[Surgical correction of astigmatism after perforating keratoplasty].

Microsurgical control of astigmatism after perforating keratoplasty has widely remained an unsolved problem in spite of many sophisticated suggestions and inventions. The frequent irregularity in the recipient cornea and poor predictability with respect to wound healing are the major obstacles. If spectacles or contact lenses cannot provide useful vision, postoperative surgical correction is needed. Ablative or thermal laser techniques have not been sufficiently tried for such cases to be justified, and one may hesitate anyway to apply destructive methods in transplants. We therefore still use T-incisions and wedge resections, which are said to be rather imprecise. Only 3 out of more than 700 keratoplasties performed in our clinic from 1987 through July 1991 required such procedures. Two more cases were referred by surgeons outside the hospital. All five surgical corrections resulted in a good longterm effect with considerable improvement of vision. Thus, as long as alternative methods for surgical correction of postkeratoplasty astigmatism have not proved to be superior, we should continue to practice these "old" methods, which, indeed, are not bad if properly applied.


[Corneal opacity after photorefractive keratectomy with an excimer laser. Cause, objective measurement and functional consequences].

A marginal loss of corneal transparency or 'haze' is a phenomenon commonly experienced after photorefractive keratectomy using excimer lasers (193 nm). The putative causes of this phenomenon are the presence in the surgical site of (1) activated keratocytes, (2) vacuoles and (3) newly synthesized collagen. A CCD camera device was employed in order to measure the corneal transparency. Both scattered and reflected light in the slit image of patients' corneas was measured using polarizing filters and image analysis software. We observed an increase in reflected and scattered light until the second postoperative month, followed by a subsequent decline. However, the combined signal generated by reflected and scattered light showed a second increase at 4 months postoperatively, whereas the signal generated by scattered light alone stayed at lower levels. These objective measures of changes in corneal transparency were correlated with changes in visual performance using psychophysical tests measuring visual acuity at different contrast levels (100%, 20% and 5%). In all patients we observed a good correlation between the signal generated by scattered light alone and the reduction in the 5% contrast visual acuity performance. These disturbances in low contrast visual performance were only significant during the first 3-4 months postoperatively, and thereafter most patients returned to their preoperative value. Eighteen percent of our patients discontinued topical steroids postoperatively. No difference in corneal transparency was observed.


[Analysis of photo-ablation products of excimer and erbium:YAG laser treated human corneas. Combined gas chromatography/mass spectroscopy].

The photoablation products from human cadaver corneas treated with an excimer laser (192 nm) or an erbium: YAG laser (2.94 microns) were qualitatively analyzed using a combined gas chromatography mass spectrometry (GC/MS) system. GC/MS is the most sensitive analyzing system in use today for molecules with a relative molecular mass of 40 to 400. More than 20 different types of molecules were detected; most of them were identified as alkanes. Comparison of the two types of laser showed larger fragments and fewer different types of molecules after excimer laser treatment than after erbium: YAG photoablation. We postulate that the smaller molecules after erbium: YAG treatment indicate a greater heat during photoablation than with excimer laser treatment.


[Effect of postmortem duration on endothelial cell density in short-term culture with McCarey-Kaufman medium. An experimental study with Swine corneas].

It is recommended by the Eye Bank Association of American that the post-mortem time of donor tissue stored in intermediate storage should not exceed 6 h. In an experimental study we investigated the impact of post-mortem time on the storage of corneas kept in McCarey-Kaufman medium. Eyeballs of freshly slaughtered pigs were kept in moist chamber storage at 4 degrees C for 0, 6, 12, 24, and 48 h. Subsequently, corneal-scleral rims were dissected and stored in MK-Medium for 2 days at 4 degrees C. The corneas were stored in organ culture for another 2 days at 31 degrees C in MEM medium containing 10% fetal calf serum. A control group consisted of corneas that had been stored in organ culture for 2 days. Morphometric analysis revealed no significant changes in endothelial cell density compared to control corneas after up to 24 h of moist chamber storage prior to storage in MK medium. A significant decrease in endothelial cell density could only be detected in corneas that had been kept in moist chamber storage for 48 h before MK medium storage. We conclude that the recommendation that only donor corneas with short post-mortem times be used may exclude large amounts of potentially feasible tissue for penetrating keratoplasty.


[Keratoplasty with stored tissue. Initial results of a prospective study].

The first results of a prospective study on 50 patients who were followed up 2, 4, 6, and 12 months after keratoplasty are reported. The patients received a human cornea transplant, which had been cultured in a modified MEM medium for up to 28 days. We observed that the loss of epithelium during organ culture leads to delayed regeneration after keratoplasty. This is especially important for patients who have had this problem almost before transplantation. The slower increase of visual acuity after keratoplasty with organ-cultured material is due to increased folding of Descemet's membrane. Nevertheless the best vision was usually reached within 6 to 12 months. We saw seven immune reactions by which five transplants were lost. A comparatively low rejection rate was observed especially in the group of high-risk patients (27.2%). Organ culture may therefore have some additional positive effects for these patients.


[Freeze preservation of swine corneas with combinations of intra- and extracellular cryoprotective agents].

Clinically employed methods of corneal cryopreservation usually use the intracellular cryoprotectant dimethyl sulfoxide (DMSO). However, it has been demonstrated that extracellular cryoprotectants such as chondroitin sulfate (ChS) also display effective cryoprotection. The purpose of our study was to investigate the effect of combinations of intra- and extracellular cryoprotectants in corneal cryopreservation. Porcine corneas were cryopreserved in a cryopreservation medium consisting of MEM-medium containing 20% fetal calf serum and 2% chondroitin sulfate. The medium was varied by the addition of 2%, 4% and 8% DMSO. Sixty corneas were cryopreserved at -196 degrees C and thawed at 37 degrees C in a water bath. Morphometric evaluation was not performed directly after thawing but after a 24-h storage period in organ culture. Cryopreservation in medium without DMSO revealed the best results concerning endothelial cell density (2581 cells/mm2). Addition of 2% or 4% DMSO revealed no significant changes in endothelial cell density. Addition of 8% DMSO, however, resulted in a significant decrease (1312 +/- 319 cells/mm2) combined with a significantly higher amount of necrotic areas in the central corneal surface. We conclude that combining intra- and extracellular cryoprotectants does not enhance endothelial cell density after corneal cryopreservation. Higher concentrations of DMSO added to the cryopreservation medium appear to have a negative impact on endothelial cell viability.


[2 years experiences with Tenon-plasty].

Tenon plasty proved useful in eye burns, especially in cases involving corneoscleral ulceration. This surgical procedure was carried out in 24 severely burned eyes of 21 patients. A total of 75 Tenon flaps were prepared, each of them covering one quadrant of the anterior eye segment. In 13 cases the burns were fresh, showing necrotic and ischemic areas in the sclera. In seven eyes an extended corneoscleral ulceration had developed and was covered with Tenon plasty. In four cases, when highly inflamed tissue was removed from the limbus the proximal conjunctiva retracted and exposed large areas of the sclera. Again, Tenon plasty was carried out. In all cases, the damage was so extensive that no conjunctiva was available to form flaps for plastic repair. Besides, the extensive ischemia would not allow free transplants. The duration of postoperative observation after Tenon plasty ranged from 6 to 42 months. In 14 of 24 eyes the denuded corneal stroma was covered with an artificial epithelium. In 11 cases keratoplasty was performed. The conjunctival epithelium regenerated in 10 eyes within 10 days, in another 10 eyes within 20 days, and in 4 eyes within 50 days. In all cases, the corneoscleral ulceration healed. Although some symblephara formed, and in a number of cases the cornea became more turbid and vascularized, Tenon plasty was very helpful in shortening the period of intensive inpatient treatment and provided a sound foundation for further reconstructive surgery.


[Holographic analysis of displacement of the bovine cornea after disruption of intact structures].

Displacement of the surface of the cornea of bovine eyes after disruption of intact structures was investigated by means of holographic interferometry. Double-T-incisions of different depths were made with a diamond knife. Starting at about 80% of the incision depth there is a change in the central holographic interference fringe pattern. These effects can be clearly demonstrated by means of double-exposure holographic interferometry and real-time holographic interferometry. The stability of an existing corneal scar was analyzed by double-exposure holographic interferometry. The region of the scar showed a higher density of holographic interference fringes compared with the non-affected corneal areas, indicating a higher degree of elasticity. All eyes were investigated at an intraocular pressure of 1340 Pa (about 10 mmHg) and an intraocular pressure change of 10 Pa and 20 Pa. Further potential ophthalmic applications of holographic interferometry are discussed.


[Computerized videokeratoscopy. Indications for postoperative suture removal].

Twenty-three patients who had a high degree of postoperative astigmatism (3 D) after extracapsular cataract extraction were examined in a prospective study with a computerized videokeratoscope. Sutures were removed within the first 3 months postoperatively, and an examination with the videokeratoscope was performed at the same time. In addition, corneal power was measured with a keratometer for comparison. A comparative map demonstrating the change in corneal shape can be obtained by simple subtraction of the pre- and postoperative keratographs (color-coded topographical maps). Immediately after suture removal the corneal curvature was flattened in the steepest meridian (3 mm and 5 mm zone), resulting in an average net change in cylindrical refraction of -1.3 (+/- 1.7)D. The steepest meridian moved slightly in a counterclockwise direction (-5.79 +/- 29.4 degrees). The topographical analysis of all cases showed that suture removal along the steepest meridian reduced astigmatism by flattening the steepest meridian and steepening the flattest meridian. As the peripheral cornea becomes steeper, the central cornea flattens in a meridian. Morphologically, three different patterns were found. In 52% the reduction in astigmatism was "symmetric", in 21% it was "round", and in 26% it was "irregular". As a result of the study, a topographical model of the cornea will be given, showing the average net change in diopters power at various locations on the surface of the cornea. These results cannot be described by the use of ordinary keratometers.


Purification of liver aldehyde dehydrogenase by p-hydroxyacetophenone-sepharose affinity matrix and the coelution of chloramphenicol acetyl transferase from the same matrix with recombinantly expressed aldehyde dehydrogenase.

p-Hydroxyacetophenone was coupled to epoxy-activated Sepharose 6B to generate an affinity chromatographic matrix to purify aldehyde dehydrogenase. Purified beef liver mitochondrial aldehyde dehydrogenase specifically bound to the support and could be eluted with p-hydroxyacetophenone. A post-ammonium sulfate (30-55%) fraction of bovine liver was applied to the affinity gel column and aldehyde dehydrogenase was effectively purified, although not to complete homogeneity, indicating the potential selectivity of the matrix. Both beef liver cytosolic and mitochondrial aldehyde dehydrogenase bound to the column. A post-Cibacron blue Sepharose Cl-6B affinity-fractionated liver mitochondrial aldehyde dehydrogenase was purified to complete homogeneity by p-hydroxyacetophenone-Sepharose, thus eliminating the need for the isoelectric focusing step often employed. p-Hydroxyacetophenone was found to be a competitive inhibitor against propionaldehyde and noncompetitive against NAD. Escherichia coli lysates of recombinantly expressed aldehyde dehydrogenase were purified from E. coli lysates with one major 25-kDa protein contaminant also binding to the column, as detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The 25-kDa contaminant was found to be chloramphenicol acetyl transferase from sequence analysis and binding studies.


Purification of erythrocyte protein 4.1 by selective interaction with inositol hexaphosphate.

Protein 4.1 is a multifunctional structural protein occupying a strategic position in the erythrocyte membrane. It is present in the erythrocyte membrane skeleton and in many nonerythroid cells. This report describes a novel method for purifying this protein based on its selective interaction with inositol hexaphosphate dimagnesium tetrapotassium salt. This interaction was discovered in the course of chromatography of high-salt extract of inside-out membrane vesicles on Procion orange MX-2R-Sepharose. The new procedure is simple and selective and produces protein 4.1 with better yield than that obtained with a previously published procedure. The purified protein 4.1 has the same immunoreactivity and the same alpha-chymotryptic digest profile as protein 4.1 purified by published methods and is fully functional in enhancing the interaction between F-actin and spectrin dimers.


Expression, purification, and characterization of inactive human coagulation factor Xa (Asn322Ala419).

We have expressed in Chinese hamster ovary cells a catalytically inactive form of human factor Xa (factor rXai). A recombinant precursor of human factor Xa was inactivated by two point mutations in the serine protease catalytic triad, Asp322Asn and Ser419Ala. A two-step purification to homogeneity of the secreted material involved immunoaffinity followed by heparin-agarose chromatography. Two forms were identified; a fully processed dimer (70%) and a partially processed monomer (30%). Limited N-terminal amino acid sequencing of factor rXai detected the predicted residues and gamma-carboxyglutamic acid content was 90% of human plasma control. Although devoid of measurable proteolytic activity, factor rXai competitively inhibited plasma factor Xa assembly into functional prothrombinase complexes (Ki = 3 x 10(-10) M). Factor rXai also inhibited plasma clotting in a dose-dependent manner. The possible use of recombinant catalytically inactive proteins as a general approach for pharmacological regulation of human diseases is discussed.


Insights into the physician's role in mammography utilization among older women.

Women who receive routine medical care and those who see obstetrician-gynecologists are more likely to get mammograms. However, fewer women see these physicians as they grow older. Results indicate that, as a group, older women see a different mixture of physicians, and the drop in mammography referrals due to obstetrician-gynecologist office visit decline is not replaced by compensating referral patterns from other physician groups. All physicians should recommend mammograms to all of their older female patients; opportunities for doing so exist if they broaden their view of when such recommendations are appropriate. It is particularly important for nongynecologists to remember that their older patients may no longer see a gynecologist and will not receive a mammography recommendation from anyone else.


Malaria and the red cell membrane.

Malarial parasites are primarily parasites of red cells and during infection ingest most of the haemoglobin within these cells, leaving the membrane as the only vestige of the original host cell. The red cell membrane thus plays a key role at all stages of infection with malarial parasites, and is modified in many ways during parasitisation, so that at least functionally it has little resemblance to the membrane from which it was originally derived. The highly specific and ordered process of parasite invasion of red cells is regulated at least in part by the uninfected red cell membrane. The red cell sialoglycoproteins or glycophorins of this membrane have been shown to play an important role in invasion by Plasmodium falciparum, the species of most importance to man because of it's high morbidity and mortality. Structurally, dynamic changes occur within the membrane during parasitisation, and a number of parasite proteins have been found to be associated within it, but changes on the surface of the infected cell have been more difficult to demonstrate. The membrane of the infected cell is important in the many metabolic processes of the parasite, as well as the critical cell-cell interactions that occur when cells containing mature parasites bind to endothelial cells (cytoadherence), bind to uninfected cells (rosetting), or interact with macrophages and other leucocytes. The recognition molecules on the red cell membrane involved in invasion, cytoadherence and rosetting appear to be quite distinct. Structural and functional changes have also been shown to occur in the membranes of uninfected red cells, both in infected patients, and in the presence of parasites in vitro. Interactions of the parasite P. falciparum with the red cell membrane hold the key to our understanding of the pathogenesis of severe falciparum infection in man.


Treatment of childhood acute lymphoblastic leukaemia: present issues and future prospects.

Modern treatment for acute lymphoblastic leukaemia (ALL) achieves long term survival in two thirds of children, many of whom are truly cured. Recent improvements have occurred as a result of progressive intensification of treatment, particularly during the first 6 months from diagnosis. This article reviews the means of identifying children for whom standard therapy is not appropriate, and the aspects of standard therapy requiring further refinement, in particular central nervous system (CNS) directed treatment and continuing (maintenance) therapy, a concept unique to ALL. Modern methods for identification of minimal residual disease afford the hope that it may become possible to identify both children who have received sufficient treatment and, conversely, those at subsequent risk of relapse. Selection of patients for alternative therapy, for example marrow transplantation in first remission is difficult and this area needs further study. Treatment for the one third of children who relapse remains unsatisfactory and when successful is only achieved with significant morbidity. Most long-term survivors of childhood leukaemia are well and problem-free but a significant number have problems with learning, concentration, growth and development; the risk of second neoplasms remains unclear. Recent years have seen undeniable progress in the treatment of ALL but there is a continuing need to develop effective forms of treatment which have less potential for damaging late effects.


Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature.

Erythroleukemia (EL) is a rare form of myelogenous leukemia the classification and definition of which has evolved over the course of its 80-year descriptive history. In 1976 the French American British (FAB) Cooperative Group included EL within the classification system of acute myelogenous leukemias as AML-M6, and agreed on a quantitative standard to be used in the diagnosis of this disorder. The standards were revised in 1985 to the form in use today. We selected a series of 15 cases from our records which specifically fit the FAB criteria for AML-M6. Extensive direct comparison between our series and the old literature is not practical because of the changes which have occurred in classification and definition of the disease. Overall we found a rough correlation between the clinical and laboratory data shown in the old literature on EL and data from our cases. These cases underscore characteristic laboratory features which correspond to what is now defined as AML-M6: these patients present with pancytopenia, frequent peripheral blood nRBCs and no, or few, peripheral blood blasts. In addition, we note the presence of a hybrid myeloid-erythroid blast in the bone marrow in this disease and suggest that this may be characteristic of this type of AML. Old literature on EL has generally shown it to be a disease of the elderly, yet we found a subset of younger patients whose clinical outcome was significantly better than that of the older patients. Finally, EL has historically been viewed as a disease in which patients progress from a prodrome through erythroleukemia to other acute myeloid leukemia (AML) subtypes. Consistent with this idea, half of our 15 patients had been previously diagnosed with myelodysplastic syndrome or received chemotherapy. On the other hand only one of the 15 patients converted to another type of AML during his course.


Intensive chemotherapy in myelodysplastic syndromes.

Patients with myelodysplastic syndrome (MDS) who have more than 10% blasts in their bone marrow have a very short survival. Treatment has not improved for these patients for the past 10 years and supportive care alone is still the gold standard. Intensive chemotherapy for poor prognosis MDS has been little tried, but complete remission rates are higher in such studies than in patients with acute myeloid leukaemia (AML) supervening on the MDS. Although these groups may not be comparable, and neither group is representative of the majority of patients with the MDS who are generally older, a case can be made for a randomised prospective study comparing intensive chemotherapy and supportive care alone in poor prognosis MDS. For patients with the myelodysplastic syndrome intensive chemotherapy may carry special risks. The involvement of the whole marrow in the neoplastic clone, and the likelihood of anthracycline resistance are two such hazards which may need to be circumvented.


Classification of large granular lymphocyte (LGL) and NK-associated (NKa) disorders.

Literature trends indicate an increasing awareness regarding the frequency, nature and clinical associations of abnormal and persistent expansions of lymphocytes with cytoplasmic granulation. These particular cells, which represent a minor normal lymphoid subpopulation and are widely referred to as large granular lymphocytes (LGL), generally (but not invariably) express monoclonal antibody-defined membrane NK-associated (NKa) determinants and appear to functionally correspond to those populations involved in cellular cytotoxicity. Increased proportions or absolute numbers of blood lymphocytes with LGL morphology and/or NKa+ phenotypes are associated with a diverse spectrum of clinical (haematological and non-haematological) disorders and may be broadly viewed as secondary (acute and chronic reactive) or primary in nature. Both primary and secondary LGL/NKa+ expansions may be persistent in type and the clinical distinction between the two may be difficult. A number of investigators have proposed schemes for the classification of these disorders but, because of their diversity, abnormal LGL/NKa+ expansions often defy rigid compartmentalisation. This communication examines the general basis of these classifications and illustrates their limitations by reviewing the data for 97 patients recorded in the largest (Yorkshire Leukaemia Group) survey to date of persistent LGL/NKa+ expansions.


Conditioning regimens for allogeneic bone marrow transplantation.

Conditioning regimens for transplantation are important in determining transplant outcome. This review focuses on transplantation in aplastic anemia and leukemia using marrow from HLA-identical siblings. Results of conditioning with newer regimens such as busulfan plus cyclophosphamide and etoposide plus total body irradiation are reviewed and compared to results achieved with cyclophosphamide and total body irradiation. The potential for improved results using recent innovations such as dose adjustment of busulfan, agents which may decrease transplant-related toxicity, and directed radiation are discussed.


Genetically determined factors as predictors of radiological change in patients with early symmetrical arthritis.

To determine whether genetic factors associated with established rheumatoid arthritis could, in combination with rheumatoid factor, predict the development of radiological erosions in patients with early symmetrical (rheumatoid-like) arthritis. Prospective study. Teaching hospital, early arthritis clinic. Forty nine patients with symmetrical polyarthritis attending the early arthritis clinic. Conserved sequence of DR beta third allelic hypervariable region, sulphoxidation capacity, rheumatoid factor, and development of radiologically determined bone erosions. None of the 49 patients had radiological erosions at presentation but 25 developed these by four years. Patients with the conserved class II major histocompatibility complex (third allelic hypervariable of DR beta 1) genes associated with rheumatoid arthritis had a relative risk for the development of erosions of 1.9 (95% confidence interval 0.8 to 4.5). For poor sulphoxidation the risk was 2.5 (1.1 to 5.6) and for the presence of rheumatoid factor 1.8 (0.9 to 3.7). Of the 33 patients who had two or three of these risk factors, 24 developed erosions, with a relative risk of 11.6 (1.7 to 78.5) compared with only one of the 16 individuals with no or one risk factor. This preliminary study shows that by using these stable markers it is possible to make clinically useful predictions of outcome in patients with early symmetrical inflammatory arthritis.


Community clinics for leg ulcers and impact on healing.

To evaluate the effectiveness of community clinics for leg ulcers. All patients with leg ulceration were invited to community clinics that offered treatment developed in a hospital research clinic. Patients without serious arterial disease (Doppler ankle/brachial index > 0.8) were treated with a high compression bandage of four layers. Six community clinics held in health centres in Riverside District Health Authority supported by the Charing Cross vascular surgical service. All patients referred to the community services with leg ulceration, irrespective of cause and duration of ulceration. Time to complete healing by the life table method. 550 ulcerated legs were seen in 475 patients of mean (SD) age 73.8 (11.9) years. There were 477 venous ulcers of median size 4.2 cm2 (range 0.1-117 cm2), 128 being larger than 10 cm2. These ulcers had been present for a median of three months (range one week to 63 years) with 150 present for over one year. Four layer bandaging in the community clinics achieved complete healing in 318 (69%) venous ulcers by 12 weeks and 375 (83%) by 24 weeks. There were 56 patients with an ankle/brachial arterial pressure index < 0.8, indicating arterial disease. The 50 patients with pressure index < 0.8 > 0.5 were treated with reduced compression, and 24 (56%) healed by 12 weeks and 31 (75%) by 24 weeks. The figures for overall healing for all leg ulcers were 351/550 (67%) at 12 weeks and 417/550 (81%) at 24 weeks, compared with only 11/51 (22%) at 12 weeks before the community clinics were set up. Community clinics for venous ulcers offer an effective means of achieving healing in most patients with leg ulcers.


Serum antioxidant vitamins and risk of cataract.

To investigate serum concentrations of alpha tocopherol, beta carotene, retinol, and selenium for their prediction of end stage cataract. A case-control study, nested within a cohort study, based on the linkage of records of subjects aged 40-83 from a health survey with those from the national Finnish hospital discharge register. 47 patients admitted to ophthalmological wards for senile cataract over 15 years and two controls per patient individually matched for sex, age, and municipality. Concentration of serum micronutrients, development of cataract according to whether operation was performed. Low serum concentrations of antioxidant vitamins predicted the development of senile cataract, the odds ratio between the lowest third and the two higher thirds of the distribution of serum concentrations of alpha tocopherol and beta carotene being 1.9 (95% confidence interval 0.9 to 4.1) and 1.7 (0.8 to 3.8), respectively. Patients with both alpha tocopherol and beta carotene concentrations in the lowest third had an odds ratio of 2.6 (1.0 to 6.8) of cataract compared with subjects in the top two thirds. The associations were strengthened by adjustment for potential confounding factors such as occupation, smoking, blood pressure, serum cholesterol concentration, body mass index, and diabetes. No association was found between the serum concentrations of selenium, retinol, and retinol binding protein and the risk of cataract. Low serum concentrations of the antioxidant vitamins alpha tocopherol and beta carotene are risk factors for end stage senile cataract. Controlled trials of the role of antioxidant vitamins in cataract prevention are therefore warranted.


Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison.

To compare the prevalence of asthma and allergic disorders among children in Munich, western Germany, and Leipzig, eastern Germany, where environmental exposure, particularly air concentrations of sulphur dioxide and particulate matter, and living conditions have differed over the past 45 years. Prevalence surveys among school-children aged 9-11 years in Leipzig and Munich. Self completion of written questionnaire by the children's parents and lung function measurements. 1051 children in Leipzig and 5030 in Munich. Primary schools. Reported lifetime prevalence of asthma and allergic disorders, and bronchial hyperresponsiveness assessed by cold air inhalation challenge. The lifetime prevalence of asthma diagnosed by a doctor was 7.3% (72) in Leipzig and 9.3% (435) in Munich; prevalence of wheezing were 20% (191) and 17% (786) respectively. The prevalence of diagnosed bronchitis was higher in Leipzig than Munich (30.9% (303) v 15.9% (739); p < 0.01). A significant drop in forced expiratory volume (> 9%) after cold air challenge was measured in 6.4% (57) of children in Leipzig and in 7.7% (345) of those in Munich. Hay fever (2.4% (24) v 8.6% (410); p < 0.01) and typical symptoms of rhinitis (16.6% (171) v 19.7% (961); p < 0.05) were reported less often in Leipzig than in Munich. No significant differences were seen in the lifetime prevalence of asthma, wheezing, and bronchial hyperresponsiveness between children in Leipzig and Munich. The lifetime prevalence of bronchitis was higher in Leipzig than in Munich. The lower prevalence rates of allergic disorders in Leipzig could point toward aetiological factors that are associated with Western lifestyle and living conditions.


Poor growth in school entrants as an index of organic disease: the Wessex growth study.

To establish whether poor height or height velocity, assessed during the year of school entry, might identify children with previously undiagnosed organic disease. Observation of a total population and their case controls. Community base. All 14,346 children in two health districts entering school during two consecutive years were screened for height by school nurses, and those whose height lay below the 3rd centile according to Tanner and Whitehouse standards (n = 180) were identified. After excluding 32 with known organic disease, five from ethnic minorities, and three who refused to take part, the remaining 140 short normal children were matched with 140 age and sex matched controls of average height (10th-90th centile) and their height velocities over 12 months measured. Height, height velocity, previously diagnosed organic disease, and organic disease diagnosed as a result of blood tests and specialist examination. Twenty five of the 180 short children (14%) were already known to have chronic organic disease which could explain their poor growth. Blood tests and specialist examination revealed a further seven with organic disease, which was acquired rather than congenital in three, and a second cause of short stature in one with known organic disease. These eight conditions had been missed at the school entry medical examination. The shorter the child, the more likely an underlying organic disorder, with seven of the 12 children whose heights were more than 3 standard deviations below the mean having some organic disease. Height velocity measured over 12 months, however, did not distinguish short normal children from those with disease or from their matched controls. Height, but not height velocity, is a useful index for identifying unrecognised organic disease at school entry. The shorter the stature the greater the prevalence of organic disease. The frequency of newly diagnosed remediable disease in this study (1 in 3-4000) is similar to that of neonatal hypothyroidism, which is routinely screened for. Routine investigation of all very short school entrants is recommended.


Job share a consultant post.

Job sharing offers advantages to both employer and employee but it is still uncommon in medicine. Based on the experiences of two psychiatrists sharing a consultant post this article describes some of the problems in obtaining a job share. The most difficult part can be getting an interview, and once a post has been obtained the terms and conditions of service may have to be modified to suit job sharing. Getting on well with your job sharing partner and good communication will not only help overcome the obstacles but ensure that the sharing is successful.


Community care in London: the prospects.

Elderly and disabled people have been led to expect great improvements in the quality of community care after April 1993. The choice to live safely at home is to be offered as an alternative to residential care. The financial and organisational relationships are all intended to support this in practice. The Tomlinson recommendations will create instability for providers, and much new and overdue investment in primary and community services is needed if the community care reforms are to work. There are, however, other obstacles looming which pose an even greater threat to the smooth transition after April 1993. The formula by which government money for implementation will be distributed discriminates against London. The sheer complexity of the organisational transformation has also been underestimated; the machinery of government both locally and centrally is ill equipped to maintain the precedence of the consumer. There are examples of good practice in London boroughs, but the dangers of Londoners ending up with the worst of all worlds are great.


Principles of antibody therapy.

The success of monoclonal antibodies in clinical practice is dependent on good design. Finding a suitable target is the most important part as other properties of the antibody can be altered by genetic engineering. Antibodies that target lymphocyte antigens offer less toxic immunosuppressive treatment than currently available drugs and the first monoclonal antibody approved for human use is an immunosuppressive agent for treating rejection of renal transplants. Human trails of monoclonal antibodies to treat septic shock have been done and antibodies are also being developed to target common pathogens such as herpes simplex virus. Although monoclonal antibodies against cancer have been much heralded, their success has been limited by the poor access to the inside of tumours. Treatment of blood cancers has been more successful and a human antibody against B cell malignancies is being clinically tested. As knowledge about natural immune responses and antibody engineering increases many more monoclonals are likely to feature in clinical practice.


Localized retinal morphology and differential light sensitivity in diabetic retinopathy. Methodology and clinical results.

The thesis presents a technique designed to allow a comparison of retinal function as assessed by computerized perimetry with retinal morphology as seen on photographs of the ocular fundus, including results from the practical application of this technique in the study of diabetic retinopathy. The basis of the technique is an optical algorithm that allows angular distances in the visual field to be transformed to match linear distances on fundus photographs and fluorescein angiograms. The visual field data is superimposed onto the corresponding retinal morphology on the photograph on the basis of two points of reference. The fixation point in the visual field is superimposed onto the foveola on the photograph of the ocular fundus, and the blind spot in the visual field is superimposed onto the optic disc on the photograph. In the practical application of this technique for the study of diabetic retinopathy, visual field scotomata were found corresponding to areas displaying signs of retinal vascular impairment in the form of vascular occlusion, while no relation was found between visual field scotomata and breakdown of the blood-retina barrier as studied on fluorescein angiograms. Furthermore, visual field scotomata were found to correspond to areas peripheral from retinal neovascularizations, a finding supporting the hypothesis that the neovascularizations develop because of stimulation from vasogenic factors released from ischaemic and hypoxic retinal tissue. Visual field scotomata were also found in relation to retinal cotton wool spots. These scotomata were localized, and not accurately extended, which could be expected if the retinal nerve fiber layer had been damaged. Finally, some visual field scotomata could not be related to any visible funduscopic or angiographical morphology. It is concluded that pathological changes in the inner retinal vascular supply may lead to impairment of visual function in diabetic retinopathy, but that also other mechanisms not manifested in a morphologically visible way, are involved. A further investigation of the pathophysiology leading to visual impairment in diabetes mellitus should focus on these unknown factors. A possible approach could be the development of new techniques for studying pathophysiological mechanisms in specific retinal layers, and especially the layers supplied by the external vascular supply to the retina from the choroidal circulation.


Structure and expression of the human insulin-like growth factor genes.

The human insulin-like growth factors (IGFs) are important regulators of growth, which exert their functions via endocrine, paracrine and autocrine mechanisms of action. Structural analysis of the genes coding for IGF-I and -II has revealed that they have a complex exon-intron structure and possess multiple promoters. The expression of the IGF genes is regulated at the levels of transcription, RNA processing and translation. This review summarizes our current knowledge of the structure and expression of these genes.


Effects of insulin-like growth factor I or human growth hormone in fasted rats.

To study the effect of insulin-like growth factor I (IGF-I) treatment on growth and metabolism in fasted rats and compare it with the effect of human growth hormone (hGH), we infused 120 micrograms/ml IGF-I continuously or injected 200 micrograms hGH twice a day in fasted rats. After a 3 1/2-day administration of IGF-I in fasted rats, the body weights, kidney, spleen and adrenal gland weights were greater than those for untreated fasted rats (control). The body weights and the organ weights in hGH treated rats did not differ from those in control rats. Serum IGF-I levels in control, hGH treated and IGF-I treated rats were 64.0 +/- 6.1, 107.5 +/- 6.9 and 129.8 +/- 6.3 ng/ml, respectively, which were significantly different from each other. Blood urea nitrogen (BUN) levels were 13.9 +/- 1.1 ng/ml in IGF-I treated rats, which were significantly lower than those of control rats. Human GH treatment did not change BUN but affected nonesterified fatty acid (NEFA) and triglyceride. In IGF-I treated rats three-day urinary excretion of nitrogen and creatine were 163.5 +/- 14.6 mg and 9.53 +/- 1.53 mg, which were significantly less than those in control rats. These data indicate that IGF-I infusion inhibits body weight loss and catabolism in fasted rats and might be a useful therapy in catabolic conditions.


Noise levels from toys and recreational articles for children and teenagers.

This study examined the noise level emitted by toys and recreational articles used by children and teenagers. The results indicate that many of the items tested emit sufficiently intense noise to be a source of noise induced hearing loss in school-age children. While the baby toys provided noise exposure within the limits of national regulations, they are most intense in a frequency range that corresponds to the resonance frequency of the external auditory canal of very young children. Hobby motors emit noise that may require protection depending upon the length of use. Fire-crackers and cap guns emit impulse noises that exceed even conservative standards for noise exposure.


Observations on the ABR I-V interval in a clinical sample of elderly patients.

ABR I-V interval in elderly patients, analysed by multiple regression analysis, was found to be dependent on hearing threshold slope and sex, while the contribution of age and hearing loss was not significant. Since these results partly disagree with other reports which demonstrate that I-V interval is significantly related to age and hearing threshold, caution is suggested in inferring general conclusions on age effects, if data are drawn from clinical samples.


The effect of temperature on the performance of audiometric mechanical coupler systems.

Measurements of mechanical coupler performance have been made over the temperature range 13 degrees C to 33 degrees C to investigate the change of force sensitivity level and mechanical impedance level with temperature for frequencies in the range 125 Hz to 5000 Hz. In addition, the temperature dependence of the voltage output of the mechanical coupler system has been measured for a coupler driven by a Radioear type B-71 bone vibrator, to investigate the net effect of these changes on an audiometer calibration. Very clear dependence on temperature has been found for all three parameters at some frequencies. In particular, coefficients approaching 0.6 dB/degrees C have been found for the rate of change of force sensitivity level at higher frequencies, and when driven by a bone vibrator coefficients around 0.5 dB/degrees C have been measured for the voltage output, again at the higher frequencies. This strong dependence of the performance of the mechanical coupler on temperature has implications for all those working in audiometric calibration, and especially for those involved in providing calibrations of audiometers in situ, where the mechanical coupler is transported from site to site and may well be exposed to extremes of temperature during transportation.


Somatic and psychological factors contributing to handicap in people with vertigo.

Questionnaires assessing symptoms, disability and handicap, predisposition to anxiety, and current anxiety and depression were completed by 127 people attending neuro-otology clinics with a major complaint of vertigo or dysequilibrium. Definite signs of vestibular dysfunction (spontaneous or positional nystagmus, or canal paresis) were found in 56% of the sample, but the presence or absence of abnormal vestibular test results was unrelated to diagnosis, reported symptoms, handicap and psychological status. Two-thirds of employed respondents admitted to occupational difficulties, and more than one in seven had left work because of vertigo. Although the number of people in the sample with a predisposition to anxiety was not unusually high, over a third of the sample had abnormally elevated levels of current anxiety. Multiple regression analyses indicated that disability was determined mainly by physical factors (vertigo severity and duration, age and sex). Handicap was influenced by a mixture of somatic and psychological variables, including the severity of autonomic symptoms. Anxiety and depression were only indirectly related to the severity and duration of the vertigo, insofar as this contributed to handicap. The partial dissociation between these different aspects of patient well-being suggests a need for separate evaluation and differing management of problems at each level of functioning.


An evaluation of commercial water irrigation systems used for caloric testing.

The post-1982 Grant Caloric Test Apparatus, and the Atmos Variotherm were evaluated and compared to BS5724 Part 1 (1989). Quality of construction is satisfactory, but design features may result in failure of tests for which this type of equipment should conform; namely splash, liquid leakage and spillage. For the Variotherm the proximity of the water piping to the electrical parts could result in wetting of the electrical units in the event of a leakage. The large vents in the Grant tanks allow easy access of water to electrical parts in the event of splashing. Both sets of equipment fail BS5724 Part 1 (1989) with respect to labelling. The Grant irrigation nozzle is well designed, but the Variotherm nozzles are not so, as they can accidentally pass down the external auditory meatus causing meatal wall or tympanic membrane damage. Both sets of equipment passed on electrical safety test for Class I Type B equipment. Cut-outs are fitted to prevent heating in the absence of water or over-heating of the water. The 44 degrees C Grant tank cut out after 20 s in the absence of water and at 49 degrees C as the water temperature rose above the operating temperature. The Variotherm heater did not operate in the absence of a water supply. The Variotherm thermal cut-out was not assessed. The force of the water at recommended flow rates using the Variotherm 'standard' metal nozzle was considered to pose a potential hazard of tympanic membrane perforation, and has subsequently been withdrawn by the supplier. The plastic nozzle minimized any such risk. The Variotherm is easier to use due to the well-designed trigger handle for controlling water delivery. Both sets of equipment performed at the correct temperature to within +/- 0.5 degrees C and achieved a flow rate of 250 ml in 30 s.


Quantification of hearing disability for medicolegal purposes based on self-rating.

Current practice for medicolegal assessment of individuals entails the use of an impairment measure obtained from average hearing threshold levels as a surrogate for hearing disability, and conversion of the surrogate to disability via a formula. Several different formulae are in use, but none is based explicitly on experimental data. To address this lack of empirical foundation in the assessment process, numerical self-ratings of hearing ability by 2058 subjects with a wide range of hearing threshold levels who had taken part in the National Study of Hearing in the UK were analysed to examine their relation to average hearing threshold level. The relation between self-rated hearing disability (the complement of self-rated hearing ability) and hearing threshold level was found to be sigmoid in form, and could be closely modelled by a modified Gompertz function. Functions for the median, upper quartile and lower quartile disability ratings with hearing threshold level are presented in graphical, parametric and tabular form. The median function gives a quantitative foundation for medicolegal assessments.


Apportionment of noise-induced hearing disability and its prognosis in a medicolegal context: a modelling study.

Apportionment of liability for noise-induced hearing loss is required in medicolegal work when two or more separate instances of noise exposure have occurred. In general there are insufficient audiometric records to determine how much hearing loss was caused by each noise exposure, and hence there is insufficient information on which to base apportionment of liability. Apportionment must then be based on a theoretical understanding of the way in which hearing loss is related to patterns of noise exposure and how the increased hearing threshold levels lead to greater disability. A model is developed which combines existing models of the relationship of hearing impairment to noise exposure and age, and the relationship of hearing disability to impairment. The model is evaluated for a wide range of notional patterns of noise exposure, leading to a simple equation which predicts the relative attribution of disability to previous noise exposures sufficiently accurately for the purposes of apportionment. The model also shows that disability due to noise exposure generally increases slightly with increasing age even after noise exposure has ceased. Thus the difference in disability between a person exposed to noise and a noise-free control of the same age and sex can be expected to increase somewhat as the subject and control grow older. However, the magnitude of this effect, often termed prognosis, is shown to be small and can be assumed to be zero in practice.


Motion sickness and perception: a reappraisal of the sensory conflict approach.

This review examines the role of activity and perceptual learning in motion sickness by means of a survey of the two kinds of recent research relevant to this topic. The first is a body of literature concerned not with motion sickness as such, but with perception of orientation and self-motion under the conditions of 'sensory conflict' which are thought to provoke motion sickness. The second consists of investigations into the prediction and prevention of motion sickness itself. A major weakness is identified in the methodologies employed in both types of research: namely, a neglect of the way in which responses to unusual and disorienting environments, whether nauseogenic or not, may be affected by the activities, skills and strategies of the perceiver. New directions are outlined for future research into immediate reactions and longer-term adaptation to such environments.


Effects of mood manipulation and anxiety on performance of an emotional Stroop task.

In Study 1 subjects high and low in trait anxiety were asked to identify the colour of anxiety-related, anxiety-matched neutral, happiness-related and happiness-matched neutral words. There were two types of stimulus presentation: blocked trials, where stimuli were blocked with respect to their valence, and mixed trials, where stimuli were mixed with respect to their valence. Subjects high in trait anxiety took longer to identify the colour of anxiety-related compared to matched neutral words for blocked-trial presentation only. In Study 2 subjects were exposed to either a positive or a negative mood-manipulation followed by a mixed-trial Stroop task. The mood manipulation procedure was successful in producing predicted changes in self-reported state anxiety. Analyses showed that high-trait-anxiety subjects exhibited interference effects consistent with the induced mood. No such effects were observed for the low-trait-anxiety subjects.


Spatial ability in subgroups of left- and right-handers.

Two tests of spatial ability, mental paper folding given to 459 14-15-year-olds representative of the secondary school population, and recall of the Rey figure given to 428 undergraduates, found significant relationships between ability and hand preference when preferences were classified in subgroups of left- and right-handers (Annett, 1970a). In 14-15-year-olds and in female undergraduates there was a W-shaped relation between hand preference and spatial ability. The highest scores were in the centre for right-handers with strong sinistral tendencies. Male undergraduates showed a linear trend, with spatial ability highest in strong left-handers and declining from left to right across levels of hand preference. When spatial test scores were considered in relation to differences between the hands in skill a decline of ability with increasing dextrality was found in right-handers and in left-handers. In terms of the right shift theory (Annett, 1972, 1985), the evidence suggests that there are costs for spatial ability associated with the presence of the rs+ gene, even in single dose (rs+ - genotypes), and that those who lack the gene (rs- - genotypes) have advantages for spatial ability (Annett, 1991 c).


Differences in vividness ratings of perceived and imagined patterns.

The present research focuses on the different subjective experiences evoked by perceived and imagined matrices of letters of the alphabet. In three experiments adult subjects were asked to rate the vividness of a letter included in a matrix of letters which varied due to manipulations in colour, rotation and movement. Subjects were asked to observe (perceptual modality), draw and observe (drawing modality), retrieve (memory modality) or imagine (imagery modality) the matrices. For some manipulations of the critical letter (in particular, 45 degrees inclination and high contrast colour), the perceptual modality produced comparatively higher vividness ratings than the other two modalities. The perceptual effect of inclination was also duplicated with the memory modality group. It is argued that different visual processes, either immediate and pre-attentive, or sequential and attentive, may be operating under voluntary control. Although visual imagery varies in some ways from immediate visual perception, the similarities found, between the drawing and imagery modalities, on the one hand, and the perceptual and memory modalities, on the other hand, suggest that they share some common underlying processes.


Chest radiography in the management of breast cancer.

This study was undertaken to assess the utility of chest radiography (CXR) in the management of patients with breast cancer and to devise a suitable imaging policy for such patients. A retrospective analysis was performed of the case notes and the CXRs of a series of 141 patients presenting to this hospital in 1980 with a diagnosis of early breast cancer. Data retrieved covered the entire clinical course to date and included the number of CXRs performed for a clinical reason and the number performed as "routine". Correlation of the result of every CXR requested to subsequent therapeutic decision-making throughout the complete clinical course of each patient was undertaken and the proportion of CXRs initiating a management change, or performed for a clinical reason, out of the total requested was assessed. A total of 1161 CXRs were performed on the 141 patients studied. Of these, only 174 (15%) were undertaken for a direct clinical reason and 987 (85%) were undertaken as part of "routine" follow-up procedures and had no impact on patient management. Four "routine" CXRs (< 0.4%) demonstrated previously undiagnosed pulmonary metastases, in patients with no other history of metastatic disease. Thus, routine chest radiography is not a cost-effective method of monitoring asymptomatic patients with breast cancer for metastasis. It is recommended that outside staging procedures for clinical trials, the CXR is used only to address a clinical problem relating specifically to the thorax. It is anticipated that the cessation of all other chest radiography in patients being followed up for breast cancer at this institution will have significant budgetary implications.


The dependence of the scattered radiation dose to personnel on technique factors in diagnostic radiology.

The measurement and prediction of scattered radiation dose to staff in diagnostic radiology is particularly important, owing to the increased use and complexity of interventional radiology. The air kerma-area product and scattered radiation dose in the vicinity of the patient couch, for both overcouch and undercouch X-ray tube geometries, were simultaneously monitored. The scattered radiation distribution at the couchside was deduced at a range of tube potentials for both overcouch and undercouch X-ray tube geometries. The variation of scattered radiation with field size on both geometries was investigated, as well as the variation with focus-table distance on an overcouch tube geometry. It was discovered that the scattered radiation dose at a point correlated with the air kerma-area product and the result may be used for radiation protection purposes. A method of predicting the scattered radiation dose at a given position is described.


Improved image quality for dense breasts in mammography.

Within the UK breast scanning age range of 50-65 years, about 15% of breasts show a dense structure that is underexposed in conventional mammography. This gives rise to a severe reduction in contrast. Methods of improving this contrast by variation of exposure factors are explored, using a Dupont phantom that has a simulated dense breast structure. Results are assessed by considering measured contrast from a Perspex stepwedge, and by obtaining relative scores, on a scale of 1-10, from 15 radiologists involved in mammography. It is concluded from both these methods that approximately doubling the mAs at the normal kV is preferable to increasing the kV by more than a small amount. A modified mammographic technique on these lines could be valuable in selected cases where a previous conventional mammogram was available, i.e. assessment stage or repeat screening in a screening programme, or symptomatic patients. Practical problems in choosing exposure factors and the magnitude and implications of the increased dose are discussed.


A standardized multifield irradiation technique for breast tumours using asymmetrical collimators and beam angulation.

Combined angulation and asymmetrical collimator matching techniques are used for field alignment in breast irradiation. A local regional irradiation technique has been developed that allows a uniform dose distribution to the entire target volume. The localization is characterized by simple measurement of a few patient co-ordinates. The equipment settings to produce a theoretical exact field alignment are calculated by a special computer program. These settings guide the simulation. We have designed the method such that the technique is standardized for all patients receiving breast and lymph node irradiation. This allows an easy, accurate and fast patient throughput at the simulator and accelerators.


The labelling index in carcinoma of the uterine cervix: its correlation with tumour sterilization.

The pre-treatment labelling index (LI) was measured in 72 patients with carcinoma of the cervix. It was not correlated with patient age, stage of the disease or histological grade. 46 patients underwent hysterectomy after intracavitary irradiation with or without external radiotherapy. The mean LI in patients with tumour sterilization or microscopic residue was significantly higher than in patients with gross disease. These results suggest that tumours with low LI may be difficult to sterilize with conventional therapeutic measures, or that doomed cells may require several weeks to be eliminated in tumours with low LI.


Percutaneous removal of retained intrahepatic stones with a pre-shaped angulated catheter: review of 96 patients.

Intrahepatic biliary stone disease is prevalent in East Asia and there is a high frequency of retained intrahepatic stones after surgical treatment. Percutaneous removal of retained intrahepatic stones with a pre-shaped angulated catheter and a Dormier basket was attempted in a group of 96 patients who had a T-tube. Seventy-six had multiple intrahepatic stones, confined to one hepatic lobe in 52 patients. Stones were exclusively intrahepatic in 68 cases. Biliary strictures were present in 92 cases (95.8%). A combination of techniques was used including pre-shaped angulated catheters, irrigation suction, balloon dilatation of strictures, crushing of large stones and extracorporeal shockwave lithotripsy. Retained stones were completely removed in 48 cases, and incompletely removed in 22 cases. The overall success rate was 72.9%. There were only minor complications. No mortality or significant morbidity requiring hospitalization occurred. Angular deformity, stricture of bile ducts and impacted stones were the most frequent factors responsible for failure or incomplete removal of retained stones. Fluoroscopically guided percutaneous interventional procedures with a pre-shaped angulated catheter are useful complementary procedures to surgery for patients with intrahepatic stones. The major benefits of an individually angulated catheter are safety and easy access to small peripheral bile ducts.


Surgical management of renal carcinoma with extensive involvement of the vena cava and right atrium.

Between 1988 and 1990, 8 patients with a renal tumour extending into the vena cava and with supradiaphragmatic extension were treated by an operative technique involving extracorporeal circulation and deep hypothermic circulatory arrest. In 4 patients the thrombus extended into the right atrium. Six patients appeared to have a renal carcinoma. Intra-operatively one patient's tumour proved to be a metastasis of a squamous cell carcinoma of the lung and another patient was found post-operatively to have a leiomyosarcoma of the vena cava. Two of these 6 patients died from metastases 6 weeks and 8 months post-operatively. Four patients are symptom-free, although 3 of them have liver or lung metastases 10, 20 and 37 months post-operatively. One has no evidence of disease 18 months post-operatively. The use of extracorporeal circulation and deep hypothermic circulatory arrest provides optimal surgical exposure and gives the patients a considerable complaint-free interval post-operatively. How often cure is also achieved is as yet unclear.


Extracorporeal shock wave lithotripsy of ureteric stones with the Modulith SL 20.

A series of 138 patients with ureteric calculi was treated by in situ extracorporeal shock wave lithotripsy (ESWL) during the clinical introduction of the Modulith SL 20. This machine represents a newly developed lithotriptor with an electromagnetic cylinder as shock wave source and a dual localisation system consisting of in-line ultrasound and an integrated fluoroscope C-arm. During the first 2 months, 12 patients (phase 1) were treated under ultrasound localisation alone; during the next 5 months, 37 patients (phase 2) were treated using dual imaging modalities with reduced peak pressure (max. 18 kV = 800 bar); during the final 7 months, 89 patients (phase 3) were treated under ultrasonic and fluoroscopic localisation combined with an increased maximal shock wave pressure (20 kV = 1024 bar). The introduction of fluoroscopic targeting (phases 2 and 3) resulted in satisfactory localisation of calculi in the mid-ureter, previously limited by use of only coaxial ultrasound. The extension of stone localisation to the whole length of the ureter was associated with a marked decrease in treatment time, reflecting the easy handling of the dual localisation system. The rise in generator voltage (phase 3) improved the disintegration rate from 81% (phase 2) to 85%, whereas the number of impulses remained unchanged. However, the rate of auxiliary procedures following ESWL (adjuvant and curative) was reduced from 33% (phase 2) to 24.5%. Thus the Modulith SL 20 in its final design enables in situ ESWL to be the treatment of choice for all ureteric calculi, rendering special positioning techniques or multiple treatment unnecessary.


Extracorporeal lithotripsy of ureteric calculi using the Dornier HM-3 lithotriptor.

Over a 5-year period (November 1984-November 1989), we treated 356 patients with ureteric calculi; 170 were treated by extracorporeal shock wave lithotripsy (ESWL) on a Dornier HM-3 lithotriptor. The calculi (n = 176) were uniformly distributed along the length of the ureter: 44 were just below the pelviureteric junction, 59 were lumbo-iliac, 42 were in the upper bony pelvis and 32 in the lower bony pelvis. The mean diameter of the upper ureteric calculi was 10 mm and for the others it was 8 mm. Thirty-four patients with acute obstructive pyelonephritis required pre-ESWL drainage of the urine. X-ray localisation required intravenous urography during lithotripsy in 52 cases (30%). On plain X-ray the following day 170 stones (96%) were judged to have disintegrated. The 6 patients whose stones were not fragmented received further treatment (ureterotomy (4) and ureteroscopy (2)). Five patients required additional treatment because of pain or fever (catheterisation (3) and ureterotomy (2)) and 2 patients had a second lithotripsy owing to insufficient fragmentation. Four patients were lost to follow-up. In 153 patients (90%) the fragments were eliminated completely, 146 in the first month and the remainder before the sixth month. No serious sequelae were observed. In addition to the 5 patients who required supplementary treatment. 11 patients with pain or fever needed medical treatment. We recommend first intention in situ ESWL for all ureteric calculi.


Assessment of the use of bladder washouts/instillations in patients with long-term indwelling catheters.

A randomised cross-over study of 3 bladder washout treatments--saline, Suby G and Solution R--was conducted on 25 elderly females with long-term catheters in order to examine crystal formation and catheter encrustation. With 2 exceptions, all patients produced crystals; only 14 completed the study. While a significant reduction in struvite crystals was found in the returned acidic washout fluid, there was no significant reduction of crystals in the neutral (saline) washout following any of the 3-week periods of treatment. Uric acid crystals appeared with Suby G and Solution R and these solutions were associated with higher red cell deposits in the urine. There was no significant difference in catheter encrustation between the various washouts.


Morphological effects of photodynamic therapy on rabbit bladder using Photofrin II and Photosan intravesically and intravenously.

Photodynamic therapy (PDT) has proved effective against superficial papillary bladder tumours and focal and diffuse carcinoma in situ. Effective topical administration of the sensitiser would be a welcome improvement. The morphological effects of PDT on the normal bladder were examined in 13 rabbits when 2 photosensitisers (Photofrin II and Photosan III) were applied intravesically (5 mg/kg for 1 h) and compared with intravenous administration (3 or 5 mg/kg). Four animals served as controls without a sensitiser. Intravesical red light (630 nm) from an argon dye laser was used to activate the photosensitiser, using light doses of 12 or 24 J/cm2. The animals were sacrificed either 1 or 5 to 7 days after the laser treatment. Intravenous dosage induced bladder wall oedema/haemorrhage and total necrosis of the epithelium. There was no difference between the effects of the 2 sensitisers. Intravesical application induced superficial epithelial necrosis. The control animals treated with laser light alone showed slight superficial injury to the cell layer.


The value of nuclear area as a prognostic factor in T1 papillary transitional cell carcinoma of the bladder.

In a series of 131 T1 papillary transitional cell carcinomas of the bladder, the nuclear areas of 100 nuclei (50 from the external papillary zone and 50 from the internal papillary zone) were measured. An attempt was made to correlate retrospectively the value of the mean nuclear area with histological grade and with survival. A higher value was obtained for the mean nuclear area of the internal papillary zone than for that of the external papillary zone. A better survival rate was found after 10 years' follow-up for those tumours whose mean nuclear area in the internal papillary zone was < or = 28 microns2, which suggests that it is in this zone that the nuclear area should be measured. A correlation was observed between the increase in the mean nuclear area value and higher histological grade.


Prognostic correlation of morphometric values with survival in invasive transitional cell carcinoma of the bladder.

A morphometric study was made of 95 invasive bladder tumours, differentiating 34 papillary and 61 solid carcinomas. In the invasive papillary tumours, the deeper the zone of the tumour measured, the higher the value of the mean nuclear area. A higher histological grade was also seen to correspond to a higher mean nuclear area value except for Grade IV tumours, whose nuclear area was no larger than that for Grade III tumours. This led us to separate Grade IV tumours from transitional cell carcinomas and classify them as undifferentiated. A better prognosis was found for those tumours whose mean nuclear area was < or = 30 microns2 in category T2. For T3 and T4A tumours no conclusive results were obtained in this respect.


Clinical information system that enhances the use of resources in endoscopic prostatic procedures.

In this study we evaluated, by means of an automated management system, the identification of subgroups of patients within certain operative categories whose predictable length of stay was compatible with treatment on a 5-day ward. This was achieved by using a computer directed analysis of urological workload on prospectively collected clinical data. Graphical presentation of the results was achieved by a technique known as the patient-bed dissociation curve. Patients with bladder outflow obstruction treated by transurethral prostatic resection (701) and bladder neck incision (113) were selected from a total of 7,162 hospital admissions. The main outcome measures were length of stay and complication rates for the 2 procedures. The results demonstrated that a group of patients about to undergo transurethral resection could be selected by age and source which would indicate an 18% greater probability of discharge within 5 days. These patients were easily identifiable in advance and would be suitable for treatment on a 5-day ward. It was concluded that computer-held clinical data were easily accessible to the surgeon. The process of detailed analysis need not take time. With properly directed studies the information retrieved could be used to effect change. The patient-bed dissociation curve may prove a valuable tool in examining and comparing discharge patterns in any groups of patients.


Phase II study of epirubicin in advanced hormone-resistant prostatic carcinoma.

Twenty-nine patients with metastatic prostate cancer that had progressed following orchiectomy were treated with intravenous epirubicin 90 mg/m2 every 28 days. Their median age was 71 years (range 49-78) and the median Zubrod scale (WHO score) was 1. Two patients had soft tissue lesions, 20 had bone metastases and 7 had both. Tumour response was assessed according to the National Prostatic Cancer Project criteria. Of 29 patients, 11 (38%) achieved a partial remission. The median duration of response was 6 months and the median survival time of all patients was 9 months (range 2-27). It seemed that treatment with epirubicin was not associated with an increase in survival. Toxicity was moderate and consisted of alopecia and mild nausea/vomiting. There was no significant haematological toxicity and no clinical cardiotoxicity. It was concluded that epirubicin was active in hormone-resistant metastatic prostate cancer in approximately 33% of the patients.


The treatment of Peyronie's disease with tamoxifen.

This is a preliminary study of the treatment of 36 patients with Peyronie's disease who received tamoxifen 20 mg twice daily for 3 months. An improvement occurred in 16 of 20 patients with penile pain, in 11 of 31 patients with an erectile deformity and 12 of 35 patients had a plaque shrinkage of at least 1 cm. Some improvement occurred in 6 of the 8 patients with a histologically confirmed inflammatory infiltrate of the plaque but not in any of the 4 patients without an infiltrate. The inflammatory infiltrate was found in patients in whom the duration of the disease was less than 4 months.


A new vacuum device as alternative treatment for impotence.

Vacuum erection devices are an acceptable alternative for the management of erectile dysfunction. The safety of such devices has been questioned because of their effects on penile blood flow. We report the use of Doppler ultrasonography to assess arterial flow and its value in ensuring long-term safety of a new external vacuum device. Sixteen patients were studied. At 3 months it was possible to confirm the efficacy and safety of the method and model in 14 patients, 12 of whom had a significant improvement in their sexual function. By 10 months, only 6 were continuing to use the device. Doppler sonography appears to be an effective technique for assessing penile blood flow during restriction from a vacuum device. The new vacuum device provides a satisfactory short-term alternative to other more invasive forms of therapy.


Instillation of silver nitrate in the treatment of chyluria.

A series of 62 patients with chyluria received instillations of 1% silver nitrate in the renal pelvis over an 8-year period; 51 patients responded well but 11 showed no response to treatment. Follow-up ranged from 2 to 7 years. The treatment was found to be safe, effective and minimally invasive.


Continent cutaneous diversions in children: experience with the Mitrofanoff procedure.

Continent cutaneous diversions with a urinary reservoir emptied by clean intermittent self-catheterisation (CISC) using a non-refluxing conduit--the Mitrofanoff principle--were carried out in 10 children. Their age range was 3.9 to 17.1 years (average 12.2). The underlying diagnoses were ectopia vesicae (7), myelodysplasia (2) and a cervical cord injury secondary to birth trauma (1). The indications were incontinence secondary to poor bladder neck resistance in 8 children and an inaccessible urethral orifice in 2. The catheterising conduits used were the appendix in 9 and a vascularised gastric tube in 1. Eight children are bone-dry with CISC. Another child needed a reoperation following dehiscence of her bladder neck closure. The other child has an intact bladder neck and urethra and occasionally leaks overnight. Mitrofanoff diversions are a reliable means of continence with CISC. This means of urinary diversion can be permanent or temporary in children who cannot or will not catheterise urethrally. Elective appendicectomy in children with potential urinary incontinence or complicated urogenital anomalies is not recommended.


Epispadias surgery--Belgrade experience.

From 1987 to 1991, 46 patients underwent surgical treatment for epispadias. Of these, 14 had isolated epispadias and 22 had epispadias within the exstrophy/epispadias complex. The patients ranged in age from 6 months to 20 years. To correct the genital aspect of the anomaly the basic principles of Ransley's technique were used. In addition, the island flap technique was used for the most severe, so-called "cripple" form. In patients with exstrophy/epispadias complex, only elongation of the penis was performed during primary reconstruction, while the correction of epispadias, using the above techniques, was performed in the second-stage operation. Complications occurred in 6 patients.


Bladder exstrophy and anterior pelvic osteotomy.

Between August 1988 and December 1991, 36 children with bladder exstrophy underwent surgery for primary bladder reconstruction. Each child was either untreated or had already been treated unsuccessfully. The operative technique involved bilateral osteotomy of the superior ramus of the pubic bone. In infants the cartilaginous ischiopubic junction, acting as an articulation, allowed symphyseal approximation, while in older children this was achieved by fracture of the inferior ramus of the pubic bone. The bladder was either closed or, in most cases, the exstrophic bladder plate was inserted deep into the pelvis, allowing subsequent epithelialisation of the bladder and further formation and growth. Follow-up up for 3.5 years showed bladder capacities of 40 to 150 ml. Some patients underwent an additional augmentation enterocystoplasty. Primary bladder reconstruction remained uncompromised in 7 patients who developed moderate (and 1 complete) rediastasis of the pubic bones. All exstrophic bladders are reconstructible, particularly in older children.


Results of surgical treatment in children with bladder exstrophy.

A series of 42 children (30 boys and 12 girls) underwent surgery for bladder exstrophy between 1972 and 1989. Primary bladder closure was performed in 11 patients and was successful in 6. Four of these children are about 2 years old and so it is not yet possible to assess their continence. Ureterosigmoidostomy was performed in 35 children, one of whom was converted to cutaneous ureterostomy. Follow-up ranges from 2 to 20 years (average 9 years 3 months) and 50% of the patients are symptom-free. The most frequent problems were acidosis and urinary tract dilatation. Other complications, such as hypokalaemia and pyelonephritis, were seldom seen. Although ureterosigmoidostomy has some disadvantages, our patients have adapted well and lead a normal life.


Prosthetic vascular graft infection.

The aetiology, diagnosis and management of prosthetic vascular graft infection are reviewed. The importance of contamination at the time of surgery as the crucial aetiological factor is highlighted. Staphylococcus epidermidis is the causative organism in over 50 per cent of cases and the reasons for this are explored. Sound surgical technique, use of prophylactic antibiotics and the avoidance of a groin incision are emphasized as the most important factors in prevention of graft infection. Difficulties of diagnosis are highlighted and the diagnostic role of various imaging methods is assessed. Graft excision with extra-anatomic revascularization is presented as the conventional surgical solution, while the roles of less radical surgical solutions and non-operative management are discussed.


Metastasectomy.

The literature on metastasectomy abounds in anecdote and retrospective studies of non-randomized patients. In this paper, the published evidence concerning the efficacy of metastasectomy in the lung, liver, brain, gastrointestinal tract and omentum is reviewed to formulate practical recommendations for patient selection and treatment. At some sites metastasectomy can be recommended with little hesitation for more widespread application, but surgery for liver metastases should still be regarded with some reservation.


Mechanical properties of the aneurysmal aorta.

The mechanical properties of the abdominal aorta were investigated non-invasively in 30 patients with aortic aneurysm and 11 with peripheral arterial disease. The distensibility of the aorta was measured using M-mode ultrasonography, permitting non-invasive assessment of the pressure--strain elastic modulus or aortic stiffness, Ep. The median Ep value increased from 4.0 N/cm2 in control subjects in their third decade of life (n = 10) to 10.4 N/cm2 in middle age (n = 11) to 14.0 N/cm2 in the elderly (n = 13). In the presence of a normal diameter, peripheral arterial disease with aortic atherosclerosis had little effect on aortic stiffness, median Ep being 16.0 N/cm2. Aneurysmal dilatation was associated with a significant increase in aortic stiffness, median Ep being 31.3 N/cm2 (P < 0.001). For aortas of normal diameter, Ep was at all ages dependent on mean arterial pressure. In patients with aortic aneurysms there was no clear relationship between Ep and mean arterial pressure or aortic diameter. Of the patients studied, 15 underwent aortic reconstruction; increasing aortic stiffness (log Ep) was associated with a decreased medial elastin content of the aortic biopsy (r = -0.63, P < 0.02). This study demonstrates the marked stiffness or inelasticity of dilated or aneurysmal vessels, part of which is attributable to the loss of elastin.


Long-term reduction of intimal hyperplasia by the selective alpha-1 adrenergic antagonist doxazosin.

Studies have shown that alpha 1-adrenergic blockade reduces intimal hyperplasia in the rabbit aorta. In this study a selective alpha 1-adrenergic antagonist, doxazosin, has been used to examine whether this effect is persistent and dose dependent. Forty-eight New Zealand White rabbits underwent endothelial denudation of the abdominal aorta using a Fogarty balloon catheter. Test rabbits were given low-dose (2 mg) or high-dose (8 mg) doxazosin daily and all animals killed at either 1 or 12 weeks after the procedure. The aortas were harvested after fixation in situ with 4 per cent glutaraldehyde and neointimal hyperplasia was measured, using an x-y digitizer, as the percentage reduction in luminal cross-sectional area. At 1 week after surgery, rabbits receiving the low dose had a median area reduction of 7.7 per cent and those receiving the high dose a reduction of 8.2 per cent; both had significantly less intimal hyperplasia than control rabbits, which had a median area reduction of 14.8 per cent (P < 0.01). However, at 12 weeks, when compared with the 32.6 per cent reduction in the control group, only those rabbits receiving high-dose doxazosin had significantly less intimal hyperplasia, with a reduction of 5.5 per cent (P < 0.001). It is concluded that selective alpha 1-adrenergic blockade significantly reduces neointimal hyperplasia, that this effect is dose dependent, and that it persists for at least 3 months.


Effect of free radical scavenging on skeletal muscle blood flow during postischaemic reperfusion.

After 6-h tourniquet ischaemia of one hindlimb in male Sprague-Dawley rats, gastrocnemius muscle blood flow was measured following 10, 120 and 240 min of reperfusion using radiolabelled microspheres. A perfusion index was calculated (experimental limb: contralateral limb) for each of these times. Comparison of perfusion indices in ten control animals (6 h ischaemia, 4 h reperfusion) with similar measurements in ten normal rats with no ischaemia and in ten ischaemic animals with the tourniquet in situ demonstrated low median (interquartile range (i.q.r.)) reflow after 10 min (control 0.12 (0.02-0.43), ischaemia 0.04 (0.00-0.07), normal 1.05 (0.68-1.18); control versus ischaemia, P not significant; control versus normal, P < 0.01). Relative reperfusion occurred at 120 min (control 0.48 (0.11-0.70), ischaemia 0.02 (0.01-0.07), normal 0.97 (0.79-1.13); control versus ischaemia, P < 0.05; control versus normal, P < 0.05) and reperfusion injury after 240 min of revascularization, with muscle blood flow being little different from that in the ischaemic group (control 0.05 (0.01-0.38), ischaemia 0.03 (0.00-0.07), normal 1.01 (0.73-1.16); control versus ischaemia, P not significant; control versus normal, P < 0.01). Two groups of 12 rats were given either intravenous superoxide dismutase and catalase or dimethylthiourea 30 min before tourniquet release, continuing throughout the period of reperfusion. Superoxide dismutase and catalase reversed low reflow, producing a median (i.q.r.) perfusion index of 0.94 (0.54-1.12) (P < 0.01 versus control, P not significant versus normal), but had no effect on relative reperfusion (0.66 (0.42-1.01), P not significant versus control) or on reperfusion injury (0.27 (0.01-0.35), P not significant versus control). In contrast, dimethylthiourea had no effect on perfusion at either 10 min (0.10 (0.03-0.15), P not significant versus control) or 240 min (0.04 (0.00-0.11), P not significant versus control), but abolished the phase of relative reperfusion at 120 min (0.04 (0.02-0.21), P < 0.01 versus control). These results indicate that, although superoxide radicals are harmful during postischaemic reperfusion, hydroxyl radicals may be beneficial.


Comparison of POSSUM with APACHE II for prediction of outcome from a surgical high-dependency unit.

POSSUM and APACHE II scores from 117 consecutive admissions to a high-dependency unit after major surgery were correlated with 30-day morbidity and mortality rates. Thirteen patients (11 per cent) died and 59 (50 per cent) developed a postoperative complication. Receiver-operating characteristic curve analysis showed POSSUM to have good predictive value for mortality (area under curve 0.75) and morbidity (area under curve 0.82). APACHE II scores had a significantly inferior predictive value for mortality (area under curve 0.54) (P < 0.002). POSSUM was superior to APACHE II in prediction of mortality in patients admitted to a high-dependency unit after general surgery. Prediction of postoperative complications by POSSUM is accurate and may be useful for audit.


Autopsy analysis in surgical patients: a basis for clinical audit.

An autopsy study was performed to quantify diagnostic fallibility in clinical surgery. Autopsy results in 312 surgical patients were compared with clinical findings. The primary clinical diagnosis was correct in 93 per cent of patients; complications had been correctly diagnosed in 60 per cent and error in treatment was found in 16 per cent. Error in treatment had an adverse impact on the course of disease in 11 per cent of patients. Infective complications such as abdominal sepsis and bronchopneumonia were encountered most often. Sensitivity was low for the clinical diagnosis of pulmonary embolism, bronchopneumonia, myocardial infarction and terminal haemorrhage. Statistical analysis showed that sudden unexpected death is the most obvious condition in which a high yield is expected from a post-mortem examination. Autopsy remains a valuable means of quality control in clinical surgery and could be a basis for surgical audit.


Circadian variation in unexpected postoperative death.

Unexpected deaths still occur following major surgical procedures. The cause is often unknown but may be cardiac or thromboembolic in nature. Postoperative ischaemia, infarction and sudden cardiac death may be triggered by episodic or constant arterial hypoxaemia, which increases during the night. This study examined the circadian variation of sudden unexpected death following abdominal surgery between 1985 and 1989 inclusive. Deaths were divided into those occurring during the day (08.00-16.00 hours), evening (16.00-24.00 hours) and night (24.00-08.00 hours). Twenty-three deaths were considered to have been totally unexpected. Of 16 such patients undergoing autopsy, pulmonary embolism was the cause of death in five. In the remaining 11 patients, death occurred at night in eight (P < 0.005). Five of the seven patients without an autopsy died at night (P < 0.04); overall, 13 of 18 unexpected deaths occurred at night-time. These results suggest a need for further studies of sleep- and respiration-related effects on postoperative nocturnal cardiac function. The efficacy of monitoring during this apparent high-risk period should be evaluated.


Traumatic amputation by explosive blast: pattern of injury in survivors.

Explosive blast causes a pattern of injury including primary blast lung, secondary fragment injury and traumatic amputation of limbs. Major traumatic amputation is rare in survivors of bomb blast but common in those who die. The mechanism of such injury has not been previously determined, but must be established if protective measures are to be developed for members of the armed forces. The nature of 41 traumatic amputations in 29 servicemen who survived to reach medical care after blast injury was investigated to determine the anatomical level of amputation and the pattern of soft tissue damage. Joints were an infrequent site of amputation and the tibial tuberosity was a particularly frequent site of lower-limb severance. Comparison of the pattern of injury was made with that seen in ejecting fast-jet pilots, who frequently suffer major flailing injury; there appears to be a substantially different injury distribution. The accepted mechanism of traumatic amputation, avulsion by the dynamic overpressure, is challenged; it is suggested that the shockwave resulting from an explosion is capable of causing at least bone disruption in a limb.


Management of Gulf War casualties.

During the Gulf War 84 patients underwent surgery in the Jubail Armed Forces Hospital, Saudi Arabia. The median time to evacuate casualties to hospital was 8 h 40 min. Fragments caused 88 per cent of injuries; 11 per cent were caused by bullets. Multiple lesions were encountered in 70 per cent of patients. The extremities (76 per cent) were the most frequently injured site, the lower limbs more so than the upper. Soft tissue injuries prevailed (59 per cent).


Tumour oestrogen receptor content allows selection of elderly patients with breast cancer for conservative tamoxifen treatment.

Immunocytochemical analysis was used to determine tumour oestrogen receptor (ER) content in elderly patients with primary operable breast cancer. Only those ER positive were selected for conservative treatment with tamoxifen alone. Initial response was compared with that of historical controls not selected according to ER status. Early progressive disease was markedly reduced at 6 months, from 30 per cent in the unselected control group to 2 per cent in the study group (P < 0.001). Immunocytochemical analysis is useful for the initial selection of elderly patients with breast cancer who may be treated with tamoxifen alone.


Indications for primary tamoxifen therapy in elderly women with breast cancer.

A group of 66 elderly women with primary breast cancer were treated with tamoxifen and followed for a minimum of 2 years. Of these, 32 whose disease remained controlled for the 2-year period were considered to have had a 'worthwhile' response, 27 in whom disease progressed were considered to have had an unsatisfactory result and seven opted for alternative treatment. By Union Internacional Contra la Cancrum (UICC) criteria, 14 women had a complete response, 20 a partial response, in five disease remained static and in 20 it progressed without response. Prediction of outcome after assessment according to UICC criteria at 3 and 6 months was unsatisfactory (19 and 34 of 59 correctly predicted respectively). Analysis of multiple tumour measurements over 12 weeks was no better (33 of 59 correctly predicted). Immunocytochemical assay of fine-needle aspirates for oestrogen receptor (ER) provided a better predictor (38 of 47 correct) and the difference in survival between patients with and without ER activity was significant (P < 0.001). Conventional assessments of response at 3 and 6 months are unsatisfactory for judging the long-term benefit to the patient. ER status is the best predictor of response and outcome.


Autotransplantation of splenic tissue in an isolated segment of small intestine.

The ability of splenic tissue to regenerate when implanted in an isolated segment of small intestine with intact circulation was studied in six pigs. After total splenectomy, 10 per cent of the weight of the spleen was implanted in a 10-15-cm long isolated segment of small intestine with an intact vascular supply. Bowel continuity was established by end-to-end anastomosis. Before implantation, the mucosal layer was completely removed from the isolated segment of the small intestine. The animals were killed 6 months later and the isolated segment of small bowel containing the splenic tissue identified. Most of the implanted splenic tissue was recovered in the isolated segment of small intestine; the weight ranged from 43 to 120 (mean 80) per cent of that of the implanted tissue. An isolated segment of small intestine with an intact circulation produces a higher index of regeneration than other previously reported sites.


Prospective study in adults of splenic preservation after traumatic rupture.

Seventy-five adults with splenic injury were evaluated prospectively over 45 months to examine the possibility of splenic preservation. Haemodynamically unstable patients underwent surgery with the intent of splenic preservation. Stable patients received non-operative treatment regardless of the grade of splenic injury determined by ultrasonography and computed tomography. Thirty-seven patients required splenectomy and in 38 the organ was preserved (20 operative preservation, 18 non-operative treatment). Of 22 patients initially receiving non-operative treatment, there were four secondary haemorrhages after 7, 7, 10 and 13 days making surgery necessary. Three of these patients underwent splenectomy and in one the spleen was preserved by partial resection. After splenectomy four patients required reoperation because of rebleeding or for evacuation of a haematoma. Patients who had undergone splenectomy had a significantly increased infection rate (P < 0.005) compared with those in whom the spleen was preserved, even when patients were matched with respect to multiple trauma using the Injury Severity Score (P < 0.01).


Ascaris-induced acute pancreatitis.

The incidence, clinical disease and outcome of acute pancreatitis caused by ascariasis in an endemic area of Kashmir, India, was studied prospectively. Ascariasis was an aetiological factor in 59 of 256 patients (23.0 per cent) with acute pancreatitis. Worms had invaded the bile duct in 51 patients, the pancreatic duct in four and both ducts in four. Pancreatitis was mild in 46 patients and severe in 13. Associated pyogenic cholangitis was present in eight. Acute complications occurred in 11 patients. Endoscopic retrograde cholangiopancreatography (ERCP) was performed in all cases within 72 h of admission and delineated ascarides in the duodenum invading the ampullary orifice (44 patients), in the bile duct (55) and in the pancreatic duct (eight). At ERCP, worms were extracted from the ampullary orifice and removed via the mouth of 33 patients with intractable epigastric pain, leading to rapid relief of symptoms. The eight patients with pyogenic cholangitis underwent endoscopic nasobiliary drainage to decompress the bile ducts; worms were extracted from the bile duct of three of these patients using a Dormia basket. A total of 56 patients recovered from acute illness with a combination of conservative and endoscopic treatment; the other three required emergency surgery. At a mean(s.d.) follow-up of 19(7) months, ten patients showed symptomatic worm reinvasion of the biliary tree. The overall mortality rate was 3 per cent.


Endoscopic management of postoperative bile leaks.

Thirty-two patients aged 15-89 years developed postoperative bile leakage. Twenty-eight had undergone cholecystectomy, with choledocholithotomy in 11, and four had had miscellaneous operations. Endoscopic retrograde cholangiopancreatography (ERCP) was performed 2-75 days after operation and revealed leakage from the cystic duct stump in 19 cases, from a T tube track in five, from the gallbladder and liver abscess cavity in two and from the major bile ducts in six. Major bile duct lesions were not generally amenable to endoscopic treatment, but the remaining 26 patients were treated successfully with internal stenting (22) or endoscopic sphincterotomy (four); bile secretion in all cases stopped within 1 week. One patient with cholangitis after an ERCP procedure was managed by antibiotics; no other complication occurred and there were no deaths related to the procedure. ERCP procedures are well tolerated in the postoperative period and may be performed under sedation. ERCP is the method of choice for dealing with bile leakage and ERCP procedures are effective for the most common causes of postoperative bile leakage; complications are rare.


Role of endoscopic retrograde cholangiopancreatography in the investigation of pain after cholecystectomy.

Patients who continue to have or who develop abdominal pain after apparently successful cholecystectomy pose diagnostic difficulties. This study reports 384 such patients, investigated by endoscopic retrograde cholangiopancreatography (ERCP). There were 146 patients with abdominal pain alone with no previous history of common bile duct (CBD) exploration, of whom only 17 (11.6 per cent) had CBD stones on ERCP. Bile duct calculi were present in 76 of 140 patients (54.3 per cent) with abnormal biochemical findings (raised alkaline phosphatase and/or amylase level) and in 34 of 57 (60 per cent) with an abnormality detected on ultrasonography or intravenous cholangiography. A combination of biochemical and radiological abnormalities was present in 37 patients and was associated with CBD stones in 28 (76 per cent). Patients who had undergone CBD exploration represented a special group, of whom the majority (75 per cent) had common duct stones at ERCP even in the absence of biochemical and radiological abnormalities. ERCP is a useful investigation in patients with persistent postcholecystectomy symptoms. Other features in addition to pain or a history of CBD exploration may be relevant to the decision to perform ERCP in the investigation of these patients.


Common bile duct diameter and complications of endoscopic sphincterotomy.

To assess the relationship between distal common bile duct (CBD) diameter and the incidence of an immediate complication following endoscopic sphincterotomy (ES), all patients undergoing ES between January 1986 and October 1990 were studied. The overall risk of an immediate complication following ES in 655 patients was 5.6 per cent (37 patients). Patients with calculi were at greater risk if the distal CBD was dilated (P < 0.001); the complication in those with stones was most likely to be haemorrhage (81 per cent). The relative risk of a complication increased ten times if the distal bile duct diameter was > 0.8 cm. Patients with stricture of the distal CBD did not have a significantly greater risk of complication than those with stones (9.7 versus 4.9 per cent). There was no significant difference between the mean distal CBD diameter of those with stricture and controls (0.61 versus 0.44 cm).