Nonoperative management of blunt hepatic and splenic injury in children

OBJECTIVE: The authors assessed the risks of nonoperative management of solid visceral injuries in children (age range, 4 months-14 years) who were consecutively admitted to a level I pediatric trauma center during a 6-year period ending in 1991. METHOD: One hundred seventy-nine children (5.0%) sustained injury to the liver or spleen. Nineteen children (11.2%) died. Of the 160 children who survived, 4 received emergency laparotomies; 156 underwent diagnostic computer tomography and were managed nonoperatively. The percentage of children who were successfully treated nonoperatively was 97.4%. Delayed diagnosis of enteric perforations occurred in two children. Fifty-three children (34.0%) received transfusions (mean volume 16.7 mL/kg); however, transfusion rates during the latter half of the study decreased from 50% to 19% in children with hepatic injuries, despite increasing grade of injury, and decreased from 57% to 23% in the splenic group with similar injury grade (p < 0.005, chi square test and Student's t test). CONCLUSION: Pediatric blunt hepatic and splenic trauma is associated with significant mortality. Nonoperative management based on physiologic parameters, rather than on computed tomography grading of organ injury, was highly successful, with few missed injuries and a low transfusion rate.     

K+ is an endothelium-derived hyperpolarizing factor in rat arteries

In arteries, muscarinic agonists such as acetylcholine release an unidentified, endothelium-derived hyperpolarizing factor (EDHF) which is neither prostacyclin nor nitric oxide. Here we show that EDHF-induced hyperpolarization of smooth muscle and relaxation of small resistance arteries are inhibited by ouabain plus Ba2+; ouabain is a blocker of Na+/K+ ATPase and Ba2+ blocks inwardly rectifying K+ channels. Small increases in the amount of extracellular K+ mimic these effects of EDHF in a ouabain- and Ba2+-sensitive, but endothelium-independent, manner. Acetylcholine hyperpolarizes endothelial cells and increases the K+ concentration in the myoendothelial space; these effects are abolished by charbdotoxin plus apamin. Hyperpolarization of smooth muscle by EDHF is also abolished by this toxin combination, but these toxins do not affect the hyperpolarizaiton of smooth muscle by added K+. These data show that EDHF is K+ that effluxes through charybdotoxin- and apamin-sensitive K+ channels on endothelial cells. The resulting increase in myoendothelial K+ concentration hyperpolarizes and relaxes adjacent smooth-muscle cells by activating Ba2+-sensitive K+ channels and Na+/K+ ATPase. These results show that fluctuations in K+ levels originating within the blood vessel itself are important in regulating mammalian blood pressure and flow.     

Relative contribution of polar interactions and conformational compatibility to the binding of neurokinin-1 receptor antagonists

Based on single residue substitutions, previous studies suggested that Gln165, His197, and His265 of the neurokinin-1 receptor interact directly with many nonpeptide antagonists, including CP-96,345. To further test this model, all three residues have been substituted simultaneously with alanine. The Q165A-H197A-H265A triple mutant bound CP-96,345 and eight analogs with similar affinity (2-20 microM), even though the same series of compounds bound to the wild-type receptor with affinities over a range of 1000-fold. These observations correspond exactly to the prediction of the binding site model. The micromolar binding affinity of all tested CP-96,345 analogs for the triple mutant seems to reflect solely van der Waals interactions, which suggests a significant contribution of conformational compatibility (or shape complementarity) to binding affinity. The primary role of conformational compatibility in ligand binding was consistent with the observation that simply transferring the residues involved in polar interactions with beta2-agonists into the neurokinin-1 receptor did not lead to increased binding affinity for the beta2-agonists. Taken together, these results support a general principle of ligand-receptor binding in which specific polar interactions can take place only if the overall ligand conformation is compatible with the stereochemistry of the binding pocket. In addition, double-residue and triple-residue substitutions, in combination with single-residue substitutions, can provide an alternative route to reveal multiple interactions that may not be detectable by single-residue substitutions and represent a novel approach to examine ligand-receptor interactions in the absence of high-resolution structural data.     

Radiologic placement of long-term subcutaneous venous access ports in children

OBJECTIVE: The purpose of this study was to review the results of radiologically placed subcutaneous venous access ports in a pediatric population requiring long-term venous access. CONCLUSION: Sixteen of 20 patients had no significant problems with their ports. In the pediatric population, radiologically placed subcutaneous venous access ports offer a high success rate, a low complication rate, and significant cost savings over surgically placed ports.     

Ultrasonography for inguinal hernias in boys

BACKGROUND/PURPOSE: History taking and physical examination alone no longer meet the surgeon's need in the diagnosis of inguinal hernia. Ultrasonography (US) provides a good and safe diagnostic tool for inguinal hernias in boys. METHODS: From 1995 to 1997, 244 boys with inguinal hernias (41 bilateral and 203 unilateral), received preoperative US on both groins to confirm the diagnosis. Those with positive US findings, such as viscera or fluid in inguinal canal or widening of the internal inguinal ring, underwent surgery. RESULTS: The accuracy of diagnosis with US and clinical assessment were 97.9% and 84%, respectively. More than 95% of widening of internal inguinal rings (>4 mm) proved to be hernias. There were two direct inguinal hernias and two femoral hernias, which were misdiagnosed by clinical examination, but proved to be diagnosed correctly by US. CONCLUSIONS: US serves as a noninvasive and highly accurate diagnostic tool for inguinal hernias in boys. Using 4 mm as the upper limit of the normal diameter of the internal inguinal ring, an occult inguinal hernia can be easily detected before surgery.     

Benign anal lesions, inflammatory bowel disease and risk for high-risk human papillomavirus-positive and -negative anal carcinoma

A central role in anal carcinogenesis of high-risk types of human papillomaviruses (hrHPV) was recently established, but the possible role of benign anal lesions has not been addressed in hrHPV-positive and -negative anal cancers. As part of a population-based case-control study in Denmark and Sweden, we interviewed 417 case patients (93 men and 324 women) diagnosed during the period 1991-94 with invasive or in situ anal cancer, 534 patients with adenocarcinoma of the rectum and 554 population controls. Anal cancer specimens (n = 388) were tested for HPV by the polymerase chain reaction. Excluding the 5 years immediately before diagnosis, men, but not women, with anal cancer reported a history of haemorrhoids [multivariate odds ratio (OR) 1.8; 95% confidence interval (CI) 1.04-3.2] and unspecific anal irritation (OR 4.5; CI 2.3-8.7) significantly more often than controls. Women with anal cancer did not report a history of benign anal lesions other than anal abscess to any greater extent than controls, but they had used anal suppositories more often (OR 1.5; CI 1.1-2.0). Patients with hrHPV in anal cancer tissue (84%) and those without (16%) reported similar histories of most benign anal lesions, but anal fissure or fistula was more common among hrHPV-positive cases. Ulcerative colitis and Crohn's disease, reported by <1% of study participants, were not associated with anal cancer risk. The higher proportion of hrHPV-positive anal cancers among case patients with anal fissure or fistula suggests that such mucosal lesions may provide direct viral access to basal epithelial layers. Since risk associations with benign anal lesions in men may be confounded by unreported sexual behaviour, and since risk associations in women were generally negative, it seems unlikely that benign anal lesions act as promoters in hrHPV-associated anal carcinogenesis. Moreover, benign anal lesions appear not to be linked to an alternative, hrHPV-unassociated causal pathway to anal cancer. Ulcerative colitis and Crohn's disease were not supported as causal factors for anal cancer.     

Molecular biology of hepatitis D virus: research and potential for application

Superinfection by hepatitis D virus (HDV) leads to acute hepatitis and causes progression to liver cirrhosis in a significant proportion of hepatitis B surface antigen (HBsAg) carriers. Current regimens (interferon) to treat hepatitis D patients has only transient but no lasting effects. New approaches are, therefore, warranted. Recently, several laboratory studies have discovered interesting properties of HDV that may become targets for antiviral chemicals. Viral replication requires the small hepatitis delta antigen (s-HDAg). The s-HDAg is a nuclear phosphoprotein. There is evidence indicating that phosphorylation is important for HDV replication. A second step of replication requires HDV-RNA self-cleavage and self-ligation. Interestingly, one group of antibiotics, the aminoglycosides, exerts strong suppression effects on HDV ribozyme activities. In the following stage of viral assembly, two post-translational modifications, namely isoprenylation of large HDAg and glycosylation of HBsAg are involved. Agents capable of blocking the two modifications should reduce viral production. These four possible targets are reviewed. For prevention, effective vaccines are not yet available. Two novel approaches are discussed. The first demonstrates the immunogenicity of a nucleic acid vaccine in mice. The second approach assembled an empty HDV particle in yeast. Advances on such laboratory investigations may provide new methods for the control of hepatitis D in the future.     

Heterotopic ossification as a complication of toxic epidermal necrolysis

The development of heterotopic ossification (HO) as a complication of toxic epidermal necrolysis (TEN) has not been previously reported. TEN, also known as Lyell's syndrome, is a rare but serious skin disorder that typically occurs after the administration of drugs, especially sulfonamides, barbiturates, phenytoin, and nonsteroidal anti-inflammatory agents. TEN is characterized by the development of large fluid-filled bullae with separation of large sheets of skin. Complications of TEN can include extensive denudation of skin with dehydration and electrolyte abnormalities, gastrointestinal hemorrhage, acute tubular necrosis, secondary infection of denuded skin, pneumonia, bacterial conjunctivitis, keratitis, and septic infarcts of internal organs. We report a case of HO in a patient with TEN after treatment with trimethoprim-sulfamethoxazole. A 49-year-old man developed an erythematous rash, bullae, fever, and extensive skin loss consistent with a diagnosis of TEN. He was intubated for complications of TEN (pneumonia) and maintained on bed rest for several weeks. In addition, he developed HO that resulted in multiple joint contractures. He was treated with aggressive range of motion by physical therapy, surgical resection of the HO followed by radiation to both elbows, right hip, and right knee. Postoperative outpatient rehabilitation enabled improved function in his mobility and activities of daily living. HO is known to occur after spinal cord and brain injuries and burns. It has not been reported to occur after TEN. Our experience with this case suggests that HO may merit inclusion into the list of complications of TEN.     

The influence of the C1-inhibitor BERINERT and the protein-free haemodialysate ACTIHAEMYL20% on the evolution of the depth of scald burns in a porcine model

Lactose intolerance (LI) often results in decreased calcium intake. To test if long-term low intake of calcium affects bone strength, we examined fracture risks related to LI in women aged 38-57 years. The 11,619 Finnish women aged 47-56 years who responded to the baseline postal inquiry of the Kuopio Osteoporosis Risk Factor and Prevention Study in 1989 formed the study population. In all, 896 women reported LI and 1299 women reported a fracture in 1980-1989. Current intake of dairy calcium was lower in women with LI (570 mg/d) than in the other women (850 mg/d) (p < 0.0001). The fracture risk in general was slightly elevated in women with LI compared with the other women, with an odds ratio (OR) (95% CI) of 1.33 (1.09-1.62). However, the fractures at the three most common sites (wrist, ankle, and rib) were not related to LI. In contrast, fractures at the tibia and metatarsal were strongly related to LI with ORs of 3.31 (1.51-7.24) and 2.84 (1.47-5.50), respectively. The adjusted OR for nonankle lower body fractures combined was 2.15 (1.53-3.04), whereas that for all upper body fractures combined was 1.15 (0.88-1.54). The 10 women with LI and a tibial or metatarsal fracture showed a 19% lower femoral BMD than all the other women in the densitometry subsample of 3222 women (p < 0.001). Long-term premenopausal calcium deficiency differentially affects bones with weight-bearing nonankle bones being at the greatest risk of suffering reduced strength.