Structural basis of the butyrylcholinesterase H-variant segregating in two Danish families.

The rare H-variant of human butyrylcholinesterase is a quantitative variant that reduces serum butyrylcholinesterase activity by about 90%. Individuals who are heterozygous for both the H-variant and the atypical variant are abnormally sensitive to the muscle relaxant succinylcholine. By using standard phenotypic serum assays, the Danish Cholinesterase Research Unit identified four individuals from two unrelated pedigrees who were heterozygous for both the H-variant (H) and the atypical (A) variant. DNA of these A/H individuals was extracted from white blood cells. Using the polymerase chain reaction and subsequent DNA sequencing, a point mutation was found at nucleotide 424 which changed amino acid 142 from valine to methionine. The previously identified atypical mutation, Asp 70 to Gly, was also seen, which segregated apart from the H-variant mutation in family studies. These two mutations were found in all four A/H individuals.

Haemostatic activation before and after surgery in patients with and without gastric malignancy.

Pre- and postoperative plasma levels of Prothrombin Fragment 1 + 2 (F1 + 2), Thrombin-antithrombin III complex (TAT), Fibrinopeptide A (FpA), Fibrin and Fibrinogen Degradation Products (FbDP, FgDP) and Soluble Fibrin (SF) were measured in 40 patients undergoing gastric surgery in order to compare patients operated for benign (n = 21) and malignant (n = 19) disease. Plasma levels of F1 + 2, TAT, FbDP and SF on the first postoperative day were significantly higher than before operation. F1 + 2 and FbDP levels were further increased one week after surgery, at which time FgDP levels were also higher than preoperatively. A significant postoperative increase in FpA levels was found only in patients with malignant disease. When age was taken into consideration, significant differences between patients with and without malignancy were found only in the late postoperative period, as cancer patients had higher FpA and FbDP levels one week after surgery and higher FbDP levels one month after discharge from hospital.

Clinical importance of plasma cholinesterase for the anaesthetist.

Plasma cholinesterase is a glycoprotein synthesized in the liver and is found in plasma, liver, intestinal mucosa and other tissues. Six percent to 7% of patients in most surgical populations have an abnormal plasma cholinesterase activity and about 65% of all cases of prolonged neuromuscular blockade following succinylcholine are due to genetic factors. This review focuses on the causes and clinical significance of plasma cholinesterase for the hydrolyses of succinylcholine. Diagnosis and treatment of prolonged response to succinylcholine in phenotypically normal patients, heterozygous abnormal patients and patients homozygous for the atypical gene is mentioned. Also presented is the relationship between plasma cholinesterase and the new relaxant mivacurium, and bambuterol, a prodrug to terbutaline. Additionally, the recent developments in the identification of the plasma cholinesterase genotypes are presented.

[Testicular varicocele. Reason for surgery and recurrence frequency]. / Varicocele testis. Operationsårsag og recidivfrekvens.

In the period 1979-1989, 63 patients were operated on for testicular varicocele. The study was a retrospective follow-up from case records and from a questionnaire. Thirty-eight had local complaints, 19 were operated on because of infertility and six had an asymptomatic varicocele. 10% had minor, reversible complications. 92% answered the questionnaire and 38% had a personal contact. 21% had recurrence of the varicocele although to a minor degree. In the infertility group, 42% succeeded in conception after operation.

[A case of male breast cancer with an unusual clinical course]. / Viril mammacancer med usaedvanligt klinisk forløb.

A case of male cancer of the breast with an unusual clinical course is presented. The local manifestations which simulated dermaphytosis are described.

[Herpes zoster induced reversible neurogenic bladder dysfunction. Urodynamic documentation of reversible bladder paralysis]. / Herpes zoster betinget reversibel neurogen blaeredysfunktion. Urodynamisk dokumenteret reversibel blaereparalyse.

A case of sacral herpes zoster with reversible neurogenic bladder dysfunction causing urinary retention is presented. Gradual reversibility of the motoric paralysis of the detrusor was demonstrated in cystometrograms. It is stressed that treatment should be primarily conservative and that repeated urodynamic examinations is essential.

[Plasma cholinesterase and abnormal reaction to suxamethonium injection. 20-year experience with the Danish Cholinesterase Registry]. / Plasmakolinesterase og unormal reaktion på injektion af suxamethon. Tyve års erfaring med Dansk Kolinesterase Kartotek.

For more than 20 years, the Danish Cholinesterase Research Unit (DCRU) has collected information about patients showing an abnormal response to succinylcholine. The purpose of this study was to evaluate our clinical findings in patients referred because of prolonged response following succinylcholine. Also, we wanted to evaluate the results of our prospective controlled studies of the effect of succinylcholine in patients with normal and abnormal plasma cholinesterase genotypes. An explanation for the apparent abnormal response to succinylcholine was only found in roughly 60% of the 1247 patients referred to the Unit. In the remaining nearly 40% of the patients the reason for the abnormal response remained obscure, though our results indicate that the anaesthetic technique, including hyperventilation or central respiratory depression, was most likely to be the reason. The significance of the different genotypes, including two newly discovered genotypes (AK, AH), for the reaction to succinylcholine was evaluated and found to be comparable to previous findings. Our results indicate that it is a problem for many anaesthetists to correctly diagnose a prolonged response to succinylcholine. We therefore urge the anaesthetist to use a peripheral nerve stimulator when faced with a case of apparent abnormal response to succinylcholine.

[Leiomyosarcoma of the spermatic cord]. / Leiomyosarkom i funiculus spermaticus.

Sarcoma of the spermatic cord is a rare disease with less than 300 cases reported in the literature. A case of leiomyosarcoma is presented, and an analysis of the therapeutic approaches of radical orchidectomy, and in some cases retroperitoneal lymph node dissection, chemotherapy and radiation is given. The total numbers of different types of sarcomas in the spermatic cord, reported to The Danish Department of Cancer Registration are briefly presented as well.

[Chronic volvulus of the stomach]. / Kronisk ventrikelvolvulus.

Gastric volvulus is an abnormal rotation of the stomach. The incidence seems to be equal for men and women, and all ages are represented. Gastric volvulus may present as an emergency or as a chronic condition. Acute volvulus is potentially lethal if unrecognized, while a chronic volvulus may cause symptoms for years if not treated. Gastric volvulus may be more common than previously estimated. Approximately 700 cases have thus far been documented. Two case reports of chronic gastric volvulus are presented, of which one was treated by laparoscopic surgery.

[Lengthening of the femur and tibia using Wagner's method]. / Forlaengelse af femur og tibia a.m. Wagner.

Thirty-nine patients (19 girls and 20 boys with an average age of 14 years) were submitted to 41 lengthening osteotomies by Wagner's method. The average preoperative shortening was 6.4 cm (3.5-25) and the average lengthening achieved in the femur was 6.4 cm (2.0-10.3) while the lengthening achieved in the tibia was 5.5-5.6 cm. In five patients, residual anisomelia varied between 3.5 to 10 cm and two of these patients have subsequently been submitted to supplementary lengthening. Complications occurred in 12 patients and, in particular, the postoperative course was complicated in two patients over the age of 20 years. It is concluded that lengthening of the femur and tibia by Wagner's method, and undertaken before growth has ceased, is a safe method of correction of considerable anisomelia.

[Colonoscopic appendectomy. Removal of a persisting iatrogenic invaginated appendix with colonoscopy]. / Koloskopisk appendektomi. Persisterende iatrogent invagineret appendix fjernet koloskopisk.

A case in which the appendix was invaginated with the object of incidental appendectomy but survived is described. Colonoscopic appendectomy was successfully performed.

[Experience from the first year of treatment of renal calculi with extracorporeal piezoelectric shockwave lithotripsy]. / Første års erfaring ved behandling af nyresten med ekstrakorporal nyrestensknusning med piezoelektrisk trykbølgedannelse.

The experience of the first year with piezoelectric extracorporeal lithotripsy is described. One hundred and eighty-eight patients commenced treatment of 194 renoureteric stone units (a total of 328 stones). Twelve per cent required analgesics during therapy. The median number of treatments was two (1-6) and median number of shock waves 4,200 (450-24,606). One hundred and twenty-three stone units had concluded treatment and control schedules at the follow up end date. After six months, 59% of the stone units were stone-free, while 17% had residual fragments up to 2 mm, and additional 15% had residual fragments between 2 and 6 mm. Only few and insignificant complications were observed. Extracorporeal shock wave lithotripsy by the Wolf Piezolith 2300 is a well-tolerated, effective, relative painless and not complicated treatment of renal stones, and an important part of modern treatment of staghorn- and ureteric stones.

Urethral cancer presenting with scrotal abscess formation. A differential diagnosis of acute epididymitis.

Primary urethral cancer in male subjects is briefly described, and a case is presented in which the formation of a scrotal abscess was the unusual presenting symptom.

Reaction to succinylcholine in two patients segregating for the plasma cholinesterase allele Ek.

Recently, several new alleles have been identified at plasma cholinesterase locus E1. We have had the opportunity for the first time to monitor the response to succinylcholine in two patients with the newly discovered genotype Ea1Ek1. The duration of action and type of neuromuscular block following succinylcholine 1.0 and 1.5 mg kg-1 i.v., respectively, were evaluated using train-of-four nerve stimulation and a Myograph 2000. One patient was anaesthetized with halothane, and the other was given a modified neurolept anaesthesia. Time to first response to nerve stimulation was 15 and 16 min, and time to 50% twitch height recovery was 19 and 20 min, respectively in the two patients. Both showed a depolarizing block. One of the patients received three bolus doses of succinylcholine 1 mg kg-1. This patient gradually developed a phase II block, which was easily reversed by edrophonium. The results indicate that patients with genotype Ea1Ek1 are slightly more sensitive to succinylcholine than are genotypically normal patients (Eu1Eu1) and patients heterozygous for the normal and the atypical gene (Eu1Ea1).

Plasma cholinesterase and abnormal reaction to succinylcholine: twenty years' experience with the Danish Cholinesterase Research Unit.

For more than 20 years, the Danish Cholinesterase Research Unit (DCRU) has collected information about patients showing an abnormal response to succinylcholine. The purpose of this study was, on the basis of the 20 years' experiences with the Unit, to evaluate our clinical findings in patients referred because of prolonged response following succinylcholine. Also, we wanted to evaluate the results of our prospective controlled studies of the effect of succinylcholine in patients with normal and abnormal plasma cholinesterase genotypes. An explanation for the apparent abnormal response to succinylcholine was found in 61.1% of the 1,247 patients referred to the Unit. Of the 1,247 patients, 28.5% were genotypically normal and 46.5% had an abnormal genotype. In the remaining 24.9% of the patients, the genotype could not be established. The time to sufficient recovery of neuromuscular function following succinylcholine 1.0-1.5 mg kg-1 was 15-30 min in patients heterozygous for one abnormal gene, 35-45 min in patients heterozygous for two abnormal genes and 90-180 min in patients homozygous for the atypical gene. Patients with two newly discovered genotypes (AK (5 patients) and AH (1 patient) showed slightly prolonged (20 min) and markedly prolonged (90 min) duration of action of succinylcholine, respectively. Our results indicate that it is a problem for many anaesthetists to correctly diagnose a prolonged response to succinylcholine. We therefore urge the anaesthetist always to use a peripheral nerve stimulator when faced with a case of apparent abnormal response to succinylcholine.

Transurethral prostatectomy compared with incision of the prostate in the treatment of prostatism caused by small benign prostate glands.

In a prospective, randomized study 60 patients with prostatism caused by small prostate glands (estimated weight < 20 g) had either transurethral prostatectomy (TURP, n = 31) or transurethral incision of the prostate (TUI, n = 29). Operating time and blood loss were significantly less in the group that underwent TUI. There were no differences between the groups in number of days with an indwelling catheter or days in hospital after operation. Eight patients in the TUI group required further operation, as did four in the TURP group, one of whom was discharged with a permanent indwelling catheter. In addition one patient developed a urethral stricture. Nine of the failures of treatment occurred within the first month. Fifty-one patients were followed up at 3 months and 47 were also seen at 12 months. Both operations significantly improved symptom scores and maximum flow rates compared with preoperatively, but the improvement in maximum flow rate was significantly better in the TURP group than in the TUI group. At 12 months TURP had also improved micturition time and voided volume, which TUI had not. Neither operation caused any significant change in sexual activity or erective potency postoperatively. Retrograde ejaculation was, however, seen in more than half of the patients in the TURP group, and only one in the TUI group. We recommend TUI for the treatment of prostatism caused by small prostate glands in patients who want to preserve normal ejaculation or are at poor surgical risk.

Detection of the plasma cholinesterase K variant by PCR using an amplification-created restriction site.

Ten individuals registered at the Danish Cholinesterase Research Unit were examined at the DNA level for the presence of the K allele of plasma cholinesterase, using amplification-created restriction sites (ACRSs). A further nine members of a family registered at the unit were tested for mutations of the K and atypical variants. The frequency of the K allele was calculated from examination of normal material from 25 individuals, representing 50 random alleles. The results show that the ACRS method successfully demonstrates the presence of the K variant, whose frequency in the Danish population was found to be 0.18. We conclude that this technique is a reliable and rapid non-radioactive diagnostic assay for detecting the plasma cholinesterase K variant.

Identification of human plasma cholinesterase variants using molecular biological techniques.

Genetic variation is one of several factors determining the level and quality of plasma cholinesterase activity (butyrylcholinesterase, BChE). The many genetic variants known today, and the resulting large number of genotypes and phenotypes, have complicated the problem of identifying individual BChE genotypes and phenotypes on the basis of enzymatic analyses alone. Modern molecular biological techniques have, however, permitted the development of diagnostic tests which allow BChE variants to be identified at the DNA level. Today, at least 20 genetic variants have been identified in this way. This review is an introduction to the principles of molecular biology used to identify the variants forms of the BCHE gene.