Detubularized right colonic reservoir with intussuscepted ileal nipple valve or stapled ileal (“Lundiana”) outlet

Summary In a prospective randomized study, patients undergoing cystectomy and continent urinary diversion by means of a detubularized right colonic reservoir were randomized to one of two types of outlet: either an intussuscepted ileal nipple value (n=15) or a stapled ileal (Lundiana) outlet (n=15). There were no early complications from the reconstruction. Subsequently, one ileal nipple outlet required revision because of progressive catheterization difficulties. In the Lundiana group, perforation of the reservoir occurred in one case and a narrow stomal opening was revised in local anesthesia in two cases. Urodynamic assessment revealed similar pressures at rest for the two outlets. At stress (concomitant with reservoir contraction), there was a distinct increase in outlet pressure in the nipple valves, but this was rarely encountered in the Lundiana group. Questionnaires showed episodes of urinary leakage to be more common in the Lundiana group, whereas the reverse applied to catheterization difficulties. In both groups, however, the great majority of patients were satisfied or very satisfied with the function of the urinary tract.     

Electroconvulsive therapy in Parkinson's syndrome with “on-off” phenomenon

Summary During long-term treatment with L-dopa in Parkinson's syndrome on-off phenomenon develops in many cases, often entailing considerable therapeutic problems. Decreased sensitivity in postsynaptic striatal dopamine (DA) receptors has been shown to occur in parkinsonian patients during long-term treatment with L-dopa. This has been suggested as one possible mechanism for development of the on-off phenomenon. In contrast to L-dopa treatment electroconvulsions have been shown to increase sensitivity in the DA receptors, when administered to animals.The antiparkinsonian effect of electroconvulsive therapy (ECT) was investigated in five parkinsonian patients with on-off phenomenon, with or without concomitant signs of mental depression. ECT was administered according to praxis in treatment of mental depression. Drug therapy, including L-dopa, was maintained on previously adjusted doses during and after ECT.A marked improvement in the parkinsonian symptoms as well as in the on-off phenomenon occurred in three of the patients, persisting for several months. The other two patients showed only slight and transient improvement.It thus seems that ECT may be useful as a supplementary treatment in parkinsonian patients with on-off phenomenon. The antiparkinsonian effect of ECT is probably mediated by increased sensitivity in postsynaptic DA structures.     

Can a community development model be used for health programmes in an industrialized country?

Injury resulting from accident is a serious public health problem in Sweden, as it is in the rest of the world. Theoretically, almost all incidents can be prevented. However, in practice, injury-prevention is a complex problem. A community-level intervention programme for prevention of accidents was developed in the municipality of Sollentuna, Stockholm County. The primary strategy has been to involve the community through representatives as well as through local organizations and groups. Project organization has been built up in cooperation with the municipal primary health-care department, local authorities, voluntary organizations and citizen agencies. A common opinion is that it is the actual process in a community programme which is important, that alters the type of involvement from a ‘top-down’ to a ‘bottom-up’ approach. Can a local community take over responsibility for running such a programme which has been initiated by an external authority or organization? We think that, at least for Swedish circumstances, the community development approach is far too optimistic in its expectation that community members should and can stay actively involved in programme decisions. Based on our experience, it does not seem possible to maintain a broad self-sustained programme solely with input from community members.     

Prognostic potential of flow cytometric S-phase and ploidy prospectively determined in primary breast carcinomas

In a prospective study of a consecutive breast cancer series accumulated in the period 1978–82, the S-phase fraction (SPF) and ploidy status were determined by flow cytometry performed on cell nuclei derived from samples of 580 primary tumors. Sixty percent of the tumors were non-diploid. After correction for debris the median SPF values were 7.3% overall, 12% for non-diploid tumors, and 2.9% for diploid tumors (2.6% when nodal subsets N2 and N3 and cases with metastases at presentation were excluded). The SPF values correlated both to tumor size (p=0.008) and to the number of positive axillary lymph nodes (p=0.03).At clinical follow-up in 1986, 467 unilateral breast cancer patients who had undergone radical treatment for cure could be evaluated with respect to the prognostic value of both the SPF value and ploidy status. The median duration of follow-up was then 59 months (range 2–90), and the median time-to-recurrence 24 months (range 2–69, n=137).At follow-up in 1991, 201/467 of the patients had died, the median duration of follow-up being 50 months (range 2–126) for the deceased, and 119 (range 6–148) for the survivors. In multivariate analysis (Cox's proportional hazards models), the strongest independent predictors of distant recurrence-free survival (DRFS) were the number of positive axillary lymph nodes (p<0.0001), the debris-corrected SPF value alone (p=0.003,versus p=0.05 for uncorrected value), and ploidy status combined with the corrected SPF value (p=0.0002). When age was taken into account, both the corrected SPF value and the ploidy-SPF combination were predictors of crude survival (p=0.006 and p=0.002, respectively).In univariate life-table analysis, the 5-year DRFS rate was 93% in node-negative (N0) cases with an SPF<7.3%, as compared to 80% in those with an SPF7.3% (p=0.005). Among node-positive cases, the prognostic value of the SPF was confined to those with 1–3 positive nodes, the 5-year DRFS rate being 68% in cases with an SPF<7.3%, as compared to 40% in cases with an SPF7.3% (p=0.01).Ploidy status and SPF were combined to form four groups: diploid & SPF<2.6% (DL), diploid & SPF2.6% (DH), non-diploid & SPF<12% (NDL), and non-diploid & SPF12% (NDH). Among node-negative patients, the DRFS rate fell from 95% in the DL group to 87% in the NDL group, with the DH group at an intermediate level, as compared with 74% (p=0.03) for the NDH group which accounted for the bulk of the early distant recurrences. Among patients with 1–3 positive lymph nodes, the 5-year DRFS rate was 68% in both the groups with low SPF values (DL and NDL), as compared with 45% in the DH group (p=0.03), and 37% in the NDH group (p=0.006).In this study, the flow cytometry SPF value, alone or in combination with ploidy status, yielded the most profound additional prognostic information, enabling both node-negative patients with a high probability of cure and patients at risk of early relapse to be identified. Among node-positive patients, the prognostic value of the SPF value was confined to those with 1–3 positive axillary lymph nodes (the predominant node-positive subgroup), enabling a high and a low DRFS rate subgroup to be distinguished – a useful distinction where selection for adjuvant drug treatment is concerned. As the predictive strength of the SPF value was enhanced when correction was made for debris, we would recommend that the effect of such factors as debris be minimized as far as possible when flow cytometry-derived SPF values are to be used for prognostic purposes.     

Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia

Summary Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg · kg^-1 i.p., followed by an i.v. infusion of 225 g · kg^-1 · min^-1 for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg · kg^-1 given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg · kg^-1 i.p., followed by an i.v. infusion of 225 g · kg^-1 · min^-1 for 6 h), with dizocilpine 0.33 mg · kg^-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40116 [D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] 10 mg · kg^-1 given i.p.. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist. We conclude that neuronal damage continues to develop in the striatum and in cortical brain regions in the posthypoglycemic period and that both NMDA- and AMPA-receptors contribute to this process, possibly by a change in the cellular response to both AMPA- and NMDA-receptor stimulation.     

Pancreatic tumors in multiple endocrine neoplasia type 1: Clinical presentation and surgical treatment

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-erm outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors. This strategy should be applied especially in patients with aggressive family histories to possibly reduce the risk of malignant tumor progression.

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Resumen Entre 33 individuos con tumores pancréaticos endocrinos como componente del síndrome de neoplasia endocrina múltiple tipo 1 (NEM-1), 19 pacientes (58%) tenían hipergastrinemia, 7 (21%) hiperinsulinismo y 7 (21%) lesiones clínicas no funcionantes. En la totalidad de los pacientes sometidos a cirugía pancreática fue hallado por lo menos un tumor, incluso en aquellos con examenes de localización negativos anteriores a la operación. Estos pacientes también albergaban tumores macroscópicos, así como numerosos microadenomas; con frecuencia las lesiones demostraron inmunocoloración con diferentes hormonas, principalmente polipéptido, insulina, glucagón y somatostatina. Se encontraron lesiones endocrinas duodenales en 4 de cada 5 pacientes investigados, las cuales colorearon con gastrina y anticuerpos a la somatostatina. Se practicó resección pancreática distal (principalmente resección subtotal) en 18 pacientes, eventualmente combinada con enucleación del tumor (cuando éste se hallaba ubicado en la cabeza del páncreas) o duodenectomía; solamente unos pocos pacientes fueron sometidos a simple enucleación del tumor o al procedimiento de Whipple. El resultado a largo plazo fue más favorable en los pacientes con hiperinsulinismo, puesto que sólo uno presentó recurrencia clínica. Los pacientes con hipergastrinemia exhibieron apenas una disminución transitoria de los valores de gastrina sérica luego de la cirugía pancreática. Cuarenta y siete por ciento del conjunto tuvo o desarrolló metástasis, en tanto que la extensión local del tumor se presentó en 57% de los casos con lesiones no funcionantes. Nueve pacientes murieron por progresión de la neoplasia en el curso del seguimiento. En acuerdo con sugerencias previas, se considero quo la cirugía está indicada en pacientes con NEM-1 e hiperinsulinismo, aún en los casos en que no se visualiza radiológicamente la lesión, pero que la indicación puede ser ampliada para incluir también pacientes con sólo marcadores bioquímicos, tales como niveles elevados de gastrina, indicativos de la presencia de tumores macroscópicos. Esta estrategia debe ser aplicada principalmente en aquellos pacientes con historia familiar agresiva, con lo cual tal vez se reduce el riesgo de progesión maligna del tumor.

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Résumé Parmi 33 patients ayant une tumeur pancréatique endocrine due à une néoplasie endocrine multiple de type 1 (MEN-1), 19 (58%) avaient une hypergastrinémie, 7 (21%) un hyperinsulinisme et 7 (21%) une lésion cliniquement muette. On a mis en évidence au minimum une grosse tumeur chez tous les patients, y compris chez ceux dont les examens préopératoires de dépistage tumoral étaient négatifs. Les patients étaient également porteurs de tumeurs macroscopiques et de nombreux microadénomes. Les lésions montraient souvent un immunomarquage positif pour de multiples hormones, principalement le polypeptide pancréatique, l'insuline, le glucagon et la somatostatine. Des lésions endocrines duodénales furent retrouvées chez 4 des 5 patients explorés; elles montraient un immunomarquage avec les anticorps angigastrine et anti-somatostatine. Une résection pancréatique distale, le plus souvent subtotale, a été réalisée chez 18 patients. Elle était éventuellement complétée par une énucléation tmorale de la tête ou par une duodénotomie. Peu de patients ont bénéficié d'une simple énucléation ou d'une intervention de Whipple. L'évolution postopératoire à long terme a été plus favorable en cas d'insulinome puisque seul un patient a eu une récidive clinique. Les patients atteints de gastrinome n'ont présenté que transitoirement une diminution des taux sériques de gastrine après la chirurgie pancréatique. Quarante sept pour cent de ces patients avaient ou ont développé des métastases contre 57% des patients porteurs de lésions sans traduction clinique. Neuf patients sont décédés en raison de l'extension tumorale au cours du suivi. Conformément à des suggestions antérieures, la chirurgie semble indiquée chez les patients atteints de MEN-1 avec hyperinsulinisme même si la radiologie ne visualise pas de lésion. Mais cette indication peut être élargie aux patients dont seuls les paramètres biologiques sont en faveur d'une grosse tumeur (dont l'hypergastrinémie). Cette stratégie pourrait convenir particulièrement aux patients ayant des antécédents familiaux importants; elle permettrait peut-être de réduire le risque d'extension tumorale.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.     

Pre-operative and post-operative radiotherapy and rectal cancer

The appropriate role for additional radiotherapy in patients with resectable rectal cancer is not yet settled. Irradiation has been considered by surgeons and radiotherapists as superfluous since no effect on survival has been shown. However, numerous trials have demonstrated that perioperative radiotherapy decreases an often high local recurrence rate while others believe it has a definite place in routine management. Several surgeons have, on the contrary, claimed that a skilled surgeon compared to a less skilled surgeon, will get the same acceptably low local recurrence rates. Since we will probably never have a randomized trial comparing good and bad surgeons, this argument cannot be settled. A further obstacle arises in the difficulty of persuading surgeons to organize their routine work so that it is performed in an optimal way by those specializing in this field. The question also arises whether radiotherapy should be delivered pre-operatively, postoperatively or as a sandwich technique, i.e., both pre-operatively and postoperatively. According to radio-biological considerations and results from reported trials, the best effect on local tumor control has been achieved using pre-operative radiotherapy.

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Resumen Aún no se ha defindo la indicación apropriada para radioterapia adicional en pacientes con cáncer rectal. La irradiación ha sido considerada como superflua por cirujanos y radioterapeutas, puesto que no se ha demostrado efecto sobre la sobrevida. Sin embargo, numerosos ensayos clínicos han demostrado que la radioterapia perioperatoria disminuye la que con frecuencia es una elevada tasa de recurrencía local, mientras ostros creen que tiene un lugar definido en el manejo rutinario. Por el contrario, varios cirujanos han planteado que un cirujano hábil comparado con uno menos hábil, logra las mismas aceptables tasas de recurrencia, alg que jamás se ha decidido, puesto que nunca habremos de realizar ensayos comparando buenos cirujanos con malos cirujanos. Un obstáculo adicional surge de la dificultad en cuanto a persuadir a los cirujanos de organizar su trabajo rutinario de tal manera que sea realizado en forma óptima por aquellos que se especializan en este campo. También ha surgido el interrogante sobre si la radioterapia debe ser administrada preoperatoriamente, postoperatoriamente o como técnica de sandwich, o sea tanto pre como postoperatoriamente. Según consideraciones radio-biológicas y los resultados de los ensayos clínicos, el mejor efecto sobre el control local del tumor ha sido logrado mediante el uso de radioterapia preoperatoria.

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Résumé La place de la radiothérapie adjuvante chez les patients ayant un cancer du rectum reste discutée. La radiothérapie est estimée superflue par certains chirurgiens et radiothérapeutes car aucun bénéfice n'a eté clairement démontré en ce qui concerne la survie. De nombreux essais cliniques ont indiqué, cependant, que la radiothérapie périopératoire diminuait le taux habituellement élevé des récldives locales, et certains estiment que la radiothérapie a toujours une place dans le schéma thérapeutique. D'autres, au contraire, croient que la quialité et l'expérience de l'opérateur influencent directement le taux de récidives, et équivalent l'efficacité de la radiothérapie. Puisqu'il est peu probable qu'on réalise une étude randomisée entre les bons et les mauvais chirurgiens, on ne peut régler cette querelle. Un autre obstacle incontournable semble être de persuader les chirurgiens d'organiser leur travail de façon à ce que cette chirurgie soit faite par des spécialistes. Le meilleur moment pour réaliser la radiothérapie (préopératoire, postopératoire, ou les deux) reste à déterminer. Selon les données radiobiologiques et les résultats des essais contrôlés, il semble que le meilleur contôle sur les récidives locales soit obtenu par la radiothérapie préopératoire.

     

Developmentally Regulated Expression of HDNF/NT-3 mRNA in Rat Spinal Cord Motoneurons and Expression of BDNF mRNA in Embryonic Dorsal Root Ganglion

Northern blot analysis was used to demonstrate high levels of hippocampus-derived neurotrophic factor/neurotrophin-3 (HDNF/NT-3) mRNA in the embryonic day (E) 13 - 14 and 15 - 16 spinal cord. The level decreased at E18 - 19 and remained the same until postnatal day (P) 1, after which it decreased further to a level below the detection limit in the adult. In situ hybridization revealed that the NT-3 mRNA detected in the developing spinal cord was derived from motoneurons and the decrease seen at E18 - 19 was caused by a reduction in the number of motoneurons expressing NT-3 mRNA. The distribution of NT-3 mRNA-expressing cells in the E15 spinal cord was very similar to the distribution of cells expressing choline acetyltransferase or nerve growth factor receptor (NGFR) mRNA. Moreover, a striking similarity between the developmentally regulated expression of NT-3 and NGFR mRNA was noted in spinal cord motoneurons. A subpopulation of all neurons in the dorsal root ganglia expressed brain-derived neurotrophic factor (BDNF) mRNA from E13, the earliest time examined, to adulthood. These results are consistent with a trophic role of NT-3 for proprioceptive sensory neurons innervating the ventral horn, and imply a local action of BDNF for developing sensory neurons within the dorsal root ganglia.     

Screening for chlamydia trachomatis in military personnel by urine testing

Summary In order to determine the infection rate ofChlamydia trachomatis in young males in Austria an epidemiological study was performed on 335 male Austrian soldiers attending the military hospital for a health check-up procedure. Three hundred twenty-nine (98.2%) of the screened males were clinically asymptomatic. Chlamydial diagnosis was established by testing first catch urine (FCU). Urine sediment was tested by an enzyme immunosorbent assay (EIA) and by a direct immunofluorescent test (DIF test). Positive results in both tests were defined true positives. In 41 (12.2%) of all the 335 soldiers a genital chlamydial infection could be demonstrated by a positive result of the sediment of the FCU in both tests. 93% of the positive results in the DIF test could be confirmed by the EIA whereas only 77% of the positive EIA tests were also positive in the DIF test. Data on genital symptoms and the history of sexually transmitted diseases (STDs) as well as information about sexual relationships were available from all persons included in the study and did not differ between chlamydia positive and negative ones. The study demonstrates a high infection rate withC. trachomatis in mostly asymptomatic young males when using FCU for chlamydial diagnosis. Due to the discrepancy between the EIA and the DIF test, positive results of the sediment of FCU in the EIA test should be confirmed by the DIF test to eliminate false positive cases.

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Screening auf Chlamydia trachomatis im Urin bei Militärpersonal

Zusammenfassung Um bei vorwiegend asymptomatischen männlichen Jugendlichen die Infektionsrate mitChlamydia trachomatis zu bestimmen, wurde im Rahmen einer Routinekontrolle in einem Militärspital eine Chlamydienuntersuchung bei insgesamt 335 Soldaten durchgeführt. Neben der Diagnose vonC. trachomatis wurden Daten über klinische Beschwerden, die Zahl früherer genitaler Kontaktinfektionen sowie über das Sexualverhalten der untersuchten Personen erhoben. Die Chlamydiendiagnostik erfolgte durch die Antigenbestimmung des Harnsediments mittels Enzymimmunassay (EIA) und direkter Immunfluoreszenz (DIF). Der Nachweis vonC. trachomatis im Harnsediment war bei 41 (12,2%) Männern durch ein positives Resultat in beiden Testverfahren möglich. 93% der im DIF-Test positiven Ergebnisse stimmten mit jenen im EIA überein, während nur 77% der positiven Resultate des EIA im DIF-Test bestätigt werden konnten. 98,2% der untersuchten Männer waren klinisch asymptomatisch, chlamydien-positive Personen unterschieden sich weder im Sexualverhalten noch in der Zahl früherer Infektionen von jenen mit negativem Chlamydienergebnis. Die erhobenen Daten weisen auf eine hohe Zahl klinisch asymptomatischer Chlamydieninfektionen bei vorwiegend jungen Männern hin. Aufgrund der diskrepanten Ergebnisse positiver Resultate in beiden Testverfahren sollte ein Antigennachweis im EIA aus dem Harnsediment durch den DIF-Test bestätigt werden. Der Nachweis einer Chlamydieninfektion aus dem Harnsediment kann lediglich dann empfohlen werden, wenn die Gewinnung von Patientenmaterial aus dem Urethralsekret nicht möglich ist.

     

The costs of treating hypertension--an analysis of different cut-off points

In this article the effects of different cut-off points for hypertension treatment are analysed, with respect to treatment costs. A theoretical blood pressure distribution is used to calculate the potential annual cost of treating all persons in Sweden above certain cut-off points for drug treatment. A lowering of the cut-off point from 105 mm Hg to 100 mm Hg diastolic blood pressure could potentially lead to an increase in annual costs of approximately 80m pounds. Further lowering from 100 to 95 mm Hg in turn could increase annual costs by about 110m pounds. The potential annual cost of treating all persons (roughly 1.6 million) with a diastolic blood pressure of greater than or equal to 95 mm Hg with drugs is calculated as being roughly 40 pounds per inhabitant in Sweden. The Swedish cut-off point for treatment (95 mm Hg) can be expected to lead to roughly 50 per cent higher treatment costs than the British cut-off point (100 mm Hg).