Upper and midureteral calculi: percutaneous extraction with an occlusion balloon catheter

In 44 patients with one or more calculi in the upper two-thirds of the ureter, single-stage percutaneous nephrolithotomy was performed through a middle or upper calyceal nephrostomy after cystoscopic placement of an occlusion balloon catheter distal to the calculus; in 42, the procedure was successful. The occlusion balloon catheter permitted retrograde opacification of all systems for enhanced renal puncture. In the last 30 patients an attempt was made either to push the calculus upward mechanically or to flush it upward into the renal pelvis with carbon dioxide or dilute contrast material. This was successful in 24 of these patients. Prior overnight occlusion of the ureter by means of ureteral dilatation further facilitates dislodgment of the calculus, which was successful in 12 of 13 patients.     

The nature of the autoimmune antibody repertoire in human immunodeficiency virus type 1 infection.

Human immunodeficiency virus type 1 (HIV-1) seropositive donors typically have high serum antibody titers to a range of autoantigens, and the corresponding autoantibodies have been suggested to be of importance in the pathogenesis of HIV-1 infection. We have prepared 38 IgG human monoclonal autoantibodies from asymptomatic HIV-1 seropositive donors with elevated serum titers to autoantigens by construction of Fab combinatorial libraries on the surface of phage and affinity selection using a range of autoantigens, including double-stranded DNA, major histocompatibility complex class II, CD14, epidermal growth factor receptor, and ganglioside GD2. The autoantibodies are shown to be of moderate affinity and exhibit marked cross-reactivity with a range of antigens. This contrasts with the specific high-affinity antibodies selected (i) against infectious agents using the same libraries and (ii) against one of the autoantigens using a library from a donor with established autoimmune disease. The results lend no support to the presence of specific autoantibodies in HIV-1 infection and instead suggest attention should be focused on the pathological significance of high serum levels of antibodies capable of interacting with multiple molecular species.     

Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation

Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and beta2 adrenergic receptors and the dopamine receptor type 1A on variation of systolic blood pressure in young Caucasians. We measured eight highly polymorphic markers spanning this positional candidate gene-rich region in 427 individuals from 55 three-generation pedigrees containing 69 discordant sibling pairs, and calculated multipoint identity by descent (MIBD) probabilities. The results of genetic linkage and association tests indicate that the region between markers D5S2093 and D5S462 is significantly linked to one or more polymorphic genes influencing interindividual variation in systolic blood pressure levels. Since the alpha1B adrenergic receptor and dopamine receptor type 1A genes are located close to these markers, these data suggest that genetic variation in one or both of these G protein-coupled receptors, which participate in the control of vascular tone, plays an important role in influencing interindividual variation in systolic blood pressure levels.      

A simple scoring system to estimate perioperative mortality following liver resection for primary liver malignancy—the Hepatectomy Risk Score (HeRS)

BackgroundSelection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections.MethodsThe 2005–2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7–10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1–4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values.ResultsA total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16–8.99), P=0.025; HeRS =3: OR =6.54 (2.39–17.90), P<0.001; HeRS =4: OR =13.69 (4.90–38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model.ConclusionsThe HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.     

Clinical and genetic features of variegate porphyria in a Chinese patient

Acute porphyria is rare in orientals. We describe a Chinese woman with recurrent generalised tonic-clonic seizures and abdominal pain. Genomic DNA studies identified a heterozygous base substitution from guanine to adenine at nucleotide position 503, resulting in substitution of arginine by histidine at position 168 of the protein (R168H). This genetic abnormality is similar to the mutation reported in Caucasians with variegate porphyria. To the best of our knowledge, this is the first report in the English literature a Chinese patient with variegate porphyria with an identifiable mutation. A brief review of porphyria is presented.     

Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion

Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.