Chirurgische Therapie der fulminanten Lungenembolie

Zusammenfassung Die fulminante Lungenembolie wird nur noch selten chirurgisch behandelt. Die Operation wird als „Ultima-Ratio“-Therapie insbesondere bei Patienten mit kardiopulmonaler Reanimation angesehen. Vor dem Hintergrund eines erheblichen Anteils von Patienten mit residualer Obstruktion nach Lysetherapie mit der Gefahr der Entwicklung einer chronischen pulmonalen Hypertonie und besserer Risikostratifizierung haben einzelne Zentren wieder mehr Patienten einer offenen chirurgischen Embolektomie zugeführt. Hier sind Überlebensraten bis 89% in der perioperativen Phase erzielt worden. Möglich war dies durch Operationen am schlagenden, normothermen Herzen unter Verwendung spezieller Instrumente, wie sie bei der Pulmonalisthrombendarteriektomie Verwendung finden. Die Bestätigung dieser guten Ergebnisse bei noch hämodynamisch stabilen Patienten mit mäßiger bis starker Einschränkung der rechtsventrikulären Funktion durch die Autoren und andere rechtfertigt den Einsatz dieses Verfahrens an Kliniken mit angeschlossener Herzchirurgie in einer früheren Phase, in welcher der Patient noch nicht reanimationspflichtig ist. Die Durchführung einer kontrollierten, randomisierten Studie zur Erfassung des tatsächlichen Stellenwerts im Vergleich zur Lysetherapie wäre wünschenswert im Sinne einer bestmöglichen Therapie für den Patienten. Abstract Surgical embolectomy for massive pulmonary embolism (PE) has become a rare procedure. Often, it is viewed as a last-chance option for patients undergoing cardiopulmonary resuscitation after massive PE. Thus thrombolytic therapy has become the treatment of choice. However, a significant proportion of patients suffers from residual obstruction after thrombolytic therapy and faces the development of chronic pulmonary hypertension. Therefore, some centers have regained interest in surgical embolectomy after improved risk stratification and reported very good results. Perioperative survival rates up to 89% have been reported. This was accomplished by surgery on the ECC-(extracorporeal circulation-)supported, beating, normothermic heart and utilization of special instruments. These encouraging results have been confirmed by the authors and others in patients with stable systemic hemodynamics but moderate to severe right ventricular dysfunction. The more widespread use of surgical embolectomy seems warranted. A randomized, controlled trial is overdue to determine the benefits of this therapy in stable patients compared with thrombolytic therapy if “best-practice” therapy is to be achieved for the patients’ benefit.     

Transplantation of monocytes: a novel strategy for in vivo augmentation of collateral vessel growth

Therapeutic augmentation of collateral vessel growth (arteriogenesis) is of particular clinical interest. Because monocytes localize to areas of collateral growth and create a highly arteriogenic environment through secretion of multiple growth factors, we tested the hypothesis that monocyte "homing" can therapeutically be exploited. We have used a rabbit model of arteriogenesis to investigate the therapeutic potential of transplanted rabbit monocytes that were either ex vivo stimulated or adenovirally transduced to express a transgene encoding an arteriogenic growth factor. The monocytes were intravenously injected 24 hr or 7 days after ligation of the animal's right femoral artery. Seven days after transplantation collateral flow was determined with a doppler flow probe and collateral vessels were quantified angiographically. Whereas transplantation of allogeneic cells (same species) resulted in a strong promotion of arteriogenesis, most likely through induction of local inflammation and recruitment of recipient monocytes, transplantation of autologous cells (same animal) was not able to significantly augment collateralization. However, when autologous monocytes were used as vehicles to deliver granulocyte macrophage-colony stimulating factor as therapeutic transgene, collateralization was strongly augmented. Their localization to the site of collateral development posttransplantation was demonstrated by ex vivo transduction with beta-galactosidase. Because isolation of monocytes is clinically widely available their ex vivo engineering and transplantation represents an intriguing new strategy for therapeutic arteriogenesis.     

Early and late complications following laparoscopic adjustable gastric banding

There is limited U.S. data on short- and long-term complications of laparoscopic adjustable gastric banding (LAGB) as a treatment option for morbid obesity. Hereafter, we present our experience with the first 154 consecutive LAGBs performed at Loyola University Medical Center. Inpatient and outpatient charts were reviewed retrospectively for all patients undergoing LAGB between November 2001 and February 2003 for perioperative morbidity and mortality and repeat operations. Thirty-seven men (24%) and 117 women (76%) underwent LAGB in a 16-month period. There was one (0.6%) death from postoperative myocardial infarction (MI) and one (0.6%) pulmonary embolism. Six (3.9%) patients required readmission to the hospital for dehydration. During a mean follow-up of 33 weeks (range, 4-69 weeks), 14 (9%) patients required repeat operations. There were five (3.2%) band slippages and one (0.6%) gastric erosion. Three bands were removed laparoscopically. Three slippages were revised laparoscopically. One patient underwent laparoscopic cholecystectomy. Seven patients (4.5%) required port revisions for catheter disconnection (4), leak at port site (2), or flipped port (1). LAGB is a safe operative approach for the management of morbid obesity. The incidence of postoperative complications can be minimal with application of a standardized technique. LAGB should be strongly considered for morbidly obese patients who have failed nonoperative management.     

Minimally invasive direct coronary artery bypass in a cardiac transplant recipient with allograft vasculopathy

Coronary bypass operation with cardiopulmonary bypass has provided disappointing results for the treatment of cardiac allograft vasculopathy (CAV). We describe a 61-year-old man who underwent heart transplantation for secondary dilated cardiomyopathy in 1995. Consecutively, CAV developed with clinically silent left anterior descending occlusion. After angiographic diagnosis in 1998 he successfully underwent a minimally invasive direct coronary artery bypass procedure. Annual coronary angiography showed a patent left internal mammary to left anterior descending bypass graft more than 4 years after operation. In select cases, minimally invasive direct coronary artery bypass is a therapeutic option for the treatment of CAV.     

Insulin secretion in type 1 diabetes

Type 1 diabetes, a chronic autoimmune disease, causes destruction of insulin-producing beta-cells over a period of years. Although many markers of the autoimmune process have been described, none can convincingly predict the rate of disease progression. Moreover, there is relatively little information about changes in insulin secretion in individuals with type 1 diabetes over time. Previous studies document C-peptide at a limited number of time points, often after a nonphysiologic stimulus, and under non-steady-state conditions. Such methods do not provide qualitative information and may not reflect physiologic responses. We have studied qualitative and quantitative insulin secretion to a 4-h mixed meal in 41 patients with newly diagnosed type 1 diabetes and followed the course of this response for 24 months in 20 patients. Newly diagnosed diabetic patients had an average total insulin secretion in response to a mixed meal that was 52% of that in nondiabetic control subjects, considerably higher than has been described previously. In diabetic patients there was a decline of beta-cell function at an average rate of 756 +/- 132 pmol/month to a final value of 28 +/- 8.4% of initial levels after 2 years. There was a significant correlation between the total insulin secretory response and control of glucose, measured by HbA(1c) (P = 0.003). Two persistent patterns of insulin response were seen depending on the peak insulin response following the oral meal. Patients with an early insulin response (i.e., within the first 45 min after ingestion) to a mixed meal, which was also seen in 37 of 38 nondiabetic control subjects, had a significantly accelerated loss of insulin secretion, as compared with those in whom the insulin response occurred after this time (P < 0.05), and significantly greater insulin secretory responses at 18 and 24 months (P < 0.02). These results, which are the first qualitative studies of insulin secretion in type 1 diabetes, indicate that the physiologic metabolic response is greater at diagnosis than has previously been appreciated, and that the qualitative insulin secretory response is an important determinant of the rate of metabolic decompensation from autoimmune destruction.     

Purinergic modulation of synaptic input to Purkinje neurons in rat cerebellar brain slices

Adenosine triphosphate (ATP) is a cotransmitter and an extracellular neuromodulator in nervous systems, and it influences neural circuits and synaptic strength. We have studied a stimulating effect of ATP (100 micro m) on the synaptic input of Purkinje neurons in acute cerebellar brain slices of juvenile rats (p14-19). Bath application of ATP increased the frequency of spontaneous postsynaptic currents (sPSCs) almost twofold, and increased their amplitude. These effects were fully suppressed by the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid (PPADS; 10 microm), or after blocking action potentials with tetrodotoxin (TTX; 0.5 microm), but were not impaired by inhibiting ionotropic, non-NMDA glutamate receptors with 2,3-dioxo-6-nitro-1,2,3,4,-tetrahydrobenzo[f]quinoxaline-7-sulphonamide (NBQX; 5 microm). The frequency of sPSCs was reduced by 35% by PPADS and increased by 50% after inhibiting ectonucleotidase with ARL67156 (50 microm), suggesting intrinsic, 'tonic', stimulation of synaptic activity via P2 receptors. The pharmacological profile indicated that the ATP effect was mediated by both P2X and P2Y receptors, most probably of the P2X5- and P2Y(2,4)-like subtypes. The action potential frequency in the inhibitory basket cells was increased by 65%, and decreased in Purkinje neurons by 25%, in the presence of ATP. Our results suggest that ATP continuously modulates the cerebellar circuit by increasing the activity of inhibitory input to Purkinje neurons, and thus decreasing the main cerebellar output activity, which contributes to locomotor coordination.     

Synthesis of new hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives with an arylpiperazine moiety as ligands for 5-HT(1A) and 5-HT(2A) receptors, Part 2

The synthesis of new of 4-aryl-hexahydro- (11-16) and (R,R)(S,S)4-aryl-octahydropyrido[1,2-c]pyrimidine (23-27) derivatives bearing a aryl- or heteroarylpiperazinyl moiety in position 2 is described. The derivatives of 4-aryl-hexahydro- (1-5) and (R,R)(S,S)4-aryl-octahydropyrido[1,2-c]pyrimidin-1,3-dion (17-19) served as starting compounds for further synteses. The N-alkylation of the imide moiety in compounds 1-5 and 17-19 by 1,4-dibromobutane gave the respective monbromobutyl derivatives 6-10 and 20-22. The final derivatives 11-16 and 23-27 have been produced by condensation of the obtained bromoderivatives with selected 1-aryl and 1-heteroarylpiperazines. Compounds 11-16 and 23-27 were tested for their affinity towards 5-HT(1A), 5-HT(2A) and alpha1 receptors, using a radioligand binding assay.     

Use of mandelic acid condensation polymer (SAMMA), a new antimicrobial contraceptive agent,for vaginal prophylaxis

OBJECTIVE: To assess the contraceptive properties, antimicrobial activity, and safety of mandelic acid condensation polymer (SAMMA). DESIGN: Experimental study of SAMMA's in vitro and in vivo properties. SETTING: Academic research laboratories. PATIENT(S): Healthy volunteers for semen donation in an academic research environment. INTERVENTION(S): Inhibition of sperm function indicators, conception, sexually transmitted infection-causing pathogens (including HIV), and lactobacilli was evaluated. Safety indicators were studied. MAIN OUTCOME MEASURE(S): Quantitation of SAMMA's effect on microbial infectivity or multiplication and on sperm function in vitro; evaluation of contraceptive efficacy in vivo; assessment of safety in vitro and in vivo. RESULT(S): Mandelic acid condensation polymer is not cytotoxic toward lactobacilli, microbial host cells, and spermatozoa. The compound inhibits hyaluronidase and acrosin, induces sperm acrosomal loss, and is contraceptive in the rabbit model. Mandelic acid condensation polymer prevents infectivity of HIV and herpesviruses 1 and 2 and, to a lesser extent, of Chlamydia trachomatis. It inhibits the multiplication of Neisseria gonorrhoeae. Mandelic acid condensation polymer is not mutagenic, has low acute oral toxicity, and is safe in the rabbit vaginal irritation assay. CONCLUSION(S): Mandelic acid condensation polymer inhibits sperm function, is contraceptive, has broad-spectrum antimicrobial activity, and is highly safe. Further development as a microbicide is warranted.     

A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in patients with chronic anal fissures

BACKGROUND: Anal fissure is a common painful condition affecting the anal canal. The majority of acute fissures heal spontaneously. However, some of these acute fissures do not resolve but become chronic. Chronic anal fissures were traditionally treated by anal dilation or by lateral sphincterotomy. However, both of these surgical treatments may cause a degree of incontinence in up to 30% of patients. Several recent trials have shown that nitric oxide donors such as glyceryl trinitrate (GTN) can reduce sphincter pressure and heal up to 70% of chronic fissures. AIM: This study addressed the dose-response to three different concentrations of GTN ointment compared with placebo in a double blind randomised controlled trial. METHOD: A double blind, multicentre, randomised controlled trial was set up to compare placebo ointment against three active treatment arms (0.1%, 0.2%, and 0.4% GTN ointment applied at a dose of 220 mg twice daily) in chronic anal fissures. The primary end point was complete healing of the fissure. RESULTS: Two hundred patients were recruited over an eight month period from 18 centres. After eight weeks of treatment the healing rate in the placebo group was 37.5% compared with 46.9% for 0.1%, 40.4% for 0.2%, and 54.1% for 0.4% GTN. None was significantly better than the placebo response. A secondary analysis excluded fissures without secondary criteria for chronicity. Healing rates were then found to be 24% in the placebo group compared with 50% in the 0.1% GTN group, 36% in the 0.2% group, and 57% in the 0.4% GTN group. These values were statistically significantly different for the placebo group compared with 0.1% GTN, 0.4% GTN, and for the GTN treated group as a whole. CONCLUSIONS: The results of this study have demonstrated the significant benefit of topical GTN when applied to patients suffering from chronic anal fissures but acute fissures showed a tendency to resolve spontaneously. The high proportion of fissures which healed in the placebo group suggests that the definition of "chronicity" needs to be reassessed. Further studies are required to confirm the optimal therapeutic strategy.