Characterization and management of paraesophageal hernias in children after antireflux operation

PURPOSE: The aim of this study was to determine the important factors in the development and subsequent treatment of postoperative paraesophageal hernia (PPEH). METHODS: A retrospective analysis was performed in 464 consecutive children (ages 3 days to 18 years) for PPEH after a primary antireflux operation performed at a Children's Hospital and University Hospital between 1985 and 1997. All operations included a crural repair, but the Nissen fundoplication was performed with (n = 162) and without (n = 70) plication of the esophagus to the crus at 3 points. Patients with and without PPEH were compared with respect to the type of antireflux operation, the patient's age at operation, and the preoperative and postoperative clinical courses. A preoperative corrected gastric emptying value was obtained from a radionuclide gastric emptying study in 289 patients. The treatment of PPEH also was examined. RESULTS: The incidence of PPEH in our patients was 4.5% (21 of 464). Although there was a lower incidence of PPEH in patients with crural plication compared with patients without crural plication during Nissen fundoplication (5 of 162, 3% v 7 of 70, 10%; P = .035), 2 patients with crural plication had a postoperative esophageal leak. Patients with PPEH had a significantly increased prevalence of gagging before the initial antireflux operation compared with patients without PPEH (3 of 21, 14.3% v 7 of 443, 1.6%; P = .007). A higher prevalence of slow corrected gastric emptying preoperatively also was seen in patients with PPEH compared with patients without PPEH (8 of 15, 53% v 79 of 274, 29%; P = .046). The prevalences of central nervous system disease, young age (<6 months) at initial operation, and a particular type of antireflux operation were not higher in patients with PPEH. Nine patients with a small PPEH treated by simple observation alone subsequently had resolution of symptoms. CONCLUSIONS: Patients who have gagging or slow corrected gastric emptying before an antireflux operation are at higher risk for a postoperative paraesophageal hernia. Patients with a small postoperative paraesophageal hernia can be treated nonoperatively. Crural plication of the esophagus during Nissen fundoplication reduces the occurrence of postoperative paraesophageal hernia, but also may result in significant morbidity.     

A Kiswahili version of the SF-36 Health Survey for use in Tanzania: translation and tests of scaling assumptions

The objective of the study was to translate and adapt the SF-36 Health Survey for use in Tanzania and to test the psychometric properties of the Kiswahili SF-36. A cross-sectional study was conducted as part of a household survey of a representative sample of the adult population of Dar es Salaam, Tanzania. The IQOLA method of forward and backward translation was used to translate the SF-36 into Kiswahili. The translated questionnaire was administered by trained interviewers to 3,802 adults (50% women, mean (SD) age 31 (13) years, 50% married and 60% with primary education). Data quality and psychometric assumptions underlying the scoring of the eight SF-36 scales were evaluated for the entire sample and separately for the least educated subgroup (n=402), using multitrait scaling analysis. Forward and backward translation procedures resulted in a Kiswahili SF-36 that was considered conceptually equivalent to the US English SF-36. Data quality was excellent: only 1.2% of respondents were excluded because they answered less than half of the items for one or more scales; ninety percent of respondents answered mutually exclusive items consistently. Median item–scale correlations across the eight scales ranged from 0.47 to 0.81 for the entire sample. Median scaling success rates were 100% (range 87.5–100.0). The median internal consistency reliability of the eight scales for the entire sample was 0.81 (range 0.70–0.92). Floor effects were low and ceiling effects were high on five of the eight scales. Results for n=402 people without formal education did not differ substantially from those of the entire sample. The results of data quality and psychometric tests support the scoring of the eight scales using standard scoring algorithms. The Kiswahili translation of the SF-36 may be useful in estimating the health of people in Dar es Salaam. Evidence for the validity of the SF-36 for use in Tanzania needs to be accumulated.     

GlycineB antagonists and partial agonists in rodent models of Parkinson's disease--comparison with uncompetitive N-methyl-D-aspartate receptor antagonist

Antiparkinsonian-like activity of glutamate receptor antagonists (mostly of N-methyl-D-aspartate (NMDA) receptors) has been demonstrated in animals and for uncompetitive agents, also in humans. In the present study we investigated the potential antiparkinsonian-like activity of compounds acting at the glycine site of the NMDA receptor complex in three animal models of Parkinson's disease and compared them with the new uncompetitive NMDA receptor antagonist MRZ 2/579. Haloperidol-induced catalepsy was inhibited by the Merz glycine site antagonists MRZ 2/570, MRZ 2/571 and MRZ 2/576 but not by another antagonist L-701,324 or the glycine site partial agonists ACPC and D-CS. None of the tested glycine site antagonists or partial agonists increased locomotor activity or potentiated L-DOPA responses in reserpine and alpha-MT treated rats. In rats with a unilateral 6-OHDA medial forebrain bundle lesion neither glycine site antagonists nor partial agonists affected rotations on their own or enhanced the contralateral rotations induced by L-DOPA. In contrast, the uncompetitive NMDA receptor antagonist MRZ 2/579 was active in all antiparkinsonian tests used in this study. Based on the present data the therapeutic potential of the glycine site antagonists and partial agonists tested for the treatment of Parkinson's disease is rather doubtful. Uncompetitive NMDA receptor antagonists seem to possess a better profile as antiparkinsonian agents.     

Atypical antipsychotic-induced neutropenia in dogs

DMP 406 is an atypical antipsychotic, antischizophrenic drug, biochemically related to clozapine, which exerts its desired pharmacologic effects through selective antagonism of 5-hydroxytryptamine and dopamine-receptor subtypes. Clozapine therapy is clinically associated with severe granulocytopenia in a small subset of patients. In the course of a 3-month toxicity study in dogs, severe neutropenia, thrombocytopenia, marked myeloid and erythroid left-shifted bone marrow hyperplasia with increased erythrophagocytosis, positive Coombs' tests, and hypergammaglobulinemia occurred in individual females dosed with 30 mg/kg/day of DMP 406. Related but less severe changes were also observed in males. Sera or purified immunoglobulins from affected and control dogs were tested in methylcellulose-based, canine hematopoietic colony-forming unit (CFU) assays with or without DMP 406. Neither size nor number of erythroid or myeloid CFUs differed between cultures containing control or affected dog serum components. Sera from individual affected dogs but not controls resulted in moderate numbers of fibroblast-like CFUs, suggesting DMP 406-associated marrow stromal cell-modifying, serum activities to be present. DMP 406 alone resulted in a concentration-dependent reduction of erythroid and myeloid CFUs with an approximate IC50 of 3.0 microg/mL. Taken together, DMP 406-induced granulocytopenia and bone marrow dyscrasia appear likely to result from both immune-mediated and direct drug-induced myelotoxicity.     

Fetal wound healing. The ontogeny of scar formation in the non-human primate.

OBJECTIVE: This study determined how scar formation develops in a non-human primate model of fetal skin repair. SUMMARY BACKGROUND DATA: A transition from healing scarlessly to healing with scar formation characterizes skin repair in rat and sheep fetuses. New knowledge of the regulatory processes occurring in the fetal wound at the initial stages of scar formation may provide insights into the early mechanisms of scar formation. METHODS: Full-thickness wounds were made in fetal rhesus monkey lips from 75 through 114 days gestation (n = 6, term = 165 days). Wounds were harvested at 14 days postwounding and processed for histology (hematoxylin & eosin, Masson's trichrome) as well as immunohistochemistry (human type I or type III collagen). RESULTS: Wounds healed with complete restoration of normal tissue architecture in the 75-day gestation fetus. However in the 85-100 day gestation fetuses, wounds healed with an absence of hair follicles and sebaceous glands, but the dermal collagen pattern remained reticular and similar to that in unwounded dermis. At 107 days, a thin scar was present in the wound, thereby demonstrating a transition to scar formation between 100 and 107 days gestation (early 3rd trimester) in the non-human primate. CONCLUSIONS: In the non-human primate fetus, a transition from scarless repair to adult-type repair with scar formation occurs in the early third trimester. These data provide insight into the transition process; the ontogeny of scar formation is characterized initially by wounds healing without the presence of epidermal appendages but with a normal reticular dermal collagen pattern, which we term the "transition wound."     

Improving dietitians' teaching skills.

Many health professionals lack important teaching skills, perhaps adding to patient difficulties in understanding and adopting therapeutic diets. Research suggests that teaching skills improved after dietitians took a continuing education course entitled "Effective Patient Teaching." Our study tested whether dietitians' new skills would persist in the field and whether selected patient outcomes would differ as a result. Thirty staff dietitians from six urban hospitals were videotaped teaching patients, then randomly assigned to take the Effective Patient Teaching course or not (control group). Follow-up videotapes were made after 1 week, 1 month, and 3 months. After each teaching session, patient satisfaction and recall were assessed. Two judges rated 20 teaching skills, which were divided into four subsets for analysis. Repeated measures analyses of variance showed overall gains only for the group that took the Effective Patient Teaching course, which scored higher than the control group at 1 week and 1 month, but not at baseline or 3 months. Gains occurred in presentation skills and essential teaching functions. Throughout the study, interpersonal skills were high and adherence promotion skills were low for dietitians in both groups. Groups did not differ on patient satisfaction or recall. Improvements in dietitians' teaching skills translated to the field immediately after they completed the continuing education program, but not all gains were sustained after 3 months. We recommend that dietitians assess their teaching and adherence promotion skills, obtain training where warranted, and periodically reassess the application of those skills during patient teaching sessions.     

Influence of cold ischemia time, pretransplant anti-porcine antibodies, and donor/recipient size matching on hyperacute graft rejection after discordant porcine to cynomolgus kidney transplantation

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to hyperacute rejection (HAR). This form of xenograft rejection is mediated by preformed natural antibodies and is believed to occur invariably in discordant xenografts thus leading to rapid destruction and complete thrombosis of the graft. Recent data, however, have shown that in the porcine to cynomolgus monkey setting, HAR is not inevitably seen after porcine kidney transplantation. The influence of preoperative antiporcine antibody levels in the recipient, cold ischemia time, and donor organ weight on the onset of HAR was investigated by using unmodified large white pigs (aged 3-12 weeks) as organ donors and adult cynomolgus monkeys (aged 1.5-3.5 years) as recipients. Porcine kidney xenotransplantation was performed in either a non-life-supporting model (n=7) or in a life-supporting model (n=8). In both models, no correlation was found between cold ischemia time and HAR. When preoperative anti-porcine antibody levels were investigated, a significant increase in incidence of HAR was observed in animals with elevated anti-porcine IgM (P<0.05) but not IgG levels (P=NS). Interestingly, although 5 of 12 grafts with an organ weight of less than 50 g underwent HAR, none of three grafts with a donor organ weight of more than 70 g showed signs of HAR. In addition, all three larger grafts showed intraoperative and postoperative urine production, although only in 1 (48 g) of the 12 grafts weighing less than 50 g primary graft function was observed. In one animal, a second porcine kidney (23 g) was successfully transplanted (without HAR) immediately after HAR and subsequent removal of a first porcine kidney (20 g). These results indicate that in the porcine to cynomolgus monkey setting anti-porcine IgM rather than IgG anti-porcine antibody levels seem to be of predominant importance for the induction of HAR. By increasing the donor organ size and weight the frequency of the onset of HAR can be at least reduced. This is most likely due to immunoabsorption of the recipients preformed antibodies in the porcine kidney without lethal damage for the graft.     

Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma.

PURPOSE: Increased bone resorption is a hallmark of multiple myeloma and is attributable to osteoclast activation. Recent studies showed that the receptor activator of nuclear factor kappaB ligand (RANKL) is the key mediator of osteoclastogenesis and plays a crucial role in bone destruction in malignant bone disease. We found that human myeloma cells express RANKL and analyzed the association of the RANKL expression with the presence of osteolytic bone disease in patients with multiple myeloma. EXPERIMENTAL DESIGN: Flow cytometry was performed on bone marrow samples derived from controls and multiple myeloma patients with or without osteolytic bone lesions on conventional radiography. Plasma cells were identified as CD38++/CD138+ cells. The level of RANKL expression on the surface of bone marrow plasma cells was correlated with the bone status of the patients. RESULTS: The bone marrow plasma cells from controls showed no or only a weak surface expression of RANKL, and the median mean fluorescence index (MFI) was 6. In contrast, expression of RANKL could be detected on bone marrow plasma cells from all of the patients with multiple myeloma, and median MFI was 47. The difference in MFI for RANKL expression of bone marrow plasma cells from controls and myeloma patients was highly significant (P < 0.0005). Myeloma patients with osteolytic bone lesions showed a significantly higher expression of RANKL (median MFI = 60; range, 16-2494) compared with patients without osteolysis (median MFI = 16; range, 6-229; P < 0.0005). CONCLUSIONS: These results show for the first time that the level of RANKL expression by myeloma cells correlates significantly with osteolytic bone disease.