Biomedical subjects
Publications and source records attributed to D R Webb.
Fifteen hundred consecutive cases of renal and ureteric calculi were treated in an integrated stone centre; 1464 of these were treated by extracorporeal shockwave lithotripsy, percutaneous nephrolithotomy, ureterorenoscopy and ureteroscopic lasertripsy. Only 36 (2.4%) required open surgery.
32 steinstrasse formations in the first 600 extracorporeal shockwave lithotripsy treatments required intervention. Their radiological appearance has been classified into 3 types and the aetiology of each type is discussed. 24 cases received a primary needle nephrostomy to relieve obstruction and of these 18 passed spontaneously, 5 required ureteroscopic manipulation and 1 underwent open surgery. Primary ureteroscopic removal was successful in 3 out of 5 cases. 3 upper ureteric steinstrassen were removed by a percutaneous intrarenal approach. A suggested plan of management for complicated steinstrassen is outlined.
Early experience with the rigid ureteroscopy has identified two regions of the ureter that can be difficult to negotiate, the first at the vesicoureteric junction and the second anterior to the iliac bifurcation. Placing the patient in varying degrees of lithotomy has been proposed to overcome these problems. In this study the effects of these alterations of hip flexion on the course of the ureter have been studied by radiographs in patients undergoing ureteroscopy. The lower ureter was demonstrated to possess two curves, an upper curve at the iliac bifurcation which straightens with increasing degrees of lithotomy and a lower vesical curve in the pelvis which is unaltered by patient position. These findings and their clinical significance are described.
One of the problems that has plagued the investigation of soluble suppressor T cell factors (TsF) has been the lack of sufficient material for direct assessment of their serological reactivities and biochemical characteristics. In the studies described in this communication, biosynthetically radiolabelled TsF and purified, radio-iodinated TsF were used to address these issues. We found that the cell-associated form of a factor specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT-TsF1) is a 66 kDa protein which exhibits a slightly acidic isoelectric point, but no carbohydrate as determined by enzymatic analysis and lectin-affinity chromatography. The biological analysis of suppression is specific for GAT and the specific activity of GAT-TsF1 is 2 x 10(9) suppressive units/micrograms. Direct measurement of the antigen binding capacity of GAT-TsF1 by affinity chromatography demonstrated that it binds to GAT but not an irrelevant antigen, and that only GAT-binding TsF1 is biologically active. Furthermore, GAT-TsF1 can be specifically eluted from GAT-Sepharose with soluble GAT. Lastly, purified GAT-TsF1 binds to polyvalent anti-TsF1 and alloantisera produced against the I region histocompatible cells of the H-2q haplotype, the so-called anti-I-J antibodies, but does not bind to immunosorbents containing antisera to irrelevant I-region haplotypes. Thus, these data physically verify the serological characteristics of GAT-TsF1 that were originally defined solely on the basis of biological activity.
One thousand patients underwent extracorporeal shockwave lithotripsy for renal and ureteric calculi at this clinic. An overall success rate of 91.8% was achieved (stone free or less than 2 mm fragments at three months) and for stones measuring 1 cm 96.3%. Lithotripsy produced extremely low morbidity, and no deaths have occurred at the clinic. Patients who had lithotripsy alone had a mean hospital stay of three days and in most instances were able to perform their full range of activities on discharge. Planned combination of lithotripsy with minimally invasive endourological procedures such as percutaneous nephrolithotomy and ureterorenoscopy has allowed us to extend the range of treatable cases to include large stones. Prophylactic use of Double-J ureteric stents in selected cases has reduced the incidence of obstruction by stone fragments after lithotripsy, thereby decreasing morbidity and hospital stay.
Of all ureteral calculi 20 per cent will require removal. The use of extracorporeal shock wave lithotripsy has changed dramatically the treatment of ureteral stones requiring intervention. We reviewed 111 procedures for 108 stones in 100 consecutive patients. Primary techniques included extracorporeal shock wave lithotripsy after retrograde manipulation (63 cases), percutaneous nephrolithotomy alone (1) and after retrograde manipulation (3), ureteroscopic removal (29), cystoscopic removal (2) and open ureterolithotomy (2). These techniques and the results are discussed. Of the patients 11 required a secondary procedure, including extracorporeal shock wave lithotripsy in 3, ureterorenoscopy for failed extracorporeal shock wave lithotripsy in 2, an open operation for complications of ureterorenoscopy in 2 and correction of associated stricture in 2. All patients ultimately were free of stones. Our experience with in situ extracorporeal shock wave lithotripsy is described. An open operation was done only when less invasive forms of treatment failed or electively to correct an associated anatomical abnormality.
Gallium arsenide (GaAs) is an intermetallic compound that is recognized as a potential toxicological risk to workers occupationally exposed to its dust. Previous results have shown that rats intratracheally instilled with a fraction of GaAs particulates, characterized with a mean count diameter of 8.30 microns and a mean volume diameter of 12.67 microns, developed signs of systemic arsenic intoxication, pulmonary inflammation, and pneumocyte hyperplasia. The results of the present study confirm these findings and also show that a significantly smaller fraction of GaAs is a relatively more severe pneumotoxicant. Decreasing the particle mean count and mean volume diameter to 1.63 micron and 5.82 microns, respectively, increased the in vivo dissolution rate of GaAs, increased the severity of pulmonary lesions previously associated with GaAs exposure, and resulted in unique pathological sequelae in affected lung tissue. Pulmonary fibrosis, as indicated by analysis of lung 4-hydroxyproline content, was not considered statistically significant although histological examination of lung tissue revealed a mild fibrotic response. These results provide additional evidence that pulmonary exposure to respirable GaAs particulates is a potential health hazard in the semiconductor industry.
Nebulized bitolterol solution and isoproterenol solution were compared when used on a regular basis, 2.5 mg three times a day for 1 month by patients with chronic asthma. In this multicenter, double-blind trial; 130 nonsteroid-dependent patients were randomized to receive one of the two treatments concomitantly with their regular asthma medications. On study days, at the beginning of the study and after 2 and 4 weeks, treatments were given in the office or laboratory and patients were monitored with pulmonary function tests for eight hours. Both medications induced rapid bronchodilation that had a longer duration after bitolterol. The incidence of tremor was similar with the two medications. Tachycardia and palpitations were more frequent following isoproterenol. Bitolterol has a much longer duration of action and should be considered as a suitable bronchodilator for regular nebulizer treatment of chronic asthma.
A GAT-specific, MHC-restricted "second-order" suppressor T cell factor (TsF2) from the hybridoma 762 B3.7 was biosynthetically radiolabeled with 35S-methionine and was isolated from cell extracts. The isolation procedure involved two-dimensional nonreducing/reducing SDS-PAGE and electroelution of the reduced off-diagonal polypeptide chains from the gel. Biochemical characterization studies revealed that TsF2 is a disulfide-linked heterodimer composed of a basic and an acidic polypeptide chain, both having m.w. of 30,000. Both chains are glycosylated and contain sialic acid residues. The basic polypeptide reacts with anti-I-J antisera, whereas the acidic chain contains the antigen-binding capacity. Monoclonal antibodies induced by immunizing rats with TsF2 purified from hybridoma supernatants were selected for the ability to block immunosuppression mediated by TsF2 in vitro. These antibodies, but not irrelevant antibodies, immunoprecipitated the 35S-methionine-labeled protein that migrates off the diagonal in two-dimensional gels. Thus, we have verified that the immunosuppressive protein that migrates off the diagonal in two-dimensional gels binds to antibodies that are known to inhibit the biologic activity of unpurified TsF2.
This study was designed to compare different methods of treating renal calculi in order to establish which was the most cost effective and successful. Of 1052 patients with renal calculi, 350 underwent open surgery, 350 percutaneous nephrolithotomy, 328 extracorporeal shockwave lithotripsy (ESWL), and 24 both percutaneous nephrolithotomy and ESWL. Treatment was defined as successful if stones were eliminated or reduced to less than 2 mm after three months. Success was achieved in 273 (78%) patients after open surgery, 289 (83%) after percutaneous nephrolithotomy, 301 (92%) after ESWL, and 15 (62%) after percutaneous nephrolithotomy and ESWL. Comparative total costs to the NHS were estimated as 3500 pounds for open surgery, 1861 pounds for percutaneous nephrolithotomy, 1789 pounds for ESWL, and 3210 pounds for both ESWL and nephrolithotomy. ESWL caused no blood loss and little morbidity and is the cheapest and quickest way of returning patients to normal life.
The relative toxicity of gallium arsenide (GaAs) and its metal oxides was assessed by intratracheally instilling particulate suspensions of GaAs (100 mg/kg), equimolar gallium as Ga2O3 (65 mg/kg), or a maximally tolerated nonlethal dose of arsenic as As2O3 (17 mg/kg). Two weeks after dosing, five rats from each group were randomly selected for the biochemical determination of lung lipid, protein, DNA, and collagen (4-hydroxyproline; 4-HP) content. The pulmonary retention of gallium and/or arsenic and the concentration of these metals in blood were also determined. Lungs from the remaining rats (n = 3) were examined histopathologically. Pulmonary exposure to Ga2O3 particulates significantly (p less than 0.05) increased the total lipid content of lungs relative to that observed in the vehicle-treated control animals. This response appeared to be associated with the pulmonary retention of gallium particulates (means = 36% of the gallium dose). In contrast, As2O3 particulates were not retained in the lung. Blood arsenic concentrations were 36 ppm which represented 20% of the total arsenic administered. Treatment with As2O3 significantly elevated lung dry weight as well as protein, DNA, and 4-HP content. These data suggest that As2O3 induced an acute fibrogenic response. The intratracheal instillation of GaAs particulates produced effects similar to those observed with the individual oxides. The total lung content of lipids, protein, and DNA was significantly elevated. These biochemical changes were accompanied by significant increases in lung dry weight and lung wet weight. Lungs from rats receiving GaAs particulates retained 44% of the dose as gallium and 28% of the dose as arsenic at the end of the 14-day study. Blood arsenic concentrations were 44 ppm (7% of the arsenic dose) while gallium was not detected in blood at this time. The primary histopathological observations 14 days after the intratracheal instillation of all metal particulates were an inflammatory response and pneumonocyte hyperplasia. The biological severity of these lesions, in descending order, was GaAs greater than As2O3 much greater than Ga2O3. It must be noted, however, that As2O3 was dosed at 0.25 X moles of GaAs.
Glucagon may act as a relaxant of smooth muscle and it has been suggested that this action may assist in the passage of ureteric calculi and diminish ureteric colic. These effects may be of clinical use to avoid inpatient admission to hospital for the symptomatic relief of ureteric colic. Ten successive patients with acute ureteric colic were given 1 mg of glucagon and two litres of fluid administered by the intravenous route and analgesia as required over three hours. Progress was monitored radiologically and clinically. In no case did significant progression or passage of stones occur and seven patients required parenteral analgesia. We conclude that glucagon is not effective for the management of ureteric colic in a casualty department.
The combination of ESWL and Endourology (EU) enables a wider range of stones to be treated without open surgery than either modality alone. EU frequently involves the maintenance of a plastic prosthesis in or near the area of maximal shock wave concentration during ESWL. Prostheses subjected to a standard test treatment by ESWL and others removed from patients after ESWL were examined visually, microscopically and biochemically by electron microscopy (SEM) and X-ray emission spectroscopy (XES) to investigate the effects of ESWL on the prosthesis itself. Foley catheter balloons leaked. Previously smooth surfaces were disrupted and possibly toxic additives may be released. Care should be taken in selecting indwelling EU prostheses if ESWL treatment is likely to follow.
Although percutaneous nephrolithotomy (PCNL) and extracorporeal shockwave lithotripsy (ESWL) were introduced clinically at approximately the same time (1980-1981), their clinical progress appeared to progress along separate paths and to compete with each other. After 5 years it has become apparent that for optimal removal of nearly all renal stones by minimal or noninvasive techniques, PCNL and ESWL are required either separately or as combined procedures. This review traces the development, introduction and progress of these procedures and defines the current indications for extracorporeal, percutaneous and open renal stone surgery.
The sapphire crystal infrared photocoagulator and polyglactin (Vicryl) mesh, two new methods for closure of radial nephrotomies, were assessed in 16 dogs. Six radial nephrotomies were carried out in each dog; in 10 the nephrotomies were sealed by the infrared photocoagulator and in six they were left open, but the kidney was covered with a polyglactin mesh. Functional and morphological studies were performed using creatinine clearance, microfil casting, corrosion cast angiography and histology. There was no significant loss of function or loss of renal tissue. Both methods were shown to be safe and effective in the closure of radial nephrotomies.
Extracorporeal shockwave lithotripsy has been shown to be a safe and effective method of treating most upper urinary tract stones. Major complications, although few, include haemorrhage, septicaemia, "Steinstrasse" formation and cardiac arrhythmias. The experience from 600 consecutive cases is reviewed and methods of prevention are discussed.
Patients with ASA-sensitive asthma form a clinically homogeneous subgroup of asthmatics characterized by nonatopic eosinophilia, sinusitis, nasal polyps, and frequent steroid dependency. Twenty-six Caucasian patients with ASA-sensitive asthma and 22 Caucasian patients with uncomplicated asthma were typed for HLA Class I and II antigens. A significant increase in HLA-DQw2 (relative risk, 4.06) was found in ASA-sensitive asthmatics. Asthmatic patients who were not ASA-sensitive had HLA frequencies that did not differ significantly from healthy Caucasian control subjects. These findings suggest that ASA-sensitive asthma represents a disease entity unique from other forms of asthma. Presumably, DQw2 or an associated genetic factor is involved in the pathogenesis of ASA-sensitive asthma.