrome and was probably induced by heterogenous and complicated autoimmune reactions.