[Does magnetic resonance imaging allow the assessment of the loco-regional extension of cancer of the prostate? Report of 27 anatomo-radiologic comparisons]. 27 patients with histologically proven prostatic carcinoma were investigated by magnetic resonance imaging (MRI) (0.5 Tesla) in order to determine the local spread of the cancer. These patients then underwent ilio-obturator lymph node dissection with frozen section examination, followed by radical prostatectomy. Histological examination of the resection specimens was performed on slides prepared from large transverse sections every 5 mn. The MRI examination was especially designed to confirm the diagnosis of capsular effraction based on the signals of the periprostatic fat (PF), periprostatic venous plexuses (PVP) and seminal vesicles (SV). An abnormality of at least one of these structures was considered to indicate the diagnosis of capsular effraction. The MRI data were compared to the histological findings. The results demonstrated a sensitivity of 62% for the PF signal, 52% for the PVP signal and 40% for the SV signal. The overall MRI-Histology correlation was found to be exact in 23 out of 27 cases (Accuracy = 85%). All of our four errors represented understaging (Sensitivity = 81%). When a rigorous methodology is respected, the high accuracy and sensitivity of MRI makes this modality an investigation of choice for the study of the prostatic capsule, as part of the routine staging of prostatic cancer. It should allow a better selection of patients with intracapsular cancer (T1-2), who constitute candidates for radical treatment.


[Color doppler echography in the exploration of vasculogenic impotence]. 102 patients with suspected vasculogenic impotence were evaluated with color doppler sonography. Measurement of normal systolic and diastolic velocities were obtained from the cavernosal arteries of patients responding by a full erection after intra-cavernosal injection of 20 mg of Papaverine. A correlation with cavernosometry was obtained in 61 patients and with selective internal pudendal arteriography in 11. The 10 patients with abnormal arteriograms had a systolic velocity < 25 cm/sec. 13 out of the 15 patients with an end diastolic velocity > 5 cm/sec had a venous leak defined by a maintenance flow rate of erection during cavernosometry > 25 ml/mn. End diastolic velocity is an excellent index of the function of the veno-occlusive system, provided the systolic velocity remains at a normal value. In case of arterial insufficiency, a diastolic flow < 5 cm/sec is of no value and cavernometry is mandatory to detect a mixed arterio-venous impotence. The addition of color doppler sonography permitted a more rapid detection of vessels and an easily reproducible measurement of velocities which makes color doppler sonography an excellent screening test for examining patients with potential vasculogenic impotence.


[Electrophoretic study of the protein composition of human seminal vesicle secretion]. The SDS-PAGE and two-dimensional reductived electrophoretic study of the liquid aspirated from human seminal vesicles showed that this medium contains high molecular weight proteins (greater than 150 kDa). In addition to these high molecular weight proteins, native seminal vesicle secretion is characterised by the presence of a large 47.4 kDa protein band corresponding to seminogelin, described by Lilja. The high molecular weight proteins actually correspond to associations of three types of protein subunits with molecular weights of 75-76, 63-64 and 47-48 kDa, which represent the structural elements of the coagulum; one of these subunits consists of seminogelin. Seminal vesicle secretion contains very little or no proteolytic enzymes, so that its protein composition remains stable even after incubation for 24 hours.


[Urinoma: a complication of celiac plexus infiltration]. A case is described in which a major complication resulted from this technique. We have found no previous record of urinoma due to infiltration of a caustic agent.


[Endo-urologic treatment of ureteral fistulas occurring after pelvic surgery for carcinoma: report of 5 cases]. The authors report 5 cases of ureteric fistula after radical pelvic cancer surgery. Three patients had a recurrent tumour and 3 had received radiotherapy. Endourological methods achieved 4 immediately satisfactory results, but only one complete long-term success. Isolated percutaneous drainage of the pyelocaliceal cavities effectively dried up the urine leak, but carried a high risk of secondary stenosis of the excretory tract in the absence of concomitant intubation of the fistula zone. However, endourological treatment, combined with urinary diversion and catheterisation of the pathological ureter, represented a reliable alternative to conventional surgery.


[Postoperative rectoprostatic fistulas. Report of 2 cases. Review of the literature]. The authors report two cases of acquired prostatorectal fistulae after TURP, which were treated by a Kraske approach. They review the literature of iatrogenic fistulae and all of the techniques of approaching the prostatorectal region. If the bladder drainage is always necessary and may be sufficient in as much as 34% of the patients, the need for a colostomy and the choice of the approach is discussed.


[Pyeloureteral lieberkuhn adenocarcinoma after trans-intestinal ureterostomy for bladder exstrophy]. The authors report a case of pyeloureteric adenocarcinoma in a urinary diversion inserted for bladder exstrophy and in a context of chronic pyelonephritis secondary to renal stones. The various aetiopathogenic hypotheses are discussed. Renal stones and chronic inflammation very probably played an important role in the development of this type of adenocarcinoma in the urothelium.


[Burkitt's lymphoma: an exceptional cause of testicular tumor]. Based on a case of Burkitt's lymphoma presenting in the form of a testicular mass in a 66 year old man, the authors stress the importance of making the diagnosis as early as possible. This malignant lesion has one of the greatest capacities for proliferation and any delay in treatment can decrease the chances of curability of the tumour.


[A rare psychogenic anejaculation. Report of a case of prolactin adenoma]. The authors report a case of prolactinoma discovered during assessment of a case of ejaculation failure attributed for more than eight years to a psychogenic cause. Because of the size of the tumour, surgical resection of the lesion left a persistent hyperprolactinaemia, which only returned to normal after treatment with bromocriptine. The persistence of sexual disorders justified adjuvant treatment with exogenous testosterone. Despite the unusual mode of presentation of hyperprolactinaemia, these data correspond to those reported in the literature. Prolactin assay should therefore be performed in any case of male sexual dysfunction to allow the early diagnosis of prolactinoma and to improve the functional prognosis.


[Anterior sacral meningocele with urologic manifestations. Report of 3 cases]. Anterior sacral meningocele is defined as a spinal fluid-filled thecal sac in the pelvis communicating with the spinal subarachnoid space through a defect in the anterior sacral wall. Since scimitar shape of the sacrum is characteristic, diagnosis is easily confirmed by echography and myelography. The sac very often contains benign tumors and a thickened filum terminale which can achieve a tethered cord syndrome. This congenital malformation, whose autosomal inherited condition has been proposed, has usually few characteristic symptoms but can present itself as a neurogenic bladder from tethered cord origin. Neurosurgical treatment can prevent rupture of the meningocele with meningitis. In addition to symptomatic treatment of the neurogenic bladder, the urologist must advise neurosurgical operation to preserve potency and cure specific bladder dysfunction secondary to tethered cord syndrome.


[The Bourne's test: a relevant contribution to the diagnosis of vesico-enteric fistulas]. Diagnostic verification of vesicoenteric fistulae is necessary in order to establish the indication for surgical therapy, but this is frequently difficult. This is because uroradiological and endoscopic methods are unreliable and the symptoms are often nonspecific. The Bourne test is a simple noninvasive screening method. If necessary, it can be supplemented by computer tomography. The problems are discussed with reference to a case report.


[Microsurgical vaso-vasostomy: a reliable method of vasectomy reversal]. An original microsurgical technique has been used since 1971 to reverse the vasectomies of 2,110 men. Both sides were anastomosed if possible using a meticulous two layered technique with further reinforcing sutures to prevent strain on the join. Other important points include testing the fluid emerging from the testicular end, checking patency of the prostatic end and insisting on good scrotal support in the recovery phase, particularly the important first few days. The series returned a 95% baby rate, with a return of sperm to the ejaculate in 93% of cases.


[Complications of prostatic biopsies. Analysis of a series of 4,764 biopsies]. A multicentre, retrospective series of 4,764 prostatic biopsies revealed 89 complications (1.86%). The commonest complications were infectious (including 10 cases of septicaemia) and antibiotic prophylaxis does not appear to be able to totally prevent them. Thirty three complications occurred after negative biopsies. Many minor complications are probably treated at home by the local doctor and would therefore not be reported to the urologist.


[What is new in the diagnosis of tumors of the testis?]. The major new developments in the diagnosis of testicular tumours over the last 11 years consist of imaging techniques and tumour markers. Doubtful clinical diagnoses of testicular tumours can now be clarified as a result of progress and diffusion of ultrasonography. Ultrasonography, a reliable (90%) and non-invasive examination, is more of a diagnostic aid than a decisive element, except in a few special cases. At the present time, magnetic resonance imaging is of no value in the diagnosis of testicular tumours. Alpha-foetoprotein and human chorionic gonadotrophin are the two essential markers for the follow-up, rather than for the diagnosis, of a testicular tumour. Lactate dehydrogenase and placental alkaline phosphatase are useful, especially in the seminomas, but are much less specific. The other markers studied have either not proven to be of any clinical value or are still in the field of research. Computed tomography appears to be gradually replacing lymphography for lymph node staging. The combination of the two examinations reduces the number of false negatives (10%) at the price of a higher number of false positives (38%). The diagnosis of testicular cancer can sometimes be made at the stage of carcinoma in situ, a precancerous lesion which progresses towards an invasive tumour in one half of cases. The practical indications for screening for carcinoma in situ are still controversial.


[Intracavernous injections].

[Intracavernous injections]. Virag's paper concerning erection induced by intracavernous injection of papaverine was published 10 years ago, in 1982. Since this time, several substances have been tested; some have been abandoned, while others have demonstrated their efficacy and relative safety. After briefly recalling the physiology of erection and the principal substances used (papaverine, phentolamine, moxisylyte, PGE1, ceritine and VIP), the indications for intracavernous injection are reviewed in the context of investigation and treatment of certain forms of impotence. Lastly, the injection technique, the results and the complications are discussed, with emphasis on the ways to prevent or treat these complications.


[100 percutaneous endopyelotomies. Technique, indications, results]. 100 percutaneous endopyelotomies were performed in 95 patients from October 1985 to February 1991 to treat 46 cases of acquired stenosis and 54 cases of congenital hydronephrosis. The acquired stenoses were treated by scalpel incision, while the congenital hydronephrosis were generally treated by electrocautery. The evaluable results for 81 ureteric units with a mean follow-up of 37 months showed an overall success rate of 84%. No significant difference in the results was observed in relation to the patient's age, the technique used or the stage of the hydronephrosis (81% success rate): the results in the treatment of congenital hydronephrosis (86%) are slightly inferior to the results of surgical pyeloplasty.


[First clinical experience with extracorporeal lithotriptor EDAP LT.02]. A preliminary study of the EDAP LT.02 extracorporeal lithotriptor is presented. The apparatus includes a double isocentric detection system (ultrasonographic and radiological), facilitating the in situ treatment of ureteric stones. Seventy patients with a total of 89 urinary stones were treated by primary extracorporeal lithotripsy (ECL) with no preliminary selection. 69 stones (77.5%) were located in the kidney and 20 stones (22.5%) were situated in the ureter. Anaesthesia was only required in 2 cases. The patients received an average of 1.2 lithotripsy sessions. Out of the 70 patients treated, there were 46 (66%) complete successes, 12 (17%) partial successes and 12 (17%) failures [corrected].


[Correlation between chemical composition, density, and results of extracorporal lithotripsy in renal and ureteral lumbar calculi]. Based on a series of 388 patients with a total of 466 renal and lumbar ureteric stones (414 kidneys) treated between 1987 and 1990 by extracorporeal shock wave lithotripsy (ESWL) using the SONOLITH 3000* apparatus, the authors analyse the indications and results criteria for ESWL. The success criteria adopted excluded any residual fragment and considered patients lost to follow-up as failures. The success rate varied between 48.3% and 73.8% when residual fragments less than 5 mm were included and when drop-outs were excluded. A correlation was established between the radiographic appearance of the stone (dense, smooth, spiculated), its predominant spectrophometric nature and the results of ESWL: low density, spiculated Weddellite (WD) stones gave good results and very dense, smooth Whewellite (WW) stones gave less favourable results. The authors propose a refinement of the indications for ESWL in order to improve the results. Predominantly WW stones may be suitable for primary percutaneous nephrolithotomy.


[Cost-effectiveness analysis of extracorporeal lithotripsy]. The recent introduction of extracorporeal lithotripsy (ECL) for the treatment of urinary stones has raised new questions for doctors and economic policy decision makers. This study presents a cost-effectiveness analysis of extracorporeal lithotripsy conducted in an Italian hospital which has used a Sonolith 3000 lithotriptor since 1989. The overall cost of treatment by ECL (of a simple case of urinary stones) is 5,080 FF and the cost per cured case (taking into account the number of sessions per patient and the percentage of cured cases) varies between 6,200 FF and 9,500 FF. The results obtained (influenced by the lack of certain clinical data due to the recent use of this technique) appear to be in favour of extension of ECL treatments in comparison with surgical treatment due to their lower cost, lower morbidity and shorter convalescent period.


[Endo-surgical dissection of the upper urinary tract through the retroperitoneal and transperitoneal route: an experimental study with pigs and cadavers]. In order to define the best method for endosurgical dissection of the upper urinary tract, an experimental study comparing the retroperitoneal and transperitoneal approaches was performed. Between September 1991 and February 1992, 15 female pigs and 8 human cadavres underwent endosurgical dissection of the upper urinary tract. The retroperitoneal approach was used in 8 pigs and 5 cadavres. In the lateral supine position, the retroperitoneum was insufflated at the lower pole of the kidney, via a 2 cm cutaneo-muscular incision, followed by a blind dissection with the finger to create a space in the retroperitoneal fat. Four trocars were inserted into the retroperitoneal space allowing dissection of the ureter, kidney and its vascular pedicle. The renal vessels and the ureter were then clipped or stapled with the endo-GIA then sectioned. The operation was successfully performed in all of the pigs with a mean operating time of 2 hours. Complications were limited to two peritoneal effractions. Retroperitoneal endosurgical dissection was much longer and more difficult to perform on the cadavre (mean operating time: 3 hours). Satisfactory retropneumoperitoneum was never able to be obtained due to the large amount of retroperitoneal fat and the proximity of the twelfth rib and posterior iliac crest interfered with the insertion of the trocars and made dissection more difficult. The transperitoneal approach was performed in 7 pigs and three cadavres. In the lateral supine position, after creating pneumoperitoneum using a Veress needle, 4 trocars were inserted into the peritoneal cavity. Toldt's fascia was gripped and incised allowing retraction of the colon towards the midline, thereby exposing the renal region. The ureter and the renal vessels were dissected. The renal artery and vein were then clipped or stapled with the endo-GIA then sectioned, while the ureter was clipped and sectioned. The complications of the transperitoneal route were: an injury to the small intestine during insertion of a trocar and haemorrhage due to accidental section of a lower pole renal artery, which was able to be controlled by application of clips. In the pig, the transperitoneal approach was as simple to perform as the retroperitoneal approach and the mean operating time was the same (two hours).(ABSTRACT TRUNCATED AT 400 WORDS)


[Flow cytometry in bladder lavage fluid for the diagnosis and surveillance of bladder tumors. Preliminary results]. The authors evaluate the accuracy and practical applications of flow cytometry (FCM) on bladder lavage fluid in the diagnosis and follow-up of bladder tumours. The apparatus used was a Coultronics Epics Profile II cytofluorograph. Two hundred and fifteen samples were obtained with a yield of 86%. The specimens were preserved in ethanol. The staining was performed on whole cells with preservation of the cytoplasm. The analysis of a control group of 45 patients confirmed that the FCM study of ploidy was specific (0.97 for normal bladders and 0.8 for inflammatory lesions). Four aspects were evaluated: Correlation between FCM and the histological type of the tumour: a significant difference was observed between the control group, the invasive tumour group (p < 0.01) and the carcinoma in situ group (< 0.001). A significant difference was observed in the case of high-grade PTA and PT1 tumours. No significant difference was observed between FCM and classical cytodiagnosis when this technique was performed by a trained cytologist. Predictive value of FCM for the recurrence of PTA and PT1 tumours: 40 patients were followed with a mean follow-up of 13 months. The relative risk of recurrence in the case of a tumour with an abnormal FCM was 2 (p < 0.05). FCM and monitoring of conservatively treated tumours: 30 patients with normal endoscopic examination after endoscopic resection of a PTA or PT1 tumour underwent cytometric analysis and cytodiagnosis. In the case of an abnormality on cytometry, randomised bladder biopsies and urography were performed. The positive predictive value for the presence of a lesion not diagnosed by cystoscopy and detected by FCM was 0.38 +/- 0.26. FCM and intravesical chemotherapy: 16 patients with PT1 tumours and abnormal FCM received BCG therapy (11 patients) or mitomycin C instillations (5 patients). A significant difference (p < 0.01) was observed between the 2 treatments in terms of normalisation of cytometry.(ABSTRACT TRUNCATED AT 400 WORDS)


[Continent urinary diversion with the Florida pouch]. Continent urinary diversion (Florida Pouch) has been performed on 151 patients. The surgical technique utilizes a detubularized extended right colon segment, a doubly-plicated segment of ileum and a non-tunneled uretero-intestinal anastomosis. Mortality rate was 1.3%. Early and late complication rates have been minimal. 2.8% were incontinent. No radiographic renal damage has been noted and electrolyte abnormalities have not been a problem. The procedure is highly recommended to those surgeons performing continent urinary diversions.


[Scrotal trauma. Report of 33 cases].

[Scrotal trauma. Report of 33 cases]. We report a serial case study of 33 patients from May 1980 to November 1990 presenting a scrotal contusion. In 2/3 of cases, the physical examination showed a scrotal oedema or an hematocele. Ultrasonography showed a testicular injury while clinical examination was subnormal in 2 patients. In the other cases, ultrasonography showed an hematocele without asserting in all cases the traumatic rupture of the tunica albuginea. 27 patients have been surgically explored: 14 ruptures of the testicle, 3 intratesticular haematoma, 3 scrotal open traumatic injuries, and 7 extratesticular haematoma. Only 3 orchidectomies were required for the 6 patients who have not been explored surgically, the testis was normal at one month. The follow-up of these young patients is difficult, 11 had been seen again at 1 month. At long term follow-up, three patients had been seen at 1, 3 or 6 years without testicular after-effects.


[Endoscopic internal urethrotomy. Retrospective studies of 132 cases]. The authors report a series of 132 patients with urethral stricture all treated by the same surgical technique between 1979 and 1984: direct vision internal urethrotomy. 62% of good results were obtained after a single operation with a follow-up ranging between 18 months and 5 years. There was no mortality and the morbidity was considered to be 5%. The authors indicate that the results were more favourable when the operation was performed in a solitary, short (less than 2 cm) non-infected stricture of the proximal urethra. The duration of postoperative catheterization was 10 days; catheterization for a longer period did not provide any significant advantage. The poor results (38%) were reported in cases of extensive strictures situated in the distal urethra or in patients with a history of urethral surgery. These cases were treated by repeated internal urethrotomy; 32% were cured after a second urethrotomy, while the others required maintenance sessions of urethral dilatation or even a urethroplasty procedure.


[Management of incidentalomas].

[Management of incidentalomas]. An incidentaloma is defined by the exclusion of other lesions, primarily phaeochromocytomas, by means of MRI and metanephrine and normetanephrine assays, followed by other secreting tumours by means of clinical examination and limited laboratory assays (potassium, cortisol, aldosterone). Tumours which need to be operated because of the risk of (malignant) adrenal cortical tumour can be distinguished from radiological adrenal anomalies which simply need to be monitored on the basis of the initial size of the lesion or its rate of growth on repeated CT scans.


[Prostatic involvement in leukemia. Report of a case]. Infiltration of the prostate is frequent in the course of leukaemia. It is usually asymptomatic or may present in the form of classical bladder neck obstruction. The diagnosis is generally established during investigation of benign prostatic hypertrophy by biopsy or during treatment by resection. Treatment of leukaemia by systemic chemotherapy is unable to sterilize the prostatic site and must therefore be combined with local radiotherapy.


[Treatment of bladder instability with interferential current. Report of 20 cases: preliminary results]. 20 patients with unstable bladder unresponsive to medical treatment by anticholinergics were treated by interferential current retraining stimulations. This technique combines the advantages of retraining stimulation with external application. Each patient received 6 to 20 stimulation sessions at a rate of one per week in children and two per week in adults. 18 patients were clinically and urodynamically improved with resolution of incontinence and the follow up urodynamic assessment showed return of normal bladder volume and tone. No adverse effects were observed. No recurrences of the symptoms were observed with a mean follow-up of 18 months. The authors believe that this reliable technique constitutes an alternative to other retraining stimulation methods.


[Treatment of post-partum urogenital fistulas in Africa. 261 cases observed in 10 years]. A homogeneous series of 261 post-partum urogenital fistulae treated over the last ten years in Africa by the same operator is analysed. Mostly occurring in young, primiparous women in a rural environment, the predominant cause was neglected dystocic delivery in the bush (65.5%). The fistula was traumatic in 27.9% of cases and secondary to hysterectomy in 6.8%. 247 patients underwent surgical repair. The choice of repair procedure, generally performed via the transvaginal route (92.3%), was based on the anatomical classification of the various lesions into three groups of indications: Group I: simple fistulae (98), in which surgical treatment consisted of closing the fistula orifice by simple separate suture of the bladder and vagina, generally followed by success. Group II: more difficult fistulae (109) with severe tissue damage, raising the dual problem of continence and healing and requiring the use of mattressing with a well vascularised adjacent tissue (55 cases). Group III: complicated fistulae (54) with the presence of associated lesions, often requiring multiple urological, genital and intestinal operations as well as complementary plastic techniques (31 cases): double autoplasty of the labia major (17) and adipocutaneous pedicle skin flap (14). 212 of the 261 patients (81.2%) were cured, 23 obtained partial cure (insufficient continence, amenorrhoea, vaginal sclerosis making sexual activity impossible) and there were 26 failures. Urinary diversion was the only solution in 14 patients (7.8%). The objective in surgical correction of urogenital fistulae is twofold: to obtain good quality cure (81.2%), i.e. controlled micturition and a normal, genital, conjugal and social life. overcome the limitations of palliative operations which are always poorly accepted in Africa, at the cost of repeated, staged surgery designed to simplify the lesions in the most severely damaged cases. Prevention programmes designed to eradicate urogenital fistulae, which constitutes a real public health problem in developing countries, will only be made credible by an improvement in the quality of the results obtained in the treatment of this disease.


[Value of intravesically instilled oxybutynin in refractory bladder hyperactivity. Study of 15 cases]. 15 patients with neurogenic detrusor hyperactivity refractory to oral anticholinergics received a daily intravesical instillation of 5 mg of oxybutinin for 6 days. An improvement was observed clinically in 10 cases and on urodynamic parameters (60% increase in bladder capacity, doubling of the volume inducing an urge to void) in 12 cases. The mechanism of action is discussed.


[Impotence in pelvic fractures. Report of 16 cases]. The authors study impotence secondary to a pelvic fracture on the basis of a retrospective series of 16 cases. All these patients had a lesion of the membranous urethra and seven of them underwent a deferred emergency urethral repair. Although the constancy of the urethral lesion is probably related to the fact that this series was recruited from a urology department, impotence is classically considered to be more frequent in the presence of a urethral lesion than in the absence of such a lesion. Two patients presented with incomplete impotence and fourteen with complete impotence. Ten of these sixteen patients spontaneously regained satisfactory erections. When erections were not obtained, the authors analysed the various therapeutic possibilities available, stressing the arterial factor which is usually insufficiently investigated.


[The combination of oral trazodone-moxisylyte: diagnostic and therapeutic value in impotence. Report of 110 cases]. An oral drug treatment was prescribed systematically for one month in 110 unselected patients suffering from impotence: Tradozone (75 mg/day)+Moxisylite (180 mg/day) daily, or at higher doses if possible, and Trazodone (25 mg/day)+Moxisylite (60 mg/day) one hour before any sexual intercourse. Adverse effects were uncommon (6.3%). Satisfactory sexual activity was restored in 28% of cases and an improvement in spontaneous erections was obtained in 42% of cases. No improvement was observed in 30% of cases. This oral drug test therefore presents 3 advantages: a) it facilitates the diagnosis and treatment of impotence by eliminating moderate forms of psychogenic impotence, b) it reduces both the morbidity and cost of investigation of impotence by reducing the number of tests performed, c) it emphasizes the role of oral treatment in impotence. In conclusion, this oral drug test should be used because of its simplicity, safety and real efficacy. The current objectives of this test are to improve the efficacy of oral treatment as a result of pharmacological progress.


[Uretero-rectal diversion with rectal enlargement. Clinical results]. In some patients, after total cystectomy, the urethra cannot be used, preventing the creation of a replacement enterocystoplasty. In these cases, ureterocolonic or ureterorectal diversion constitutes an alternative to cutaneous diversion if its classical complications could be minimized. A ureterorectal diversion technique with rectal enlargement was performed in 6 patients: a segment of small intestine was raised, opened along its antimesenteric border, folded into a U-shape and sutured to the edges of a large rectotomy. The ureters were implanted into this patch of small intestine according to the mucosal tunnel technique. This technique was used in 4 men after total cystectomy with invasion of the prostatic urethra by their bladder tumour and in 2 women for incontinence due to sphincter destruction who refused cutaneous diversion. There was no mortality in this series. The postoperative complications consisted one prolonged but resolving fever in 2 cases. Out of 12 ureteric units, 4 cases of severe stenosis had to be reoperated and 3 cases of moderate stenosis were observed. All patients were continent during the day except for one women who complained of incontinence when changing positions. All patients were continent at night and had to get up to urinate twice. This preliminary experience shows that rectal enlargement as part of a ureterorectal diversion is followed by very satisfactory functional results. The creation of a colorectal invagination valve to prevent metabolic disturbances does not appear to be necessary. The ureteric implantation technique in the mucosal tunnel should be abandoned in favour of a procedure using an ileal tube interposed between the ureters and the rectum.


[What can be expected from the ligation of the deep dorsal vein of the penis in the treatment of caverno-venous impotence? Report of a series of 21 cases]. 21 patients with venous vasculogenic impotence were treated by ligation of the dorsal vein of the penis. 71% of the patients were improved after 8 months, but only 53% were still improved after 25 months. However, this simple operation can be proposed palliatively to patients selected on the basis of cavernosometry, in combination with other medical treatments.


[Perineal gangrene. Analysis of 24 cases]. Fournier's syndrome, characterised by anaerobic necrotising cellulitis of the soft tissues situated below the diaphragm, is a serous disease with an unpredictable course. From 1978 to 1991, we treated 24 men with a mean age of 57 years (27 to 90 years). Following the diagnosis of this disease, rigorous treatment was instituted immediately, consisting of a triple antibiotic combination, repeated surgical exposure, debridement and drainage with a frequent, almost systematic indication for faecal diversion (n = 16), hyperbaric oxygen therapy and classical intensive care measures. The mean interval between the first clinical signs and the diagnosis was 7.4 days. The lesions were limited to the perineum in 11 cases and extended to the abdomen, thighs and/or loins in 13 cases. The microorganisms responsible for the infection were identified in 19 cases and blood cultures were positive in 5 cases. This infection was of coloproctological origin in 12 cases, urogenital origin in 4 cases and postoperative in 2 cases, while no aetiology could be identified in 6 patients. There were 6 deaths and 18 cures without sequelae. 1. The prognosis of this disease is better in younger subjects (under the age of 60 years) with a localised clinical form, with no deterioration in the general status, sterile blood cultures and treated by a diversion colostomy. 2. A detailed aetiological work-up must be performed, looking for local or regional infection, cancer, haematological malignancy or arterial disease.


[Carcinoma in situ of the testis].

[Carcinoma in situ of the testis]. Carcinoma in situ (C.I.S.) of the testis is the only known precancerous lesion of germ cell tumours. The prevalence and the incidence of C.I.S. are both unknown, although predisposing factors have been identified: history of germ cell tumour of the contralateral testis, cryptorchidism or history of ectopic testis, decreased fertility or sterility. The incidence is higher in the presence of a combination of several of these factors. No complementary investigations have been demonstrated to be of any value in the detection of C.I.S. which can only be diagnosed, at the present time, by means of surgical biopsy. Once C.I.C. has developed, it never resolves spontaneously. In one half of cases the C.I.S. evolves into an invasive tumour over a period of 5 years. There is no consensus concerning the population in which testicular biopsy should be proposed looking for C.I.S. A large scale C.I.S. screening and detection programme has been proposed in Denmark. However, it is not clear that there is any major gain in testicular cancer morbidity and mortality in comparison with a surveillance programme of patients at risk. Apart from conservative follow-up, two types of treatment can be proposed: orchidectomy or external beam radiotherapy which appears to eradicate the C.I.S. while preserving endocrine function.


[Precancerous conditions of the prostate]. Carcinoma in situ, dysplasia, prostatic intra-epithelial neoplasia, duct-acinar dysplasia and large-acinar hyperplasia are various terms describing more or less identical forms of prostatic epithelial atypia. The precancerous nature of these lesions can be demonstrated by: morphological and functional similarities with carcinoma, a younger age than that of carcinoma, a higher incidence in cancerous prostates, an identical zonal distribution and a significant progression of high-grade lesions towards carcinoma. These hypoechoic lesions can be detected or monitored by transrectal ultrasonography. They also secrete PSA at levels intermediate between those of benign prostate and adenocarcinoma. Because of the occasional risk of malignant transformation and a frequent association with carcinoma, these lesions should be regularly monitored by digital rectal examination, PSA assays and possibly by ultrasound-guided biopsies.


[Extraperitoneal endoscopic lymph node dissection with insufflation in the staging of bladder and prostate cancer]. Endoscopic pelvic lymph node dissection was performed in 30 patients as part of the staging of prostate (19) or bladder (11) cancers. The technique, using a procedure of detachment of the retroperitoneal space with CO2 insufflation, is described. Complete bilateral dissection of the ilio-obturator lymph nodes was performed in 24 patients (80%) using conventional laparoscopic surgical equipment. Only a unilateral dissection could be performed in 6 other patients because of technical difficulties. The mean operating time was 72 minutes. The intraoperative and postoperative complications consisted of 2 venous injuries and one infection. A prospective study of systemic diffusion of CO2 demonstrated that the blood Co2 level increased significantly during the procedure, but could be controlled by adaptation of the ventilation. Postoperative monitoring of blood CO2 levels using a capnograph is recommended. 4 out of 30 patients (13%), 2 with prostate cancer and 2 with bladder cancer, had lymph node metastases. Amongst the other 26 patients, 12 were treated by radiotherapy (bladder cancer), 12 patients underwent perineal prostatectomy and 12 others underwent retropubic prostatectomy (5) or prostatocystectomy (7]). No intraoperative and postoperative morbidity related to endoscopic lymph node dissection was observed in the patients subsequently undergoing a radical operation. Endoscopic retroperitoneal lymph node dissection with CO2 insufflation is a rapid, safe and effective technique for staging of malignant pelvic tumours and constitutes an alternative to open surgery and to endoscopic transperitoneal surgery.


[Posterior urethral valves in newborns and infants. Treatment and clinical course]. Severe forms of posterior urethral valve are essentially seen in neonates and infants. In 6 neonates under the age of 3 months, the predominant presenting features were a deterioration in the general status and renal failure. Transurethral section of the valves, after urinary drainage for an average of one month, restored patency of the lower urinary tract in every case. All children have persistent renal failure, which is moderate or severe in 4 cases. In 6 infants between the ages of 3 and 11 months, the clinical presentation was dominated by signs of infection. Section of the valve was able to be performed earlier, with subsequent urethral stricture in one case. Five infants, initially presenting with renal failure, have persistent moderate renal failure. The degree of obstruction accounts for the severity of the uropathy and its early clinical presentation. The renal prognosis is poor and related to the uretero-renal consequences of the valve as well as associated renal dysplasia.


[Primary bladder lymphoma in kidney transplant recipients: report of a case]. The authors report the case of a type B EBC (+) primary lymphoma of the bladder occurring in a renal transplant patient 14 months after the graft. The postoperative course had been marked by three episodes of early rejection, the last of which required the use of anti-CD3 antibody, then the later addition of cyclosporin. After immune labelling showing oligoclonal proliferation, the lesion was treated with CD24 and CD21 monoclonal antibodies. Ten months after treatment, the patient is in remission with renal function at 200 mumol plasma creatinine. Azathioprine and cyclosporin have been stopped. This apparently unique case provides the authors with an opportunity to review the usual characteristics of lymphocyte tumours in transplant patients and to stress the rarity of primary lesions of the urinary tract. They conclude that the new therapeutic approach based upon monoclonal antibodies is of value in comparison with the attempts at surgery, radiotherapy and/or chemotherapy used in the past.


[Rhabdomyosarcoma of the prostate. Diagnostic course and current therapy. Report of a case of a 17-year-old boy]. The authors report a case of rhabdomyosarcoma in a 17 year old boy which recurred after combination chemotherapy and radical prostatectomy, followed by death of the patient due to haematological complications of second-line chemotherapy. The diagnosis of these rhabdomyosarcomas is facilitated by the various immunohistochemical stains now available. Chemotherapy is undeniably effective and, combined with surgery and radiotherapy, ensures a 5-year survival of 47% to 93% depending on the stage. The first-line chemotherapy avoids the need for radiotherapy in the early stages and allows less mutilating surgical procedures, while maintaining the survival rate.


[An exceptional complication of bladder cancer: intestinal metastases with obstruction of the small intestine]. Intestinal metastases from bladder cancers are extremely rare and all of the cases reported in the international literature have concerned patients in whom the tumour was resected by open surgery. The authors report a unique case of obstructive intestinal metastases from a bladder cancer resected via the transurethral route and regularly followed by endoscopy and systematic biopsies.


[New uretero-cystoneostomy in cystocecoplasties. Technique and results]. Ureteric reimplantations into an intestinal segment are frequently followed by early, secondary or late stenoses. In UCN, it is essential to perform atraumatic ureteric dissection followed by reimplantation of a short ureter well vascularized by a single superior pedicle, i.e. the simplest UCN, putting the least strain on the ureter both during creation of the diversion and during subsequent healing. The ileal segment of an ileocaecocystoplasty must extend above the right iliac vessels. It is open on the antimesenteric border and its distal border is stripped of a 3 mm band of mucosa. To reach its homologue, the left ureter passes underneath the common root of the sigmoid mesocolon. Each optimally shortened ureter is placed in and fixed to the start and the end of a longitudinal mucosal tunnel, about 3 cm long. The ileum is sutured as a cuff around the orifice of each ureter. A ureteric stent is left in place for a fortnight. The ileum is sutured to the right laterocaval retroperitoneal tissue. This UCN is simple and rapid to perform.


[Vesico-sphincteric disorders in patients with Parkinson's disease]. Vesicosphincteric disorders are frequent in patients with Parkinson's disease, due to a lesion of the locus niger of the extrapyramidal tract which no longer secretes sufficient dopamine to activate the nigrostriatal tract. The commonest symptoms are urgent micturition, dysuria or a combination of the two. 50% of patients with Parkinson's disease present with disturbances of micturition and these symptoms may be presenting complaint of the disease in 10% of cases. Cystomanometry reveals detrusor hyperactivity in more than 60% of cases and hypoactivity in less than 30% of case, while dyssynergia is less common. Delayed relaxation of the striated sphincter may sometimes be observed. Urological problems must therefore be distinguished from urological problems in these patients. A combined urological and urodynamic assessment is essential as the risk of incontinence following prostate surgery is 20%. Stress urinary incontinence in women may mask or be associated with urgency. These vesicosphincteric disorders must therefore be treated cautiously with a combination of medical treatment (dopatherapy increases detrusor control), retraining and occasionally surgery after a detailed urodynamic assessment.


[Corynebacteria D2 and encrusted cystitis with alkaline urine]. In the light of an informative clinical case report, the authors emphasise the pathogenic role of Corynebacteria D2 in urinary tract disease. This microorganism can be easily detected by bacteriologists by the use of special media and such infection is suggested clinically by urinary tract infection with "sterile", strongly alkaline urine. The clinical features of incrusted cystitis with alkaline urine may be accompanied by serious upper urinary tract complications with renal failure, recurrent haematuria with anaemia, decreased bladder capacity and incontinence. Corynebacteria D2, an opportunistic pathogenic bacteria, responsible for nosocomial infection, is resistant to the majority of antibiotics. The authors complete their case report with a review of the literature.


[Leiomyosarcoma of the inferior vena cava]. The authors report a case of leiomyosarcoma of the infrarenal inferior vena cava presenting as an abdominal mass. CT and MR imaging and immunotyping led to the diagnosis of retroperitoneal leiomyosarcoma whose origin in the inferior vena cava was only confirmed by histological examination of the resection specimen. Surgical resection was followed by radiotherapy (4,500 rads) with a favourable course after 12 months. The progress in medical imaging and histology has considerably simplified the diagnosis of these rare retroperitoneal tumours. In the absence of any truly effective adjuvant therapy, treatment essentially consists of surgery and the clinical course is characterised by a high incidence of local recurrences.


[Epididymitis disclosing an idiopathic urethroseminal reflux in children]. Idiopathic urethroseminal reflux is exceptional in children. In both of our cases, it presented in the form of epididymitis and was confirmed by suprapubic cystography, which also eliminated an obstructive cause and any associated malformations. Long-term antiseptic treatment prevented recurrent infections.


[Penile endoscopy: technique, results].

[Penile endoscopy: technique, results]. The authors report their experience based on 200 consecutive examinations. Peniscopy is an outpatient examination of the penis using a magnification system: commercial magnifying glass or colposcope. It consists of examining the whole penis in detail with the naked eue and then with a magnitification system after application of 5% acetic acid to the glans and prepuce in order to identify subclinical lesions. Biopsies can be performed when necessary. Three basic types of lesions may be observed: concylomas, macules, papules. However, the signs of mucocutaneous lesions are difficult to interpret, especially when they are subclinical. There are 2 types of false lesions: physiological papules of the corona of the glans and a diffuse acidophilic reaction. Topical treatment or laser destruction of the lesions can be performed at the same time as the examination, when necessary. The current indications for this technique are discussed. When learning this technique, the authors recommend the extensive use of biopsies and training with an experienced examiner.


[Role of pathologic anatomy in the diagnosis, prognostic evaluation, and surveillance of bladder tumors]. The usual histological techniques are necessary and sufficient for the routine diagnosis of bladder tumours. Many laboratory tools are designed to determine prognostic factors but require such technical conditions that they cannot be used routinely. The determination of DNA ploidy by flow cytometry of voided urine, fresh, formalin-fixed or paraffin-embedded tumour fragments is a simple, standardised and reproducible technique and the method of choice of pathologists as it allows morphological control of the element analysed. Based on a series of 720 bladder tumours collected by 3 different centres, the authors demonstrate how to use, correlate and integrate into routine practice the data of image analysis flow cytometry in relation to conventional cytology and histology. 5% of grade 1 tumours, 27% of grade 2 tumours, and 92% of grade 3 tumours were DNA aneuploid. 17% of non-invasive tumours (PTa) and 79% of invasive tumours (PT1 and more) were DNA aneuploid. These proportions are in line with the results of various series in the literature. DNA ploidy is therefore an objective and measurable element completing histological grading. The determination of DNA ploidy also helps the cytologist in difficult cases of urine cytology.


[Sub-venous iliac lymphatic dissection with celioscopy for the staging of prostatic cancer (16 patients)]. Subvenous external iliac lymph node dissection is an essential element for the staging of prostatic cancer. 7 to 30% of patients with intracapsular prostatic cancer have lymph node metastases despite normal imaging examinations. Laparoscopic surgery allows lymph node dissection through a limited incision. Sixteen patients underwent laparoscopic lymph node dissection (LLND) for prostatic cancer. The mean duration of the operation was 100 +/- 50 minutes (35-180 min: 130 minutes for the first nine operations, then 60 minutes for the last seven operations). One patient died on the second day from a cerebral vascular accident. There was one technical failure (pneumoperitoneum leak), one vascular injury, one ureteric injury, one transient paresis of the obturator nerves and one case of perineal lymphoedema. The mean number of lymph nodes removed in bilateral lymph node dissection was 7.5 +/- 2 (14-20) per patient. Three patients had lymph node metastases. The mean hospital stay related to laparoscopy was 4 +/- 2 days with a median of 2 days. Laparoscopic surgery, like any conventional or innovative surgical technique, requires specific training to become safe and effective. It allows complete histological examination of the lymph nodes removed and planning of prostatectomy, which may be subsequently performed through a perineal approach.


[Vesico-ureteral reimplantation on psoas bladder in lesions of the pelvic ureter. Review of 50 patients]. Between 1979 and 1991, the authors performed 50 psoas bladder ureterovesical reimplantations for lesions of the pelvic ureter. 90% of very good results were obtained with this technique at the cost of a low morbidity. This series confirms the influence of previous pelvic radiotherapy on the postoperative complication rate. On the basis of the excellent results in this series, confirmed by those reported in the literature, this technique can be proposed as treatment of choice for lesions of the pelvic ureter when suture-resection or simple reimplantation cannot be performed after failure of endoluminal dilatation in patients with a life expectancy greater than 6 months to one year.


[Rehabilitation of patients after cystectomy and construction of a continent intestinal reservoir]. Close follow-up and rehabilitation are necessary in order to ensure a good life quality for patients who have undergone cystectomy operations combined with continent reservoir operations. A questionnaire survey was carried out on 19 of our patients with continent reservoirs of different types. Furthermore a number of the leading clinics and urologists were consulted in an effort to find out a common and reliable method for rehabilitation. The most frequently encountered problems were the sexual (13 cases: 72.2%) and psychosocial adaptation (11 cases: 61.1%) among our patients. These figures were lowered to 50% (9 cases) and 33.3% (6 cases) respectively after organizing a special club for these patients in our hospital.


[Long-term prognosis of kidney cancer with vena cava thrombus. Report of 30 cases]. The authors present a retrospective analysis of 30 cases of renal cancer with vena cava thrombus with a sufficient follow-up to allow analysis of the long-term prognosis. Only three patients are still alive with a follow-up of 12, 34 and 57 months. The actuarial survival for the overall population was 55%, 37% and 22% at 1, 2 and 3 years respectively. Three essential factors influenced the prognosis of these patients: the presence of distant metastases, lymph node invasion and the highest cephalic level of extension of the thrombus. Renal cancer with vena cava thrombus without metastases and without lymph node involvement has a good prognosis (100% 2-year survival), but is very rare (4 out of 30 cases), so that renal cancer with vena cava thrombus must be considered to be a serious disease (3 survivors out of 30).


[POEMS syndrome and papilledema].

[POEMS syndrome and papilledema]. The Crow-Fukase syndrome or POEMS syndrome (Polyneuropathy, Organomegaly, Edema, Monoclonal protein, Skin changes) is an uncommon plasma cell dyscrasia leading to a multisystemic disorder. An optic disc swelling is often related to this syndrome. We report the case of a 51-year-old man with a papilledema. We presume that vasculitis or plasma cell infiltration is the cause of the papilledema.


Are bifocal intraocular posterior chamber lenses superior to monofocals? Twenty-eight eyes of 26 patients underwent a phacoemulsification with implantation of a bifocal posterior chamber lens (Storz-True Vista). The mean visual acuity increased from 0.28 to 0.74. To obtain best visual acuity for near, 19 eyes needed additional reading addition. A subgroup of 14 patients underwent also a phacoemulsification with implantation of a monofocal posterior chamber lens into the other eye. The mean visual acuity increased from 0.25 to 0.84. All monofocal eyes obtained an optimal near vision with a reading addition of 3 diopters. In this subgroup 9 patients preferred their monofocal eye for distance vision and 10 for near vision. Not a single patient preferred the bifocal eye.


[The eye and acromegaly: apropos of a case of ptosis]. A 60-year-old woman presents with bilateral ptosis and tearing, predominant on the right and existing since many years. Upper tarsus is much enlarged on the right; lacrymal glands are palpable under the upper lid and seem enlarged as well. CT scan and RMN confirms the hypertrophy of subcutaneous lid tissues, lacrymal glands and ocular muscles. The patient is aware of a progressive change in her physical aspect since years. Medical work-up diagnoses major acromegaly. Discussion about the consequences of acromegaly upon the ocular adnexa.


Acanthamoeba keratitis.

Acanthamoeba keratitis. During the last year we came across three cases of Acanthamoeba keratitis. They were all contact lens wearers. The diagnosis of Acanthamoeba keratitis was established by the history, clinical picture and the culture of corneal and conjunctival swabs. The patients were treated with metronidazole (Flagyl) 0.5% eyedrops, propamidine isethionate (Brolene) 0.1% eyedrops, Neomycin eyedrops, topical corticosteroids, mydriatics and beta-blockers. One tablet or itraconazole (Sporanox) a day was given orally. Infection subsided in two patients. The third patient still suffers from recurrent corneal erosions and shows a pronounced corneal immune reaction.


Ocular manifestations of Alport's syndrome: a case report. A review is given of the ocular signs characteristic for Alport's syndrome. The corneal, lenticular and fundus lesions are described. They occur in 15% of the cases. The patient reported here, showed the typical macular spots.


The Walker-Warburg syndrome.

The Walker-Warburg syndrome. The Walker-Warburg syndrome is characterized by lissencephaly type II, cerebellar and retinal anomalies and congenital muscular dystrophy. A clinical and histopathological study of a case is presented and the differential diagnosis discussed.


Leber's hereditary optic neuropathy: clinical and molecular genetic aspects. Preliminary results in our families. Leber's hereditary optic neuropathy (LHON) is a genetic maternally transmitted disorder characterised by sudden bilateral loss of vision. The discovery of at least one mitochondrial DNA mutation associated with the disease has provided the basis for a molecular diagnosis in about 50% of families with LHON. We present a brief review of the clinical and molecular genetic aspects of LHON along with our results in 13 patients.


Endogenous pneumococcal endophthalmitis after splenectomy: report of two cases. Two cases of pneumococcal sepsis, meningitis and unilateral endophthalmitis after total splenectomy are described. The first patient, a 9-year-old girl, had severe panuveitis complicated by traction retinal detachment, eventually requiring vitrectomy. Due to large chorioretinal scars the visual recovery was poor. Minor residual neurological signs remained. The second patient, a 39-year-old man, showed endophthalmitis of the right eye. The recovery of the pneumococcal meningitis was complicated by severe neurological impairment. The right eye progressed to phthisis bulbi. The importance of early recognition of postsplenectomy sepsis (PSS) is emphasised since the survival rate is poor and the risk of visual loss high.


A. carotis thrombosis with ocular ischemic syndrome: acute glaucoma postendarterectomy: a case report. A patient develops neovascular glaucoma a few weeks after endarterectomy for carotid artery occlusion. The ocular tension is normalised after retinal photocoagulation, followed by trabeculectomy.


Hyaluronidase induced orbital pseudotumor as complication of retrobulbar anesthesia. The authors describe 5 patients who developed an orbital pseudotumor as a complication of retrobulbar anesthesia. Allergy tests revealed a hypersensitivity to hyaluronidase, suggesting an immunoallergic etiology of the pseudotumor, which needed to be differentiated from other causes of proptosis after retrobulbar injection.


Retinal detachment surgery following implantation of a keratoprosthesis. A case report. Retinal detachment is an eye with a keratoprosthesis usually has an extreme poor prognosis. We describe the successful repair of a total retinal detachment following implantation of a new type Worst-keratoprosthesis in the only eye of a 70-year-old patient. A vitrectomy, epiretinal peeling, 180 degrees superior retinotomy, subretinal membrane peeling and an injection of perfluorooctane were performed to flatten the retina. After the endophotocoagulation a perfluorooctane-silicone oil exchange was performed. An additional intervention was necessary to treat a redetachment. After 3 months follow-up the retina has remained attached and the patient regained ambulatory vision.


[Sturge-Weber syndrome: apropos of an anatomo-clinical case report with prepapillary glial proliferation]. The authors report the case of a woman with Sturge-Weber syndrome (oculotrigeminate form) presenting with neovascular glaucoma of abrupt onset during pregnancy. Since medical treatment failed, she underwent a retrobulbar alcoholisation. Three months after delivery, enucleation was performed for esthetic reasons. The enucleated eye showed diffuse choroidal angioma, total retinal detachment and a prepapillary glial proliferation. We discuss this uncommon association.


Foveomacular retinitis as a result of ocular contusion. Foveomacular retinitis is typically associated with eclipse burns. However a macular hole similar to that seen in cases of solar retinopathy, may be observed after ocular contusion or after whiplash injury. The case histories of 3 men, who sustained an ocular contusion and subsequently developed as aspect typical for foveomacular retinopathy, are described.


[Anatomical modification of the levator muscle of the eyelid in congenital ptosis]. Congenital ptosis of the upper lid is classified as a developmental anomaly of the levator muscle. We report the histochemical findings in 38 specimens of levator muscle removed in patients with congenital ptosis and operated on by a resection of the levator muscle. Results demonstrated a close relationship between the presence or the absence of muscular fibres in the specimen and the degree of ptosis and the levator function. We suggest that congenital ptosis may result from a failure of differentiation and/or fusion of the anterior portion of the superior orbital mesoderm complex.


[Adherence syndrome of the lateral recti and inferior oblique muscles]. Case report of a 28-year-old woman presenting with a right abduction paresis. She also has right esotropia which was operated 14 years ago. Forced duction test was positive and there was a widening of the right palpebral fissure on attempted abduction. During reoperation we found thick adhesions between inferior oblique and lateral rectus. Freeing these adhesions restored the abduction and a normal palpebral aperture on abduction.


[Photographic screening for amblyopia, strabismus and refraction errors]. The authors present a photographical method to screen infants on the presence of refractive errors and squint. The photoscreener indicates an absence of focusing in one or both eyes and/or a squint. This method can be used in mass-screening of siblings, the evaluation of glasses, the monitoring of the effects of occlusion and the postoperative follow-up of patients.


[Screening and treatment of fixation dominance in primary microstrabismus]. The Gracis biprism appears to be the best actual method of testing eye fixation as early as 6 months. It is the appropriate test for microstrabismus screening. The treatment of the late onset microstrabismus is more simple than the treatment of the early onset microstrabismus, where the dominance of fixation is stronger. If the calibrated filters are sufficient in the first case, the optical penalisation (+ 2 D to + 3 D) on the dominant eye is the best long-term treatment in primary microstrabismus. Based on the specific aspects of the early onset strabismus, such as bi-ocularity and latent nystagmus, optical penalization without atropine offers an alternative long-term method to occlusion without any trouble of visual development of the fixating eye.


[Orthoptic indications for radial keratotomy: esophoric myopia]. In addition to aniseikonia, binocular factors are to be taken into consideration for refractive surgery. If important exophoria can be a contraindication to refractive surgery, this surgery can be indicated in cases of marked esophoria at near and distance vision. It can then prevent the need for prismatic treatments which become necessary in these cases.


[Spiral implants in phacoemulsification and in secondary implants]. The spiral I.O.L. with a rectangular optic (6 mm x 4.8 mm) is particularly convenient for small incision surgery. A series of rhexis and a series of envelope technique were compared: centering was definitely better after rhexis. In secondary implantation after ICCE the spiral implant could be secured to the posterior face of the iris.


[Characteristics and prognosis of retinal detachment following uncomplicated extracapsular extraction of the crystalline lens]. In a retrospective study dealing with 52 eyes, we compare the features and prognosis of retinal detachment following intracapsular cataract extraction, non complicated extracapsular cataract extraction, extracapsular cataract extraction followed by YAG laser posterior capsulotomy, extracapsular cataract extraction complicated by peroperative rupture of the posterior capsule with phakic retinal detachment. Our results show several common features between retinal detachment after non complicated cataract extraction and phakic retinal detachment. Cataract extraction, no matter the technique, is not per se an anatomic or functional prognosis factor for a subsequent retinal detachment.


[Treatment of choroidal nevi and melanomas using cryo-applications: preliminary study]. Since 1989 we use cryocoagulations (alone or in association with Argon laser coagulations) to treat selected cases of evolutive choroidal naevi or melanomas located near the posterior pole of the eye. We report our results in 9 consecutively treated patients.


Radiation-induced optic neuropathy.

Radiation-induced optic neuropathy. Radiation-induced optic neuropathy is a well-known complication of cranial radiotherapy. We describe four cases. In two cases, the diagnosis was made on MRI. After administration of Gadolinium-DTPA, there was an enhanced captation at the level of the optic nerve. In addition we reviewed 47 cases reported in the literature. Visual prognosis is less than 1/10 in 78% of affected eyes. In case of associated brain necrosis, the mortality rate is 62%.


The French multicentre study of ramipril in ambulatory patients with mild-to-moderate hypertension. The aim of this 16-week trial was to determine the safety and efficacy of a step-care regimen of ramipril, an angiotensin converting enzyme inhibitor, from the minimal active dose (2.5 mg) in patients treated for mild to moderate hypertension. The trial was conducted by 102 general practitioners in 770 patients with mild to moderate hypertension. After a response rate to a 4-week placebo therapy of 9.1%, 57.0% of patients given active treatment with ramipril responded to daily doses of 2.5 mg. Ramipril 5 mg daily was effective in 55.6% of the remaining patients. There was no apparent statistically significant difference between the treatments with ramipril 10 mg or a combination of ramipril 5 mg + Lasix 20 mg daily (44.7% and 47.4% response respectively) in a 6-week double-blind arm of the study. In total, more than 90% of patients responded to treatment with ramipril by the end of the study. The incidence of adverse events was generally low, such as headache, cough, dizziness, asthenia, cramps and nausea. The incidence of cough appeared to be related both to the dosage of ramipril given and to outbreaks of influenza syndrome. Thirty-eight patients discontinued active treatment as a result of minor events such as cough, dizziness or diarrhoea, and one case each of myalgia and papular rash. There were no significant variations in laboratory parameters during the study, especially fasting blood glucose and apolipoprotein A1 and B. The results of this study provide evidence of the safety and efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of ramipril on plasma atrial natriuretic peptide, antidiuretic hormone, angiotensin II and aldosterone in patients with chronic congestive heart failure. In an open trial 5 mg ramipril daily for 2 weeks was administered to 11 patients with congestive heart failure. 24-hour plasma profiles of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), angiotensin II (Ang II) and aldosterone (Aldo) were determined before and on days 1 and 15 of ramipril treatment, respectively. Urinary sodium excretion was also measured at the same time points. There were no relevant differences in the 24-hour profiles of ANP and ADH. Ang II values dropped as expected on the first day of ramipril treatment from 11.2 pg/ml to 2.9 pg/ml at 3 h post administration and from 6.7 pg/ml (predose) to 1.8 pg/ml at 2 h post administration on day 15. Plasma aldosterone values increased slightly from day 1 to day 15, sodium excretion increased from 125.9 mmol to 166.5 mmol/24 h; however, both changes in the 24-hour profiles were nonsignificant. A clinically relevant improvement in the severity of CHF was observed. From a total of 121 reported symptoms according to McKee et al., 35 showed an improvement; 81 remained unchanged, in only 5 symptoms a deterioration was observed. According to the NYHA-classification 5 patients improved from grade III to II, 6 remained unchanged. ACE inhibition does not induce changes in ANP or ADH levels in the resting state while Ang II decreases. A slight increase in aldosterone levels may be due to increased sodium excretion.


ACE inhibition and renal protection.

ACE inhibition and renal protection. In patients with renal disease, altered renal function causes elevation of blood pressure, but hypertension in its turn accelerates progression of renal failure. Lowering of blood pressure into the normotensive range is beneficial for slowing progression. Increasing incidence suggests that in this respect ACE inhibitors have unique benefits (renoprotective action).


Cardioprotection and ACE inhibitors.

Cardioprotection and ACE inhibitors. Angiotensin converting enzyme inhibitors are now widely used in the treatment of hypertension and heart failure. They are clearly as effective as other conventional antihypertensive agents in reducing blood pressure and combined with diuretics seem likely to transform current management of chronic heart failure. Myocardial infarction remains the major cause of death in patients with raised blood pressure and current studies should establish whether the attractive features of ACE inhibitors translate into reduction in the rate of infarction or its consequences. Similarly, whilst symptomatic benefit undoubtedly accrues from their use in heart failure it is less clear that they can prolong life particularly when used in the immediate setting of a myocardial infarction. Again a number of ongoing major trials are set to establish whether these drugs reduce death in patients with chronic heart failure (V-HeFT II, SOLVD) and in patients immediately after myocardial infarction (CONSENSUS II, SAVE,. AIRE, GISSI III and ISIS IV). The physician has a wide choice of ACE inhibitors with different pharmacological profiles for clinical use.


Acute effects of experimental diabetes on skeletal muscle contractile functions. The study was planned to explore the short term effects of experimental diabetes on the contractile characteristics of soleus and diaphragm. Experimental diabetes was induced in rats by streptozotocin (50 mg/kg, IP). On the 5th day, the isometric contractions were studied in soleus (in situ) and in diaphragm strip (in vitro). The soleus of the diabetic group showed similar twitch characteristics and tetanic tensions, decreased maximal relaxation rate (MRR; p < 0.01) and increased endurance time (ET; p < 0.05) as compared to the control group. The diaphragm of the diabetic group showed greater twitch tension (p < 0.05) and tetanic tension (p < 0.01), increased MRR (p < 0.02) and similar ET compared to the control group. It is concluded that the streptozotocin-induced diabetic state produces differential effects on the skeletal muscle contractile characteristics.


Postoperative hyperfibrinogenemia in gastrointestinal surgery. Fibrinogen titres were determined in two groups of patients undergoing major abdominal and thoracic surgical operations. Patients who underwent gastrointestinal surgical procedures had higher fibrinogen levels than those subjected to other appropriate thoracic surgical procedures. Fibrinogen titre elevation in patients with gastrointestinal abnormalities were significant on the 3rd, 5th and 7th days after surgery compared with the other group of patients. This higher response in fibrinogen could be attributable to the greater smooth muscle content in the gastrointestinal system than in the other tissues considered in this study. Smooth muscle tissue inflammation may lead to acute circulatory problems through postoperative increase in fibrinogen concentration.


Serum sex hormone binding globulin in prepubertal girls and adult women. Serum SHBG concentration depends on the hormonal status. Androgens decrease while estrogens increase SHBG biosynthesis in the liver. In the present study an attempt was made to investigate whether the changes that occur in the ratio of estrogen to androgen concentration between prepubertal girls and women could have influenced plasma SHBG levels. For this reason serum concentrations of SHBG, E2, T and DHEA-S were measured in 31 girls, aged 4.5-9 years, at Tanner stage I of pubertal development, and in 24 normal women. The girls were divided into 2 groups of different ages. The concentrations of non-SHBG-bound E2 and T and free E2 and T were calculated. The results showed a negative correlation between SHBG serum levels and the age of prepubertal girls while the ratio of E2/T did not change. Although the ratio of E2/T was found increased by 10 times between older prepubertal girls and women in the luteal phase of menstrual cycle, serum SHBG levels only slightly decrease in the group of women. The non-SHBG-bound E2 and free E2 levels were significantly higher in women than those in prepubertal girls indicating an increase of estrogen milieu in target tissues. It seems that apart from the changes that occur in the ratio of E2/T the serum SHBG levels may be also under the control of other factors.


Role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine-induced stimulation of H+ output in the rat. A new hypothesis for the mechanism of gastric acid secretion. This study was undertaken in the rat to examine the role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine (0.1 mg/kg)-induced stimulation of gastric acid secretion. Reserpine significantly (p < 0.001) stimulated acid secretion relative to control values (197 +/- 3.1 vs 61 +/- 1.7 mumol, mean +/- SEM, n = 10). Atropine (5 mg/kg) and cimetidine (40 mg/kg) were equally effective in achieving a significant (p < 0.001) suppression of the reserpine-induced acid secretion (98 +/- 3.4 and 91 +/- 2.9 mumol, respectively, vs 197 +/- 3.1 mumol, mean +/- SEM, n = 10), an action intensified by administering them together, but not significantly so (84 +/- 5.3 mumol). Vagotomy was more effective (p < 0.001) than the latter combination in preventing acid stimulation by reserpine and allowed an acid output similar to that of vagotomy controls (14 +/- 1.2 vs 13 +/- 1.4 mumol, mean +/- SEM, n = 10). Dose dependent inhibition of the reserpine-induced stimulation of acid secretion was achieved by the 5-HT receptor antagonist methysergide, an inhibition significantly (p < 0.001) more effective than that afforded by vagotomy coupled with achlorhydria in 80% of animals was noted with the 5-20 mg/kg doses. Reserpine produces vagal adrenergic delivery to the stomach, which releases acid secretagogues and sensitizes parietal cells to them besides stimulating acid secretion, and 5-HT is discharged into the gastric mucosa by vagal adrenergic activity and by reserpine and liberates acid secretagogues by a paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)


Iron accumulation by bovine aortic endothelial cells. Bovine aortic endothelial cells in monolayers were used to study iron and transferrin binding and transport mechanisms. Diferric bovine transferrin labeled with 59Fe was used as an iron donor. We have shown the presence of saturable iron uptake when cells were incubated with varying concentrations of diferric transferrin. This uptake decreased when the cells were treated with trypsin, ammonium chloride and methylamine. The effects of the latter two could be reversed by the addition of 2.0 mM Ca2+. Energy dependence was shown by using various electron transport/oxidative phosphorylation inhibitors. The presence of transferrin receptors on the cell surface was confirmed by their isolation, SDS-PAGE and autoradiography. There were approximately 1.5 x 10(6) transferrin receptors per cell with a Kd of 9.1 x 10(-7) M in the physiological iron range. Iron was also taken up when the cells were incubated with radioactive ferrous iron without transferrin. Uptake was not affected by receptor-mediated endocytosis inhibitors. Calcium increased ferrous iron uptake and overcame the effects of metabolic inhibitors on iron uptake from transferrin. A ferrireductase was detected in cell membranes. It is proposed that iron is transported by bovine endothelial cells by two mechanisms: one is receptor-mediated endocytosis from transferrin, and the other involves a non-endocytic mechanism from transferrin and Fe2+, which is possibly promoted by Ca2+.


A novel study on the effect of acetylsalicylic acid on the binding capacity of estrogen receptors from MCF-7 cells. The effect of acetylsalicylic acid (ASA, aspirin) was investigated on [3H]-estradiol-17 beta ([3H]-E2) binding to estrogen receptors (ER) from MCF-7 mammary tumour cells. No effect was observed using the monoclonal estrogen receptor-enzyme immunoassay (ER-EIA). In contrast to the ER-EIA, the radioreceptor assay (RRA) showed decreases of [3H]-E2 specific binding in the presence of increasing amounts of ASA. It is therefore concluded that these results demonstrate that ASA possibly affects the direct binding of E2 to region E of the ER of human breast cancer MCF-7 cells, but does not affect binding of monoclonal antibodies to regions D and F of the ER.


Is re-communication of vagal branches responsible for the recurrence of duodenal ulceration after proximal gastric vagotomy? A study in the rat. This study was carried out in the rat to examine whether preventing the re-communication of vagal fibres with their distal stumps after proximal gastric vagotomy (PGV), by placing a patch against the bare area of lesser curvature, impairs the return of gastric secretory patterns to their pre-operative levels and reduces the incidence of duodenal ulceration. PGV alone or with a patch significantly depressed the basal acid output. Administration of insulin (1 unit/kg i.p.) failed to stimulate this output. Two years later, the basal acid output of PGV was significantly (p < 0.05) higher than that of PGV with a patch (7.8 +/- 0.2 vs 3.7 +/- 0.3 mumol, mean +/- SEM), but significantly (p < 0.01) lower than that of the control animals (7.8 +/- 0.2 vs 14.2 +/- 0.8 mumol, mean +/- SEM). Insulin did not stimulate the acid output of PGV with a patch, but significantly (p < 0.001) stimulated the PGV acid output (7.8 +/- 0.2 vs 28.9 +/- 0.6 mumol, mean +/- SEM). This stimulation was significantly (p < 0.001) less than that noted in the control animals. PGV alone or with a patch equally prevented acid stimulation and production of duodenal ulceration by the infusion of pentagastrin (4 micrograms/kg/min) and carbachol (0.8 microgram/kg/min) for 24 hours. Two years later, these secretagogues significantly (p < 0.001) stimulated acid secretion in the PGV group relative to control values (24.1 +/- 2.3 vs 13.9 +/- 0.5 mumol, mean +/- SEM) and produced duodenal ulceration in 19% of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Genes for the biosynthesis of beta-lactam compounds in microorganisms. Rapid progress has recently been made in the characterization of genes and gene clusters involved in the biosynthesis of beta-lactam antibiotics such as penicillins, cephalosporins and cephamycins. The biosynthetic pathways are found in a wide range of microorganisms, including fungi, actinomycetes and Gram-negative bacteria. Comparisons of gene sequences (particularly the genes encoding isopenicillin N synthetase) and gene organization in these different microorganisms have led to proposals about the evolution of this group of pathways, and how they might have been transferred from prokaryotes to eukaryotes. The isolation and characterization of the genes encoding ACV (tripeptide) synthetase, the first step in the beta-lactam biosynthetic pathway, have revealed the presence of three partly repeated domains, most likely responsible for the recognition, adenylation and activation of the three amino acid precursors of the penams and cephems. This has confirmed their classification as peptide synthetases, distantly related to enzymes responsible for the synthesis of peptide antibiotics in Bacillus brevis and other bacteria and fungi.


Regulation of gibberellin formation by the fungus Gibberella fujikuroi. Gibberellins are a classic example of the production of plant growth regulators by microorganisms. They are important biotechnological products and are increasingly used in agriculture and horticulture. The economic importance of these plant hormones has led to an extensive study of the regulation of gibberellin biosynthesis. There have been reports of light, growth rate, inoculum size and carbon and ammonium sources acting as regulators of gibberellic acid biosynthesis. Besides light stimulation, nitrogen repression is a well-known regulatory principle of secondary metabolite formation. In Gibberella fujikuroi ammonium interferes with the production of gibberellic acid whereas phosphate does not influence the biosynthesis. It was found that the negative effect of ammonium ions is due to both the inhibition of activity and the repression of de novo synthesis of specific gibberellin-producing enzymes. Besides nitrogen control, the biosynthesis of gibberellins is suppressed by glucose. This glucose effect can be overcome by the addition of mevalonic acid. Therefore, the key enzyme of the isoprenoid pathway, the HMG-CoA reductase, seems to be the target of C-catabolite repression. A detailed knowledge of the regulation of gibberellin biosynthesis is important for fermentation processes. The biological function of gibberellin formation for the producing fungus is discussed.


Genetic regulation of secondary metabolic pathways in Streptomyces. Streptomyces species are (along with the fungi) the best-known antibiotic-producing organisms. Often, they make several different antibiotics. The biosynthesis of each antibiotic is encoded by a complex gene cluster that usually also contains regulatory and resistance genes. Typically, there may be more than one such pathway-specific regulatory gene per cluster. Both activator and repressor genes are known. Some of the regulatory genes for different pathways are related. In S. coelicolor, expression of several such biosynthetic gene clusters also depends on at least 11 globally acting genes, at least one of which is involved in the translation of a rare codon (UUA). A protein phosphorylation cascade also seems to be involved. Gene clusters closely similar to those for the biosynthesis of aromatic polyketide antibiotics determine spore pigment in some species. These genes show different regulation from antibiotic production genes. The evolution of gene clusters for polyketide antibiotics, and the possible adaptive benefits of secondary metabolism, are discussed.


Terpenoid cyclases: design and function of electrophilic catalysts. Terpenoid cyclases catalyse the cyclization of the universal acyclic precursors geranyl and farnesyl diphosphate to monoterpenes and sesquiterpenes, respectively. All such cyclases investigated to date are operationally soluble, moderately lipophilic proteins of relative molecular weight 40,000-100,000, requiring no cofactors other than a divalent metal, usually Mg2+ and occasionally Mn2+. The focus of most work has been on the mechanisms of the cyclization reactions themselves. It is currently proposed that the cyclase binds the acyclic substrate in a suitable conformation and initiates the cyclization by ionization of the labile allylic diphosphate moiety. The use of stereospecifically labelled substrates and analysis of the sites of labelling in the derived cyclization products has allowed the proposal of detailed cyclization mechanisms. Further insight into the architecture and function of the cyclase active site has come from the study of substrate and intermediate analogues designed to act as potential inhibitors or anomalous substrates of the normal cyclization reaction. Progress has also been made on the cloning of the relevant structural genes for sesquiterpene cyclases. This has led to new insights into the basic requirements for cyclase catalysis and specificity.


Roles of secondary metabolites from microbes. The common feature of the seemingly diverse array of biological activities exhibited by microbial secondary metabolites is their survival value for the producing organism. The propensity to form these compounds is unevenly distributed in microbial taxa and seems more closely associated with existence in a competitive environment than with phylogeny. The characteristic multibranched elaboration of secondary biosynthetic pathways and the marked species specificity of the end products are consistent with their evolution by an 'inventive' mechanism. The species specificity suggests that distinctive terminal reactions may be of recent origin. However, comparisons of the nucleotide sequence of genes involved in the biosynthesis of phenazine and polyketide metabolites with related genes of primary pathways indicate that the secondary pathways have not evolved exclusively within the organisms in which they are now found. Sequence similarities with related primary pathway genes in phylogenetically distant organisms suggest that gene transfer has played an important part in the evolution of secondary metabolism. The diversity of products may reflect the many roles for which secondary metabolites have been selected after the genes for their biosynthesis have transferred to organisms with different physiologies and different environment challenges.


Self-protection mechanisms in antibiotic producers. Various ways in which antibiotic-producing organisms are able to resist the actions of their products are discussed. Examples are given of antibiotic inactivation and also the modification of antibiotic target sites (most notably, ribosomes) to which drugs would otherwise bind and thereby exert their usual inhibitory effects. An interesting variation on the latter theme involves the duplication of target enzymes so that both sensitive and resistant versions are produced, the latter inducibly. Speculative discussion of antibiotic efflux leads to examples of cloned resistance determinants that probably encode components of efflux systems. Although of interest in their own right, resistance mechanisms should not be viewed narrowly when the physiology of antibiotic producers is considered. Thus, chemical modification of drug molecules may not only fulfil a protective role within the cell but may also provide substrates for efflux. Recent evidence that such considerations apply to macrolide antibiotics is presented. The control of resistance in producing organisms is also discussed with particular reference to the induction of novobiocin resistance in Streptomyces sphaeroides. This involves the interplay of novobiocin-sensitive and -resistant forms of DNA gyrase and features a promoter that displays a dramatic response to changes in DNA topology.


Useful functions of microbial metabolites. The mood-enhancing effects of fungi and their medicinal properties have been recognized for centuries. Ergot was initially used by midwives to speed childbirth in the Middle Ages. More recently their pharmacological action on dopamine receptors has been exploited to treat post-partum bleeding, migraine, Parkinson's disease and senile dementia. Further indications of the potential value of microbial metabolites are exemplified by the discovery and development of cyclosporin, to treat organ rejection, and mevinolin, a cholesterol-lowering drug. Such discoveries are not unexpected because we have known for some time that fungi regulate morphogenesis, differentiation and sexuality via hormonal molecules, ranging from peptides through to steroidal molecules similar in structure to human sex hormones. A combination of the power of molecular biology to design screens based on isolated disease mechanisms with the chemical inventiveness of microorganisms is providing numerous new pharmacophores for drug development.


Secondary metabolites from marine organisms. Marine macroorganisms and microorganisms, like terrestrial species, produce a dizzying array of secondary metabolites, including terpenes, steroids, polyketides, peptides, alkaloids and porphyrins. Most of the marine metabolites are found in terrestrial species as such or have close counterparts in land-based species, but some are sufficiently unusual to constitute a separate class (e.g. marine sterols). Although in many cases the functions of these secondary metabolites in the marine species themselves are unclear, other compounds play well-defined roles-for example as trail markers, sexual attractants, antifouling substances or antifeedants. What is clear is that many of the most interesting marine secondary metabolites have potent activities largely unrelated to their in situ roles. Examples abound of antitumour, antiviral, immunosuppressive and antimicrobial agents, as well as neurotoxins, hepatotoxins and cardiac stimulants. Relatively few biosynthetic studies of marine secondary metabolites have been done because of the logistical problems of working under water and the primitive state of techniques for growing marine invertebrates in culture. However, recent studies indicate that many compounds isolated from marine macrospecies (e.g. sponges) may instead be produced by microorganisms (e.g. bacteria or phytoplankton). Studies of these symbionts may facilitate efforts to understand the biosyntheses of these metabolites.


Evolution of secondary metabolite production: potential roles for antibiotics as prebiotic effectors of catalytic RNA reactions. It has been proposed that organic molecules related to known secondary metabolites have existed since the beginning of biochemical evolution and were present in primordial soups. Under primitive earth conditions certain of these molecules may have played roles as effectors in prebiotic reactions, especially those involving catalytic RNA (ribozymes). We demonstrate that a number of antibiotic-related secondary metabolites bind to group I introns and either inhibit splicing reactions or promote the formation of intron oligomers. This is consistent with the functional co-evolution of catalytic RNA and secondary metabolites as antibiotic inhibitors of translation, and supports the notion of an evolutionary relationship between group I introns and ribosomal RNA.


Roles for secondary metabolites in plants. More than about 20,000 secondary metabolites have now been identified and their isolation and characterization continues at an undiminishing rate. Although the production of most secondary metabolites is under genetic control, in relatively few cases have convincing arguments been put forward to rationalize their occurrence in terms of primary metabolic functions. Whatever the initial reason for their evolution, secondary metabolites are now an essential part of the armamentaria used by plants in the battle to survive and propagate, to the extent where the expenditure of energy, photosynthate and nutrients for their production can be demonstrated to be 'cost effective' for that. Their role may centre on defence of the producer against predators (herbivores), pathogens or competitors, on aid to pollination or seed dispersal, or on protection against or adaptation to extrinsic abiotic factors, or on combinations of these functions. Various examples are given in support of this argument.


Defensins: endogenous antibiotic peptides from human leukocytes. A variety of endogenous antimicrobial peptides equip mammals, amphibians, insects and plants to defend themselves against microbial pathogens. Defensins are small peptides of mammalian cells that contain 29-35 amino acid residues, including six invariant cysteines that form three intramolecular disulphide bonds. They are produced by the sequential proteolysis of precursors that contain approximately 95 amino acids and are synthesized by several types of cells, especially the bone marrow precursors of blood neutrophils. Defensins constitute 5-7% of the total protein in human neutrophils and are present in high concentration in the azurophil granules and phagocytic vacuoles. The production of defensins by human neutrophils amounts to approximately 10 mg/kg body weight per day. In certain mammalian species lung macrophages and specialized epithelial (Paneth) cells in the small intestine also produce defensins. Defensins are complexly folded, amphipathic, rich in antiparallel beta-sheet but devoid of alpha-helical domains. Their unusually broad antimicrobial spectrum encompasses Gram-positive and Gram-negative bacteria, many fungi, mycobacteria, spirochetes and several enveloped viruses. The antimicrobial properties of defensins result from their insertion into target cell membranes and the formation of voltage-sensitive channels. Given their abundance and broad spectrum of antimicrobial activity, defensins may contribute substantially to innate resistance to infection.


Microbial secondary metabolism: a new theoretical frontier for academia, a new opportunity for industry. Microbial secondary metabolites are the low molecular mass products of secondary metabolism. They include antibiotics, pigments, toxins, effectors of ecological competition and symbiosis, pheromones, enzyme inhibitors, immunomodulating agents, receptor antagonists and agonists, pesticides, antitumour agents and growth promoters of animals and plants. They have a major effect on the health, nutrition and economics of our society. They have unusual structures and their formation is regulated by nutrients, growth rate, feedback control, enzyme inactivation and induction. Regulation is influenced by unique low molecular mass compounds, transfer RNA, sigma factors and gene products formed during post-exponential development. The synthases of secondary metabolism are often coded by clustered genes on chromosomal DNA and infrequently on plasmid DNA. The pathways of secondary metabolism are still not understood to a great degree and thus provide a new frontier for basic investigations of enzymology, control and differentiation. Cloning and expression of genes in industrial microorganisms offer new opportunities for strain improvement and discovery. Microbial metabolites have already established themselves as coccidiostats, immunosuppressants, antihelminthic agents, herbicides and cholesterol-reducing drugs. Great potential exists for the discovery of antiviral, antiparasitic, antitumour and pharmacological compounds and new agricultural products. The future for natural products is bright indeed.


Why are secondary metabolites biosynthesized? Sophistication in the inhibition of cell wall biosynthesis by vancomycin group antibiotics. The evidence that secondary metabolites serve sophisticated roles in the survival strategy of the producer is briefly reviewed. This evidence stems from the common involvement of tens of kilobases of DNA in the programming of their synthesis, of up to several tens of discrete enzymic conversions in their biosynthesis, and of the existence of sophisticated mechanisms in the producers for resistance against their physiological effects. It also stems from a study of the molecular basis for these physiological effects. The molecular basis for the antibacterial action of the vancomycin group antibiotics is presented, and demonstrates that essentially every portion of these molecules appears to be finely honed to promote efficient antibacterial action.


Origins of secondary metabolism.

Origins of secondary metabolism. Secondary metabolites generally benefit their producers as poisons that protect them against competitors, predators or parasites. They are produced from universally present precursors (most often acetyl-CoA, amino acids or shikimate) by specific enzymes that probably arose by the duplication and divergence of genes originally coding for primary metabolism. Most secondary metabolites are restricted to single major taxa on the universal phylogenetic tree and so probably originated only once. But different secondary metabolic pathways have originated from different ancestral enzymes at radically different times in evolution. Secondary metabolites are most abundantly produced by microorganisms in crowded habitats and by plants, fungi and sessile animals like sponges, where chemical defence and attack rather than physical escape or fighting are at a premium. The first secondary metabolites were probably antibiotics produced in microbial mats over 3500 million years ago. These first ecosystems probably consisted entirely of eubacteria: archaebacteria and eukaryotes arose much later. As a phylogenetic context for considering the earliest origins of antibiotics I summarize a cladistic analysis of the explosive eubacterial primary diversification. This suggests that the most primitive surviving cells are the photosynthetic heliobacteria. Study of these and of the nearly as primitive chloroflexibacteria, spirochaetes and deinobacteria may provide the best evidence on the origins of secondary and primary metabolism.


Genes for polyketide secondary metabolic pathways in microorganisms and plants. Recent advances in molecular genetics have led to the isolation, sequencing and functional analysis of genes encoding synthases that catalyse the formation of several classes of polyketides. The structures of the genes and their protein products differ strikingly in the various examples. For Streptomyces aromatic polyketides, exemplified by granaticin and tetracenomycin, the synthases correspond to Type II (bacterial and plant) fatty acid synthases in consisting of distinct proteins for such processes as condensation, acyl carrier function and ketoreduction. In contrast, for actinomycete macrolides such as erythromycin, similar catalytic functions are performed by a set of multifunctional proteins resembling Type I (animal) fatty acid synthases, but with every step in chain-building being catalysed by a different enzymic domain. Penicillium patulum has a simple Type I synthase for 6-methylsalicylic acid. For plant chalcones and stilbenes, a single small polypeptide acts as a condensing enzyme for carbon chain-building and may be unrelated to any of the other polyketide and fatty acid synthases. Thus, although these systems share a common general mechanism of chain assembly, they must differ in the ways that synthase 'programming' has evolved to determine chain length, choice of chain starter and extender units, and handling of successive keto groups during chain assembly, and so control the great diversity of possible chemical products.


[Analysis of polynuclear aromatic hydrocarbons in kitchen and determination of urinary 1-hydroxypyrene of cooks]. Polynuclear aromatic hydrocarbons in the air of kitchen were determined using HPLC coupled with a fluorescence detector during the period of frying and cooking. About 40% of the benzo(a)pyrene were in the air and most of the benzo(a)pyrene were gathered on the smaller particles (less than 10 microns). Urinary 1-hydroxypyrene from 21 cooks was determined, its mean value was 0.627 mumol/mol creatinine, comparing with the control mean of 0.260 mumol/mol creatinine t test, showed that difference is statistically significant.


[Study on the frequency of primary rubella infection among early pregnant women]. Rubella virus is the common agent of prenatal infection. Congenital malformation rate is very high among pregnant women who are infected rubella primarily during the first trimester of pregnancy. Sera were taken from 10412 early pregnant women in 4 cities and 4 countries of 6 Provinces in 4 districts of China from April 1990 to October 1991 for detection of special IgM antibodies against rubella with Capture-EIA test. The results showed that the primary infection rate was 0.318% of those women without clinical symptoms of rubella during their early pregnant period. A high infection rate of 1.477% was found in those women with clinical symptoms, 4.7 times the former rate. The total infection rate of 10,412 women was 0.461%. By this rate at least some 40 thousand CRS infants will be born each year in China. This figure is more than the sum of patients suffering from poliomyelitis and Japanese encephalitis, and much more than the number disabled from these two infectious diseases. Some suggestions to prevent CRS were put forward in this paper.